Heteroaryl substituted piperidine derivatives as l-cpt1 inhibitors

(54) Title: COMPOUNDS, PROCESS FOR THEIR MANUFACTURING, PHARMACEUTICAL COMPOSITIONS THAT UNDERSTAND THEM, METHOD FOR THE THERAPEUTIC AND / OR PROPHYLACTIC TREATMENT OF DISEASES THAT ARE MODULATED BY L-CPT1 INHIBITORS, AND THEIR USE (30) Union priority: 01 / 12/2005 ep osm 560.8 (73) Holder (s): f hoffmann-la roche ag (72) Inventor (s): Jean Ackermann, Konrad Bleicher, Odile Chomienne, Patrizio Mattei, Simona M. Ceccarelli Grenz, TANJA SCHULZ-GASCH (74) Attorney (s): Vieira de Mello Advogados (57) Summary: compounds, process for their MANUFACTURE, PHARMACEUTICAL COMPOSITIONS THAT UNDERSTAND THEM, METHOD FOR THE THERAPEUTIC AND / OR PROFILATIC TREATMENT OF NURSES THAT ARE MODULATED BY L-CPT1 INHIBITORS, AND THEIR USE. The present invention relates to new substituted piperidine derivatives of formula (I), in which R¹, R², R³, R⁴, R⁵, R⁶, R⁷ and X are as defined in the description and in the re-infections, as well as their physiologically acceptable salts and esters. These compounds inhibit L-CPT1 and can be used as drugs.

(86) International order: pct EP2006068745 from

22/11/2006 (87) International Publication: wo 2007 / 0630i2de

07/06/2007

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1/

COMPOUNDS, PROCESS FOR THEIR MANUFACTURE, PHARMACEUTICAL COMPOSITIONS THAT UNDERSTAND THEM, METHOD FOR THE

THERAPEUTIC AND / OR PROFIIATIC TREATMENT OF DISEASES

THAT ARE MODULATED BY L-CPT1 INHIBITORS, AND THEIR USE

The invention relates to new substituted piperidine derivatives of formula (I)

<img file="BRPI0619086A2_D0006.tif" />

<img file="BRPI0619086A2_D0007.tif" />

(I) in which

X is C (R⁸R⁹), NR¹⁰, O, S, S (O), S (O₂);

R¹ is phenyl optionally substituted with 1 to 3 substituents selected from the group consisting of halogen, hydroxyl, lower alkyl, hydroxy-lower alkyl, fluoro-lower alkyl, lower alkoxy and CN;

R² is hydrogen or lower alkyl;

R³ and R⁴ independently of one another are hydrogen, halogen, lower alkyl or lower alkoxy, or R³ and R⁴ together they are = 0 to form a carbonyl group together with the carbon atom to which they are attached;

2/229

R⁵ and R⁶ independently of one another are hydrogen, halogen, lower alkyl or lower alkoxy, or R⁵ and R⁶ together they are = 0 to form a carbonyl group together with the carbon atom to which they are attached;

R⁷ is an oxadiazolyl or triazolyl, oxadiazolyl or triazolyl which is replaced with R¹¹ and optionally replaced with R¹²;

R⁸ and R⁹ independently of one another are hydrogen, halogen, hydroxyl, lower alkyl, lower alkoxy; or

R⁸ and R⁹ are linked together and -R⁸-R⁹- yeah - (CH2) 2-7to form a ring together with the carbon atom to which they are attached;

R¹⁰ is hydrogen, lower alkyl, lower alkylcarbonyl or lower alkylsulfonyl;

R¹¹ is aryl or a heteroaryl selected from the group consisting of pyridinyl, pyrazinyl, pyrimidinyl, pyridinyl-2-one, oxadiazolyl, indazolyl,

1.3- dihydro-benzimidazole-2-one, 1,3-dihydro-indol-2one, benztriazolyl, imidazopyridinyl, triazolpyridinyl, tetrazolpyridinyl, benzimidazolyl, 2-oxo-.

2.3- dihydro-1H-indol-5-yl, pyrimidin-4-one, furanyl, thiadiazolyl, pyrazolyl, isoxazolyl, pyrimidine-2,4-dione, benzooxazin-3-one, 1,4-dihydrobenzooxazin-2-one, indolyl, thiophenyl, oxazolyl, benzooxazin-2-one, 3,4-dihydro-quinazolin-2-one,

3/229 pyridazinyl, quinoxalinyl, benzothiazolyl, benzothiadiazolyl, naphthyridinyl, cinnolinyl, 1,4-dihydroquinoxaline-2,3-dione and 1,2-dihydro-indazol-3-one, aryl or heteroaryl which is optionally substituted with 1 up to 3 substituents selected from the group consisting of lower alkyl, hydroxyl, B (OH)₂, carboxy-lower alkoxy, carbamoyl-lower alkoxy, cyano, hydroxyl lower alkyl, fluoro-lower alkyl, lower alkoxy, halogen, S (O₂) R¹³, COLOR¹⁴, AT THE₂,

NR¹⁵R¹⁶, imidazolyl, pyrazolyl, tetrazolyl, pyrrolyl, phenyl-lower alkoxy, [1,3, 4] oxadiazol-2one, oxadiazolyl, triazolyl and isoxazolyl, imidazolyl which is optionally substituted with lower alkyl, is phenyl-lower alkoxyl which is optionally substituted with hydroxyl, halogen, lower alkyl, lower alkoxy or fluoro-lower alkyl, and pyrazolyl which is optionally substituted with lower alkyl, and isoxazolyl which is optionally substituted with lower alkyl;

R¹² is hydrogen or lower alkyl;

R¹³ is lower alkyl, NR¹⁷R¹⁸ or fluoro-lower alkyl;

R¹⁴ is OH, NR¹⁹R²⁰, lower alkoxy, lower alkenyl-oxy or lower alkyl;

R¹⁵ and R¹⁶, independently of each other, are hydrogen4 / 229 nio, lower alkyl, lower alkyl-carbonyl, lower alkyl-SO2, lower alkenyl-oxycarbonyl, NH₂-carbonyl, lower alkyl-NHcarbonyl, (lower alkyl) ₂N-carbonyl or phenyl lower alkyl, phenyl lower alkyl which is optionally substituted with hydroxyl, halogen, lower alkyl, lower alkoxy or fluoro-lower alkyl; or

NR¹⁵R¹⁶ is a heterocyclyl selected from the group consisting of morpholinyl, thiomorpholinyl,

1.1- dioxo-thiomorpholinyl, piperidinyl, piperidin-2one, piperazin-2-one, 8-oxa-3-aza-bicyclo [3.2.1] octyl, piperazinyl, pyrrolidinyl,

1.1- dioxo-isothiazolidinyl, pyrrolidin-2-one, imidazolidine-2,4-dione, 2,4-dihydro [1,2,4] triazole-3one, pyrrolidine-2,5-dione, azetidin-2-one and

1,3-dihydro-imidazol-2-one, heterocyclyl which is optionally substituted with hydroxyl-lower alkyl or lower alkyl-carbonyl;

R¹⁷ and R¹⁸ independently of one another are hydrogen, lower alkyl, hydroxyl-lower alkyl, lower alkoxy-lower alkyl; or

NR¹⁷R¹⁸ it is morpholinyl;

R¹⁹ and R²⁰ independently of one another are hydrogen, lower alkyl, cycloalkyl, hydroxyl-lower alkyl, lower alkoxy-lower alkyl, (lower alkyl)₂N-lower alkyl, pyridinyl5 / 229 lower alkyl or cyano-lower alkyl; or

NR¹⁹R²⁰ is a heterocyclyl selected from the group consisting of morpholinyl, pyrrolidinyl, 8oxa-3-aza-bicyclo [3.2.1] octyl, piperidinyl, piperazinyl, piperazin-2-one, thiazolidinyl, thiomorpholinyl, 1,3,8-triaza -spiro [4,5] decane-2,4-dione and spiro (1-phthalan) -piperidine-4-yl, which heterocyclyl is optionally substituted with hydroxyl, lower alkyl-S (O₂), lower alkyl, lower alkyl-carbonyl, carboxyl, carbamoyl, lower alkoxyl-carbonyl, cyano, phenyl, pyridinyl or lower alkoxy;

and their pharmaceutically acceptable salts and esters.

In addition, the invention relates to a process for the manufacture of the compounds exposed above, pharmaceutical preparations containing these compounds, as well as the use of these compounds for the production of pharmaceutical preparations.

High levels of free fatty acids (FFA) lead to an increase in liver mitochondrial β-oxidation, which is crucial for efficient gluconeogenesis. Mitochondrial oxidation of long-chain FFA requires the intervention of carnitine-dependent palmitoyltransferases linked by two membranes (CPTs). CPT1, the enzyme of the outer mitochondrial membrane, catalyzes the formation of long-chain acylcarnitins.

6/229

The liver (L-CPT1) and muscle (MCPT1) isoforms CPT1 are encoded by two different genes and inhibited by malonyl-CoA. The N-ter domain of L-CPT1 gives its lowest sensitivity to malonyl CoA. CPT2, the enzyme of the inner mitochondrial membrane, converts long-chain acylcarnitins into long-chain acyl-CoA esters. Long-chain acyl-CoAs are then β-oxidized to acetyl-CoA, which activates pyruvate carboxylase and gluconeogenesis. According to the mechanism of action described above, pharmaceutically active substances that inhibit L-CPT1 reduce β-oxidation of the liver, consequently, inhibit gluconeogenesis and, consequently, neutralize hyperglycemia.

The present invention relates to new compounds that inhibit the activity of liver carnitine palmitoyl transferase 1 (L-CPT1). The compounds of the present invention can be used as pharmaceutically active agents that are useful in preventing and / or treating diseases that are modulated by L-CPT1 inhibitors, particularly diseases that are related to hyperglycemia and / or glucose tolerance disorders. These diseases include, for example, diabetes and associated conditions, non-insulin dependent diabetes mellitus (also called type II diabetes), obesity, hypertension, insulin resistance syndrome, metabolic syndrome , hyperlipidemia, hypercholesterolemia, fat disease

7/229 of the liver, atherosclerosis, congestive heart failure and kidney failure.

Unless otherwise indicated, the following definitions are set out to illustrate and define the meaning and scope of the various terms used to describe the invention in this context.

In this report, the lower term is used to mean a group consisting of one to seven, preferably one to four, carbon atoms.

halogen element refers to fluorine, chlorine, bromine θ o -Fl nrw 'z «Ί xz J— -L- uv X- f _i_ x · / .i-' • x · 'being especially preferred.

combination with term alkyl hydrocarbon, individually or in other groups, aliphatic of evil, monovalent, saturated, carbon, preferably carbon, carbon.

refers to a branched chain radical or norde one most preferably one to twenty to sixteen from one to ten

Lower alkyl groups such atoms are atoms of as described below are also preferred alkyl groups.

The term lower alkyl, individually or in combination with other groups, refers to a normal or branched chain monovalent alkyl radical, of one to seven carbon atoms, preferably one to four carbon atoms. This term is further exemplified by radicals such as methyl, ethyl, n-propyl, isopropyl, n-butyl, s-butyl, t-butyl and asse8. The term hydroxy-lower alkyl refers to a lower alkyl group that is substituted with hydroxyl.

fluoro-lower alkyl refers to lower alkyl groups that are mono- or multiply substituted with fluorine. Examples of fluoro-lower alkyl groups are, for example, CFH2, CF₂H, CF₃, CF3CH2, CF₃(CH₂)₂, (CF₃)₂CH and CF₂H-CF₂.

The term alkoxy refers to the group R 'O-, where R' is an alkyl. The term lower alkoxy refers to the group R'-O-, where R 'is lower alkyl.

fluoro-lower alkoxy refers to the group RO-, where R is fluoro-lower alkyl. Examples of lower fluoroalkoxy groups are, for example, CFH₂-O, CF₂HO, CF₃-O, CF₃CH₂-O, CF₃(CH₂)₂-O, (CF₃)₂CH-O, and CF₂H-CF₂-O.

Alkenyl, individually or in combination with other groups, means a normal or branched chain hydrocarbon residue comprising an olefinic bond and up to 20, preferably up to 16 carbon atoms. The term lower alkenyl refers to a normal or branched chain hydrocarbon residue that comprises an olefinic bond and up to 7, preferably up to 4 carbon atoms, such as, for example, 2-propenyl.

The term alkynyl, individually or in combination

9/229 combination with other groups, means a normal or branched chain hydrocarbon residue that comprises a triple bond and up to 20, preferably up to 16 carbon atoms. The term lower alkynyl refers to a normal or branched chain hydrocarbon residue that comprises a triple bond and up to 7, preferably up to 4 carbon atoms, such as, for example, 2-propynyl.

The term alkylene refers to a group of saturated, divalent, normal or branched chain aliphatic hydrocarbons of 1 to 20 carbon atoms, preferably 1 to 16 carbon atoms, more preferably up to 10 carbon atoms. Lower alkylene groups, as described below, are also preferred alkylene groups. The term lower alkylene refers to a group of saturated, divalent, normal or branched chain aliphatic hydrocarbons of 1 to 7, preferably 1 to 6 or 3 to 6 carbon atoms. Normal chain or lower alkylene groups are preferred.

The term cycloalkyl refers to a monovalent carbocyclic radical of 3 to 10 carbon atoms, preferably 3 to 6 carbon atoms, such as cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl.

The term aryl, individually or in combination, refers to the phenyl or naphthyl group, preferably the phenyl group, which can be optionally substituted by up to 5, preferably from 1 to

3, substituents independently selected from the group consisting of halogen, hydroxyl, amino, NO₂, lower alkyl, hydroxyl-lower alkyl, lower alkoxy, carboxyl, carboxyl-lower alkyl, lower alkoxy-carbonyl, lower alkoxycarbonyl-lower alkyl, carbonyl lower alkyl, carbonyloxy lower alkyl, lower alkylcarbonyl-NH, H₂NC (O), (H, lower alkyl NC (O), (lower alkyl) 2NC (O), H2NC (O) -Lower alkyl, (H, lower alkyl) NC (O) -Lower alkyl, (lower alkyl) 2NC (O) -lower alkyl, fluoro-lower alkyl, fluoro-lower alkoxyl,

H₂N-lower, lower alkyl, (lower alkyl)₂N-lower alkyl, lower alkyl-S0₂, lower alkyl-S0₂0, lower alkyl-S0₂-NH, lower alkyl-S0₂-N (lower alkyl), H₂NSO₂, (H, lower alkyl) NSO₂, (lower alkyl) ₂NSO₂, lower dioxo-alkylene (forming, for example, a benzodioxyl group), cyano, heteroaryl, cycloalkyl, lower alkoxyl, lower alkenyl, lower alkynyl, phenyl and phenyloxy. Of the substituents mentioned above, halogen, lower alkyl, fluoro-lower alkyl, lower alkoxy and fluoro-lower alkoxyl are preferred. In addition, and more preferably, aryl groups can be replaced as

11/229 as described in the description which is set out below.

heteroaryl refers to an aromatic monocyclic ring, of 5 to 6 elements, or bicyclic ring of 9 to 10 elements that can comprise 1, 2 or 3 atoms selected from nitrogen, oxygen and / or sulfur, such as furyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, thienyl, isoxazolyl, oxazolyl, oxadiazolyl, imidazolyl, pyrrolyl, pyrazolyl, triazolyl, tetrazolyl, thiazolyl, isothiazolyl, 1,2,3thiadiazolyl, benzoyl, benzyl, benzyl benzoisoxazolyl, pyridinyl-2-one, oxadiazolyl, 1,3-dihydro-benzimidazole-2-one,

1.3- dihydro-indole-2-one, benzotriazolyl, imidazopyridinyl, triazolepyridinyl and tetrazolepyridinyl. Other possible heteroaryls are 2-oxo-2,3-dihydro-1H-indol5-yl, pyrimidin-4-one, furanyl, thiadiazolyl, pyrazolyl, isoxazolyl, pyrimidine-2,4-dione, benzooxazin-3-one,

1.4- dihydro-benzooxazin-2-one, indolyl, thiophenyl, oxazolyl, benzooxazin-2-one, 3,4-dihydro-quinazolin-2-one, pyridazinyl, quinoxalinyl, benzothiazolyl, benzothiadiazolil, naphthyridinyl, cinnolinyl, 1,4- dihydro-quinoxaline-2,3-dione and 1,2-dihydro-indazol-3-one. A heteroaryl group may optionally have a substitution pattern as previously described in connection with the term aryl. In addition, heteroaryl groups can preferably be substituted as set out in the description below.

The term heterocyclyl refers to a ring

12/229 monocyclic of 5 to 6 elements or bi- or tricyclic ring of 8 to 14, preferably 8 to 10 elements, which can comprise 1, 2 or 3 atoms selected from nitrogen, oxygen and / or sulfur, such as morpholinyl , thiomorpholinyl, 1,1-dioxo-thiomorpholinyl, piperidinyl, piperidin-2-one, piperazin-2-one, 8-oxa-3-azabicyclo [3.2.1] octyl, piperazinyl and pyrrolidinyl. Other possible heterocyclyls are 1,1-dioxoisothiazolidinyl, pyrrolidin-2-one, imidazolidine-2,4dione, 2,4-dihydro [1,2,4] triazol-3-one, pyrrolidine-2,5dione, azetidin-2- one, 1,3-dihydro-imidazol-2-one, thiazolidinyl, 1,3,8-triaza-spiro [4,5] decane-2,4-dione and spiro (1-phthalan) -piperidine-4-yl . A heterocyclyl can optionally have a substitution pattern as described above in connection with the term aryl. In addition, heterocyclyl groups can preferably be substituted as set out in the description below.

The compounds of formula (I) can form pharmaceutically acceptable acid addition salts. Examples of such pharmaceutically acceptable salts are salts of compounds of formula (I) with physiologically compatible mineral acids, such as hydrochloric acid, sulfuric acid, sulfurous acid or phosphoric acid; or with organic acids, such as methanesulfonic acid, p-toluenesulfonic acid, acetic acid, lactic acid, trifluoroacetic acid, citric acid, fumaric acid, maleic acid, or tartaric acid, acid

13/229 of succinic or salicylic acid. The term pharmaceutically acceptable salts refers to such salts. The compounds of formula (I) in which a COOH group is present can further form salts with bases. Examples of such salts are alkaline, alkaline earth salts and ammonium salts, such as, for example, Na-, K-, Ca and trimethylammonium salt. The term pharmaceutically acceptable salts also refers to these salts. Preference is given to salts obtained by adding an acid.

The term pharmaceutically acceptable esters encompasses derivatives of the compounds of formula (I), in which a carboxyl group has been converted to an ester. Lower alkyl, hydroxyl-lower alkyl, lower alkoxyl-lower alkyl, amino-lower alkyl, mono- or di-lower alkyl-amino-lower alkyl, morpholino-lower alkyl, pyrrolidine-lower alkyl, piperidine-lower alkyl, piperazine-alkyl lower alkyl, lower alkyl-piperazine-lower alkyl and aralkyl esters, are examples of suitable esters. The esters of methyl, ethyl, propyl, butyl and benzyl are the preferred esters. Methyl and ethyl esters are especially preferred. In addition, the term pharmaceutically acceptable esters encompasses the compounds of the formula (I) in which the hydroxyl groups have been converted to the corresponding esters with inorganic or organic acids such as nitric acid, sulfuric acid, phosphoric acid, citric acid, formic acid , maleic acid, acetic acid, suc acid

14/229 cynic, tartaric acid, methanesulfonic acid, p-toluenesulfonic acid and the like, which are not toxic to living organisms.

In detail, the present invention relates to the compounds of formula (I)

<img file="BRPI0619086A2_D0008.tif" />

on what

X is C (R⁸R⁹), NR¹⁰, O, S, S (O), S (O₂);

R¹ is phenyl optionally substituted with 1 to 3 substituents selected from the group consisting of halogen, hydroxyl, lower alkyl, hydroxy-lower alkyl, fluoro-lower alkyl, lower alkoxy and CN;

R² is hydrogen or lower alkyl;

R³ and R⁴ independently of one another comprise hydrogen, halogen, lower alkyl or lower alkoxy, or R³ and R⁴ together they are = 0 to form a carbonyl group together with the carbon atom to which they are attached;

R⁵ and R⁶ independently of one another comprise hydrogen, halogen, lower alkyl or lower alkoxy, or R⁵ and R⁶ together are = 0 for for

15/229 mark a carbonyl group together with the carbon atom to which they are attached;

R⁷ is an oxadiazolyl or triazolyl, oxadiazolyl or triazolyl which is replaced with R¹¹ and optionally replaced with R¹²;

R⁸ and R⁹ independently of one another they comprise hydrogen, halogen, hydroxyl, lower alkyl, lower alkoxy; or

R⁸ and R⁹ are linked together and -R⁸-R⁹- is - (CH2) 2-7 to form a ring together with the carbon atom to which they are attached;

R¹⁰ is hydrogen, lower alkyl, lower alkylcarbonyl or lower alkylsulfonyl;

R¹¹ is aryl or a heteroaryl selected from the group consisting of pyridinyl, pyrazinyl, pyrimidinyl, pyridinyl-2-one, oxadiazolyl, indazolyl,

1.3- dihydro-benzimidazole-2-one, 1,3-dihydro-indol-2one, benztriazolyl, imidazopyridinyl, triazolpyridinyl, tetrazolpyridinyl, benzimidazolyl, 2-oxo-

2.3- dihydro-1H-indol-5-yl, pyrimidin-4-one, furanyl, thiadiazolyl, pyrazolyl, isoxazolyl, pyrimidine-2,4-dione, benzooxazin-3-one, 1,4-dihydrobenzooxazin-2- one, indolyl, thiophenyl, oxazolyl, benzooxazin-2-one, 3,4-dihydro-quinazolin-2-one, pyridazinyl, quinoxalinyl, benzothiazolyl, benzothiadiazolil, naphthyridinyl, cinnolinyl, 1,4-dihydroquinoxaline-2,3-dione 1,2-dihydro-indazole-3-one,

16/229 aryl or heteroaryl which is optionally substituted with from 1 to 3 substituents selected from the group consisting of lower alkyl, hydroxyl, B (OH)₂, carboxy-lower alkoxy, carbamoyl-lower alkoxy, cyano, hydroxyl lower alkyl, fluoro-lower alkyl, lower alkoxy, halogen, S (O₂) R¹³, COLOR¹⁴, AT THE₂,

NR¹⁵R¹⁶, imidazolyl, pyrazolyl, tetrazolyl, pyrrolyl, phenyl-lower alkoxy, [1,3,4] oxadiazol-2one, oxadiazolyl, triazolyl and isoxazolyl, imidazolyl which is optionally substituted with lower alkyl, and this lower phenyl-alkoxy which is optionally substituted with hydroxyl, halogen, lower alkyl, lower alkoxy or fluoro-lower alkyl, and pyrazolyl which is optionally substituted with lower alkyl, and isoxazolyl which is optionally substituted with lower alkyl;

2

R and hydrogen or lower alkyl;

R¹³ is lower alkyl, NR¹⁷R¹⁸ or fluoro-lower alkyl;

R¹⁴ is OH, NR¹⁹R²⁰, lower alkoxy, lower alkenyl-oxy or lower alkyl;

R¹⁵ and R¹⁶, independently of each other, are hydrogen, lower alkyl, lower alkyl-carbonyl, lower alkyl-S0₂, lower alkenyl-oxycarbonyl, NH₂-carbonyl, lower alkyl-NH17 / 229 carbonyl, (lower alkyl) 2N-carbonyl or phenylalkyl lower, phenyl lower alkyl which is optionally substituted with hydroxyl, halogen, lower alkyl, lower alkoxyl or fluoro-lower alkyl; or

NR¹⁵R¹⁶ is a heterocyclyl selected from the group consisting of morpholinyl, thiomorpholinyl,

1.1- dioxo-thiomorpholinyl, piperidinyl, piperidin-2one, piperazin-2-one, 8-oxa-3-aza-bicyclo [3.2.1] octyl, piperazinyl, pyrrolidinyl,

1.1- dioxo-isothiazolidinyl, pyrrolidin-2-one, imidazolidine-2,4-dione, 2,4-dihydro [1,2,4] tríazol-3one, pyrrolidine-2,5-dione, azetidin-2-one and

1,3-dihydro-imidazol-2-one, heterocyclyl which is optionally substituted with hydroxyl-lower alkyl or lower alkyl-carbonyl;

R¹⁷ and R¹⁸ independently of one another are hydrogen, lower alkyl, hydroxyl-lower alkyl, lower alkoxy-lower alkyl; or

NR¹⁷R¹⁸ it is morpholinyl;

R¹⁹ and R²⁰ independently of one another are hydrogen, lower alkyl, cycloalkyl, hydroxyl-lower alkyl, lower alkoxy-lower alkyl, (lower alkyl) ₂N-lower alkyl, pyridinyl lower alkyl or cyano-lower alkyl; or

NR¹⁹R²⁰ is a heterocyclyl selected from the

18/229 group consisting of morpholinyl, pyrrolidinyl, 8oxa-3-aza-bicyclo [3.2.1] octyl, piperidinyl, piperazinyl, piperazin-2-one, thiazolidinyl, thiomorpholinyl, 1,3,8-triaza-spiro [4 , 5] decano-2,4-dione and spiro (1-phthalan) -piperidine-4-yl, which heterocyclyl is optionally substituted with hydroxyl, lower alkyl-S (O₂), lower alkyl, lower alkyl-carbonyl, carboxyl, carbamoyl, lower alkoxyl-carbonyl, cyano, phenyl, pyridinyl or lower alkoxy;

and their pharmaceutically acceptable salts and esters.

The compounds of the formula (I) are individually preferred and their physiologically acceptable salts are individually preferred and their pharmaceutically acceptable esters are individually preferred, with the compounds of the formula (I) being particularly preferred.

The compounds of the formula (I) can have one or more asymmetric carbon atoms and, therefore, can exist in the form of an enantiomeric mixture, mixture of stereoisomers or as optically pure compounds.

Preferred compounds of formula (I) as described above are those in which

X is C (R⁸R⁹), NR¹⁰, O, S, S (O), S (O₂);

R¹ is phenyl optionally substituted with 1 to 3 substituents selected from the group consisting of halogen, hydroxyl, lower alkyl,

19/229 hydroxyl-lower alkyl, fluoro-lower alkyl, lower alkoxy and CN;

R² is hydrogen or lower alkyl;

R³ and R⁴ independently of one another comprise hydrogen, halogen, lower alkyl or lower alkoxy, or R³ and R⁴ together they are = 0 to form a carbonyl group together with the carbon atom to which they are attached;

R⁵ and R⁶ independently of one another comprise hydrogen, halogen, lower alkyl or lower alkoxy, or R³ and R⁸ together they are = 0 to form a carbonyl group together with the carbon atom to which they are attached;

R⁷ is an oxadiazolyl or triazolyl, oxadiazolyl or triazolyl which is replaced with R¹¹ and optionally replaced with R¹²;

R⁸ and R⁹ independently of one another they comprise hydrogen, halogen, hydroxyl, lower alkyl, lower alkoxy; or

R⁸ and R⁹ are connected together and -R⁸-R⁹- yeah - (CH₂) 27- to form a ring together with the carbon atom to which they are attached;

R¹⁰ is hydrogen, lower alkyl, lower alkylcarbonyl or lower alkylsulfonyl;

R¹¹ is aryl or a heteroaryl selected from the group consisting of pyridinyl, pyrazinyl, pyri20 / 229 midinyl, pyridinyl-2-one, oxadiazolyl, indazolyl,

1,3-dihydro-benzimidazole-2-one, 1,3-dihydro-indol-2one, benztriazolyl, imidazopyridinyl, triazolepyridinyl, tetrazolepyridinyl and benzimidazolyl, aryl or heteroaryl which is optionally substituted with 1 to 3 substituents selected from the group consisting of lower alkyl, hydroxyl-lower alkyl, fluoro-lower alkyl, lower alkoxy, halogen, S (O₂) R¹³, COLOR¹⁴, AT THE₂, NR¹⁵R¹⁶, imidazolyl, pyrazolyl, tetrazolyl, pyrrolyl, and phenyl-lower alkoxy, imidazolyl which is optionally substituted with lower alkyl and lower phenyl-alkoxy which is optionally substituted with hydroxyl, halogen, lower alkyl, lower alkoxy or lower fluoroalkyl;

R¹² is hydrogen or lower alkyl;

R¹³ is lower alkyl, NR¹⁷R¹⁸ or fluoro-lower alkyl;

R¹⁴ is OH, NR¹⁹R²⁰, lower alkoxy or -alkenyl lower-oxy;

R¹⁵ and R¹⁶ independently of one another comprise hydrogen, lower alkyl, lower alkylcarbonyl, lower alkyl-S0₂, lower alkenyl -oxycarbonyl, NH₂-carbonyl, lower alkyl-NHcarbonyl, (lower alkyl)₂N-carbonyl or phenyl lower alkyl, phenyl lower alkyl which

21/229 is optionally substituted with hydroxyl, halogen, lower alkyl, lower alkoxy or fluoro-lower alkyl; or

NR¹⁵R¹⁶ is a heterocyclyl selected from the group consisting of morpholinyl, thiomorpholinyl,

1,1-dioxo-thiomorpholinyl, piperidinyl, piperidin-2one, piperazin-2-one, 8-oxa-3-aza-bicyclo [3.2.1] octyl, piperazinyl and pyrrolidinyl, which heterocyclyl is optionally substituted with hydroxyl-alkyl lower or lower alkylcarbonyl;

R and R independently of one another comprise hydrogen, lower alkyl, hydroxyl-lower alkyl, lower alkoxy-lower alkyl; or NR¹⁷R¹⁸ it is morpholinyl;

R¹⁹ and R²⁰ independently of one another are hydrogen, lower alkyl, cycloalkyl, hydroxyl-lower alkyl or lower alkoxy-lower alkyl; or

NR¹⁹R²⁰ is the heterocyclyl selected from the group consisting of morpholinyl, pyrrolidinyl and 8-oxa3-aza-bicyclo [3.2.1] octyl, which heterocyclyl is optionally substituted with hydroxyl or lower alkyl-S (0₂) ;

and their pharmaceutically acceptable salts and esters.

Preferred compounds of formula (I) as described above are those in which R¹

22/229 is phenyl optionally substituted with halogen, hydroxyl, hydroxyl-lower alkyl or CN, most preferably those in which R¹ is phenyl.

Other preferred compounds are those in which R² it's hydrogen. Other preferred compounds are those in which R³ it's hydrogen. Still other preferred compounds are those in which R⁴ it's hydrogen. Other preferred compounds are those in which R⁵ it's hydrogen. The compounds in which R⁶ hydrogen is also preferred.

Preferably, R⁷ comprising an oxadiazolyl is not replaced with R¹². In a preferred embodiment of the present invention, R⁷ is

<img file="BRPI0619086A2_D0009.tif" />

where R¹¹ and R¹² are as defined above.

<img file="BRPI0619086A2_D0010.tif" />

<img file="BRPI0619086A2_D0011.tif" />

<img file="BRPI0619086A2_D0012.tif" />

where R¹¹ and R¹² are as defined in claim 1.

23/229

In addition, it is preferred that R⁷ be

Λ__N

<img file="BRPI0619086A2_D0013.tif" />

where R¹¹ it is as previously defined.

Preferred compounds of formula (I), as described above, are those in which X is C (R⁸R⁹), NR¹⁰, O or S, where R⁸, R⁹ and R¹⁰ are as defined above. Preferably, X is C (R⁸R⁹) or NR¹⁰, where R⁸, R⁹ and R¹⁰ are as defined above.

In the compounds as defined above, it is preferred that R⁸ be hydrogen. Preferably, R⁹ it's hydrogen. It is also preferred that R¹⁰be hydrogen.

Another preferred embodiment in others of the present invention relates to compounds as defined above, wherein R¹¹ is phenyl or a heteroaryl selected from the group consisting of pyridinyl, pyrazinyl, pyridinyl-2-one, indazolyl, 1,3-dihydro-benzimidazol-2-one, 1,3-dihydro-indol-2-one, benztriazolyl and benzimidazolyl , phenyl or heteroaryl which is optionally substituted with 1 to 2 substituents selected from the group consisting of lower alkyl, hydroxyl-lower alkyl, lower fluoroalkyl, lower alkoxyl, halogen, S (O2) R¹³, COLOR¹⁴, NO2, NR¹⁵R¹⁶, imidazolyl, pyrazolyl,

24/229 tetrazolyl, pyrrolyl, and phenyl-lower alkoxy, imidazolyl which is optionally substituted with lower alkyl, where R¹³, R¹⁴, R¹⁵ and R¹⁶ are as defined above.

Preferably, R¹¹ is phenyl or a heteroaryl selected from the group consisting of pyridinyl, pyridinyl-2-one, indazolyl, 1,3-dihydrobenzimidazol-2-one, 1,3-dihydro-indol-2-one, benztriazolyl and benzimidazolyl, phenyl or heteroaryl which is optionally substituted with 1 to 2 substituents selected from the group consisting of lower fluoroalkyl, halogen, C (O) R¹⁴ and NR¹⁵R¹⁶, where R¹⁴, R¹⁵ and R¹⁶ are as defined above.

Most preferably, R¹¹ is lH-indazol-5yl, lH-indazol-6-yl, 1,3-dihydro-indol-2-one-6-yl, 1,3-dihydro-benzoimidazol-2-one-5-yl, 1,3-dihydro -indol-2-one -5-yl, 1H-benzotriazol-5-yl, 1H-benzoimidazol-5-yl, 1Hpiridin-2-one-4-yl, 4-fluoro-phenyl, 3-trifluoromethyl-phenyl, 1H-benzoimidazole -5-yl, 3-benzamide, 5-nicotinamide, 3- (N-acetamide) -phenyl or 3- (N-methanesulfonamide) -phenyl.

Another preferred embodiment of the present invention relates to compounds as defined above, wherein R¹¹ is phenyl or a heteroaryl selected from the group consisting of 2oxo-2,3-dihydro-1H-indol-5-yl, pyrimidin-4-one, furanyl, thiadiazolyl, pyrazolyl, isoxazolyl, pyrimidine-2,4

25/229 dione, benzooxazin-3-one, 1,4-dihydro-benzooxazin-2-one, indolyl, thiophenyl, oxazolyl, benzooxazin-2-one, 3,4 dihydro-quinazolin-2-one, pyridazinyl, quinoxalinyl, benzothiazolyl , benzothiadiazolyl, naphthyridinyl, cinnolinyl, 1,4-dihydro-quinoxaline-2,3-dione and 1,2-dihydroindazole-3-one, phenyl or heteroaryl which is optionally substituted with 1 to 3 substituents selected from the group consisting of hydroxyl, B (OH)₂, carboxyl-lower alkoxy, carbamoyl-lower alkoxy, cyano, [1,3,4] oxadiazol-2-one, oxadiazolyl, triazolyl and isoxazolyl, pyrazolyl which is optionally substituted with lower alkyl, and isoxazolyl which is optionally substituted with lower alkyl.

Preferably, R¹¹ is phenyl or heteroaryl selected from the group consisting of pyridinyl, 1,3-dihydro-indol-2-one, 1H-benzimidazolyl, 3Hpirimidin-4-one, 1H-pyrazolyl, isoxazolyl and 4Hbenzo [1,4] oxazin- 3-one, phenyl or heteroaryl which is optionally substituted with 1 to 3 substituents selected from the group consisting of lower alkyl, hydroxyl, halogen and NR¹⁵R¹⁶, where R¹⁴ and R¹⁵ are as defined in claim 1.

Most preferably, R¹¹ is 2-methyl-3Hpirimidin-4-one, 5-methyl-isoxazol-3-yl, 1H-pyrazol-3yl, 6-amino-pyridin-3-yl, 1,3-dihydro-indol-2-one, 2amino -pyridin-4-yl, 4H-benzo [1,4] oxazin-3-one, 1H

26/229 benzimidazol-5-yl, 3- (N-acetamide) -4-fluoro-phenyl or 2-hydroxyl-pyridin-4-yl.

Preferably, R¹² it's hydrogen. Compounds as defined above, where R¹³ and lower alkyl are also preferred. Other preferred compounds are those in which R¹⁴ is NR¹⁹R²⁰, where R and R are as previously defined. Other preferred compounds are those in which R¹⁴ is comprised of lower alkyl.

Another preferred embodiment of the present invention relates to compounds as defined above, wherein R¹⁵ and R¹⁶ independently of one another are hydrogen, lower alkyl, lower alkyl-carbonyl, lower alkyl-SO2, lower alkenyloxy-carbonyl or lower alkyl-NH-carbonyl; or NR¹⁵R¹⁶is a heterocyclyl selected from the group consisting of morpholinyl, thiomorpholinyl, 1,1-dioxothiomorpholinyl, piperidinyl, piperidin-2-one, piperazin2-one, piperazinyl and pyrrolidinyl, which heterocyclyl is optionally substituted with hydroxyl-lower alkyl or alkyl lower-carbonyl. Most preferably, R¹⁵ and R¹⁶ independently of one another are hydrogen, lower alkyl-carbonyl or lower alkyl-S0₂.

Other preferred compounds are those, where NR¹⁵R¹⁶ is a heterocyclyl selected from the group consisting of 1,1-dioxo-isothiazolidinyl, pyrrole27 / 229 lidin-2-one, imidazolidine-2,4-dione, 2,4-hydro [1,2,4] triazole-3- one, pyrrolidine-2,5-dione, azetidin-2-one and 1,3-dihydro-imidazol-2-one, which heterocyclyl is optionally substituted with hydroxyl lower alkyl or lower alkyl carbonyl.

Other preferred compounds are those in which R¹⁷ and R¹⁸ independently of one another are hydrogen or lower alkyl; or NR¹⁷R¹⁸ is morpholinyl.

Other preferred compounds, as defined above, are those in which R¹⁹ and R²⁰ independently of one another they comprise hydrogen, lower alkyl, cycloalkyl, hydroxyl-lower alkyl, lower alkoxy-lower alkyl; or NR¹⁹R²⁰ is a heterocyclyl selected from the group consisting of morpholinyl or pyrrolidinyl, which is optionally substituted with hydroxyl or lower alkyl-S (O₂). Most preferably, R¹⁹ and R²⁰ are hydrogen.

Other preferred compounds are those in which R¹⁹ and R²⁰ independently of each other are (lower alkyl) ₂N-lower alkyl, pyridinyl-lower alkyl or cyano-lower alkyl; or NR¹⁹R²⁰ is a heterocyclyl selected from the group consisting of piperidinyl, piperazinyl, piperazin-2-one, thiazolidinyl, thiomorpholinyl, 1,3,8-triaza-spiro [4,5] decane-2,4-dione and spiro (1 -ftalan) -piperidine-4-yl, heterocyclyl which is optionally substituted with hydroxyl, alkyl

28/229 lower-S (O₂), lower alkyl, lower alkylcarbonyl, carboxyl, carbamoyl, lower alkoxycarbonyl, cyano, phenyl, pyridinyl or lower alkoxy.

Preferred compounds of formula (I) as defined above comprise those which are R-isomers and which are characterized by formula (Ia)

<img file="BRPI0619086A2_D0014.tif" />

where R¹, R², R³, R⁴, R⁵, R⁶, R⁷ and X are as defined above.

In particular, the preferred compounds are the compounds of formula (I) described in the examples as individual compounds, as well as their pharmaceutically acceptable salts, in the same way as their pharmaceutically acceptable esters.

Preferred compounds of formula (I) are those selected from the group consisting of:

(R) —1— (2— [3— (4-Methoxy-phenyl) - [1,2,4] oxadiazol-5-yl] piperidin-1-yl} -2-phenoxy-ethanone, (R) - 3— (2— {2— [3— (4-Methoxy-phenyl) [1,2,4] oxadiazol-5-yl] piperidin-1-yl} -2-oxo-ethoxy) benzonitrile,

29/229 (R) —1— {2 - [3— (4-Methoxy-phenyl) - [1,2,4] oxadiazol-5-yl] piperidin-l-yl} -2-phenoxy-propan-l -one, (R) —1— {2— [3— (4-Bromo-phenyl) [1,2,4] oxadiazol-5-yl] piperidin-1-yl} -2-phenoxy-ethanone, (R ) -2- (4-Hydroxy-phenoxy) —1— {2— [3- (4-methoxy-phenyl) - [1,2,4] oxadiazol-5-yl] -piperidin-l-yl} -ethanone , (R) -2- (4-Chloro-phenoxy) —1— {2— [3- (4-methoxy-phenyl) - [1,2,4] oxadiazol-5-yl] -piperidin-l-yl } -ethanone, (R) -2- (4-Hydroxymethyl-phenoxy) —1— {2— [3- (4-methoxy-phenyl) - [1,2,4] oxadiazol-5-yl] -piperidin- l-il} -ethanone, (R) -2- (3-Chloro-phenoxy) -1- {2- [3- (4-methoxy-phenyl) - [1,2,4] oxadiazol-5-yl] -piperidin-l-yl} -ethanone, (R) -2- (4-Fluoro-phenoxy) —1— {2— [3- (4-methoxy-phenyl) - [1.2.4] oxadiazol-5-yl] -piperidin-l-yl } -ethanone,

R) -l- {2- [3- (4-Fluoro-phenyl) - [1,2,4] oxadiazol-5-yl] piperidin-1-yl} -2-phenoxy-ethanone, (R) —1 - {2— [3- (4-Methanesulfonyl-phenyl) - [1,2,4] oxadiazol5-yl] -piperidin-1-yl} -2-phenoxy-ethanone, (R) -4- [5 - [l- (2-Phenoxy-acetyl) -piperidin-2-yl] - [1.2.4] oxadiazol-3-yl} -benzenesulfonamide,

R) -2- (4-Fluoro-phenoxy) -1- [2- (3-pyridin-4-yl- [1.2.4] oxadiazol-5-yl) -piperidin-1-yl] -ethanone, methyl ester of (R) —3— [5— [1- (2-Phenoxy-acetyl) piperidin-2-yl] - [1,2,4] oxadiazol-3-yl} -benzoic acid,

30/229 (R) -1- {2- [3- (3-Nitro-phenyl) - [1,2,4] oxadiazol-5-yl] piperidin-1-yl} -2-phenoxy-ethanone, ( R) —1— {2— [3— (4-Nitro-phenyl) - [1,2,4] oxadiazol-5-yl] piperidin-1-yl} -2-phenoxy-ethanone, (R) —3 - {5— [1- (2-Phenoxy-acetyl) -piperidin-2-yl] - [1.2.4] oxadiazol-3-yl] -benzenesulfonamide, (R) -2-Phenoxy-1- [2- ( 3-pyrazin-2-yl- [1,2,4] oxadiazol-5yl) -piperidin-l-yl] -ethanone, (R) —1— (2— [3— [4— (Morpholine-4-sulfonyl ) -phenyl] - [1.2.4] oxadiazol-5-yl} -piperidin-1-yl) -2-phenoxyethanone, (R) -1- [2- [3- (6-Methoxy-pyridin-3-yl) - [1,2,4] oxadiazol-5yl] -piperidin-1-yl} -2-phenoxy-ethanone, ( R) —1— {2— [3- (3-Hydroxymethyl-phenyl) - [1,2,4] oxadiazol-5yl] -piperidin-1-yl} -2-phenoxy-ethanone,

Allyl (R) -6- {5- [1- (2-Phenoxy-acetyl) piperidin-2-yl] - [1,2,4] oxadiazol-3-yl} -nicotinic acid ester, (R) - 1— {2 - [3- (4-Imidazol-1-yl-phenyl) - [1,2,4] oxadiazol-5yl] -piperidin-1-yl} -2-phenoxy-ethanone, (R) -N -Methyl-4- {5- [1- (2-phenoxy-acetyl) -piperidin-2-yl] - [1.2.4] oxadiazol-3-yl} -benzenesulfonamide, (R) —1— {2— [ 3- (6-Morfolin-4-yl-pyridin-3-yl) - [1.2.4] oxadiazol-5-yl] -piperidin-1-yl} -2-phenoxyethanone,

31/229 (R) -2-Phenoxy-1- {2- [3- (4-trifluoromethanesulfonylphenyl) - [1,2,4] oxadiazol-5-yl] -piperidin-l-yl} -ethanone, (R ) -2-Phenoxy-l- {2- [3- (4-trifluoromethyl-phenyl) - [1.2.4] oxadiazol-5-yl] -piperidin-l-yl} -ethanone, (R) -1- { 2- [3- (4-Chloro-phenyl) - [1,2,4] oxadiazol-5-yl] piperidin-1-yl} -2-phenoxy-ethanone, (R) -N- (4— {5 - [1- (2-Phenoxy-acetyl) -piperidin-2-yl] - [1.2.4] oxadiazol-3-yl} -2-trifluoromethyl-phenyl) acetamide, (R) —1— {2— [3 - (3-Methanesulfonyl-phenyl) - [1,2,4] oxadiazole

5-yl] -piperidin-1-yl} -2-phenoxy-ethanone, (R) -1- [2- [3- (4-Methyl-3-nitro-phenyl) - [1,2,4] oxadiazole -5 yl] -piperidin-1-yl} -2-phenoxy-ethanone, (R) —1— [2— [3— (4-Methoxy-3-nitro-phenyl) - [1,2,4] oxadiazole5 -yl] -piperidin-l-yl} -2-phenoxy-ethanone, (R) -N- (2-Hydroxy-ethyl) - 4 - {5— [1— (2-phenoxy-acetyl) piperidin-2- il] - [1,2,4] oxadiazol-3-i1} benzenesulfonamide, (R) -N- (2-Methoxy-ethyl) -N-methyl-4- {5- [1- (2-phenoxyacetyl) - piperidin-2-yl] - [1,2,4] oxadiazol-3-yl} benzenesulfonamide, (R) -N, N-Dimethyl-4- {5- [1- (2-phenoxy-acetyl) -piperidin-2yl] - [1,2,4] oxadiazol-3-yl} -benzenesulfonamide, (R) -N, N-Diethyl-4- {5- [1- (2-phenoxy-acetyl) -piperidin-2yl] - [1,2,4] oxadiazol-3-yl} -benzenesulfonamide,

32/229 (R) —1— {2— [3- (2-Morfolin-4-yl-pyridin-4-yl) - [1,2,4] oxadiazol-5-yl] -piperidin-l-yl } -2-phenoxyethanone, (R) -2-Phenoxy-l- {2- [3- (3,4,5,6-6-tetrahydro-2H [1,2 '] bipyridinyl-4'-yl) - [l , 2,4] oxadiazol-5-yl] piperidin-l-yl} -ethanone, (R) -2-Phenoxy-l- {2- [3- (2-thiomorfolin-4-yl-pyridin-4il) - [1,2,4] oxadiazol-5-yl] -piperidin-l-yl} -ethanone, (R) —1— {2— [3- (2-Diethylamino-pyridin-4-yl) - [1.2. 4] oxadiazol-5-yl] -piperidin-l-yl} -2-phenoxy-êtaTiOnâ _z

(R) -4- {5- [1- (2-Phenoxy-acetyl) piperidin-2-yl] - [1,2,4] oxadiazol-3-yl} -pyridine-2-carboxylic acid ester, (R ) -1- (2- {3- [6- (4-Acetyl-piperazin-1-yl) -pyridin-3-yl] - [1.2.4] oxadiazol-5-yl} -piperidin-1-yl) -2-phenoxyethanone, (R) -1- {2- [3- (2-Imidazol-1-yl-pyridin-4-yl) - [1.2.4] oxadiazol-5-yl] -piperidin-1-yl } -2-phenoxyethanone, (R) -1- (3- {5- [1- (2-Phenoxy-acetyl) -piperidin-2-yl] - [1.2.4] oxadiazol-3-yl} -phenyl) -piperidin-2-one, (R) -1- (2- (3- [4- (3H-Imidazol-4-yl) -phenyl] - [1.2.4] oxadiazol-5-yl} -piperidin-1-yl) -2-phenoxyethanone ,

33/229 (R) -1- (2- {3- [4- (2-Methyl-imidazol-1-yl) -phenyl] - [1.2.4] oxadiazol-5-yl} -piperidin-1-yl ) -2-phenoxyethanone, (R) -2-Phenoxy-l- {2- [3- (2-pyrazol-1-yl-pyridin-4-yl) 5 [1,2,4] oxadiazol-5-yl ] -piperidin-1-yl} -ethanone, (R) -4- (5- {5- [1- (2-Phenoxy-acetyl) -piperidin-2-yl] - [1.2.4] oxadiazole-3- il} -pyridin-2-yl) -piperazin-2-one, (R) -2-Phenoxy-l- (2- {3- [4- (1H-tetrazol-5-yl) -phenyl] - [1.2 .4] oxadiazol-5-yl} -piperidin-1-yl) -ethanone, (R) —1- [2- [3- (1H-Indazol-5-yl) - [1,2,4] oxadiazole- 5-il] —1 - Ί Ί lf ί

--Ι _ \ _ Λ_Ι_ΛΛ u_ _l__í_ J ΧΣΪ I— Cl 1 1 1 1 Cl f (R) -l- {2- [3- (1H-Indazol-6-yl) - [1,2,4] oxadiazole-5 -yl] piperidin-l-yl} -2-phenoxy-ethanone, (R) —1— {2— [3- (4-Fluoro-3-trifluoromethyl-phenyl) 15 [1,2,4] oxadiazole-5 -il] -piperidin-l-yl} -2-phenoxyethanone, (R) —6— {5— [1- (2-Phenoxy-acetyl) -piperidin-2-yl] - [1.2.4] oxadiazole-3 -il} -1,3-dihydro-indol-2-one, (R) —5— {5— [1- (2-Phenoxy-acetyl) -piperidin-2-yl] 20 [1,2,4] oxadiazol-3-yl} -1,3-dihydro-benzoimidazole-2-one, (R) —5— {5— [1- (2-Phenoxy-acetyl) -piperidin-2-yl] - [1,2,4] oxadiazol-3-yl} -1,3-dihydro-indole-2 -one, (R) -l- {2- [3- (1H-Benzotriazol-5-yl) - [1,2,4] oxadiazol-5yl] -piperidin-l-yl} -2-phenoxy-ethanone,

34/229 (R) -l- {2- [3- (1H-Benzoimidazol-5-yl) - [1,2,4] oxadiazol-5yl] -piperidin-l-yl} -2-phenoxy-ethanone, (R) —1— (2 - [3— [6— (1,1-Dioxo-thiomorfolin-4-yl) -pyridin-3yl] - [1,2,4] oxadiazole-5-i1} -piperidin- 1-yl) -2-phenoxyethanone, (R) —N— (4 - {5 - [1— (2-Phenoxy-acetyl) -piperidin-2-yl] - [1.2.4] oxadiazol-3-yl} -pyridin-2-yl) -acetamide, (R) —1— {2— [3- (6-Benzyloxy-pyridin-3-yl) - [1.2.4] oxadiazol-5-yl] -piperidin-l- il} -2-phenoxyethanone,

(R) -5- {5- [1- (2-Phenoxy-acetyl) piperidin-2-yl] - [1,2,4] oxadiazol-3-yl} -nicotinic acid ethyl ester, (R) - 4— {5— [4- (2-Phenoxy-acetyl) -morpholin-3-yl] - [1.2.4] oxadiazol-3-yl} -1H-pyridin-2-one, (R) —5— { 5— [1- (2-Phenoxy-acetyl) -piperidin-2-yl] - [1.2.4] oxadiazol-3-i}} -1H-pyridin-2-one, (R) -2-Phenoxy-1- [2- (5-phenyl-2H- [1,2,4] triazol-3-yl) piperidin-1-yl] -ethanone, (R) —1— [2— [5— (4-Methanesulfonyl-phenyl ) -2H- [1.2.4] triazol-3-yl] -piperidin-1-yl} -2-phenoxy-ethanone, (R) -1- {2- [5- (3,4-Dimethoxy-phenyl) -2H- [1,2,4] triazol-3yl] -piperidin-1-yl} -2-phenoxy-ethanone, ( R) -1- {2- [5- (3,4-Dichloro-phenyl) -2H- [1,2,4] triazol-3yl] -piperidin-1-yl} -2-phenoxyethanone,

35/229 (R) —1— {2— [5— (4-Fluoro-phenyl) -2H- [1,2,4] triazol-3-yl] piperidin-l-yl} -2-phenoxy-ethanone , (R) -2-Phenoxy-l- {2- [5- (3-trifluoromethyl-phenyl) -2H- [1.2.4] triazol-3-yl] -piperidin-l-yl} -ethanone, (R ) —1— {2— [5— (4-Methoxy-phenyl) -2H- [1,2,4] triazol-3-yl] piperidin-1-yl} -2-phenoxy-ethanone, (R) - 1— [2 - [5— (3-Nitro-phenyl) -2H- [1,2,4] triazol-3-yl] piperidin-1-yl} -2-phenoxy-ethanone,

(R) -3- {5- [1- (2-Phenoxy-acetyl) piperidin-2-yl] -1H- [1,2,4] triazol-3-yl} -benzoic acid methyl ester, (R ) —1— {2— [5- (4-Fluoro-3-trifluoromethyl-phenyl) -2H- [1.2.4] triazol-3-yl] -piperidin-l-yl} -2-phenoxy-ethanone, ( R) —6— [5— [1— (2-Phenoxy-acetyl) -piperidin-2-yl] -1H- [1.2.4] triazol-3-yl} -1,3-dihydro-indole-2- ona,

1- {3 - [3- (4-Methoxy-phenyl) - [1,2,4] oxadiazol-5-yl] morpholin-4-yl} -2-phenoxy-ethanone, l- {3 - [3- (4-Methanesulfonyl-phenyl) - [1,2,4] oxadiazol-5yl] -morpholin-4-yl} -2-phenoxy-ethanone,

4- {5 - [4- (2-Phenoxy-acetyl) -morpholin-3-yl] - [1.2.4] oxadiazol-3-yl} -benzenesulfonamide,

1— (3— [3— [6— (1,1-Dioxo-thiomorfolin-4-yl) -pyridin-3-yl] - [1.2.4] oxadiazol-5-yl} -morpholin-4-yl) -2-phenoxy-ethanone,

N- (4- [5- [4- (2-Phenoxy-acetyl) -morpholin-3-yl] - [1.2.4] oxadiazol-3-yl} -pyridin-2-yl) -acetamide,

36/229

1— {3— [5- (4-Methanesulfonyl-phenyl) -2H- [1,2,4] triazol-3-yl] -morpholin-4-yl} -2-phenoxy-ethanone,

2- Phenoxy-l- {3- [5- (3-trifluoromethyl-phenyl) -2H- [1.2.4] triazol-3-yl] -morpholin-4-yl} -ethanone, (R) —4 - { 5— [4— (2-Phenoxy-acetyl) -morpholin-3-yl] - [1.2.4] oxadiazol-3-yl} -1H-pyridin-2-one,

1— {3— [3- (4-Methoxy-phenyl) - [1,2,4] oxadiazol-5-yl] thiomorfolin-4-yl} -2-phenoxy-ethanone,

1— {3— [3- (4-Methanesulfonyl-phenyl) - [1,2,4] oxadiazol-5-yl] -thiomorfolin-4-yl} -2-phenoxy-ethanone,

4— {5— [4— (2-Phenoxy-acetyl) -thiomorfolin-3-yl] - [1.2.4] oxadiazol-3-yl} -benzenesulfonamide,

2- Phenoxy-l- [3- (3-pyridin-4-yl- [1,2,4] oxadiazol-5-yl) thiomorfolin-4-yl] -ethanone,

1— {2— [3- (4-Methoxy-phenyl) - [1,2,4] oxadiazol-5-yl] piperazin-1-yl} -2-phenoxy-ethanone,

N- (5- {5- [1- (2-Phenoxy-acetyl) -piperazin-2-yl] - [1.2.4] oxadiazol-3-yl} -pyridin-2-yl) -acetamide,

1— {2— [3- (2-Imidazol-1-yl-pyridin-4-yl) - [1.2.4] oxadiazol-5-yl] -piperazin-1-yl} -2-phenoxy-ethanone,

N, N-Diethyl-4- {5- [1- (2-phenoxy-acetyl) -piperazin-2-yl] - [1.2.4] oxadiazol-3-yl} -benzenesulfonamide,

N, N-Dimethyl-4- {5- [1- (2-phenoxy-acetyl) -piperazin-2-yl] [1,2,4] oxadiazol-3-yl} -benzenesulfonamide,

37/229

4— {5— [1— (2-Phenoxy-acetyl) -piperazin-2-yl] - [1,2,4] oxadiazol-3-yl} -benzenesulfonamide,

1— {2— [3- (4-Methanesulfonyl-phenyl) - [1,2,4] oxadiazol-5yl] -piperazin-1-yl} -2-phenoxy-ethanone,

2-Phenoxy-l- [2- (3-pyridin-4-yl- [1,2,4] oxadiazol-5-yl) piperazin-l-yl] -ethanone,

1- {2 - [3- (2,4-Dichloro-phenyl) - [1,2,4] oxadiazol-5-yl] piperazin-1-yl} -2-phenoxy-ethanone,

2-Phenoxy-l- [2- (3-pyridin-2-yl- [1,2,4] oxadiazol-5-yl) 10 piperazin-l-yl] -ethanone,

2-Phenoxy-l- [2- (3-pyridin-2-yl- [1,2,4] oxadiazol-5-yl) piperazin-2-yl] -ethanone,

1- {2 - [3- (4-Nitro-phenyl) - [1,2,4] oxadiazol-5-yl] piperazin-l-yl} -2-phenoxy-ethanone, l- {2 - [3- (6-Methoxy-pyridin-3-yl) - [1,2,4] oxadiazol-5-yl] piperazin-1-yl} -2-phenoxy-ethanone,

1— {2— [3- (6-Morfolin-4-yl-pyridin-3-yl) - [1,2,4] oxadiazol-5-yl] -piperazin-1-yl} -2-phenoxyethanone ,

1- {2- [3- (6-Morfolin-4-yl-pyridin-3-yl) - [1,2,4] oxadiazol-5-yl] -piperazin-1-yl} -2-phenoxyethanone ,

1— {2 - [3- (3-Hydroxymethyl-phenyl) - [1,2,4] oxadiazol-5-yl] piperazin-l-yl} -2-phenoxy-ethanone,

38/229

1— {2— [3 - (4-Diethylamino-phenyl) - [1,2,4] oxadiazol-5-yl] piperazin-l-yl} -2-phenoxy-ethanone,

1- (2— {3— [4- (Morpholine-4-sulfonyl) -phenyl] - [1.2.4] oxadiazol-5-yl} -piperazin-1-yl) -2-phenoxyethanone,

N-Methyl-4- {5- [1- (2-phenoxy-acetyl) -piperazin-2-yl] - [1.2.4] oxadiazol-3-yl} -benzenesulfonamide,

N- (2-Methoxy-ethyl) -N-methyl-4- {5- [1- (2-phenoxy-acetyl) piperazin-2-yl] - [1,2,4] oxadiazol-3-yl} benzenesulfonamide , l- {2- [3- (4-Chloro-phenyl) - [1,2,4] oxadiazol-5-yl] piperazin-l-yl} -2-phenoxy-ethanone,

N— (4 - [5— [1— (2-Phenoxy-acetyl) -piperazin-2-yl] - [1.2.4] oxadiazol-3-yl} -2-trifluoromethyl-phenyl) - acetamide,

4- {5- [1- (2-Phenoxy-acetyl) piperazin-2-yl] - [1,2,4] oxadiazol-3-yl} -benzoic acid allyl ester,

1— {2— [3- (4-Methyl-3-nitro-phenyl) - [1,2,4] oxadiazol-5-yl] piperazin-1-yl} -2-phenoxy-ethanone,

1— {2— [3- (4-Methoxy-3-nitro-phenyl) - [1,2,4] oxadiazol-5yl] -piperazin-1-yl} -2-phenoxy-ethanone,

1— {2— [3- (4-Chloro-3-nitro-phenyl) - [1,2,4] oxadiazol-5-yl] piperazin-1-yl} -2-phenoxy-ethanone,

3-Fluoro-4- {5- [1- (2-phenoxy-acetyl) acid methyl ester

-piperazin-2-yl] - [1,2,4] oxadiazol-3-yl} -benzoic acid,

39/229

4- {5- [1- (2-Phenoxy-acetyl) piperazin-2-yl] - [1,2,4] oxadiazol-3-yl} -pyridine-2-carboxylic acid ethyl,

2-Phenoxy-l- {2- [3- (4-piperidin-1-yl-phenyl) - [1.2.4] oxadiazol-5-yl] -piperazin-1-yl} -ethanone,

1— {2 - [3 - (4-Morfolin-4-yl-phenyl) - [1,2,4] oxadiazol-5-yl] piperazin-1-yl] -2-phenoxy-ethanone,

1- (2— {3— [4- (2-Methyl-imidazol-1-yl) -phenyl] - [1.2.4] oxadiazol-5-yl} -piperazin-1-yl) -2-phenoxyethanone,

1- (2 - {3— [4- (3H-Imidazol-4-yl) -phenyl] - [1,2,4] oxadiazol5-yl} -piperazin-1-yl) -2-phenoxy-ethanone,

4- (5— {5— [1- (2-Phenoxy-acetyl) -piperazin-2-yl] - [1.2.4] oxadiazol-3-yl} -pyridin-2-yl) -piperazin-2-one ,

1- {2 - [3- (6-Imidazol-1-yl-pyridin-3-yl) - [1.2.4] oxadiazol-5-yl] -piperazin-1-yl} -2-phenoxyethanone,

1- (2— {3— [6- (4-Acetyl-piperazin-1-yl) -pyridin-3-yl] - [1.2.4] oxadiazol-5-yl} -piperazin-1-yl) -2 -phenoxyethanone,

2- Phenoxy-l- {2- [3- (4-pyrrol-l-yl-phenyl) - [1.2.4] oxadiazol-5-yl] -piperazin-l-yl} -ethanone,

2-Phenoxy-l- {2- [3- (4-trifluoromethanesulfonyl-phenyl) [1,2,4] oxadiazol-5-yl] -piperazin-l-yl} -ethanone,

40/229

1— {2— [3- (2-Morfolin ~ 4-yl-pyridin-4-yl) - [1.2.4] oxadiazol-5-yl] -piperazin-1-yl} -2-phenoxyethanone,

2- Phenoxy-l- {2- [3- (2-thiomorfolin-4-yl-pyridin-4-yl) - [1.2.4] oxadiazol-5-yl] -piperazin-l-yl} -ethanone,

1— (2— [3— [6— (3-Hydroxymethyl-pyrrolidin-1-yl) -pyridin-3yl] - [1,2,4] oxadiazol-5-yl} -piperazin-1-yl) -2 -phenoxyethanone, (R) —1— {2 - [3- (6-Methoxy-pyridin-3-yl) - [1,2,4] oxadiazol-5yl] -piperazin-1-yl} -2-phenoxy- ethanone, (R) —1— {2— [3- (6-Morfolin-4-yl-pyridin-3-yl) - [1.2.4] oxadiazol-5-yl] -piperazin-l-yl} -2 -phenoxyethanone, (R) -N- (4 - [5— [1— (2-Phenoxy-acetyl) -piperazin-2-yl] - [1.2.4] oxadiazol-3-yl} -2-trifluoromethyl-phenyl ) acetamide, (R) —1— [2— [3— (4-Methyl-3-nitro-phenyl) - [1,2,4] oxadiazol-5yl] -piperazin-1-yl} -2-phenoxy-ethanone, ( R) —1— {2— [3- (4-Methyl-3-nitro-phenyl) - [1,2,4] oxadiazol-5yl] -piperazin-1-yl} -2-phenoxy-ethanone, (R ) -l- {2- [3- (4-Morfolin-4-yl-phenyl) - [1,2,4] oxadiazol-5yl] -piperazin-1-yl} -2-phenoxy-ethanone, (R) -1- (2- [3- [4- (3H-Imidazol-4-yl) -phenyl] - [1.2.4] oxadiazol-5-yl} -piperazin-1-yl) -2-phenoxyethanone,

41/229 (R) -1- (2— {3— [6- (3-Hydroxymethyl-pyrrolidin-1-yl) pyridin-3-yl] - [1,2,4] oxadiazol-5-yl} - piperazin-1-yl) -2phenoxy-ethanone, (R) —1— (2— {3— [6— (4-Acetyl-piperazin-1-yl) -pyridin-3-yl] - [1.2.4] oxadiazol-5-yl} -piperazin-1-yl) -2-phenoxyethanone, (R) -N- (3— {5- [1- (2-Phenoxy-acetyl) -piperazin-2-yl] - [1.2 .4] oxadiazol-3-yl} -phenyl) -acetamide hydrochloride, (R) -l- {2- [3- (1H-Benzoimidazol-5-yl) - [1,2,4] oxadiazol-5yl] - piperazin-l-yl} -2-phenoxy-ethanone, (R) —1— {2 - [3— (1H-Benzotriazol-5-yl) - [1,2,4] oxadiazol-5yl] -piperazin-1-yl} -2-phenoxy-ethanone, (R) —1— {2— [3— (lH-Indazol-5-yl) - [1,2,4] oxadiazol-5-yl] piperazin-l-yl} -2-phenoxy-ethanone hydrochloride, (R) - 5— {5— [1- (2-Phenoxy-acetyl) -piperazin-2-yl] - [1.2.4] oxadiazol-3-yl} -1,3-dihydro-benzoimidazole-2-one,

(R) -1- (2- {3- [6- (1,1-1-Dioxo-thiomorfolin-4yl) -pyridin-3-yl] - [1,2,4] oxadiazol-5-yl hydrochloride} - piperazin-lil) -2-phenoxy-ethanone, (R) -1- {2- [3- (3-Nitro-phenyl) - [1,2,4] oxadiazol-5-yl] piperazin-l-yl} -2-phenoxy-ethanone, (R) —1— {2— [3— (4-Fluoro-phenyl) - [1,2,4] oxadiazol-5-yl] piperazin-l-yl} -2-phenoxy -ethanone, (R) - 4— {5— [1- (2-Phenoxy-acetyl) -piperazin-2-yl] - [1.2.4] oxadiazol-3-yl} -1H-pyridin-2-one,

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1- {4-Acetyl-2- [3- (4-methoxy-phenyl) - [1,2,4] oxadiazol-5yl] -piperazin-1-yl} -2-phenoxy-ethanone,

1— {4 — Acetyl — 2— [3- (4-methanesulfonyl-phenyl) - [1.2.4] oxadiazol-5-yl] -piperazin-l-yl} -2-phenoxy-ethanone,

4- {5- [4-Acetyl-1- (2-phenoxy-acetyl) -piperazin-2-yl] - [1.2.4] oxadiazol-3-yl] -benzenesulfonamide,

1- [4-Acetyl-2- (3-pyridin-4-yl- [1,2,4] oxadiazol-5-yl) piperazin-l-yl] -2-phenoxy-ethanone, l- {4-Methanesulfonyl -2- [3- (4-methoxy-phenyl) - [1.2.4] oxadiazol-5-yl] -piperazin-l-yl} -2-phenoxy-ethanone, (R) -l- {2- [5 - (4-Fluoro-phenyl) -2H- [1,2,4] triazol-3-yl] piperazin-1-yl} -2-phenoxy-ethanone, (R) -2-Phenoxy-l- {2- [5- (3-trifluoromethyl-phenyl) -2H- [1.2.4] triazol-3-yl] -piperazin-1-yl} -ethanone,

1- {2- [5- (4-Fluoro-3-trifluoromethyl-phenyl) -2H- [1.2.4] triazol-3-yl] -piperazin-1-yl} -2-phenoxy-ethanone,

1- {2 - [5- (4-Methanesulfonyl-phenyl) -2H- [1,2,4] triazol-3-yl] -piperazin-1-yl} -2-phenoxy-ethanone,

2- Phenoxy-l- {2- [5- (3-trifluoromethyl-phenyl) -2H- [1.2.4] triazol-3-yl] -piperazin-l-yl} -ethanone,

2-Phenoxy-l- [2- (5-p-tolyl-2H- [1,2,4] triazol-3-yl) piperazin-1-yl] -ethanone,

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2-Phenoxy-l- {2- [5- (4-trifluoromethyl-phenyl) -2H- [1.2.4] triazol-3-yl] -piperazin-l-yl} -ethanone,

1— {2— [5— (4-Methoxy-phenyl) -2H- [1,2,4] triazol-3-yl] piperazin-l-yl} -2-phenoxy-ethanone, l- {2- [ 5- (4-Fluoro-phenyl) -2H- [1,2, 4] triazol-3-yl] piperazin-1-yl} -2-phenoxy-ethanone,

1— {2— [5- (4-Fluoro-phenyl) -2H- [1,2,4] triazol-3-yl] piperazin-1-yl} -2-phenoxy-ethanone,

1— {2 - [5 - (3,4-Dimethoxy-phenyl) -2H- [1,2,4] triazol-3-yl] piperazin-l-yl} -2-phenoxy-ethanone, l- {2 - [5- (3,4-Dichloro-phenyl) -2H- [1,2,4] triazol-3-yl] piperazin-1-yl} -2-phenoxy-ethanone,

1- {2- [5- (2-Fluoro-phenyl) -2H- [1,2,4] triazol-3-yl] piperazin-1-yl} -2-phenoxy-ethanone,

1— {2— [5- (2-Fluoro-phenyl) -2H- [1,2,4] triazol-3-yl] piperazin-1-yl} -2-phenoxy-ethanone,

4- {5- [4-Methyl-1- (2-phenoxy-acetyl) -piperazin-2-yl] - [1.2.4] oxadiazol-3-yl} -benzamide, (R) —1— {2— [3— (lH-Indazol-5yl) - [1,2,4] oxadiazol-5-yl] -4methyl-piperazin-l-yl} -2-phenoxy-ethanone, (R) —1— [2— [ 3— (4-Fluoro-phenyl) - [1,2,4] oxadiazol-5-yl] -4methyl-piperazin-1-yl} -2-phenoxy-ethanone, (R) -5- {5- [4 -Methyl-l- (2-phenoxy-acetyl) -piperazin-2-yl] - [1.2.4] oxadiazol-3-yl} -1,3-dihydro-indol-2-one,

44/229 (R) -5- {5- [4-Methyl-1- (2-phenoxy-acetyl) -piperazin-2-yl] - [1.2.4] oxadiazol-3-yl} -1,3- dihydro-benzoimidazole-2-one, (R) —1— {2— [3— (1H-Benzoimidazol-5-yl) - [1,2,4] oxadiazol-5yl] -4-methyl-piperazin-l- yl} -2-phenoxy-ethanone, (R) —1— {2 - [3- (1H-Benzotriazol-5-yl) - [1,2,4] oxadiazol-5yl] -4-methyl-piperazin-l -yl} -2-phenoxy-ethanone, (R) -1- {4-Methyl-2- [5- (3-trifluoromethyl-phenyl) -2H- [1.2.4] triazol-3-yl] -piperazin- l-yl} -2-phenoxy-ethanone, (R) —1— {2— [5— (4-Methoxy-phenyl) -2H- [1,2,4] triazol-3-yl] -4methyl-piperazin-l-yl} -2-phenoxy-ethanone , (R) -l- {2- [5- (4-Fluoro-phenyl) -2H- [1,2,4] triazol-3-yl] -4methyl-piperazin-1-yl} -2-phenoxy- ethanone, (R) —1— {2— [5- (4-Methanesulfonyl-phenyl) -2H- [1.2.4] triazol-3-yl] -4-methyl-piperazin-l-yl} -2-phenoxyethanone ,

(R) -4- {5- [4-Methyl-1- (2-phenoxyacetyl) -piperazin-2-yl] -1H- [1,2,4] triazol-3-yl} ~ benzoic acid methyl ester , (R) -N- (3- [5- [4-Methyl-1- (2-phenoxy-acetyl) -piperazin-2yl] -1H- [1,2,4] triazol-3-yl} -phenyl ) -acetamide, (R) -N- (3- {5- [4-Methyl-1- (2-phenoxy-acetyl) -piperazin-2yl] -1H- [1,2,4] triazol-3-yl } -phenyl) -methanesulfonamide, (R) —4— {5— [4-Methyl-1- (2-phenoxy-acetyl) -piperazin-2-yl] 1H- [1,2,4] triazole-3- il} -benzamide,

45/229 (R) -4- {5- [1- (2-Phenoxy-acetyl) -piperidin-2-yl] - [1,2,4] oxadiazol-3-yl} -benzoic acid, (R ) -3- {5- [1- (2-Phenoxy-acetyl) -piperidin-2-yl] - [1.2.4] oxadiazol-3-yl} -benzoic acid (R) -6- {5- [ 1- (2-Phenoxy-acetyl) -piperidin-2-yl] - [1.2.4] oxadiazol-3-yl} -nicotinic, (R) -2-Fluoro-4- {5- [1- (2 -phenoxy-acetyl) -piperidin2-yl] - [1,2,4] oxadiazol-3-yl} -benzoic acid, (R) —5— {5— [1- (2-Phenoxy-acetyl) -piperidin-2 -il] 10 [1,2,4] oxadiazol-3-yl} -pyridine-2-carboxylic acid, (R) -4- (5- [1- (2-Phenoxy-acetyl) -piperidin-2-yl] - [1.2.4] oxadiazol-3-yl} -pyridine-2-carboxylic acid, (R) —3— {5— [1- (2-Phenoxy-acetyl) -piperidin-2-yl] -1H- [1.2.4] triazol-3-yl} -benzoic acid, 3- {5- [4- ( 2-Phenoxy-acetyl) -morpholin-3-yl] - [1.2.4] oxadiazol-3-yl} -benzoic acid, 3- {5- [4- (2-Phenoxy-acetyl) -morpholin-3-yl ] - [1.2.4] oxadiazol-3-yl} -benzoic acid,

4- {5- [4- (2-Phenoxy-acetyl) -tiomorfolin-3-yl] 20 [1,2,4] oxadiazol-3-yl} -benzamide, - {5— [4- (2-Phenoxy -acetyl) -tiomorfolin-3-yl] - [1.2.4] oxadiazol-4-yl} -benzamide, 3- {5- [4-Acetyl-l- (2-phenoxy-acetyl) -piperazin-2il] - [1,2,4] oxadiazol-3-yl} -benzoic acid,

46/229 4- {5- [4-Acetyl-1- (2-phenoxy-acetyl) -piperazin-2yl] - [1,2,4] oxadiazol-3-yl} -benzoic acid, (R) - 4- {5- [4-Methyl-1- (2-phenoxy-acetyl) -piperazin2-yl] -1H- [1,2,4] triazol-3-yl} -benzoic acid (R) -5 - {5- [1- (2-Phenoxy-acetyl) -piperidin-2-yl] - [1.2.4] oxadiazol-3-yl} -nicotinic,

1— (2— {3— [4— (Morpholine-4-carbonyl) -phenyl] - [1.2.4] oxadiazol-5-yl} -piperidin-1-yl) -2-phenoxyethanone, (R) -1 - (2— {3— [4- (3-Hydroxy-pyrrolidine-1-carbonyl) phenyl] - [1,2,4] oxadiazol-5-yl} -piperidin-1-yl) -2-phenoxy ethanone, (R) -N, N-Diethyl-4- {5- [1- (2-phenoxy-acetyl) -piperidin-2yl] - [1,2,4] oxadiazol-3-yl} -benzamide, (R) -N-Methyl-4- {5- [1- (2-phenoxy-acetyl) -piperidin-2-yl] - [1.2.4] oxadiazol-3-yl} -benzamide, (R) -N, N- Dimethyl-4- {5- [1- (2-phenoxy-acetyl) -piperidin-2yl] - [1,2,4] oxadiazol-3-yl} -benzamide, (R) -N-Ethyl-4- {5- [1- (2-phenoxy-acetyl) -piperidin-2-yl] - [1,2,4] oxadiazol-3-yl} -benzamide, (R) -N-Cyclopropyl-4- {5- [1- (2-phenoxy-acetyl) -piperidin-

2-yl] - [1,2,4] oxadiazol-3-yl} -benzamide, (R) -N- (2-Hydroxy-ethyl) —4— {5— [1- (2-phenoxy-acetyl) piperidin-2-yl] - [1,2,4] oxadiazol-3-yl} -benzamide,

47/229 (R) -N- (2-Methoxy-ethyl) -N-methyl-4- {5- [1- (2-phenoxyacetyl) -piperidin-2-yl] - [1,2,4] oxadiazole -3-yl} benzamide, (R) -N-Methyl-3- {5- [1- (2-phenoxy-acetyl) -piperidin-2-yl] - [1,2,4] oxadiazol-3-yl } -benzamide, (R) -N, N-Dimethyl-3- {5- [1- (2-phenoxy-acetyl) -piperidin-2yl] - [1,2,4] oxadiazol-3-yl} -benzamide , (R) -N-Ethyl-3- {5- [1- (2-phenoxy-acetyl) -piperidin-2-yl] - [1.2.4] oxadiazol-3-yl} -benzamide, (R) - N-Cyclopropyl-3- {5- [1- (2-phenoxy-acetyl) -piperidin2-yl] - [1,2,4] oxadiazol-3-yl} -benzamide, (R) -N- (2-Hydroxy-ethyl) —3— {5— [1- (2-phenoxy-acetyl) piperidin-2-yl] - [1,2,4] oxadiazol-3-yl} - benzamide, (R) -N- (2-Methoxy-ethyl) -N-methyl-3- {5- [1- (2-phenoxyacetyl) -piperidin-2-yl] - [1,2,4] oxadiazole- 3-yl} benzamide, (R) —1— (2— {3— [3— (Morpholine-4-carbonyl) -phenyl] - [1.2.4] oxadiazole-5-i1} -piperidin-l-yl) -2-phenoxyethanone, (R) —1— (2— {3— [3— (3-Hydroxy-pyrrolidine-1-carbonyl) phenyl] - [1,2,4] oxadiazol-5-yl} -piperidin- 1-yl) -2-phenoxy ethanone, (R) -N, N-Diethyl-3- {5- [1- (2-phenoxy-acetyl) -piperidin-2yl] - [1,2,4] oxadiazol-3-yl} -benzamide,

48/229 (R) -4- {5- [1- (2-Phenoxy-acetyl) -piperidin-2-yl] - [1.2.4] oxadiazol-3-yl] -pyridine-2-carboxylic acid methylamide, (R) -4- {5- [1- (2-Phenoxy-acetyl) 5 piperidin-2-yl] - [1,2,4] oxadiazol-3-yl} -pyridine-2-carboxylic acid dimethylamide, ethylamide (R) -4- {5- [1- (2-Phenoxy-acetyl) piperidin-2-yl] - [1,2,4] oxadiazol-3-yl} -pyridine-2-carboxylic acid, acid diethylamide (R ) -4- {5- [1- (2-Phenoxy-acetyl) piperidin-2-ill-Γ1,241 oxadiazol-3-yl1-Diridine-2carboxylic, (R) -1- (2- {3- [2- (Morpholine-4-carbonyl) -pyridin-4-yl] - [1.2.4] oxadiazol-5-yl} -piperidin-l-yl) -2 -phenoxyethanone, (R) -l- (2- {3- [2- (3-Methanesulfonyl-pyrrolidine-1carbonyl) -pyridin-4-yl] - [1,2,4] oxadiazol-5-yl} piperidin-1-yl) -2-phenoxy-ethanone, (R) -5- [5- [1- (2-Phenoxy-acetyl) -piperidin-2-yl] 20 [1,2,4] oxadiazole-3 -yl} -pyridine-2-carboxylic acid methylamide, (R) -N-Methyl-3- {5- [1- (2-phenoxy-acetyl) -piperidin-2-yl] 1H- [1,2,4 ] triazole-3-i1} -benzamide,

IN, N-Diethyl-4- {5- [1- (2-phenoxy-acetyl) -piperazin-2-yl] 25 [1,2,4] oxadiazol-3-yl} -benzamide,

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1— (2— {3— [4— (Morpholine-4-carbonyl) -phenyl] - [1.2.4] oxadiazol-5-yl} -piperazin-1-yl) -2-phenoxyethanone,

N-Methyl-4- {5- [1- (2-phenoxy-acetyl) -piperazin-2-yl] - [1.2.4] oxadiazol-3-yl} -benzamide, (R) -N-Methyl-5 - {5- [1- (2-phenoxy-acetyl) -piperidin-2-yl] - [1.2.4] oxadiazol-3-yl} -nicotinamide, (R) -N-Ethyl-5- {5- [ 1- (2-phenoxy-acetyl) -piperidin-2-yl] - [1,2,4] oxadiazol-3-yl} -nicotinamide, (R) -N-Diethyl-5- {5- [1- ( 2-phenoxy-acetyl) -piperidin-2-yl] - [1,2,4] oxadiazol-3-yl} -nicotinamide, (R) -N-Diethyl-5- {5- [1- (2-phenoxy -acetyl) -piperidin-2-yl] - [1.2.4] oxadiazol-3-yl} -nicotinamide, (R) -N- (2-Hydroxy-ethyl) —5— {5— [1- (2-phenoxy-acetyl) piperidin-2-yl] - [1,2,4] oxadiazol-3-yl} - nicotinamide, (R) -N- (2-Methoxy-ethyl) -N-methyl-5- {5- [1- (2-phenoxyacetyl) -piperidin-2-yl] - [1,2,4] oxadiazole- 3-yl} nicotinamide, (R) -N-Cyclopropyl-5- {5- [1- (2-phenoxy-acetyl) -piperidin-

2- yl] - [1,2,4] oxadiazol-3-i1} -nicotinamide, (R) -1- (2— {3- [5- (3-Hydroxy-pyrrolidine-1-carbonyl) pyridin-3 -il] - [1,2,4] oxadiazol-5-yl} -piperidin-1-yl) -2phenoxy-ethanone, (R) —4— [5— [1— (2-Phenoxy-acetyl) -piperidin -2-yl] - [1.2.4] oxadiazol-3-yl} -benzamide,

50/229 (R) —3— {5— [1- (2-Phenoxy-acetyl) -piperidin-2-yl] - [1.2.4] oxadiazol-3-yl} -benzamide, (R) acid amide -4- {5- [1- (2-Phenoxy-acetyl) -piperidin2-yl] - [1,2,4] oxadiazol-3-yl} -pyridine-2-carboxylic, (R) —3— [5 - [1— (2-Phenoxy-acetyl) -piperidin-2-yl] -1H- [1.2.4] triazol-3-yl} -benzamide,

4- {5 - [4- (2-Phenoxy-acetyl) -morpholin-3-yl] - [1.2.4] oxadiazol-3-i1} -benzamide,

4- {5 - [4- (2-Phenoxy-acetyl) -thiomorfolin-3 yl] - [1.2.4] oxadiazol-3yl} -benzamide,

4- {5 - [1- (2-Phenoxy-acetyl) -piperazin-2-yl] - [1.2.4] oxadiazol-3-yl} -benzamide,

5- {5- [1- (2-Phenoxy-acetyl) -piperidin-2-yl] - [1.2.4] oxadiazol-3-yl} -nicotinamide, (R) —1— {2— [3- ( 3-Amino-phenyl) - [1,2,4] oxadiazol-5-yl] piperidin-1-yl} -2-phenoxy-ethanone, (R) -1- {2- [3- (4-Amino- phenyl) - [1,2,4] oxadiazol-5-yl] piperidin-1-yl} -2-phenoxy-ethanone, (R) -1- {2- [5- (3-Amino-phenyl) -2H - [1,2,4] triazol-3-yl] piperidin-1-yl} -2-phenoxy-ethanone, (R) -N- (3— {5- [1- (2-Phenoxy-acetyl) - piperidin-2-yl] - [1.2.4] oxadiazol-3-yl} -phenyl) -acetamide, (R) -N- (4- {5- [1- (2-Phenoxy-acetyl) -piperidin-2-yl] - [1,2,4] oxadiazol-3-yl} -phenyl) -acetamide,

51/229 (R) -N- (5- {5- [1- (2-Phenoxy-acetyl) -piperidin-2-yl] - [1.2.4] oxadiazol-3-yl} -pyridin-2-yl ) -acetamide, (R) -N- (3— {5- [1- (2-Phenoxy-acetyl) -piperidin-2-yl] -1H- [1.2.4] triazol-3-yl} -phenyl) -acetamide, (R) -N- (3- {5- [1- (2-Phenoxy-acetyl) -piperidin-2-yl] - [1.2.4] oxadiazol-3-yl} -phenyl) -methanesulfonamide, (R) -N- (4- [5- [1- (2-Phenoxy-acetyl) -piperidin-2-yl] - [1.2.4] oxadiazol-3-yl} -phenyl) -methane-sulfonamide, allyl (R) - (3- {5- [1- (2-Phenoxy-acetyl) piperidin-2-yl] - [1,2,4] oxadiazol-3-yl} -phenyl) carbamic acid, allyl (R) - (4— {5- [1- (2-Phenoxy-acetyl) piperidin-2-yl] - [1,2,4] oxadiazol-3-yl} -phenyl) carbamic ester, (R ) -N- (3- {5- [1- (2-Phenoxy-acetyl) -piperidin-2-yl] -1H- [1.2.4] triazol-3-yl} -phenyl) -methanesulfonamide, (R) -l-Ethyl-3- (3— {5— [1- (2-phenoxy-acetyl) -piperidin-2yl] -1H- [1,2,4] triazol-3-yl} -phenyl) -urea, (R) —3— {5— [1- (2-Phenoxy-acetyl) -piperidin-2-yl] -1H- [1.2.4] triazol-3-yl} -benzonitrile, and (R) —5— [5— [1— (2-Phenoxy-acetyl) -piperidin-2-yl] - [1.2.4] oxadiazol-3-yl} -nicotinonitrile, and their pharmaceutically acceptable salts and esters .

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Particularly preferred compounds of formula (I) are those selected from the group consisting of:

(R) —1— {2 - [3— (lH-Indazol-5-yl) - [1,2,4] oxadiazol-5-yl] 5 piperidin-l-yl} -2-phenoxy-ethanone, ( R) -l- {2- [3- (1H-Indazol-6-yl) - [1,2,4] oxadiazol-5-yl] piperidin-l-yl} -2-phenoxy-ethanone, (R) —6— {5— [1— (2-Phenoxy-acetyl) -piperidin-2-yl] - [1.2.4] oxadiazol-3-yl} -1,3-dihydro-indole-2-one, (R ) —5— [5 - [1— (2-Phenoxy-acetyl) -piperidin-2-yl] - [1.2.4] oxadiazol-3-yl} -1,3-dihydro-benzoimidazole-2-one, ( R) —5— {5— [1- (2-Phenoxy-acetyl) -piperidin-2-yl] - [1.2.4] oxadiazol-3-yl} -1,3-dihydro-indol-2-one, (R) —1— {2— [3— (1H-Benzotriazol-5-yl) - [1,2,4] oxadiazol-515 yl] -piperidin-l-yl} -2-phenoxy-ethanone, (R ) —1— {2 - [3- (1H-Benzoimidazol-5-yl) - [1,2,4] oxadiazol-5yl] -piperidin-1-yl} -2-phenoxy-ethanone, (R) -4 - {5- [4- (2-Phenoxy-acetyl) -morpholin-3-yl] - [1.2.4] oxadiazol-3-yl} -1H-pyridin-2-one, (R) —1— [2 - [5— (4-Fluoro-phenyl) -2H- [1,2,4] triazol-3-yl] piperidin-1-yl} -2-phenoxy-ethanone, (R) -2-Phenoxy-1- {2- [5- (3-trifluoromethyl-phenyl) -2H- [1.2.4] triazol-3-yl] -piperidin-1-yl} -ethanone, (R) -l- {2- [3- (1H-Benzoimidazol-5-yl) - [1,2,4] oxadiazol-525 yl] -piperazin-1-yl} -2-phenoxy-ethanone,

53/229 (R) -3- (5- [1- (2-Phenoxy-acetyl) -piperidin-2-yl] - [1.2.4] oxadiazol-3-yl} -benzamide,

5- {5- [1- (2-Phenoxy-acetyl) -piperidin-2-yl] - [1.2.4] oxadiazol-3-yl} -nicotinamide, (R) -N- (3— {5- [ 1- (2-Phenoxy-acetyl) -piperidin-2-yl] -1H- [1.2.4] triazol-3-yl} -phenyl) -acetamide, and (R) -N- (3— {5- [ 1- (2-Phenoxy-acetyl) -piperidin-2-yl] -1H- [1.2.4] triazol-3-yl} -phenyl) -methanesulfonamide, and their pharmaceutically acceptable salts and esters.

Other preferred compounds of formula (I) are those selected from the group consisting of:

1 - {(R) -2- [3- (2-Methyl-1H-benzoimidazol-5-yl) - [1.2.4] oxadiazol-5-yl] -piperidin-l-yl} -2-phenoxyethanone,

1— {(R) -2- [3- (2-Amino-pyridin-4-yl) - [1,2,4] oxadiazol-5-yl] -piperidin-1-yl} -2-phenoxy-ethanone ,

1— {(R) -2- [3- (3-Hydroxy-phenyl) - [1,2,4] oxadiazol-5-yl] piperidin-1-yl} -2-phenoxy-ethanone, - {5— [(R) -1- (2-Phenoxy-acetyl) -piperidin-2-yl] - [1.2.4] oxadiazol-3-yl} -1H-pyridin-2-one,

1— {(R) -2- [3- (4-Hydroxy-phenyl) - [1,2,4] oxadiazol-5-yl] piperidin-1-yl} -2-phenoxy-ethanone, 3- { 5 - [1- (2-Phenoxy-acetyl) -piperidin-2-yl] - [1.2.4] oxadiazol-3-yl} -phenylboronic,

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4- (2-Οχο-2- {(R) -2- [3- (2-oxo-2,3-dihydro-1H-indol-5-yl) - [1.2.4] oxadiazol-5-yl] -piperidin-1-yl} -ethoxy) benzonitrile, - (2 - {(R) -2- [3- (4-Methoxy-phenyl) - [1,2,4] oxadiazol-5-yl] piperidin-1 -yl} -2-oxo-ethoxy) -benzonitrile,

2-Methyl-5- {5 - [(R) -1- (2-phenoxy-acetyl) -piperidin-2-yl] - [1.2.4] oxadiazol-3-yl} -3H-pyrimidin-4-one ,

1- [(R) -2- (3-Furan-2-yl- [1,2,4] oxadiazol-5-yl) piperidin-1-yl] -2-phenoxy-ethanone,

1 - [(R) -2- (3-Imidazo [1,2-a] pyridin-2-yl- [1.2.4] oxadiazol-5-yl) -piperidin-1-yl] -2-phenoxyethanone , l - {(R) -2- [3- (4-Methyl- [1,2,3] thiadiazol-5-yl) - [1.2.4] oxadiazol-5-yl] -piperidin-l-yl} -2-phenoxyethanone,

1— {(R) -2- [3- (2,5-Dimethyl-2H-pyrazol-3-yl) - [1.2.4] oxadiazol-5-yl] -piperidin-1-yl} -2-phenoxy - ethanone,

2- Phenoxy-1 - {(R) -2- [3- (1H-pyrazol-4-yl) - [1.2.4] oxadiazol-5-yl] -piperidin-1-yl} -ethanone,

1— {(R) -2- [3- (5-Methyl-isoxazol-3-yl) - [1,2,4] oxadiazol-5-yl] -piperidin-1-yl} -2-phenoxy-ethanone ,

2- Phenoxy-1 - {(R) -2- [3- (1H-pyrazol-3-yl) - [1,2,4] oxadiazol-5-yl] -piperidin-1-yl} -ethanone,

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5— {5 - [(R) -1- (2-Phenoxy-acetyl) -piperidin-2-yl] - [1.2.4] oxadiazol-3-yl] -1H-pyrimidine-2,4-dione,

1— {(R) -2- [3- (6-Amino-pyridin-3-yl) - [1,2,4] oxadiazol-5-yl] -piperidin-1-yl} -2-phenoxy-ethanone ,

1- [(R) -2- (3-Imidazo [1, 2-a] pyridin-6-yl- [1.2.4] oxadiazol-5-yl) -piperidin-1-yl] -2-phenoxyethanone,

6— {5— [(R) -1- (2-Phenoxy-acetyl) -piperidin-2-yl] - [1.2.4] oxadiazol-3-yl] -4H-benzo [1,4] oxazin-3 -one,

6- {5- [(R) -1- (2-Phenoxy-acetyl) -piperidin-2-yl] - [1.2.4] oxadiazol-3-yl} -1,4-dihydro-benzo [d] [ 1.3] oxazin-

2- one,

1- ((R) —2— {3— [3- (1,1-Dioxo-1À6-isothiazolidin-2-yl) phenyl] - [1,2,4] oxadiazol-5-yl} -piperidin-l -yl) -2-phenoxyethanone,

1- (3- {5 - [(R) -1- (2-Phenoxy-acetyl) -piperidin-2-yl] - [1.2.4] oxadiazol-3-yl] -phenyl) -pyrrolidin-2-one ,

1— (3— {5— [(R) -1- (2-Phenoxy-acetyl) -piperidin-2-yl] - [1.2.4] oxadiazol-3-yl} -phenyl) -imidazolidine-2,4 -diona,

4- (3— {5 - [(R) -1- (2-Phenoxy-acetyl) -piperidin-2-yl] - [1.2.4] oxadiazol-3-yl} -phenyl) -2,4-dihydro - [1.2.4] triazole-3-one,

1- (3-Fluoro-5- {5 - [(R) -1- (2-phenoxy-acetyl) -piperidin-2yl] - [1,2,4] oxadiazol-3-yl} -phenyl) -pyrrolidine -2.5dione,

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5- {5 - [(R) —1— (2-Phenoxy-acetyl) -piperidin-2-yl] -1Η- [1.2.4] triazol-3-yl}-1,3-dihydro-indole-2 -one,

1— {(R) -2- [5- (1H-Indazol-5-yl) -2H- [1,2,4] triazol-3-yl] - piperidin-l-yl} -2-phenoxy-ethanone , l- {(R) -2- [5- (lH-Indol-5-yl) -2H- [1,2,4] triazol-3-yl] piperidin-l-yl} -2-phenoxy-ethanone , l- {(R) —2— [5— (3H-Benzotriazol-5-yl) -2H- [1,2,4] triazol-3yl] -piperidin-l-yl} -2-phenoxy-ethanone,

5— {5— [(R) -1- (2-Phenoxy-acetyl) -piperidin-2-yl] -1H- [1.2.4] triazol-3-yl} -1,3-dihydro-benzoimidazole-2 -one,

1— {(R) -2- [5- (2-Methyl-1H-benzoimidazol-5-yl) -2H- [1.2.4] triazol-3-yl] -piperidin-l-yl} -2-phenoxy -ethanone, l- {(R) -2 - [5 - (2-Amino-pyridin-4-yl) -2H- [1,2,4] triazol-3yl] -piperidin-l-yl} -2- phenoxyethanone,

5— (3— [5 - [(R) -1- (2-Phenoxy-acetyl) -piperidin-2-yl] -1H- [1.2.4] triazol-3-yl} -phenyl) -3H- [ 1,3,4] oxadiazol-2-one, 1- ({(R) -2- [5- (3- [1,3,4] Oxadiazol-2-yl-phenyl) -2H- [1.2.4] triazol-3-yl] -piperidin-1-yl} -2-phenoxy-ethanone, 3- {5- [1- (2-Phenoxy-acetyl) -piperidin-2-yl] -1H- [1.2.4 ] triazol-3-yl} -phenylboronic,

6- {5 - [(R) -1- (2-Phenoxy-acetyl) -piperidin-2-yl] -1H- [1.2.4] triazol-3-yl} -4H-benzo [1,4] oxazin -3-one,

1- [(R) -2- (5-Imidazo [1,2-a] pyridin-6-yl-2H- [1.2.4] triazol-3-yl) -piperidin-1-yl] -2-phenoxy -ethanone,

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1— {(R) —2 - [5— (6-Amino-pyridin-3-yl) -2H- [1,2,4] triazol-3-yl] -piperidin-1-yl} -2-phenoxy -ethanone,

1— {(R) —2— [5— (1H-Benzoimidazol-5-yl) -2H- [1,2,4] triazole-

3-yl] -piperidin-1-yl} -2-phenoxy-ethanone,

2- Phenoxy-1 - [(R) -2- (5-pyridin-3-yl-2H- [1,2,4] triazol-3-yl) -piperidin-1-yl] -ethanone,

1- {(R) —2— [5— (3,5-Dimethyl-isoxazol-4-yl) -2H- [1,2,4] triazol-3-yl] -piperidin-l-yl} -2 -phenoxy-ethanone,

2- Phenoxy-1 - [(R) -2- (5-thiophen-2-yl-2H- [1,2,4] triazol-3-yl) -piperidin-1-yl] -ethanone,

2- Phenoxy-1 - [(R) -2- (5-pyrimidin-2-yl-2H- [1,2,4] triazole-

3-yl) -piperidin-1-yl] -ethanone,

1- {(R) -2- [5- (4-Methyl-oxazol-5-yl) -2H- [1,2,4] triazol-3-yl] -piperidin-1-yl} -2-phenoxy -ethanone,

2- Phenoxy-1 - [(R) -2- (5-pyrazin-2-yl-2H- [1,2,4] triazol-3-yl) -piperidin-1-yl] -ethanone, 1- (R) -2- [5- (2-Fluoro-phenyl) -2H- [1,2,4] triazol-3-yl] piper idin-1-yl} -2-phenoxy-ethanone,

1— {(R) -2- [5- (3,5-Difluoro-phenyl) -2H- [1,2,4] triazol-3yl] -piperidin-1-yl} -2-phenoxy-ethanone, l - {(R) -2- [5- (2-Methyl-pyridin-4-yl) -2H- [1,2,4] triazol-3yl] -piperidin-1-yl} -2-phenoxy-ethanone, 1- {(R) -2- [5- (3-Fluoro-phenyl) -2H- [1,2,4] triazol-3-yl] piperidin-l-yl} -2-phenoxy-ethanone,

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1— {(R) —2— [5— (3,4-Difluoro-phenyl) -2H- [1,2,4] triazol-3-yl] -piperidin-1-yl} -2-phenoxy-ethanone ,

6— {5 - [(R) -1- (2-Phenoxy-acetyl) -piperidin-2-yl] -1H [1,2,4] triazol-3-yl} -1,4-dihydro-benzo [ d] [1,3] oxazin-25 one, - {5 - [(R) -1- (2-Phenoxy-acetyl) -piperidin-2-yl] -lH- [1.2.4] triazol-3-yl } -3,4-dihydro-1H-quinazolin-2-one,

1- (3— {5 - [(R) -1- (2-Phenoxy-acetyl) -piperidin-2-yl] -1H- [1.2.4] triazol-3-yl} -phenyl) -imidazolidine-2 , 4-dione, l- {(R) -3- [3- (2-Amino-pyridin-4-yl) - [1,2,4] oxadiazol-5yl] -morpholin-4-yl} -2- phenoxyethanone,

1— {(R) —3— [3— (1H-Benzoimidazol-5-yl) - [1,2,4] oxadiazol-5yl] -morpholin-4-yl} -2-phenoxy-ethanone,

1— {(R) -2 - [3- (1H-Benzoimidazol-5-yl) - [1,2,4] oxadiazol-515 yl] -piperazin-1-yl} -2-phenoxy-ethanone, - { 5 - [(R) -1- (2-Phenoxy-acetyl) -piperazin-2-yl] - [1.2.4] oxadiazol-3-yl} -1,3-dihydro-indol-2-one,

1— {(R) -2- [3- (2-Amino-pyridin-4-yl) - [1,2,4] oxadiazol-5-yl] -piperazin-1-yl} -2-phenoxy-ethanone , (3- {5 - [(R) -1- (2-Phenoxy-acetyl) -piperidin-2-yl] - [1.2.4] oxadiazol-3-yl} -phenoxy) -acetic acid,

2- Phenoxy-l - ((R) —2— {5— [3- (piperidine-l-carbonyl) -phenyl] -

2H- [1,2,4] triazol-3-yl} -piperidin-1-yl) -ethanone,

1- ((R) -2- {5- [3- (Morpholine-4-carbonyl) -phenyl] -2H25 [1,2,4] triazol-3-yl} -piperidin-l-yl) -2- phenoxyethanone,

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1- ((R) —2 - {5— [3— (4-Methyl-piperazine-1-carbonyl) -phenyl] 2H- [1,2,4] triazol-3-yl} -piperidin-1-yl ) -2-phenoxyethanone, - (3— {5 - [(R) -1- (2-Phenoxy-acetyl) -piperidin-2-yl] -1H5 [1,2,4] triazol-3-yl} - benzoyl) -piperazin-2-one,

N- (2-Methoxy-ethyl) -N-methyl-3- {5 - [(R) -1- (2-phenoxyacetyl) -piperidin-2-yl] -1H- [1,2,4] triazole- 3-yl} benzamide,

1- ((R) —2— {5— [3— (4-Acetyl-piperazine-1-carbonyl) -phenyl] -

2H- [1,2,4] triazol-3-yl} -piperidin-1-yl) -2-phenoxyses 4- ο υί cs

L-UÁllVllLÁ acid 1— (3— [5 - [(R) -1- (2-Phenoxy-acetyl) -piperidin-2-yl] 1H- [1,2,4] triazol-3-yl} - benzoyl) -piperidine-4-carboxylic acid, 1- (3— [5 - [(R) -1- (2-Phenoxy-acetyl) piperidin-2-yl] -1H- [1,2,4] triazole- amide 3-yl} -benzoyl) piperidine-4-carboxylic,

2- Phenoxy-1 - ((R) -2- {5- [3- (thiazolidine-3-carbonyl) phenyl] -2H- [1,2,4] triazol-3-yl} -piperidin-1-yl ) -ethanone,

N- (2-Dimethylamino-ethyl) -N-methyl-3- {5 - [(R) -1- (2-phenoxyacetyl) -piperidin-2-yl] -1H- [1,2,4] triazole- 3-yl} benzamide,

2-Phenoxy-l - ((R) —2— [5— [3— (thiomorpholine-4-carbonyl) phenyl] -2H- [1,2,4] triazol-3-yl} -piperidin-l-yl ) -ethanone,

60/229 4- (3- {5 - [(R) -1- (2-Phenoxy-acetyl) piperidin-2-yl] -1H- [1,2,4] triazol-3-yl ethyl ester } -benzoyl) piperazine-1-carboxylic,

N- (2-Hydroxy-ethyl) —3— {5 - [(R) -1- (2-phenoxy-acetyl) 5 piperidin-2-yl] -1H- [1,2,4] triazole-3- il} -benzamide,

N-Methyl-3- {5 - [(R) -1- (2-phenoxy-acetyl) -piperidin-2-yl] 1H- [1,2,4] triazol-3-yl} -N- (2 -pyridin-2-yl-ethyl) benzamide,

N- (2-Cyano-ethyl) -N-cyclopropyl-3- {5 - [(R) -1- (2-phenoxy10 acetyl) -piperidin-2-yl] -1H- [1,2,4] triazole -3-il} / dn

K- / LAlllJ- j

1— (3— {5— [(R) —1— (2-Phenoxy-acetyl) -piperidin-2-yl] -1H- [1.2.4] triazol-3-yl} -benzoyl) -4-phenyl -piperidine-4carbonitrile,

1- ((R) -2- {5- [3- (4-Hydroxy-piperidine-1-carbonyl) phenyl] -2H- [1,2,4] triazol-3-yl} -piperidin-l-yl ) -2phenoxy-ethanone,

8— (3— {5 - [(R) -1- (2-Phenoxy-acetyl) -piperidin-2-yl] -1H- [1.2.4] triazol-3-yl) -benzoyl) -1,3 , 8-triaza-spiro [4.5] decano-2,4-dione,

1- (2- {5- [3- (Spiro (1-Phtalan) -piperidine-4-carbonyl) phenyl] -2H- [1,2,4] triazol-3-yl} -piperidin-l-yl) -2- phenoxy-ethanone,

2- Phenoxy-1 - ((R) -2- {5- [3- (3-pyridin-4-yl-pyrrolidine-1,225 carbonyl) -phenyl] -2H- [1,2,4] triazole-3- il} -piperidin-l- yl) -ethanone,

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1- ((R) —2— {5— [3- (3-Methanesulfonyl-pyrrolidine-lcarbonyl) -phenyl] -2H- [1,2,4] triazol-3-yl} -piperidin-lil) -2 -phenoxy-ethanone,

1- ((R) —2— {5— [3 - ((S) -3-Ethoxy-pyrrolidine-1-carbonyl) 5 phenyl] -2H- [1,2,4] triazol-3-yl} - piperidin-l-yl) -2phenoxy-ethanone,

1- ((R) -2- {5- [3 - ((S) -3-Hydroxy-pyrrolidine-1-carbonyl) phenyl] -2H- [1,2,4] triazol-3-yl} -piperidin -l-yl) -2-phenoxy-ethanone,

5- {5 - [(R) -1- (2-Phenoxy-acetyl) -piperidin-2-yl] -1H-

<img file="BRPI0619086A2_D0015.tif" />

- r&gt; ί ί nomí río

1 _1_ V_z OU J.11U11LIJ. V_4U4

2- (3— {5— [1- (2-Phenoxy-acetyl) -piperidin-2-yl] - [1,2,4] oxadiazol-3-yl} -phenoxy) -acetamide,

N- (3-Fluoro-5- {5 - [(R) -1- (2-phenoxy-acetyl) -piperidin-2 yl] - [1,2,4] oxadiazol-3-yl} -phenyl) - acetamide,

N- (2-Fluoro-5- {5 - [(R) -1- (2-phenoxy-acetyl) -piperidin-2yl] - [1,2,4] oxadiazol-3-yl} -phenyl) -acetamide ,

N- (3- {5 - [(R) -1- (2-Phenoxy-acetyl) -piperidin-2-yl] -1H- [1,2,4] triazol-3-yl} -phenyl) -propionamide ,

N— (3— {5 - [(R) -1- (2-Phenoxy-acetyl) -piperidin-2-yl] -1H- [1,2,4] triazol-3-yl} -phenyl) -isobutyramide ,

N- (4-Fluoro-3- {5 - [(R) -1- (2-phenoxy-acetyl) -piperidin-2yl] -1H- [1,2,4] triazol-3-yl} -phenyl) -acetamide,

N- (3-Fluoro-5- {5 - [(R) -1- (2-phenoxy-acetyl) -piperidin-225 yl] -1H- [1,2,4] triazol-3-yl] -phenyl ) -acetamide,

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N- (2-Fluoro-5- {5 - [(R) -1- (2-phenoxy-acetyl) -piperidin-2yl] -1H- [1,2,4] triazol-3-yl} -phenyl) -acetamide,

N- (4- {5 - [(R) -1- (2-Phenoxy-acetyl) -piperidin-2-yl] -1H- [1.2.4] triazol-3-yl} -pyridin-2-yl) -acetamide,

1— (3— {5 - [(R) —1— (2-Phenoxy-acetyl) -piperidin-2-yl] -1H- [1.2.4] triazol-3-yl} -phenyl) -azetidin-2 -one,

1- (3— [5— [1— (2-Phenoxy-acetyl) -piperidin-2-yl] -1H- [1.2.4] triazol-3-yl} -phenyl) -pyrrolidine-2,5-dione ,

2- Phenoxy-1 - [(R) -2- (5-pyridazin-4-yl- [1,2,4] oxadiazol-3-yl) -piperidin-1-yl] -ethanone, - {3— [ (R) -1- (2-Phenoxy-acetyl) -piperidin-2-yl] - [1.2.4] oxadiazol-5-yl} -benzonitrile,

1— {(R) -2- [5- (3-Amino-pyrazin-2-yl) - [1,2,4] oxadiazol-3yl] -piperidin-1-yl} -2-phenoxy-ethanone,

3- [3 - [(R) -1- (2-Phenoxy-acetyl) -piperidin-2-yl] - [1.2.4] oxadiazol-5-yl} -benzonitrile,

1— {(R) -2- [5- (2-Hydroxy-pyridin-3-yl) - [1,2,4] oxadiazol3 - i1] -piperidin-1-yl} -2-phenoxy-ethanone,

1— {(R) -2- [5- (5-Amino-pyridin-3-yl) - [1,2,4] oxadiazol-320 yl] -piperidin-1-yl} -2-phenoxy-ethanone,

1— {(R) -2- [5- (2-Hydroxy-pyridin-4-yl) - [1,2,4] oxadiazole-

3-yl] -piperidin-1-yl} -2-phenoxy-ethanone,

1 - {(R) -2- [5- (2-Hydroxy-6-methyl-pyridin-4-yl) - [1.2.4] oxadiazol-3-yl] -piperidin-l-yl} -2-phenoxy - ethanone,

63/229 l- {(R) -2- [5- (4-Hydroxy-pyridin-2-yl) - [1,2,4] oxadiazole-

3-yl] -piperidin-1-yl} -2-phenoxy-ethanone,

1— {(R) -2- [5- (2-Amino-5-chloro-pyrimidin-4-yl) - [1.2.4] oxadiazol-3-yl] -piperidin-1-yl} -2-phenoxy - ethanone,

2- Phenoxy-1 - [(R) -2- (5-pyrazin-2-yl- [1,2,4] oxadiazol-3-yl) -piperidin-1-yl] -ethanone,

2- Phenoxy-l - {(R) -2- [5- (4- [1,2,4] triazol-1-yl-phenyl) - [1.2.4] oxadiazol-3-yl] -piperidin-1 -il} -ethanone,

2-Phenoxy-1 - {(R) -2- [5- (4-tetrazol-1-yl-phenyl) - [1,2,4] oxadiazol-3-yl] -piperidin-1-yl} -ethanone , - {(R) —2— [5— (1H-Benzoimidazol-4-yl) - [1,2,4] oxadiazol-3yl] -piperidin-1-yl} -2-phenoxy-ethanone,

1 - {(R) -2- [5- (4-Acetyl-phenyl) - [1,2,4] oxadiazol-3-yl] 15 piperidin-l-yl} -2-phenoxy-ethanone, l- { (R) -2- [5- (6-Hydroxy-pyridin-2-yl) - [1,2,4] oxadiazole-

3-yl] -piperidin-1-yl} -2-phenoxy-ethanone,

1 - {(R) -2- [5- (5-Methyl-pyrazin-2-yl) - [1,2,4] oxadiazol-3yl] -piperidin-1-yl} -2-phenoxy-ethanone,

2-Phenoxy-1 - [(R) -2- (5-quinoxalin-2-yl- [1,2,4] oxadiazole-

3-yl) -piperidin-1-yl] -ethanone,

1— {(R) -2- [5- (3-Methanesulfonyl-phenyl) - [1,2,4] oxadiazole-

3 — il] -piperidin-1-yl} -2-phenoxy-ethanone,

1 - {(R) -2- [5- (6-Chloro-pyridin-3-yl) - [1,2,4] oxadiazol-325 yl] -piperidin-1-yl} -2-phenoxy-ethanone,

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1- [(R) -2- (5-Benzothiazol-6-yl- [1,2,4] oxadiazol-3-yl) piperidin-1-yl] -2-phenoxy-ethanone,

2- Phenoxy-l - {(R) -2- [5- (2,4,5-trifluoro-phenyl) - [1,2,4] oxadiazol-3-yl] -piperidin-l-yl} -ethanone ,

2-Phenoxy-1 - {(R) -2- [5- (6-trifluoromethyl-pyridin-3-yl) - [1.2.4] oxadiazol-3-yl] -piperidin-1-yl} -ethanone,

1 - [(R) -2- (5-Benzo [1,2,3] thiadiazol-5-yl- [1.2.4] oxadiazol-3-yl) -piperidin-1-yl] -2-phenoxyethanone,

1- [(R) -2- (5- [1,8] Naphthyridin-2-yl- [1,2,4] oxadiazol-3yl) -piperidin-1-yl] -2-phenoxy-ethanone,

1 - [(R) -2- (5- [1,6] Naphthyridin-2-yl- [1,2,4] oxadiazol-3yl) -piperidin-1-yl] -2-phenoxy-ethanone,

1 - [(R) -2- (5-Cinnolin-4-yl- [1,2,4] oxadiazol-3-yl) piperidin-1-yl] -2-phenoxy-ethanone,

1— {(R) -2- [5- (1H-Benzotriazol-5-yl) - [1,2,4] oxadiazol-3yl] -piperidin-1-yl} -2-phenoxy-ethanone,

1— {(R) -2- [5- (1H-Benzoimidazol-5-yl) - [1,2,4] oxadiazol-3 yl] -piperidin-1-yl} -2-phenoxy-ethanone,

1 - {(R) -2- [5- (3,6-Dichloro-pyridazin-4-yl) - [1.2.4] oxadiazol-3-yl] -piperidin-1-yl} -2-phenoxyethanone,

6- {3 - [(R) -1- (2-Phenoxy-acetyl) -piperidin-2-yl] - [1.2.4] oxadiazol-5-yl} -4H-benzo [1,4] oxazin-3 -one,

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1- {(R) -2- [5- (3H-Imidazo [4,5-b] pyridin-6-yl) - [1,2,4] oxadiazol-3-yl] -piperidin-l-yl} -2-phenoxyethanone,

N- (4 - {3 - [(R) -1- (2-Phenoxy-acetyl) -piperidin-2-yl] 5 [1,2,4] oxadiazol-5-yl} -pyridin-2-yl) -acetamide,

1— {(R) -2- [5- (6-Chloro-3-hydroxy-pyridazin-4-yl) - [1.2.4] oxadiazol-3-yl] -piperidin-1-yl} -2-phenoxyethanone ,

6— {3— [. (R) —1— (2-Phenoxy-acetyl) -piperidin-2-yl] 10 [1,2,4] oxadiazol-5-yl}-1,4-dihydro-quinoxaline- 2,3ki J-XJllQ f - {(R) -2- [5- (6-Hydroxy-pyridin-3-yl) - [1,2,4] oxadiazole-

3-yl] -piperidin-1-yl} -2-phenoxy-ethanone, - {3 - [(R) -1- (2-Phenoxy-acetyl) -piperidin-2-yl] 15 [1,2,4 ] oxadiazol-5-yl} -3,4-dihydro-1H-quinoxalin-2-one,

1- {(R) —2— [5— (6-Amino-pyridin-2-yl) - [1,2,4] oxadiazol-3yl] -piperidin-1-yl} -2-phenoxy-ethanone,

6— {3 - [(R) -1- (2-Phenoxy-acetyl) -piperidin-2-yl] - [1.2.4] oxadiazol-5-yl} -nicotinonitrile,

5— {3 - [(R) -1- (2-Phenoxy-acetyl) -piperidin-2-yl] - [1.2.4] oxadiazol-5-yl} -pyridine-2-carbonitrile,

4— {3 - [(R) -1- (2-Phenoxy-acetyl) -piperidin-2-yl] - [1.2.4] oxadiazol-5-yl} —1,2-dihydro-indazol-3-one , l- {(R) -2- [5- (2-Amino-pyridin-4-yl) - [1,2,4] oxadiazol-325 yl] -piperidin-l-yl} -2-phenoxy-ethanone ,

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1 - {(R) -2- [5- (6-Hydroxy-pyrimidin-4-yl) - [1.2.4] oxadiazol-3-yl] -piperidin-1-yl} -2-phenoxyethanone,

4- (3— {3 - [(R) -1- (2-Phenoxy-acetyl) -piperidin-2-yl] - [1,2,4] oxadiazol-5-yl} -phenyl) -2,4 -diidro- [1.2.4] triazole-3-one,

1- (3- (3- [- (R) -1- (2-Phenoxy-acetyl) -piperidin-2-yl] - [1.2.4] oxadiazol-5-yl} -phenyl) -imidazolidine-2, 4-diona,

1- ((R) —2— [5— [3— (1,1-Dioxo-1,6-isothiazolidin-2-yl) 10 phenyl] - [1,2,4] oxadiazol-3-yl} -piperidine- 1-yl) -2-phenoxyethanone,

1- (3— {3 - [(R) -1- (2-Phenoxy-acetyl) -piperidin-2-yl] - [1.2.4] oxadiazol-5-yl} -phenyl) -pyrrolidin-2-one ,

1— (3— [3 - [(R) -1- (2-Phenoxy-acetyl) -piperidin-2-yl] 15 [1,2,4] oxadiazol-5-yl} -phenyl) -1,3 -dihydro-imidazole-2one,

3- (3— {3 - [(R) -1- (2-Phenoxy-acetyl) -piperidin-2-yl] - [1.2.4] oxadiazol-5-yl} -phenyl) -imidazolidine-2,4 -diona,

1- {(R) -2- [5- (1-Methyl-1H-pyrazol-3-yl) - [1,2,4] oxadiazole-

3-yl] -piperidin-1-yl} -2-phenoxy-ethanone,

2- Phenoxy-l - {(R) -2- [5- (1H-pyrazol-3-yl) - [1.2.4] oxadiazol-3-yl] -piperidin-l-yl} -ethanone, l- { (R) -2- [5- (5-Methyl-isoxazol-3-yl) - [1,2,4] oxadiazol-3yl] -piperidin-1-yl} -2-phenoxy-ethanone,

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1— {(R) -2- [5- (2,5-Dimethyl-2H-pyrazol-3-yl) - [1.2.4] oxadiazol-3-yl] -piperidin-1-yl} -2-phenoxyethanone ,

1— {(R) -2- [5- (5-Methyl-2H-pyrazol-3-yl) - [1,2,4] oxadiazol5 3-yl] -piperidin-1-yl} -2-phenoxy ethanone, and

1— {(R) -2- [5- (3-Methyl-isoxazol-5-yl) - [1,2,4] oxadiazol-3-yl] -piperidin-1-yl} -2-phenoxy-ethanone , and their pharmaceutically acceptable salts and esters.

Other particularly preferred compounds of formula (I) are those selected from the group consisting of:

2- Methyl-5- {5 - [(R) -1- (2-phenoxy-acetyl) -piperidin-2-yl] - [1.2.4] oxadiazol-3-yl} -3H-pyrimidin-4-one ,

1— {(R) -2- [3- (5-Methyl-isoxazol-3-yl) - [1,2,4] oxadiazol-5-yl] -piperidin-1-yl} -2-phenoxy-ethanone ,

2- Phenoxy-1 - {(R) -2- [3- (1H-pyrazol-3-yl) - [1.2.4] oxadiazol-5-yl] -piperidin-1-yl} -ethanone,

1— {(R) -2- [3- (6-Amino-pyridin-3-yl) - [1,2,4] oxadiazol-5yl] -piperidin-1-yl} -2-phenoxy-ethanone,

5— [5 - [(R) —1— (2-Phenoxy-acetyl) -piperidin-2-yl] -1H- [1.2.4] triazol-3-yl}-1,3-dihydro-indole-2 -one,

1— {(R) -2- [5- (2-Amino-pyridin-4-yl) -2H- [1,2,4] triazol-3yl] -piperidin-1-yl} -2-phenoxy-ethanone ,

6— {5 - [(R) -1- (2-Phenoxy-acetyl) -piperidin-2-yl] -1H25 [1,2,4] triazol-3-yl} -4H-benzo [1,4] oxazin-3-one,

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1— {(R) -2- [5- (6-Amino-pyridin-3-yl) -2H- [1,2,4] triazol-3yl] -piperidin-1-yl} -2-phenoxy-ethanone ,

1— {(R) -2- [5- (1H-Benzoimidazol-5-yl) -2H- [1,2,4] triazole-

3 — il] -piperidin-1-yl} -2-phenoxy-ethanone,

N- (2-Fluoro-5- {5 - [(R) -1- (2-phenoxy-acetyl) -piperidin-2yl] -1H- [1,2,4] triazol-3-yl} -phenyl) -acetamide, and l- {(R) -2- [5- (2-Hydroxy-pyridin-4-yl) - [1,2,4] oxadiazole-

3-yl] -piperidin-1-yl} -2-phenoxy-ethanone, and their pharmaceutically acceptable salts and esters.

It should be understood that the compounds of the general formula (I) in the present invention can be derived in the functional groups to provide derivatives that are capable of conversion back to the parent compound in vivo.

The invention also relates to a process for the manufacture of compounds of formula (I) as defined above, a process which comprises reacting a compound of formula (II)

<img file="BRPI0619086A2_D0016.tif" />

^H (II) with a compound of the formula (III)

<img file="BRPI0619086A2_D0017.tif" />

69/229 where R¹, R², R³, R⁴, R⁵, R⁶, R⁷, and X are as defined in any one of claims 1 - 22 and L is halogen.

The reaction of a compound of formula (II) with a compound of formula (III) can be carried out under conditions widely known to those skilled in the art. These reactions can be conveniently carried out, for example, by mixing a compound of the formula (II) with, for example, a hydrochloric acid of the formula (III) or, alternatively, with an activated ester thereof, a compound of the formula ( III) in a solvent, such as, for example, DMF at appropriate temperatures between 25 ° C and 120 ° C, optionally in the presence of diisopropylethylamine. Preferably, L is Cl.

Alternatively, L may be an active ester. These active esters as well as their use to form amide bonds are widely known to those skilled in the art.

The present invention also relates to the 20 compounds of formula (I) as defined above, when prepared by a process as described above.

The compounds of formulas (I), (II) and (II-I) can be prepared by methods known in the art or as described below or in analogy thereto. Unless otherwise indicated, R¹, R², R³, R⁴, R⁵, R⁶, R⁷ and X are as previously described.

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The compounds of formula (I) can be prepared according to the general methods set out below.

Layout 1

<img file="BRPI0619086A2_D0018.tif" />

<img file="BRPI0619086A2_D0019.tif" />

<img file="BRPI0619086A2_D0020.tif" />

<img file="BRPI0619086A2_D0021.tif" />

<img file="BRPI0619086A2_D0022.tif" />

BOC YN

<img file="BRPI0619086A2_D0023.tif" />

Air

X = CH2, O, S, NAc, NMes

Y = O, NH

The compounds of general formula 1 are preferably dissolved in DMF and 1 equivalent of activating reagent, such as TBTU, is added. The reaction is subjected to stirring at room temperature for

10 minutes and the corresponding hydroxyamidine (compound

2) added to give the compounds of the general formula 3. The reaction mixture is heated to 80 ° C and stirred overnight and treated under microwave conditions at 120 ° C for 15-30 minutes to result in 4. After evaporation of the solvent and extracted from ethyl acetate / water the crude material is

71/229 treated with pure trifluoroacetic acid or 4N HCL in Dioxan to result in compounds of the general formula 5. The final product is obtained by treating these intermediates, either with phenoxyl chloride and its derivatives or their corresponding active esters.

The corresponding N-methylpiperazine derivatives were generated from the piperazines as indicated in scheme 2.

Layout 2

<img file="BRPI0619086A2_D0024.tif" />

<img file="BRPI0619086A2_D0025.tif" />

The compounds preferably in DMF and formaldehyde and type 1 quantity are dissolved treated with an excess of acetic acid catalytic.

The reaction mixture is stirred at room temperature for 30 minutes and 1 equivalent of NaBH is added₃CN. The reaction is subjected to stirring at room temperature for 16 hours and the product isolated by chromatography.

The carboxylic acid analogs were generated from the corresponding esters through classical saponification with NaOH or LiOH or through catalytic debenzylation procedures, where the starting material is typically dissolved in methanol and an aqueous solution is added. of NaOH or LiOH. The reaction is subjected to stirring, preferably for 2 hours at room temperature, and the product is extracted from ethyl acetate / water after acidification of the reaction mixture.

Carboxyamide analogs were generated from the corresponding carboxylates by pre-activation with reagents such as TBTU in DMF. The reaction mixtures are usually subjected to stirring at room temperature overnight.

The primary carboxyamide analogs were generated from the corresponding carboxylates through coupling to the Rink resin and subsequent dividing with TFA by pre-activating the starting material with reagents such as TBTU. The reaction mixture is usually subjected to stirring at room temperature overnight. After excessive washing of the resins with solvents, such as DMF, methanol and methylene chloride, the solid phase material is treated with TFA at room temperature for 2 hours. After evaporation, the product is isolated by chromatography.

Amino derivatives were generated from the corresponding nitro analogs through a Zink-mediated reduction where the starting material is

73/229 preferably dissolved in ethanol and saturated aqueous ammonium chloride. An excess of zinc powder is added, the reaction briefly heated to reflux and then subjected to stirring at room temperature for 16 hours. The product is isolated by extraction from ethyl acetate / water and final chromatography.

The following N-amides, -sulfonamides, -carbamates and -ureas were all generated from the corresponding amino derivatives where the amino derivatives 10 are preferably dissolved in DMF and when the corresponding activated acetyl chlorides or esters, chlorides of sulfonyl or isocyanates. The reactions proceed at room temperature. The products are isolated by chromatography.

Benzonitriles were generated from the corresponding primary benzamides by treating the latter with pure trifluoroacetic anhydride at room temperature for preferably 16 hours.

The non-commercially available amino acids were generated from 1-tert-butyl ester 2-methyl piperazine-1,2-dicarboxylic acid by coupling with either acetyl chloride or methylsulfonyl chloride in THF at room temperature, followed by saponification as previously described .

Hydroxyamidines not commercially available were generated from the corresponding nitriles by adding 5 equivalents of hydroxylamine monohydrochloride and 2.5 equivalents of carbonate of

74/229 sodium in an ethanol / water mixture (7: 3). The reaction mixture was heated to 80 ° C for usually 2 hours. The product was isolated by extraction from ethyl acetate / water.

The sulfonamide hydroxyamidines not commercially available were generated by coupling 4-cyanobenzen-1-sulfonylchloride with 2 equivalents of the corresponding amine in THF at room temperature for 16 hours. After evaporation of the solvent, the product was extracted from ethyl acetate / water. Crude nitrile is treated with hydrazine as described above.

The 2-aminopyridine hydroxyamidines not commercially available were generated from the corresponding 15 nitriles as previously described. The nitriles were obtained from the corresponding chlorocyanopyridines after dissolving in DMF and adding 2 equivalents of the amine. The reaction mixture was heated to 120 ° C under microwave conditions, usually for 30 minutes. The product was isolated by extraction from ethyl acetate / water after evaporation of the reaction solvent.

Aminoamidines were generated from the corresponding imidoethers by the addition of 1 equivalent of hydrazine monohydrate in methanol. The product was isolated by precipitation when 1.25 M HCl / methanol was added. The iminoethers were obtained from the corresponding nitriles after suspension

75/229 in methylene chloride and saturation with HCl gas at 0 ° C for 30 minutes. The reaction mixture was stirred for 16 hours at room temperature and the product removed by filtration after the addition of 5 diethyl ether.

Nitriles not commercially available were generated from the corresponding primary amides by the addition of pure trifluoroacetic acid anhydride at room temperature, preferably for 16 hours.

<img file="BRPI0619086A2_D0026.tif" />

N2H2

<img file="BRPI0619086A2_D0027.tif" />

<img file="BRPI0619086A2_D0028.tif" />

<img file="BRPI0619086A2_D0029.tif" />

<img file="BRPI0619086A2_D0030.tif" />

<img file="BRPI0619086A2_D0031.tif" />

Furthermore, as highlighted in the outline

3, compounds of the general formula 1 can preferably be dissolved in DMF and 1 equivalent of activating reagent, such as TBTU, is added in addition to 1 equivalent of a base, such as DIPEA. The reaction is cooled to 0 ° C and an excess of hi is added

76/229 drazina. The reaction is heated and stirred at room temperature to result in compound 2.

After evaporation of the solvent and extraction from ethyl acetate / water, the crude material is treated with 1 equivalent of the corresponding amidine in DMF. A catalytic amount of acetic acid is added and the reaction heated to 120 ° C overnight to result in the compounds of the general formula 4. After evaporation of the solvent and extraction from ethylacetate / water, trifluoroacetic acid or 4N is added HCL in Dioxane to generate the compounds of general formula 5. 0 final product is obtained by treating these intermediates either with phenoxyacetyl chloride and its derivatives, or with their corresponding active esters.

<img file="BRPI0619086A2_D0032.tif" />

<img file="BRPI0619086A2_D0033.tif" />

<img file="BRPI0619086A2_D0034.tif" />

<img file="BRPI0619086A2_D0035.tif" />

NH2OH

<img file="BRPI0619086A2_D0036.tif" />

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Furthermore, as highlighted in the outline

4, compound 1 can preferably be dissolved in aqueous ethanol and treated with an excess of hydrazine hydrochloride and a base, such as sodium carbonate to result in compound 2. This intermediate can be coupled with 1 equivalent of pre-activated carboxylates or their corresponding acetyl chlorides in solvents such as DMF, to result in compounds of general formula 3. Cyclization to the corresponding oxadiazole occurs under high temperature, either using conventional heating or by microwave. Boc cleavage is usually performed using either pure TFA or 4N HCl in Dioxane to result in the compounds of the general formula 5. The final product is obtained by treating9 these intermediates with either phenoxyacetyl chloride and its derivatives or their corresponding active esters.

The corresponding salts can be obtained by standard methods known to those skilled in the art, for example, by dissolving the compound of formula (I) in a suitable solvent, such as, for example, dioxane or THF and adding an appropriate amount of the corresponding acid. Products can usually be isolated by means of filtration or chromatography.

The conversion of the compounds of formula (I) into pharmaceutically acceptable esters can be carried out, for example, by treating a group of carbo

78/229 suitable xylose present in the molecule with a suitable alcohol using, for example, a condensation reagent, such as benzotriazol-1yloxitris (dimethylamino) phosphonium (BOP) hexafluorophosphate (BOP), N, N-dicylexyl5 carbodiimide (DCC), hydrochloride N- (3-dimethylaminopropyl) -Ν'-ethylcarbodiimide (EDCI) or 0- (1,2-dihydro-2oxo-1-pyridyl) -N, N, N, N-tetra-methyluronium-tetrafluorborate (TPTU). Pharmaceutically acceptable esters can, in addition, be further prepared by treating a suitable hydroxyl group present in the molecule with a suitable acid, optionally or if necessary in the presence of a condensing agent as previously described.

Insofar as their preparation is not described in the examples, the compounds of formula (I) as well as all intermediate products can be prepared according to analogous methods or according to the methods set out above. The starting materials are commercially available, are known in the art or can be prepared by methods known in the art or in analogy thereto.

As previously described, the new compounds of the present invention have been shown to inhibit the activity of liver carnitine palmitoyl transferase 1 (L-CPT1). The compounds of the present invention can, therefore, be used in the treatment and / or prophylaxis of diseases that are modulated by L79 / 229 inhibitors.

CPT1, particularly diseases that are related to hyperglycemia and / or impaired glucose tolerance. These diseases include, for example, diabetes and associated conditions, non-insulin-dependent diabetes mellitus, obesity, hypertension, insulin resistance syndrome, metabolic syndrome, hyperlipidemia, hypercholesterolemia, liver fatty disease, atherosclerosis, congestive heart deficiency and kidney failure .

Therefore, the invention also relates to pharmaceutical compositions that comprise a compound as defined above and a pharmaceutically acceptable carrier and / or adjuvant.

Similarly, the invention encompasses 15 compounds as previously described for use as therapeutically active substances, especially as therapeutically active substances for the treatment and / or prophylaxis of diseases that are modulated by L-CPT1 inhibitors, particularly as therapeutically substances. active for the treatment and / or prophylaxis of hyperglycemia, glucose tolerance disorders, diabetes and associated pathologies, non-insulin dependent diabetes mellitus, obesity, hypertension, insulin resistance syndrome, metabolic syndrome, hyperlipidemia, hypercholesterolemia, liver fat disease, atherosclerosis, congestive heart failure, as well as kidney deficiency.

In another preferred embodiment, the invention

80/229 tion refers to a method for the therapeutic and / or prophylactic treatment of diseases that are modulated by L-CPT1 inhibitors, with particularity for the treatment and / or prophylaxis of hyperglycemia, glucose tolerance disorders, diabetes and associated pathologies, non-insulin dependent diabetes mellitus, obesity, hypertension, insulin resistance syndrome, metabolic syndrome, hyperlipidemia, hypercholesterolemia, liver fat disease, atherosclerosis, 10 congestive heart failure, as well as kidney failure, which method comprises comprising administering a compound as defined above to a human or animal.

The invention also encompasses the use of compounds as previously described for the therapeutic and / or prophylactic treatment of diseases that are modulated by L-CPT1 inhibitors, particularly for the therapeutic and / or prophylactic treatment of hyperglycemia, glucose tolerance disorders , diabetes 20 and associated conditions, non-insulin dependent diabetes mellitus, obesity, hypertension, insulin resistance syndrome, metabolic syndrome, hyperlipidemia, hypercholesterolemia, liver fat disease, atherosclerosis, congestive heart failure, as well as kidney failure.

The invention also relates to the use of compounds as described above for the preparation of medicaments for therapeutic treatment

81/229 and / or prophylactic of diseases that are modulated by L-CPT1 inhibitors, particularly for the therapeutic and / or prophylactic treatment of hyperglycemia, glucose tolerance disorders, diabetes and associated pathologies, non-insulin dependent diabetes mellitus, obesity, hypertension, insulin resistance syndrome, metabolic syndrome, hyperlipidemia, hypercholesterolemia, liver fat disease, atherosclerosis, congestive heart failure, as well as kidney deficiency. Such drugs comprise a compound as described above.

The prevention and / or treatment of hyperglycemia and non-insulin-dependent diabetes mellitus is the preferred indication.

The tests set out below were carried out in order to determine the activity of the compounds of the present invention. Secondary information on the tests performed can be found at: Jackson et al., 1999, Biochem. J. 341, 483-489 and Jackson et al., 2000, J. Biol. Chem. 275, 19560-19566.

Liver and muscle CPT1 human cDNAs and rat CPT2 cDNA were subcloned into pGAPZB or pGAPZA, respectively. These plasmids were used to transform the P. pastoris X-33 variety by electroporation after preparation of electrocompetent cells. High copy number clones were selected where necessary using Zeocin 0.5 or 1 mg / ml. Cultures were induced for activity measurements

82/229 for 16 hours in YPD medium (1% yeast extract, 2% peptone, 2% glucose). Crude cell extracts were prepared by smashing the cells with glass beads or French Press, depending on the 5 fermentor dimensions. After centrifugation, the cell-free extracts were resuspended in a cell dissolution buffer (50 mM Tris, pH 7.4, 100 mM KC1, 1 mM EDTA) in the presence of a protease inhibitor cocktail before formation of 10 aliquots and freezing at -20 ° C.

CPT activity was measured using a spectrophotometric assay using 5,5'-dithio-bis- (2-nitro-benzoic acid) (DTNB), also called Ellman's reagent. HS-CoA released the formation 15 of acylcarnitine from carnitine (500 μΜ) and palmitoyl-CoA (80 μΜ) reduced DTNB (300 μΜ) forming 5-mercapto- (2-nitro-benzoic acid) which was absorbed at 410 nm with a molar coefficient extinction of 13600 M “¹.cm^-1. The test buffer contained 120 mM KCl, 25 20 mM Tris, pH 7.4, 1 mM EDTA. This assay was used to identify selective inhibitors of the liver CPT1 isoform against muscle CPT1 and CPT2 isoforms.

Preferably, the compounds according to formula (I) have an IC value₅the lower 25 to 10 μΜ, preferably 10 nM to 10 μΜ, more preferably 10 nM to 5 μΜ. The following table shows data for some examples.

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<td rowspan="2">Example</td><td>Inhibition of L-CPT1</td>

<td>IC50 [pmol / l]</td>

<td> 1</td><td> 0,066</td>

<td> 10</td><td> 0,260</td>

<td> 172</td><td> 0,242</td>

The compounds of the formula (I) and / or their pharmaceutically acceptable salts can be used as medicaments, for example, in the form of pharmaceutical preparations for enteral, parenteral or topical administration. They can be administered, for example, perorally, that is, in the form of tablets, coated tablets, dragees, hard and soft gelatin capsules, solutions, emulsions or suspensions, for rectal use, for example, in the form of suppositories, for parenteral use, for example, in the form of injectable solutions or infusion solutions, or topically, for example, in the form of ointments, creams or oils. Oral administration is preferred.

The production of pharmaceutical preparations 15 can be carried out in a manner that will be familiar to anyone skilled in the art, by bringing the compounds described in formula (I) and / or their pharmaceutically acceptable salts; optionally in combination with other therapeutically valuable substances, to a form of galenic administration, together with

84/229 therapeutically compatible solid or liquid conductive materials and, if desired, usual pharmaceutical adjuvants.

Carrier materials that are suitable include not only inorganic conductive materials, but also organic conductive materials. Thus, for example, lactose, corn starch or its derivatives, talc, stearic acid or its salts can be used as conductive materials for tablets, coated tablets, pills and hard gelatin capsules. Carrier materials that are suitable for soft gelatin capsules comprise, for example, vegetable oils, waxes, fats and semi-solid and liquid polyols (however, depending on the nature of the active ingredient, no carrier will be required in the case of soft gelatin). Carrier materials which are suitable for the production of solutions and syrups comprise, for example, water, polyols, saccharin, inverted sugar and the like. Carrier materials that are suitable for injectable solutions comprise, for example, water, alcohols, polyols, glycerol and vegetable oils. Carrier materials which are suitable for suppositories comprise, for example, natural or hardened oils, waxes, fats and semi-liquid or liquid polyols. Carrier materials that are suitable for topical preparations comprise glycerides, semi-synthetic and synthetic glycerides, hydrogenated oils, waxes

85/229 liquid, liquid paraffins, liquid fatty alcohols, sterols, polyethylene glycols as well as cellulose derivatives.

Stabilizers, preservatives, moisturizing and emulsion-forming agents, consistency-enhancing agents, aroma-enhancing agents, salts for varying osmotic pressure, damping substances, solubilizing agents, dyes and concealers, as well as antioxidants are taken into account as pharmaceutical adjuvants.

The dosage of the compounds of formula I may vary within wide limits, depending on the disease to be controlled, the age and individual condition of the patient, as well as the mode of administration and will, of course, be adjusted to the individual requirements in each particular case. For adult patients, a daily dosage of about 1 to 2000 mg, especially about 1 to 500 mg, is considered. Depending on the severity of the disease and the exact pharmacokinetic profile, the compound can be administered with one or more units of daily dosage, for example, in 1 to 3 units of dosage.

Conveniently, pharmaceutical preparations contain about 1-500 mg, preferably 1-200 mg, of a compound of formula I.

The following Examples serve to illustrate the present invention in more detail. Not

86/229 however, they are not intended to limit its scope in any way.

Examples

Example 1

CR) -l- {2- [3- (4-Methoxy-phenyl) - [1,2,4] oxadiazol-5-yl] piperidin-1-yl} -2-phenoxy-ethanone

Step 1:

(R) -2 - {[hydroxyimino- (410 methoxy-phenyl) -methyl] -carbamoyl} -piperidine-1-carboxylic acid tert-Butyl ester

23 mg (0.1 mmol) of BocD-Pipecolic acid were treated with 0.1 mmol of [Dimethylamino ([1,2,3] triazolo [4,5-b] pyridin-3-yloxy) -methylene] 15 dimethylammonium hexafluorophosphate (HATU) and diisopropylamine (DIPEA) in 1 ml of dimethylformamide (DMF) for 10 minutes, 17 mg (0.1 mmol) of NHhydroxy-4-methoxy-benzamidine were added and the reaction was stirred under temperature room for 20 minutes. The product was no longer featured.

Step 2:

(R) -2- [3- (4-methoxy-phenyl) [1,2,4] oxadiazol-5-yl] -piperidine-1-carboxylic acid tert-butyl ester

The crude material from step 1 was either treated at 80 ° C for 16 hours or heated quickly to 120 ° C under microwave conditions (10 minutes). The DMF was evaporated and the product extracted at

87/229 from ethyl acetate / water. The product was no longer featured.

Step 3:

(R) -2- [3- (4-methoxy-phenyl) [1,2,4] oxadiazol-5-yl] -piperidine trifluoroacetate

The crude material from step 2 was treated with pure trifluoroacetic acid (TFA) at room temperature for 1 hour. The TFA was evaporated. The crude product was no longer characterized.

Step 4:

(R) —1- [2- [3- (4-Methoxy-phenyl) - [1,2,4] oxadiazol-5-yl] piperidin-1-yl} -2-phenoxy-ethanone

The crude material from step 3 was dissolved in 1 ml of DMF and 0.1 mmol of DIPEA. Either 0.1 mmol of phenoxyacetyl chloride was added and the reaction was stirred at room temperature for 30 minutes, or the corresponding phenoxyacetic acid derivatives were pre-activated with HATU / DIPEA in DMF for 10 minutes and added to the crude material from from step 3. The product was isolated by means of high performance preparative liquid chromatography (HPLC).

MS (ISO): 394.4 (MH +)

In analogy, the following compounds were prepared:

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Table 1

<td>Example- plo</td><td>Compound name</td><td>Starting materials</td><td>MH⁺found</td>

<td> 2</td><td>(R) -3- (2- {2- [3- (4- Methoxy- faith- nil) [1,2,4] oxadiazole- 5-yl] -piperidin-l- yl} -2-oxo-ethoxy) benzonitrile</td><td>Boc-DPipecolic acid, NHhydroxy-4-methoxybenzamidine and 3Cyanophenoxy-acetyl chloride</td><td> 419, 5</td>

<td> 3</td><td>(R) -l- {2- [3- (4- Methoxy-phenyl) - [1,2,4] oxadiazol-5yl] -piperidin-l-yl} 2-phenoxy-propan-l-one</td><td>Boc-DPipecolic acid, NHhydroxy-4-methoxybenzamidine and 2-Phenoxy-propionic acid</td><td> 408,5</td>

<td> 4</td><td>(R) —1— {2— [3- (4-Bromophenyl) [1,2,4] oxadiazol-5yl] -piperidin-l-yl} 2-phenoxy-ethanone</td><td>Boc-DPipecolic acid, NHhydroxy-4-bromobenzamidine and phenoxyacetyl chloride</td><td> 442,2</td>

<td> 5</td><td>(R) -2- (4-Hydroxyphenoxy) —l— {2— [3— (4— methoxy-phenyl) - [1,2,4] oxadiazol-5yl] -piperidin-l-yl} ethanone</td><td>Boc-DPipecolic acid, NHhydroxy-4-methoxybenzamidine and 4-Hydroxyphenoxyacetic acid</td><td> 410,5</td>

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<td>Example</td><td>Compound name</td><td>Starting materials</td><td>MH⁺found</td>

<td> 6</td><td>(R) -2- (4-Chlorophenoxy) —l— {2— [3— (4— methoxy-phenyl) - [1,2,4] oxadiazol-5yl] -piperidin-l-yl} ethanone</td><td>Boc-DPipecolic acid, NHhydroxy-4-methoxybenzamidine and acid 4-Chlorophenoxy-acetic</td><td> 428,5</td>

<td> 7</td><td>(R) -2- (4- Hydroxymethyl-phenoxy) - 1- {2- [3- (4-methoxyphenyl) - [1,2,4] oxadiazol-5yl] -piperidin-l-yl} ethanone</td><td>Boc-DPipecolic acid, NHhydroxy-4-methoxybenzamidine and 4-hydroxymethylphenoxyacetic acid</td><td> 424,2</td>

<td> 8</td><td>(R) -2- (3-Chlorophenoxy) —1— [2— [3— (4— methoxy-phenyl) [1,2,4] oxadiazol-5yl] -piperidin-l-yl} ethanone</td><td>Boc-D- Acid Pipecolic, N- Hydroxy-4-methoxybenzamidine and acid 3-Chlorophenoxy-acetic</td><td> 428,5</td>

<td> 9</td><td>(R) -2- (4-Fluorophenoxy) —1— [2— [3— (4— methoxy-phenyl) - [1,2,4] oxadiazol-5yl] -piperidin-l-yl} ethanone</td><td>Boc-DPipecolic acid, NHhydroxy-4-methoxybenzamidine and 4-Fluorophenoxyacetic acid</td><td> 412,4</td>

<td> 10</td><td>(R) -l- {2- [3- (4- Fluoro-phenyl) [1,2,4] oxadiazol-5yl] -piperidin-1-yl} 2-phenoxy-ethanone</td><td>Boc-D- Acid Pipecolic, N- Hydroxy-4-fluorobenzamidine and phenoxyacetyl chloride</td><td> 382,5</td>

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<td>Example- plo</td><td>Compound name</td><td>Starting materials</td><td>MH⁺found</td>

<td> 11</td><td>(R) -l- {2- [3- (4Methane-sulfonylphenyl) - [1,2,4] oxadiazol-5yl] -piperidin-l-yl} 2-phenoxy-ethanone</td><td>Boc-D- Acid Pipecolic, NHhydroxy-4-methanesulfonylbenzamidine and phenoxyacetyl chloride</td><td> 442,5</td>

<td> 12</td><td>(R) -4- {5- [1- (2Fenoxy-acetyl) piperidin-2-yl] [1,2,4] oxadiazol-3yl} benzenesulfonamide</td><td>Boc-D- Acid Pipecolic, N- Hydroxy-4-sulfamoyl benzamidine and phenoxyacetyl chloride</td><td> 443,5</td>

<td> 13</td><td>(R) -2- (4-Fluorophenoxy) -1- [2- (3pyridin-4-yl [1,2,4] oxadiazol-5yl) -piperidin-l-yl] ethanone</td><td>Boc-D- Acid Pipecolic, N- Hydroxyisonicotinamidine and phenoxyacetyl chloride</td><td> 383,4</td>

<td> 14</td><td>Methyl acid ester (R) -3- {5- [1- (2- Phenoxy-acetyl) piperidin-2-yl] [1,2,4] oxadiazol-3yl} -benzoic</td><td>Boc-DPipecolic acid, 3- (Nhydroxycarbamimidoyl) -benzoic acid methyl ester and phenoxyacetyl chloride</td><td> 422,5</td>

<td> 15</td><td>(R) -1- {2- [3- (3-Nitrophenyl) - [1,2,4] oxadiazol-5yl] -piperidin-l-yl} 2-phenoxy-ethanone</td><td>Boc-DPipecolic acid, NHhydroxy-3-nitrobenzamidine and phenoxyacetyl chloride</td><td> 409, 5</td>

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<td>Example</td><td>Compound name</td><td>Starting materials</td><td>MH⁺find auger</td>

<td> 16</td><td>(R) -l- {2- [3- (4-Nitrophenyl) - [1,2,4] oxadiazol-5yl] -piperidin-l-yl} 2-phenoxy-ethanone</td><td>Boc-DPipecolic acid, NHhydroxy-4-nitrobenzamidine and phenoxyacetyl chloride</td><td> 409,5</td>

<td> 17</td><td>(R) -3- {5- [1- (2- Phenoxy-acetyl) piperidin-2-yl] [1,2,4] oxadiazol-3yl} - benzenesulfonamide</td><td>Boc-DPipecolic acid, NHhydroxy-3-sulfamoyl benzamidine and phenoxyacetyl chloride</td><td> 443,5</td>

<td> 18</td><td>(R) -2-Phenoxy-l- [2- (3pyrazin-2-yl- [1,2,4] oxadiazole-5- il) -piperidin-1-yl] ethanone</td><td>Boc-D- Acid Pipecolic, NHhydroxy-pyrazine-2carboxamidine and phenoxyacetyl chloride</td><td> 366,5</td>

<td> 19</td><td>(R) -1- (2- {3- [4 (Morpholine-4sulfonyl) -phenyl] [1,2,4] oxadiazol-5yl} -piperidin-1-yl) 2-phenoxy-ethanone</td><td>Boc-D- Acid Pipecolic, N- Hydroxy-4-N-acetylbenzamidine and phenoxyacetyl chloride</td><td> 513, 6</td>

<td> 20</td><td>(R) —1— {2— [3— (6— Methoxy-pyridin-3-yl) [1,2,4] oxadiazol-5yl] -piperidin-1-yl} 2-phenoxy-ethanone</td><td>Boc-D- Acid Pipecolic, NHhydroxy-6-methoxyinotinamidine and phenoxyacetyl chloride</td><td> 395, 5</td>

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<td>Example- plo</td><td>Compound name</td><td>Starting materials</td><td>MH⁺found</td>

<td> 21</td><td>(R) -l- {2- [3- (3- Hydroxymethyl-phenyl) [1,2,4] oxadiazol-5yl] -piperidin-l-yl} 2-phenoxy-ethanone</td><td>Boc-DPipecolic acid, NHhydroxy-3hydroxymethyl benzamidine and phenoxyacetyl chloride</td><td> 394,5</td>

<td> 22</td><td>(R) -6- {5- [1- (2-phenoxy-acetyl) piperidin-2-yl] [1,2,4] oxadiazol-3yl} -nicotinic acid allyl ester</td><td>Boc-DPipecolic acid, 6- (NHhydroxycarbamimidoyl) -nicotinic acid allyl ester and phenoxyacetyl chloride</td><td> 449,1</td>

<td> 23</td><td>(R) - 1 - {2 - [3— (4 - Imidazol-1-yl-phenyl) [1,2,4] oxadiazol-5yl] -piperidin-1-yl} 2-phenoxy-ethanone</td><td>Boc-DPipecolic acid, NHhydroxy-4-imidazole-lil-benzamidine and phenoxyacetyl chloride</td><td> 430,5</td>

<td> 24</td><td>(R) -N-Methyl-4- {5- [1 (2-phenoxy-acetyl) piperidin-2-yl] [1,2,4] oxadiazol-3yl} benzenesulfonamide</td><td>Boc-DPipecolic acid, NHhydroxy-4methylsulfamoylbenzamidine and phenoxyacetyl chloride</td><td> 457,5</td>

<td> 25</td><td>(R) -l- {2- [3- (6- Morfolin-4-ylpyridin-3-yl) [1,2,4] oxadiazol-5yl] -piperidin-1-yl} 2-phenoxy-ethanone</td><td>Boc-D- Acid Pipecolic, NHhydroxy-6-morpholin-4yl-nicotinamidine and phenoxy-acetyl chloride</td><td> 450,5</td>

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<td>Example- plo</td><td>Compound name</td><td>Starting materials</td><td>MH⁺found</td>

<td> 26</td><td>(R) -2-Phenoxy-l- {2- [3 (4trifluoromethanesulfonyl-phenyl) - [1,2,4] oxadiazol-5yl] -piperidin-l-yl} ethanone</td><td>Boc-DPipecolic Acid, N- Hydroxy-4- trifluoromethanesulfonyl-benzamidine and phenoxyacetyl chloride</td><td> 496, 5</td>

<td> 27</td><td>(R) -2-Phenoxy-l- [2- [3- (4-trifluoromethylphenyl) - [1,2,4] oxadiazol-5yl] -piperidin-l-yl} ethanone</td><td>Boc-DPipecolic acid, NHhydroxy-4trifluoromethylbenzamidine and phenoxyacetyl chloride</td><td> 432,5</td>

<td> 28</td><td>(R) -1- {2- [3- (4-Chlorophenyl) - [1,2,4] oxadiazol-5yl] -piperidin-l-yl} 2-phenoxy-ethanone</td><td>Boc-DPipecolic acid, NHhydroxy-4-chlorobenzamidine and phenoxyacetyl chloride</td><td> 398,4</td>

<td> 29</td><td>(R) -N- (4- {5- [1- (2Phenoxy-acetyl) piperidin-2-yl] [1,2,4] oxadiazol-3yl} -2-trifluoromethylphenyl) -acetamide</td><td>Boc-D- Acid Pipecolic, N- [4- (NHidroxicarbamimidoil) -2trifluoro-methylphenyl] -acetamide and phenoxyacetyl chloride</td><td> 489,5</td>

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<td>Example- plo</td><td>Compound name</td><td>Starting materials</td><td>MH⁺found</td>

<td> 30</td><td>(R) -l- {2- [3- (3- Methanesulfonylphenyl) - [1,2,4] oxadiazol-5yl] -piperidin-l-yl} 2-phenoxy-ethanone</td><td>Boc-DPipecolic Acid, NHhydroxy-3m and tanosulfonylbenzamidine and phenoxyacetyl chloride</td><td> 442,5</td>

<td> 31</td><td>(R) -l- {2- [3- (4-Methyl- 3-nitro-phenyl) [1,2,4] oxadiazol-5yl] -piperidin-1-yl} 2-phenoxy-ethanone</td><td>Boc-DPipecolic acid, NHhydroxy-4-methyl-3-nitro-benzamidine and phenoxyacetyl chloride</td><td> 423, 5</td>

<td> 32</td><td>(R) -1- {2- [3- (4- Methoxy-3-nitrophenyl) - [1,2,4] oxadiazol-5yl] -piperidin-l-yl} 2-phenoxy-ethanone</td><td>Boc-D- Acid Pipecolic, N- Hydroxy-4-methoxy-3-nitro-benzamidine and phenoxyacetyl chloride</td><td> 439,5</td>

<td> 33</td><td>(R) -N- (2-Hydroxyethyl) -4- {5- [1- (2-phenoxy-acetyl) piperidin-2-yl] [1,2,4] oxadiazol-3yl} benzenesulfonamide</td><td>Boc-DPipecolic acid, NHhydroxy-4- (2-hydroxyethylsulfamoyl) benzamidine and phenoxyacetyl chloride</td><td> 487,5</td>

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<td>Example- plo</td><td>Compound name</td><td>Starting materials</td><td>MH⁺found</td>

<td> 34</td><td>(R) -N- (2-Methoxyethyl) -N-methyl-4- {5 [1- (2-phenoxy-acetyl) piperidin-2-yl] [1,2,4] oxadiazol-3yl} benzenesulfonamide</td><td>Boc-D- Acid Pipecolic, N- Hydroxy-4 - [(2-methoxyethyl) -methyl- sulfamoyl] benzamidine and phenoxyacetyl chloride</td><td> 515, 5</td>

<td> 35</td><td>(R) -N, N-Dimethyl-4- {5- [1- (2-phenoxy-acetyl) piperidin-2-yl] [1,2,4] oxadiazol-3yl} benzenesulfonamide</td><td>Boc-D- Acid Pipecolic, 4Dimethylsulfamoyl-Nhydroxy-benzamidine and phenoxyacetyl chloride</td><td> 471,5</td>

<td> 36</td><td>(R) -N, N-Diethyl-4- {5 [1- (2-phenoxy-acetyl) piperidin-2-yl] [1,2,4] oxadiazol-3yl} benzenesulfonamide</td><td>Boc-D- Acid Pipecolic, 4Diethylsulfamoyl-Nhydroxy-benzamidine and phenoxyacetyl chloride</td><td> 499, 6</td>

<td> 37</td><td>(R) —l— {2— [3— (2— Morfolin-4-ylpyridin-4-yl) [1,2,4] oxadiazol-5yl] -piperidin-1-yl} 2-phenoxy-ethanone</td><td>Boc-D- Acid Pipecolic, N- Hydroxy-2-morpholin-4yl-isonicotinamidine and phenoxyacetyl chloride</td><td> 450,5</td>

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<td>Example</td><td>Compound name</td><td>Starting materials</td><td>MH⁺found</td>

<td> 38</td><td>(R) -2-Phenoxy-l- {2- [3- (3,4,5,6-tetrahydro2H- [1,2 '] bipyridinyl4'-yl) - [1,2,4] oxadiazol-5yl] -piperidin-l-yl} ethanone</td><td>Boc-DPipecolic Acid, NHhydroxy-3,4,5,6tetrahydro-2H- [1,2 '] bipyridinyl-4'carboxamidine and phenoxyacetyl chloride</td><td> 448,5</td>

<td> 39</td><td>(R) -2-Phenoxy-l- {2- [3 (2-thiomorpholin-4-ylpyridin-4-yl) [1,2,4] oxadiazol-5yl] -piperidin-l-yl} ethanone</td><td>Boc-D- Acid Pipecolic, N- Hydroxy-2tiomorfolin-4-ilisonicotinamidine and phenoxyacetyl chloride</td><td> 466, 5</td>

<td> 40</td><td>(R) -1- {2- [3- (2- Diethylamino-pyridin4-yl) - [1,2,4] oxadiazol-5yl] -piperidin-l-yl} 2-phenoxy-ethanone</td><td>Boc-D- Acid Pipecolic, 2Dethylamino-Nhydroxy-isonicotin amidine and phenoxyacetyl chloride</td><td> 436,5</td>

<td> 41</td><td>(R) —4— {5— [1— (2— phenoxy-acetyl) piperidin-2-yl] [1,2,4] oxadiazol-3yl} -pyridine-2-carboxylic acid ethyl ester</td><td>Boc-DPipecolic acid, phenoxyacetyl ethyl chloride esterand 4 (N-Hydroxycarbamimidoyl) -pyridine-2-carboxylic acid</td><td> 437,5</td>

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<td>Example</td><td>Compound name</td><td>Starting materials</td><td>MH⁺found</td>

<td> 42</td><td>(R) —l— (2— {3— [6— (4— Acetyl-piperazin-1yl) -pyridin-3-yl] [1,2,4] oxadiazol-5yl} -piperidin-1-yl) 2-phenoxy-ethanone</td><td>Boc-DPipecolic acid, 6- (4Acetyl-piperazinlyl) -N-hydroxynicotinamidine and phenoxyacetyl chloride</td><td> 491,5</td>

<td> 43</td><td>(R) —l— {2— [3— (2— Imidazol-1-ylpyridin-4-yl) [1,2,4] oxadiazol-5yl] -piperidin-1-yl} 2-phenoxy-ethanone</td><td>Boc-DPipecolic acid, NHhydroxy-2-imidazole-lil-isonicotinamidine and phenoxyacetyl chloride</td><td> 431,5</td>

<td> 44</td><td>(R) —1— (3— {5— [1— (2— Phenoxy-acetyl) piperidin-2-yl] [1,2,4] oxadiazol-3yl] -phenyl) -piperidin2-one</td><td>Boc-DPipecolic acid, NHhydroxy-3- (2-oxopiperidin-1-yl) benzamidine and phenoxyacetyl chloride</td><td> 461,5</td>

<td> 45</td><td>(R) -1- (2- {3- [4- (3H- Imidazol-4-yl) phenyl] - [1,2,4] oxadiazol-5yl} -piperidin-1-yl) 2-phenoxy-ethanone</td><td>Boc-DPipecolic acid, NHhydroxy-4- (3Himidazol-4-yl) benzamidine and phenoxyacetyl chloride</td><td> 430,5</td>

<td> 46</td><td>(R) —1— (2— {3— [4— (2— Methyl-imidazol-1-yl) phenyl] - [1,2,4] oxadiazol-5yl} -piperidin-1-yl) 2-phenoxy-ethanone</td><td>Boc-D- Acid Pipecolic, N- Hydroxy-4- (2-methylimidazol-1-yl) benzamidine and phenoxyacetyl chloride</td><td> 444,5</td>

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<td>Example</td><td>Compound name</td><td>Starting materials</td><td>MH⁺find auger</td>

<td> 47</td><td>(R) -2-Phenoxy-l- {2- [3- (2-pyrazol-l-ylpyridin-4-yl) - [1,2,4] oxadiazol-5yl] -piperidin-l-yl} ethanone</td><td>Boc-D- Acid Pipecolic, NHhydroxy-2-pyrazol-lil-isonicotin amidine and phenoxy-acetyl chloride</td><td> 431,5</td>

<td> 48</td><td>(R) -4- (5— {5- [1- (2- Phenoxy-acetyl) piperidin-2-yl] [1,2,4] oxadiazol-3yl} -pyridin-2-yl) piperazin-2-one</td><td>Boc-DPipecolic acid, NHhydroxy-6- (3-oxopiperazin-l-yl) nicotinamidine and phenoxyacetyl chloride</td><td> 463,5</td>

<td> 49</td><td>(R) -2-Phenoxy-1- (2- {3- [4- (1H-tetrazole-5- il) -phenyl] - [1,2,4] oxadiazol-5yl} -piperidin-1-yl) ethanone</td><td>Boc-D- Acid Pipecolic, N- Hydroxy-4- (1Htetrazol-5-yl) benzamidine and phenoxyacetyl chloride</td><td>430, 1 (M-H +)</td>

<td> 50</td><td>(R) -1- {2- [3- (1HIndazol-5-yl) [1,2,4] oxadiazol-5yl] -piperidin-1-yl} 2-phenoxy-ethanone</td><td>Boc-D- Acid Pipecolic, N- Hydroxy-1H-indazole-5carboxamidine and phenoxyacetyl chloride</td><td> 404,5</td>

<td> 51</td><td>(R) -l- {2- [3- (1H- Indazol-6-yl) [1,2,4] oxadiazol-5yl] -piperidin-1-yl} 2-phenoxy-ethanone</td><td>Boc-D- Acid Pipecolic, N- Hydroxy-1H-indazole-5carboxamidine and phenoxyacetyl chloride</td><td> 404,1</td>

99/229

<td>Example- plo</td><td>Compound name</td><td>Starting materials</td><td>MH⁺find auger</td>

<td> 52</td><td>(R) -l- {2- [3- (4- Fluoro-3- trifluoromethylphenyl) - [1,2,4] oxadiazol-5yl] -piperidin-l-yl} 2-phenoxy-ethanone</td><td>Boc-D- Acid Pipecolic, 4-Fluoro- N-hydroxy-3trifluoromethylbenzamidine and phenoxyacetyl chloride</td><td> 450, 4</td>

<td> 53</td><td>(R) -6- {5- [1- (2- Phenoxy-acetyl) piperidin-2-yl] [1,2,4] oxadiazol-3yl}-1,3-dihydro-indol2-one</td><td>Boc-DPipecolic acid, NHhydroxy-2-oxo-2,3-dihydro-1H-indole-6carboxamidine and phenoxyacetyl chloride</td><td> 419,3</td>

<td> 54</td><td>(R) -5- {5- [1- (2- Phenoxy-acetyl) piperidin-2-yl] [1,2,4] oxadiazol-3yl} -1,3-dihydrobenzoimidazole-2-one</td><td>Boc-DPipecolic acid, NHhydroxy-2-oxo-2,3-dihydro-1Hbenzoimidazole-5carboxamidine and phenoxyacetyl chloride</td><td> 420, 4</td>

<td> 55</td><td>(R) -5- {5- [l- (2- Phenoxy-acetyl) piperidin-2-yl] [1,2,4] oxadiazol-3yl} -1,3-dihydro-indol2-one</td><td>Boc-DPipecolic acid, NHhydroxy-2-oxo-2,3-dihydro-1H-indole-5carboxamidine and phenoxyacetyl chloride</td><td> 419,4</td>

100/229

<td>Example- plo</td><td>Compound name</td><td>Starting materials</td><td>MH⁺find auger</td>

<td> 56</td><td>(R) -l- {2- [3- (1H- Benzotriazol-5-yl) [1,2,4] oxadiazol-5yl] -piperidin-1-yl} 2-phenoxy-ethanone</td><td>Boc-DPipecolic acid, NHhydroxy-1H-benzotriazole-5carboxamidine and phenoxyacetyl chloride</td><td> 405,4</td>

<td> 57</td><td>(R) -1- {2- [3- (1H- Benzoimidazol-5-yl) [1,2,4] oxadiazol-5yl] -piperidin-1-yl} 2-phenoxy-ethanone</td><td>Boc-DPipecolic acid, NHhydroxy-1Hbenzoimidazole-5carboxamidine and phenoxyacetyl chloride</td><td> 404,5</td>

<td> 58</td><td>(R) -1- (2- {3- [6- (1,1Dioxo-thiomorfolin-4yl) -pyridin-3-yl] [1,2,4] oxadiazol-5yl} -piperidin-l-yl) 2 -phenoxy-ethanone</td><td>Boc-D- Acid Pipecolic, 6- (1,1Dioxo-thiomorpholin-4yl) -N-hydroxynicotinamidine and phenoxyacetyl chloride</td><td> 498,5</td>

<td> 59</td><td>(R) -N- (4- {5- [1- (2- Phenoxy-acetyl) piperidin-2-yl] [1,2,4] oxadiazol-3yl} -pyridin-2-yl) acetamide</td><td>Boc-DPipecolic acid, N- [4- (NHhydroxycarbamimidoyl) pyridin-2-yl] acetamide and phenoxyacetyl chloride</td><td> 422,5</td>

<td> 60</td><td>(R) -l- {2- [3- (6- Benzyloxy-pyridin-3yl) - [1,2,4] oxadiazol5-yl] -piperidin-lil] -2-phenoxy-ethanone</td><td>Boc-D- Acid Pipecolic, 6- Benzyloxy-N-hydroxynicotinamidine and phenoxyacetyl chloride</td><td> 470, 8</td>

101/229

<td>Example</td><td>Compound name</td><td>Starting materials</td><td>MH⁺found</td>

<td> 61</td><td>(R) -5- {5- [1- (2Phenoxy-acetyl) piperidin-2-yl] [1,2,4] oxadiazol-3yl} -nicotinic acid ester</td><td>Boc-D- Acid Pipecolic, 5- (NHhydroxycarbamimidoyl) nicotinic acid ethyl ester and phenoxyacetyl chloride</td><td> 337,5</td>

<td> 62</td><td>(R) —4— {5— [1— (2— Phenoxy-acetyl) piperidin-2-yl] [1,2,4] oxadiazole-3yl} -1H-pyridin-2-one</td><td>Boc-DPipecolic Acid, NHhydroxy-2-oxo-1, 2-hydroxy-pyridine-4-carboxamidine and phenoxyacetyl chloride</td><td> 381,5</td>

<td> 63</td><td>(R) -5- {5- [1- (2Fenoxy-acetyl) piperidin-2-yl] [1,2,4] oxadiazol-3yl} -1H-pyridin-2-one</td><td>Boc-DPipecolic acid, NHhydroxy-6-oxo-l, 6-hydroxy-pyridine-3-carboxamidine and phenoxyacetyl chloride</td><td> 381,5</td>

<td> 64</td><td>(R) -2-Phenoxy-l- [2- (5phenyl-2H- [1,2,4] triazol-3-yl) piperidin-1-yl] ethanone</td><td>Boc-DPipecolic acid, N-Aminobenzamidine and phenoxyacetic acid</td><td> 363,5</td>

<td> 65</td><td>(R) -1- {2- [5- (4- Methanesulfonylphenyl) -2H- [1,2,4] triazol-3-yl] piperidin-l-yl} -2phenoxy-ethanone</td><td>Boc-DPipecolic acid, N-Amino4-methanesulfonylbenzamidine and phenoxyacetic acid</td><td> 441,5</td>

102/229

<td>Example- plo</td><td>Compound name</td><td>Starting materials</td><td>MH⁺found</td>

<td> 66</td><td>(R) -l- {2- [5- (3,4Dimethoxy-phenyl) -2H [1,2,4] triazol-3-yl] piperidin-l-yl} -2phenoxy-ethanone</td><td>Boc-D- Acid Pipecolic, N-Amino3,4-Dimetoxybenzamidine and phenoxyacetic acid</td><td> 423, 5</td>

<td> 67</td><td>(R) -1- {2- [5- (3,4Dichloro-phenyl) -2H [1,2,4] triazol-3-yl] piperidin-l-yl} -2phenoxyethanone</td><td>Boc-DPipecolic Acid, N-Amino- 3,4-Dichlorobenzamidine and phenoxyacetic acid</td><td> 431,4</td>

<td> 68</td><td>(R) -1- {2- [5- (4- Fluoro-phenyl) -2H [1,2,4] triazol-3-yl] piperidin-l-yl} -2phenoxy-ethanone</td><td>Boc-DPipecolic acid, N-Amino4-Fluoro-benzamidine and phenoxyacetic acid</td><td> 381, 5</td>

<td> 69</td><td>(R) -2-Phenoxy-l- {2- [5- (3-trifluoromethylphenyl) -2H- [1,2,4] triazol-3-yl] ~ piperidin-l-yl} ethanone</td><td>Boc-D- Acid Pipecolic, N-Amino- 3-Trifluoromethylbenzamidine and phenoxyacetic acid</td><td> 431,5</td>

<td> 70</td><td>(R) -1- {2- [5- (4- Methoxy-phenyl) -2H [1,2,4] triazol-3-yl] piperidin-l-yl} -2phenoxy-ethanone</td><td>Boc-DPipecolic Acid, N-Amino4-Methoxy-benzamidine and phenoxyacetic acid</td><td> 393,5</td>

103/229

<td>Example</td><td>Compound name</td><td>Starting materials</td><td>MH⁺found</td>

<td> 71</td><td>(R) -l- {2- [5- (3-Nitrophenyl) -2H- [1,2,4] triazol-3-yl] ~ piperidin-l-yl} -2phenoxy-ethanone</td><td>Boc-D- Acid Pipecolic, N-Amino3-Nitro-benzamidine and phenoxyacetic acid</td><td> 408,5</td>

<td> 72</td><td>(R) -3- {5- [1- (2-phenoxy-acetyl) piperidin-2-yl] -1H [1,2,4] triazol-3-yl} benzoic acid methyl ester</td><td>Boc-DPipecolic acid, N-amino-3-benzoic acid methyl ester-benzamidine and phenoxyacetic acid</td><td> 421, 5</td>

<td> 73</td><td>(R) -l- {2- [5- (4- Fluoro-3- trifluoromethyl- phenyl) -2H- [1,2,4] triazol-3-yl] piperidin-l-yl} -2phenoxy-ethanone</td><td>Boc-D- Acid Pipecolic, N-Amino4-Fluoro-3trifluoromethylbenzamidine and phenoxyacetic acid</td><td> 449, 0</td>

<td> 74</td><td>(R) -6- {5- [1- (2- Phenoxy-acetyl) piperidin-2-yl] -1H- [1,2,4] triazol-3-yl} - 1,3-dihydro-indole-2one</td><td>Boc-D- Acid Pipecolic, N-Amino2-Oxo-2,3-dihydro-1Hindole-6carboxamidine benzamidine and phenoxyacetic acid</td><td> 418,5</td>

104/229

<td>Example- plo</td><td>Compound name</td><td>Starting materials</td><td>MH⁺find auger</td>

<td> 75</td><td>l- {3- [3- (4-Methoxyphenyl) - [1,2,4] oxadiazole-5- il] -morfolin-4-yl} -2phenoxy-ethanone</td><td>4-tert-Butyl ester of morpholine-3,4-bicarboxylic acid, NHhydroxy-4-methoxybenzamidine and phenoxyacetyl chloride</td><td> 396, 4</td>

<td> 76</td><td>l- {3- [3- (4Methanesulfonylphenyl) - [1,2,4] oxadiazole-5- il] -morfolin-4-yl} -2phenoxy-ethanone</td><td>4-tert-Butyl ester of morpholine-3,4-bicarboxylic acid, NHhydroxy-4- methanesulfonylbenzamidine and phenoxyacetyl chloride</td><td> 444,5</td>

<td> 77</td><td>4- {5- [4- (2-Phenoxyacetyl) -morpholin-3yl] - [1,2,4] oxadiazol3-yl} benzenesulfonamide</td><td>4-tert-Butyl ester of morpholine-3,4-bicarboxylic acid, NHhydroxy-4-sulfamoyl benzamidine and phenoxyacetyl chloride</td><td> 445, 5</td>

<td> 78</td><td>1- (3— {3- [6- (1,1Dioxo-thiomorfolin-4yl) -pyridin-3-yl] [1,2,4] oxadiazol-5yl} -morpholin-4-yl) -2-phenoxy-ethanone</td><td>4-tert-Butyl ester of morpholine-3, 4-bicarboxylic acid, 6- (1,1-Dioxothiomorfolin-4-yl) -Nhydroxynicotinamidine and phenoxyacetyl chloride</td><td> 500,5</td>

105/229

<td>Example- plo</td><td>Compound name</td><td>Starting materials</td><td>MH⁺found</td>

<td> 79</td><td>N- (4- {5 - [4- (2-Phenoxyacetyl) -morpholin-3yl] - [1,2,4] oxadiazole- 3-yl} -pyridin-2-yl) acetamide</td><td>Morpholine-3,4-bicarboxylic acid 4-tert-butyl ester, N- [4- (NHidroxicarbamimidoil) -pyridin-2-yl] acetamide and phenoxyacetyl chloride</td><td> 424,6</td>

<td> 80</td><td>l- {3- [5- (4- Methanesulfonyl- phenyl) -2H- [1,2,4] triazol-3-yl] morpholin-4-yl} -2phenoxy-ethanone</td><td>4-tert-Butyl ester of morpholine-3,4-bicarboxylic acid, 4Methanesulfonyl-Namino-benzamidine and phenoxyacetyl chloride</td><td> 443,4</td>

<td> 81</td><td>2-Phenoxy-l- {3- [5- (3- trifluoromethylphenyl) -2H- [1,2,4] triazol-3-yl] morpholin-4-yl} ethanone</td><td>4-tert-Butyl ester of morpholine-3, 4bicarboxylic acid, 3Trifluoromethyl-Namino-benzamidine and phenoxyacetyl chloride</td><td> 433, 4</td>

<td> 82</td><td>(R) -4- {5- [4- (2- Phenoxy-acetyl) morpholin-3-yl] - [1,2,4] oxadiazol-3yl} -lH-pyridin-2-one</td><td>(R) -Morpholine3,4-bicarboxylic acid 4-tert-butyl ester, NHhydroxy-2-oxo-1,2,2hydro-pyridine-4carboxamidine and phenoxyacetyl chloride</td><td> 383,4</td>

106/229

<td>Example</td><td>Compound name</td><td>Starting materials</td><td>MH⁺found</td>

<td> 83</td><td>1- {3- [3- (4-Methoxyphenyl) - [1,2,4] oxadiazole-5il] -tiomorfolin-4il} -2-phenoxy-ethanone</td><td>4- (2-tertButoxy-acetyl) thiomorpholine-3-carboxylic acid, NHhydroxy-4-methoxybenzamidine and phenoxyacetyl chloride</td><td> 412,5</td>

<td> 84</td><td>l- {3- [3- (4- Methanesulfonyl- phenyl) - [1,2,4] oxadiazole-5il] -tiomorfolin-4il} -2-phenoxy-ethanone</td><td>4- (2-tert-) acid Butoxy-acetyl) thiomorpholine-3-carboxylic acid, N- Hydroxy-4-methanesulfonyl-benzamidine and phenoxyacetyl chloride</td><td> 460,4</td>

<td> 85</td><td>4- [5- [4- (2-Phenoxyacetyl) -tiomorfolin3-yl] - [1,2,4] oxadiazol-3yl} benzenesulfonamide</td><td>4- (2-tert-Butoxyacetyl) -thiomorpholine3-carboxylic acid, N-Hydroxy-4sulfamoyl-benzamidine and phenoxyacetyl chloride</td><td> 461,4</td>

<td> 86</td><td>2-Phenoxy-l- [3— (3— pyridin-4-yl [1,2,4] oxadiazol-5yl) -tiomorfolin-4il] -ethanone</td><td>4- (2-tertbutoxy-acetyl) thiomorpholine-3-carboxylic acid, NHhydroxy-isonicotinamidine and phenoxyacetyl chloride</td><td> 383,4</td>

107/229

<td>Example</td><td>Compound name</td><td>Starting materials</td><td>MH⁺found</td>

<td> 87</td><td>1- {2- [3- (4-Methoxyphenyl) - [1,2,4] oxadiazol-5yl] -piperazin-l-yl} - 2- phenoxy-ethanone</td><td>1-tert-Butyl ester of piperazine-1,3-bicarboxylic acid, NHhydroxy-4-methoxybenzamidine and phenoxyacetic acid</td><td> 395,5</td>

<td> 88</td><td>N— (5— [5— [1— (2-Phenoxyacetyl) -piperazin-2yl] - [1,2,4] oxadiazol3-yl} -pyridin-2-yl) acetamide</td><td>1-tert-butyl ester of piperazine-1,3bicarboxylic acid, N- [5 (N- Hydroxycarbamimido- il) -pyridin-2-yl] acetamide and phenoxyacetic acid</td><td> 423, 5</td>

<td> 89</td><td>1— {2— [3- (2-Imidazole- 1- il-pyridin-4-yl) - [1,2,4] oxadiazol-5yl] -piperazin-l-yl} - 2- phenoxy-ethanone</td><td>1-tert-butyl ester of piperazine-1,3-bicarboxylic acid, NHhydroxy-2-imidazole-lil-isonicotinamidine and phenoxyacetic acid</td><td> 432,5</td>

<td> 90</td><td>N, N-Diethyl-4- {5- [1- (2-phenoxy-acetyl) piperazin-2-yl] [1,2,4] oxadiazol-3yl} benzenesulfonamide</td><td>1-tert-Butyl ester of piperazine-1,3-bicarboxylic acid, 4Diethylsulfamoyl-N-hydroxybenzamidine and phenoxyacetic acid</td><td> 500, 5</td>

108/229

<td>Example</td><td>Compound name</td><td>Starting materials</td><td>MH⁺found</td>

<td> 91</td><td>N, N-Dimethyl-4- {5- [1- (2-phenoxy-acetyl) - piperazin-2-yl] - [1,2,4] oxadiazol-3yl} benzenesulfonamide</td><td>1-tert-Butyl ester of piperazine-1,3-bicarboxylic acid, 4Dimethylsulfamoyl-N-hydroxybenzamidine and phenoxyacetic acid</td><td> 472,5</td>

<td> 92</td><td>4- {5- [1- (2-Phenoxyacetyl) -piperazin-2yl] - [1,2,4] oxadiazol3-yl} benzenesulfonamide</td><td>1-tert-Butyl ester of piperazine-1,3-bicarboxylic acid, NHhydroxy-4-sulfamoyl benzamidine and phenoxyacetic acid</td><td> 444,4</td>

<td> 93</td><td>1- {2- [3- (4- Methanesulfonylphenyl) - [1,2,4] oxadiazol-5yl] -piperazin-l-yl} - 2- phenoxy-ethanone</td><td>1-tert-Butyl ester of piperazine-1,3-bicarboxylic acid, NHhydroxy-4-methanesulfonyl-benzamidine and phenoxyacetic acid</td><td> 443,5</td>

<td> 94</td><td>2-Phenoxy-l- [2- (3pyridin-4-yl- [1,2,4] oxadiazol-5yl) -piperazin-1-yl] ethanone</td><td>1-tert-Butyl ester of piperazine-1,3-bicarboxylic acid, NHhydroxyisonicotinamidine and phenoxyacetic acid</td><td> 366, 4</td>

<td> 95</td><td>1— {2— [3- (2,4-Dichlorophenyl) - [1,2,4] oxadiazol-5yl] -piperazin-l-yl} - 2- phenoxy-ethanone</td><td>1-tert-Butyl ester of piperazine-1,3-bicarboxylic acid, 2,4Dichloro-N-hydroxybenzamidine and phenoxyacetic acid</td><td> 433,3</td>

109/229

<td>Example</td><td>Compound name</td><td>Starting materials</td><td>MH⁺find auger</td>

<td> 96</td><td>2-Phenoxy-l- [2- (3pyridin-2-yl- [1,2,4] oxadiazol-5yl) -piperazin-1-yl] ethanone</td><td>1-tert-Butyl ester of piperazine-1,3bicarboxylic acid, NHhydroxy-pyridine-2carboxamidine and phenoxyacetic acid</td><td> 366, 4</td>

<td> 97</td><td>2-Phenoxy-l- [2- (3pyridin-2-yl [1,2,4] oxadiazol-5yl) -piperazin-2-yl] ethanone</td><td>1-tert-Butyl ester of piperazine-1,3bicarboxylic acid, NHhydroxy-pyridine-3carboxamidine and phenoxyacetic acid</td><td> 366, 4</td>

<td> 98</td><td>1— {2— [3- (4-Nitro- phenyl) - [1,2,4] oxadiazol-5yl] -piperazin-l-yl} - 2- phenoxy-ethanone</td><td>1-tert-Butyl ester of piperazine-1,3-bicarboxylic acid, NHhydroxy-4-nitrobenzamidine and phenoxyacetic acid</td><td> 410,4</td>

<td> 99</td><td>1- {2- [3- (6-Methoxypyridin-3-yl) [1,2,4] oxadiazol-5yl] -piperazin-l-yl} - 2- phenoxy-ethanone</td><td>1-tert-Butyl ester of piperazine-1,3-bicarboxylic acid, NHhydroxy-6-methoxycinotinamidine and phenoxyacetic acid</td><td> 396, 4</td>

<td> 100</td><td>1— {2— [3- (6-Morpholin- 4-yl-pyridin-3-yl) [1,2,4] oxadiazol-5yl] -piperazin-l-yl} - 2- phenoxy-ethanone</td><td>1-tert-Butyl ester of piperazine-1,3-bicarboxylic acid, NHhydroxy-6-morpholin-4yl-nicotinamidine and phenoxy-acetic acid</td><td> 451,5</td>

110/229

<td>Example- plo</td><td>Compound name</td><td>Starting materials</td><td>MH⁺find auger</td>

<td> 101</td><td>1- {2- [3- (6-Morfolin4-yl-pyridin-3-yl) [1,2,4] oxadiazol-5yl] -piperazin-l-yl} - 2- phenoxy-ethanone</td><td>1-tert-Butyl ester of piperazine-1,3-bicarboxylic acid, N— Hydroxy-pyrazine-2carboxamidine and phenoxy-acetic acid</td><td> 367,4</td>

<td> 102</td><td>1- {2- [3- (3- Hydroxymethyl-phenyl) [1,2,4] oxadiazol-5yl] -piperazin-l-yl} - 2- phenoxy-ethanone</td><td>1-tert-Butyl ester of piperazine-1,3-bicarboxylic acid, NHhydroxy-3-hydroxymethyl-benzamidine and phenoxy-acetic acid</td><td> 395,4</td>

<td> 103</td><td>1— {2— [3- (4- Diethylamino-phenyl) [1,2,4] oxadiazol-5yl] -piperazin-l-yl} - 2- phenoxy-ethanone</td><td>1-tert-Butyl ester of piperazine-1,3-bicarboxylic acid, 4Diethylamino-N-hydroxy-benzamidine and phenoxy-acetic acid</td><td> 436, 5</td>

<td> 104</td><td>1- (2- {3- [4- ί Mor f olina— 4 - sulfonyl) -phenyl] [1,2,4] oxadiazol-5yl} -piperazin-l-yl) - 2- phenoxy-ethanone</td><td>1-tert-Butyl ester of piperazine-1,3-bicarboxylic acid, NHhydroxy-4- (morpholine4-sulfonyl) benzamidine and phenoxyacetic acid</td><td> 514,6</td>

111/229

<td>Example</td><td>Compound name</td><td>Departure materials</td><td>MH⁺found</td>

<td> 105</td><td>N-Methyl-4- {5- [1- (2- phenoxy-acetyl) piperazin-2-yl] [1,2,4] oxadiazol-3yl} benzenesulfonamide</td><td>1-tert-Butyl ester of piperazine-1,3-bicarboxylic acid, N— Hydroxy-4-methylsulfamoyl-benzamidine and phenoxyacetic acid</td><td> 458,4</td>

<td> 106</td><td>N- (2-Methoxy-ethyl) -Nmethyl-4- {5- [1- (2-phenoxy-acetyl) piperazin-2-yl] [1,2,4] oxadiazol-3yl} benzenesulfonamide</td><td>1-tert-Butyl ester of piperazine-1,3bicarboxylic acid, NHhydroxy-4 - [(2-methoxyethyl) -methylsulfamoyl] -benzamidine and phenoxy-acetic acid</td><td> 516, 4</td>

<td> 107</td><td>1- {2- [3- (4-Chlorophenyl) - [1,2,4] oxadiazol-5yl] -piperazin-l-yl} - 2- phenoxy-ethanone</td><td>1-tert-Butyl ester of piperazine-1,3-bicarboxylic acid, 4-Chloro-N-hydroxybenzamidine and phenoxyacetic acid</td><td> 399,3</td>

<td> 108</td><td>N- (4- {5 - [1- (2-Phenoxyacetyl) -piperazin-2yl] - [1,2,4] oxadiazol3-yl} -2- trifluoromethylphenyl) -acetamide</td><td>1-tert-Butyl ester of piperazine-1,3bicarboxylic acid, N- [4 (NHhydroxycarbamimidoyl) -2-trifluoromethyl-phenyl] acetamide and phenoxyacetic acid</td><td> 490,4</td>

112/229

<td>Example- plo</td><td>Compound name</td><td>Starting materials</td><td>MH⁺found</td>

<td> 109</td><td>4- {5- [1- (2-Phenoxyacetyl) -piperazin-2yl] - [1,2,4] oxadiazol3-yl} -benzoic allyl acid ester</td><td>1-tert-Butyl ester of piperazine-1,3bicarboxylic acid, 4- (NHhydroxycarbamimidoyl) -benzoic acid allyl and phenoxyacetic acid</td><td> 449, 4</td>

<td> 110</td><td>1- {2- [3- (4-Methyl-3-nitro-phenyl) - [1,2,4] oxadiazol-5yl] -piperazin-l-yl} - 2- phenoxy-ethanone</td><td>1-tert-Butyl ester of piperazine-1,3-bicarboxylic acid, NHhydroxy-4-methyl-3-nitro-benzamidine and phenoxyacetic acid</td><td> 424,4</td>

<td> 111</td><td>1- {2- [3- (4-Methoxy-3nitro-phenyl) - [1,2,4] oxadiazol-5yl] -piperazin-l-yl} - 2- phenoxy-ethanone</td><td>1-tert-Butyl ester of piperazine-1,3-bicarboxylic acid, NHhydroxy-4-methoxy-3-nitro-benzamidine and phenoxyacetic acid</td><td> 440,4</td>

<td> 112</td><td>1- {2- [3- (4-Chloro-3-nitro-phenyl) [1,2,4] oxadiazol-5yl] -piperazin-l-yl} - 2- phenoxy-ethanone</td><td>1-tert-Butyl ester of piperazine-1,3-bicarboxylic acid, 4-Chloro-N-hydroxy-3-nitro-benzamidine and phenoxyacetic acid</td><td> 444,8</td>

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<td>Example- plo</td><td>Compound name</td><td>Starting materials</td><td>MH⁺find auger</td>

<td> 113</td><td>3-Fluoro-4- {5— [l— (2— phenoxy-acetyl) piperazin-2-yl] [1,2,4] oxadiazol-3yl} -benzoic acid methyl ester</td><td>Piperazine-1,3-bicarboxylic acid 1-tert-butyl ester, 3Fluoro-4- (N-hydroxycarbamimidoyl) benzoic acid methyl ester and phenoxyacetic acid</td><td> 441,4</td>

<td> 114</td><td>Ethyl acid ester 4- {5- [1- (2-phenoxyacetyl) -piperazin-2yl] - [1,2,4] oxadiazol3-yl} -pyridine-2carboxylic</td><td>1-tert-Butyl ester of piperazine-1,3-bicarboxylic acid, ethyl ester of 4- (NHhydroxycarbamimidoyl) -pyridine-2-carboxylic acid and phenoxyacetic acid</td><td> 438,4</td>

<td> 115</td><td>2-Phenoxy-l- {2- [3- (4- piperidin-l-ylphenyl) - [1,2,4] oxadiazol-5yl] -piperazin-l-yl} ethanone</td><td>1-tert-Butyl ester of piperazine-1,3bicarboxylic acid, NHhydroxy-4-piperidin1-yl-benzamidine and phenoxyacetic acid</td><td> 448,5</td>

<td> 116</td><td>1— {2— [3- (4-Morfolin4-yl-phenyl) - [1,2,4] oxadiazol-5yl] -piperazin-l-yl} - 2- phenoxy-ethanone</td><td>1-tert-Butyl ester of piperazine-1,3-bicarboxylic acid, NHhydroxy-4-morpholin-4yl-benzamidine and phenoxyacetic acid</td><td> 450,4</td>

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<td>Example</td><td>Compound name</td><td>Starting materials</td><td>MH⁺found</td>

<td> 117</td><td>1- (2- {3- [4- (2-Methylimidazol-1-yl) phenyl] - [1,2,4] oxadiazol-5yl} -piperazin-1-yl) - 2- phenoxy-ethanone</td><td>1-tert-Butyl ester of piperazine-1,3-bicarboxylic acid, NHhydroxy-4- (2-methylimidazol-1-yl) benzamidine and phenoxyacetic acid</td><td> 445,4</td>

<td> 118</td><td>1- (2- {3- [4- (3H- Imidazol-4-yl) phenyl] - [1,2,4] oxadiazol-5yl} -piperazin-1-yl) - 2- phenoxy-ethanone</td><td>1-tert-Butyl ester of Piperazine-1,3-bicarboxylic acid, NHhydroxy-4- (3Himidazol-4-yl) benzamidine and phenoxyacetic acid</td><td> 431,4</td>

<td> 119</td><td>4— (5— [5— [1— (2-Phenoxyacetyl) -piperazin-2yl] - [1,2,4] oxadiazol3-yl} -pyridin-2-yl) piperazin-2-one</td><td>1-tert-Butyl ester of piperazine-1,3bicarboxylic acid, NHhydroxy-6- (3-oxopiperazin-1-yl) nicotinamidine and phenoxyacetic acid</td><td> 464,4</td>

<td> 120</td><td>1— {2— [3- (6-Imidazole- 1- il-pyridin-3-yl) - [1,2,4] oxadiazol-5yl] -piperazin-l-yl} - 2- phenoxy-ethanone</td><td>1-tert-Butyl ester of piperazine-1,3-bicarboxylic acid, NHhydroxy-6-imidazole-lil-nicotinamidine and phenoxyacetic acid</td><td> 432,4</td>

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<td>Example</td><td>Compound name</td><td>Starting materials</td><td>MH⁺find auger</td>

<td> 121</td><td>1- (2- {3- [6- (4-Acetylpiperazin-1-yl) pyridin-3-yl] [1,2,4] oxadiazol-5yl} -piperazin-1-yl) - 2- phenoxy-ethanone</td><td>1-tert-Butyl ester of piperazine-1,3bicarboxylic acid, 6- (4Acetyl-piperazin-1yl) -N-hydroxynicotinamidine and phenoxyacetic acid</td><td> 492, 4</td>

<td> 122</td><td>2-Phenoxy-l- {2- [3— (4— pyrrol-l-yl-phenyl) [1,2,4] oxadiazol-5yl] -piperazin-l-yl} ethanone</td><td>1-tert-Butyl ester of piperazine-1,3-bicarboxylic acid, NHhydroxy-4-pyrrole-lil-benzamidine and phenoxyacetic acid</td><td> 430, 4</td>

<td> 123</td><td>2-Phenoxy-l- [2- [3- (4trifluoromethanesulfonyl-phenyl) [1,2,4] oxadiazol-5yl] -piperazin-l-yl} ethanone</td><td>1-tert-Butyl ester of piperazine-1,3-bicarboxylic acid, NHhydroxy-4trifluoromethanesulfonyl-benzamidine and phenoxyacetic acid</td><td> 497,4</td>

<td> 124</td><td>1— {2— [3- (2-Morpholin- 4-yl-pyridin-4-yl) [1,2,4] oxadiazol-5yl] -piperazin-l-yl} - 2- phenoxy-ethanone</td><td>1-tert-Butyl ester of piperazine-1,3-bicarboxylic acid, NHhydroxy-2-morpholin-4yl-isonicotinamidine and phenoxyacetic acid</td><td> 451,4</td>

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<td>Example</td><td>Compound name</td><td>Starting materials</td><td>MH⁺found</td>

<td> 125</td><td>2-Phenoxy-l- {2- [3- (2tiomorfolin-4-ylpyridin-4-yl) - [1,2,4] oxadiazol-5yl] -piperazin-l-yl} ethanone</td><td>1-tert-Butyl ester of piperazine-1,3-bicarboxylic acid, NHhydroxy-2tiomorfolin-4-ylisonicotinamidine and phenoxyacetic acid</td><td> 467,4</td>

<td> 126</td><td>1- (2- {3- [6- (3- Hydroxymethylpyrrolidin-l-yl) pyridin-3-yl] [1,2,4] oxadiazol-5yl} -piperazin-l-yl) - 2- phenoxy-ethanone</td><td>1-tert-Butyl ester of piperazine-1,3bicarboxylic acid, NHhydroxy-6- (3hydroxymethylpyrrolidin-1-yl) nicotinamidine and phenoxyacetic acid</td><td> 4 65,4</td>

<td> 127</td><td>(R) -1- {2- [3- (6- Methoxy-pyridin-3-yl) [1,2,4] oxadiazol-5yl] -piperazin-1-yl} 2-phenoxy-ethanone</td><td>D-piperazine acid 1-tert-Butyl ester 1,3-bicarboxylic acid, NHhydroxy-6-methoxycinotinamidine and phenoxyacetic acid</td><td> 396, 4</td>

<td> 128</td><td>(R) —l— {2— [3— (6— Morfolin-4-ylpyridin-3-yl) [1,2,4] oxadiazol-5yl] -piperazin-1-yl} 2-phenoxy-ethanone</td><td>D-piperazine acid 1-tert-Butyl ester 1,3-bicarboxylic acid, NHhydroxy-6-morpholin-4yl-nicotinamidine and phenoxyacetic acid</td><td> 451,4</td>

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<td>Example- plo</td><td>Compound name</td><td>Starting materials</td><td>MH⁺found</td>

<td> 129</td><td>(R) -N- (4 - {5- [1- (2- Phenoxy-acetyl) piperazin-2-yl] [1,2,4] oxadiazole-3- il} -2-trifluoromethylphenyl) -acetamide</td><td>D-Piperazine-1-tert-Butyl ester 1,3-bicarboxylic, N- [4- (N- Hydroxycarbamimidoyl) -2-trifluoromethylphenyl] -acetamide and phenoxyacetic acid</td><td> 490,4</td>

<td> 130</td><td>(R) -1- {2- [3- (4-Methyl- 3-nitro-phenyl) [1,2,4] oxadiazol-5yl] -piperazin-1-yl} 2-phenoxy-ethanone</td><td>D-piperazine acid 1-tert-Butyl ester 1,3-bicarboxylic acid, NHhydroxy-4-methyl-3-nitro-benzamidine and phenoxyacetic acid</td><td> 424,4</td>

<td> 131</td><td>(R) -l- {2- [3- (4-Methyl- 3-nitro-phenyl) [1,2,4] oxadiazol-5yl] -piperazin-1-yl} 2-phenoxy-ethanone</td><td>1- D-piperazine acid tert-Butyl ester 1,3-bicarboxylic, 1 {2 - [3- (4-Methoxy-3-nitro-phenyl) - [1,2,4] oxadiazol-5yl] -piperazin-l-yl} - 2- phenoxy-ethanone and phenoxyacetic acid</td><td> 440, 4</td>

<td> 132</td><td>(R) -l- {2- [3- (4Morfolin-4-yl-phenyl) - [1,2,4] oxadiazol-5yl] -piperazin-l-yl} 2-phenoxy-ethanone</td><td>D-piperazine acid 1-tert-Butyl ester 1,3-bicarboxylic acid, NHhydroxy-4-morpholin-4yl-benzamidine and phenoxyacetic acid</td><td> 450,4</td>

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<td>Example</td><td>Compound name</td><td>Starting materials</td><td>MH⁺found</td>

<td> 133</td><td>(R) —l— (2— {3— [4— (3H— Imidazol-4-yl) phenyl] - [1,2,4] oxadiazol-5yl} -piperazin-1-yl) 2-phenoxy-ethanone</td><td>D-piperazine acid 1-tert-Butyl ester 1,3-bicarboxylic acid, NHhydroxy-4- (3Himidazol-4-yl) benzamidine and phenoxyacetic acid</td><td> 431,4</td>

<td> 134</td><td>(R) -1- (2— {3- [6- (3Hydroxymethylpyrrolidin-1-yl) pyridin-3-yl] [1,2,4] oxadiazol-5yl} -piperazin-1-yl) 2-phenoxy- ethanone</td><td>D-piperazine acid 1-tert-Butyl ester 1,3-bicarboxylic acid, NHhydroxy-6- (3hydroxymethylpyrrolidin-l-yl) nicotinamidine and phenoxyacetic acid</td><td> 465,4</td>

<td> 135</td><td>(R) -1- (2- {3- [6- (4Acetyl-piperazin-1yl) -pyridin-3-yl] [1,2,4] oxadiazol-5yl} -piperazin-1-yl) 2-phenoxy -ethanone</td><td>D-piperazine acid 1-tert-Butyl ester 1,3-bicarboxylic acid, 6 (4-Acetyl-piperazinyl-yl) -N-hydroxynicotinamidine and phenoxyacetic acid</td><td> 492,5</td>

<td> 136</td><td>(R) -N- (3- {5- [1- (2- Phenoxy-acetyl) piperazin-2-yl] [1,2,4] oxadiazol-3yl} -phenyl) -acetamide hydrochloride</td><td>D-piperazine acid 1-tert-Butyl ester 1,3-bicarboxylic acid, N [3- (NHidroxicarbamimidoil) -phenyl] -acetamide and phenoxyacetic acid</td><td> 422,4</td>

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<td>Example- plo</td><td>Compound name</td><td>Starting materials</td><td>MH⁺found</td>

<td> 137</td><td>(R) -l- {2- [3- (1H- Benzoimidazol-5-yl) [1,2,4] oxadiazol-5yl] -piperazin-1-yl} 2-phenoxy-ethanone</td><td>D-Piperazine-1-tert-Butyl ester 1,3-bicarboxylic acid, NHhydroxy-1H-benzimidazole-5carboxamidine and phenoxyacetic acid</td><td> 405,5</td>

<td> 138</td><td>(R) —1— {2— [3- (1H- Benzotriazol-5-yl) [1,2,4] oxadiazol-5yl] -piperazin-1-yl} 2-phenoxy-ethanone</td><td>D-piperazine acid 1-tert-Butyl ester 1,3-bicarboxylic acid, NHhydroxy-1H-benzotriazole-5carboxamidine and phenoxyacetic acid</td><td> 406, 4</td>

<td> 139</td><td>(R) -l {2- [3- (1H-Indazol-5yl) - [1,2,4] oxadiazol5-yl] -piperazin-lil} -2-phenoxy-ethanone hydrochloride</td><td>D-piperazine acid 1-tert-Butyl ester 1,3-bicarboxylic acid, NHhydroxy-1H-indazole-5carboxamidine and phenoxyacetic acid</td><td> 405, 4</td>

<td> 140</td><td>(R) -5- {5- [1- (2- Phenoxy-acetyl) piperazin-2-yl] - [1,2,4] oxadiazole-3il} -1,3-dihydrobenzoimidazole-2-one</td><td>D-piperazine acid 1-tert-Butyl ester 1,3-bicarboxylic, NHhydroxy-2-oxo-2,3-dihydro-1H- benzoimidazole-5carboxamidine and phenoxyacetic acid</td><td> 421,5</td>

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<td>Example</td><td>Compound name</td><td>Starting materials</td><td>MH⁺found</td>

<td> 141</td><td>(R) -l (2- {3- [6- (1,1-Dioxothiomorfolin-4-yl) pyridin-3-yl] [1,2,4] oxadiazol-5yl} -piperazin-l-yl hydrochloride ) 2-phenoxy-ethanone</td><td>D-piperazine acid 1-tert-Butyl ester 1,3-bicarboxylic, 6 (1,1-Dioxo- thiomorfolin-4-yl) -Nhydroxynicotinamidine and phenoxyacetic acid</td><td> 499,1</td>

<td> 142</td><td>(R) —1— {2 - [3- (3-Nitro- phenyl) - [1,2,4] oxadiazol-5yl] -piperazin-l-yl} 2-phenoxy-ethanone</td><td>D-piperazine acid 1-tert-Butyl ester 1,3-bicarboxylic acid, NHhydroxy-3-nitrobenzamidine and phenoxyacetic acid</td><td> 410,1</td>

<td> 143</td><td>(R) -1- {2- [3- (4Fluoro-phenyl) [1,2,4] oxadiazol-5yl] -piperazin-1-yl} 2-phenoxy-ethanone</td><td>D-piperazine acid 1-tert-Butyl ester 1,3-bicarboxylic acid, 4Fluoro-N-hydroxybenzamidine and phenoxyacetic acid</td><td> 383, 4</td>

<td> 144</td><td>(R) -4- {5- [1- (2- Phenoxy-acetyl) piperazin-2-yl] [1,2,4] oxadiazol-3yl} -1H-pyridin-2-one</td><td>D-piperazine acid 1-tert-Butyl ester 1,3-bicarboxylic acid, NHhydroxy-2-oxo-1,2,2hydro-pyridine-4carboxamidine and phenoxyacetic acid</td><td> 382,4</td>

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<td>Example- plo</td><td>Compound name</td><td>Starting materials</td><td>MH⁺found</td>

<td> 145</td><td>1- {4-Acetyl-2- [3- (4-methoxy-phenyl) [1,2,4] oxadiazol-5yl] -piperazin-l-yl} - 2- phenoxy-ethanone</td><td>1-tert-Butyl ester of 4-acetylpiperazine-1,2bicarboxylic acid, N- Hydroxy-4-methoxybenzamidine and phenoxyacetic acid</td><td> 437,5</td>

<td> 146</td><td>1- {4-Acetyl-2- [3- (4- methanesulfonylphenyl) - [1,2,4] oxadiazol-5yl] -piperazin-l-yl} - 2- phenoxy-ethanone</td><td>1-tert-Butyl ester of 4-acetylpiperazine-1,2bicarboxylic acid, NHhydroxy-4- methanesulfonylbenzamidine and phenoxyacetic acid</td><td> 485,5</td>

<td> 147</td><td>4- {5- [4-Acetyl-l- (2- phenoxy-acetyl) piperazin-2-yl] [1,2,4] oxadiazol-3yl} - benzenesulfonamide</td><td>1-tert-Butyl ester of 4-acetylpiperazine-1,2bicarboxylic acid, NHhydroxy-4-sulfamoyl benzamidine and phenoxyacetic acid</td><td> 486, 5</td>

<td> 148</td><td>1- [4-Acetyl-2- (3- pyridin-4-il- [1,2,4] oxadiazol-5yl) -piperazin-1-yl] - 2- phenoxy-ethanone</td><td>1-tert-Butyl ester of 4-acetylpiperazine-1,2-bicarboxylic acid, NHhydroxyisonicotinamidine and phenoxyacetic acid</td><td> 408,5</td>

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<td>Example</td><td>Compound name</td><td>Starting materials</td><td>MH⁺found</td>

<td> 149</td><td>1- {4-Methanesulfonyl- 2- [3- (4-methoxyphenyl) - [1,2,4] oxadiazol-5yl] -piperazin-l-yl} 2-phenoxy-ethanone</td><td>1-tert-Butyl acid ester 4- methanesulfonylpiperazine-1,2bicarboxylic, NHhydroxy-4-Methoxybenzamidine and phenoxyacetic acid</td><td> 473,2</td>

<td> 150</td><td>(R) -1- {2- [5- (4Fluoro-phenyl) -2H- [1,2,4] triazol-3-yl] piperazin-l-yl} -2phenoxy-ethanone</td><td>D-piperazine acid 1-tert-Butyl ester 1,3-bicarboxylic acid, 4Fluoro-N-aminobenzamidine and phenoxyacetic acid</td><td> 382,4</td>

<td> 151</td><td>(R) -2-Phenoxy-l- {2- [5- (3-trifluoromethylphenyl) -2H- [1,2,4] triazol-3-yl] piperazin-l-yl} ethanone</td><td>D-piperazine acid 1-tert-Butyl ester 1,3-bicarboxylic acid, 3Trifluoromethyl-Namino-benzamidine and phenoxyacetic acid</td><td> 432,4</td>

<td> 152</td><td>1- {2- [5- (4-Fluoro-3trifluoromethylphenyl) -2H- [1,2,4] triazol-3-yl] piperazin-l-yl} -2phenoxy-ethanone</td><td>1-tert-Butyl ester of piperazine-1,3bicarboxylic acid, 4Fluoro-3trifluoromethyl-Namino-benzamidine and phenoxyacetic acid</td><td> 450,4</td>

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<td>Example</td><td>Compound name</td><td>Starting materials</td><td>MH⁺find auger</td>

<td> 153</td><td>l- {2- [5- (4- Methanesulfonyl- phenyl) -2H- [1,2,4] triazol-3-yl] piperazin-l-yl} -2phenoxy-ethanone</td><td>1-tert-Butyl ester of piperazine-1,3bicarboxylic acid, 4Methanesulfonyl-Namino-benzamidine and phenoxyacetic acid</td><td> 442,4</td>

<td> 154</td><td>2-Phenoxy-l- [2— [5— (3— phenyl) -2H- [1,2,4] triazol-3-yl] piperazin-l-yl} ethanone</td><td>1-tert-Butyl ester of piperazine acid — 4,3-bicarboxylic acid, 3Trifluoromethyl-Namino-benzamidine and phenoxyacetic acid</td><td> 432,4</td>

<td> 155</td><td>2-Phenoxy-l- [2- (5-ptolyl-2H- [1,2,4] triazol-3-yl) piperazin-1-yl] ethanone</td><td>1-tert-Butyl ester of piperazine-1,3-bicarboxylic acid, 4Methyl-N-aminobenzamidine and phenoxyacetic acid</td><td> 378,4</td>

<td> 156</td><td>2-Phenoxy-l- {2- [5- (4trifluoromethylphenyl) -2H- [1,2,4] triazol-3-yl] piperazin-l-yl} ethanone</td><td>1-tert-Butyl ester of piperazine-1, 3-bicarboxylic acid, 4Trifluoromethyl-Namino-benzamidine and phenoxyacetic acid</td><td> 432,4</td>

<td> 157</td><td>1— {2— [5— (4-Methoxyphenyl) -2H- [1,2,4] triazol-3-yl] piperazin-l-yl} -2- phenoxy-ethanone</td><td>1-tert-Butyl ester of piperazine-1,3-bicarboxylic acid, 4Methoxy-N-aminobenzamidine and phenoxyacetic acid</td><td> 394,4</td>

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<td>Example</td><td>Compound name</td><td>Starting materials</td><td>MH⁺found</td>

<td> 158</td><td>1- {2- [5- (4-Fluoro- phenyl) -2H- [1,2,4] triazol-3-yl] piperazin-l-yl} -2phenoxy-ethanone</td><td>1-tert-Butyl ester of piperazine-1,3-bicarboxylic acid, 4Fluoro-N-aminobenzamidine and phenoxyacetic acid</td><td> 382,4</td>

<td> 159</td><td>1- {2- [5- (4-Fluorophenyl) -2H- [1,2,4] triazol-3-yl] piperazin-l-yl} -2phenoxy-ethanone</td><td>1-tert-Butyl ester of piperasine acid — 1,3 bicarboxylic acid, 2,4Difluoro-N-aminobenzamidine and phenoxyacetic acid</td><td> 400,4</td>

<td> 160</td><td>l- {2- [5- (3,4- Dimethoxy-phenyl) -2H [1,2,4] triazol-3-yl] piperazin-l-yl} -2phenoxy-ethanone</td><td>1-tert-Butyl ester of piperazine-1,3-bicarboxylic acid, 3,4-dimethoxy-N-aminobenzamidine and phenoxyacetic acid</td><td> 424,4</td>

<td> 161</td><td>1- {2- [5- (3,4-Dichlorophenyl) -2H- [1,2,4] triazol-3-yl] piperazin-l-yl} -2phenoxy-ethanone</td><td>1-tert-Butyl ester of piperazine-1,3-bicarboxylic acid, 3,4Dichloro-N-aminobenzamidine and phenoxyacetic acid</td><td> 432,4</td>

<td> 162</td><td>1— {2— [5- (2-Fluorophenyl) -2H- [1,2,4] triazol-3-yl] piperazin-l-yl} -2phenoxy-ethanone</td><td>1-tert-Butyl ester of piperazine-1,3-bicarboxylic acid, 3Fluoro-N-aminobenzamidine and phenoxyacetic acid</td><td> 382,4</td>

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<td>Example- plo</td><td>Compound name</td><td>Starting materials</td><td>MH⁺found</td>

<td> 163</td><td>1— {2— [5- (2-Fluorophenyl) -2H- [1,2,4] triazol-3-yl] piperazin-l-yl} -2phenoxy-ethanone</td><td>1-tert-Butyl ester of piperazine-1,3-bicarboxylic acid, 2Fluoro-N-aminobenzamidine and phenoxyacetic acid</td><td> 382,4</td>

4- {5- [4-Methyl-1- (2-phenoxy-acetyl) -piperazin-2-yl] [1,2,4] oxadiazol-3-yl} -benzamide

0.1 mmol of 4- {5- [1- (2-phenoxy5 acetyl) -piperazin-2-yl] - [1,2,4] oxadiazol-3-yl} benzamide is dissolved in 1 ml of DMF and 1 equivalent of DIPEA and Na2CO is added₃. To the suspension, 1 equivalent of honey is added and the reaction is subjected to stirring at room temperature overnight. The product is isolated by means of preparation HPLC.

MS (ISO): 422.4 (MH +)

The following examples were prepared in the analogy:

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Table 2

<td>Example</td><td>Compound name</td><td>Starting material</td><td>MH⁺find auger</td>

<td> 165</td><td>(R) -1- {2- [3- (1H- Indazol-5il) - [1,2,4] oxadiazole-5- il] -4-methylpiperazin-l-yl} -2phenoxy-ethanone</td><td>(R) -1- {2- [3- (1H- Indazol-5 il) - [1,2,4] oxadiazol-5 ylj-piperazin-l-yl} 2-phenoxy-ethanone</td><td> 419, 5</td>

<td> 166</td><td>(R) -l- {2- [3- (4- Fluoro-phenyl) - [1,2,4] oxadiazol-5yl] -4-methylpiperazin-l-yl} -2phenoxy-ethanone</td><td>(R) -l- {2- [3- (4- Fluoro-phenyl) - [1,2,4] oxadiazole-5- il] -piperazinl-il} -2phenoxy-ethanone</td><td> 397, 4</td>

<td> 167</td><td>(R) -5- {5- [4-Methyl-l- (2-phenoxy-acetyl) piperazin-2-yl] [1,2,4] oxadiazol-3yl}-1,3-dihydro-indol2-one</td><td>(R) -5- {5- [1- (2- Phenoxy-acetyl) piperazin-2-yl] [1,2,4] oxadiazol-3yl}-1,3-dihydro-indol2-one</td><td> 434,5</td>

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<td>Example</td><td>Compound name</td><td>Starting material</td><td>MH⁺found</td>

<td> 168</td><td>(R) -5- {5- [4-Methyl-l- (2-phenoxy-acetyl) piperazin-2-yl] [1,2,4] oxadiazol-3yl} -1,3-dihydrobenzoimidazole-2-one</td><td>(R) —5— {5— [1— (2— Phenoxy-acetyl) piperazin-2-yl] - [1,2,4] oxadiazole-3il} -1,3-dihydrobenzoimidazole-2-one</td><td> 435,5</td>

<td> 169</td><td>(R) -1- {2- [3- (1H- Benzoimidazol-5-yl) - [1,2,4] oxadiazole-5- il] -4-methylpiperazin-l-yl} -2phenoxy-ethanone</td><td>(R) -1- {2- [3- (1H- Benzoimidazol-5-yl) [1,2,4] oxadiazol-5yl] -piperazin-1-yl} 2-phenoxy-ethanone</td><td> 419,5</td>

<td> 170</td><td>(R) -1- {2- [3- (1H- Benzotriazol-5-yl) - [1,2,4] oxadiazole-5- il] -4-methyl- piperazin-l-yl} -2phenoxy-ethanone</td><td>(R) -l- [2- [3- (lH- Benzotriazol-5-yl) [1,2,4] oxadiazol-5yl] -piperazin-1-yl} 2-phenoxy-ethanone</td><td> 420,5</td>

<td> 171</td><td>(R) -l- {4-Methyl-2- [5- (3-trifluoromethylphenyl) -2H- [1,2,4] triazol-3-yl] piperazin-l-yl} -2phenoxy-ethanone</td><td>(R) -2-Phenoxy-l- {2- [5- (3-trifluoromethylphenyl) -2H- [1,2,4] triazol-3-yl] piperazin-l-yl} ethanone</td><td> 446, 4</td>

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<td>Example</td><td>Compound name</td><td>Starting material</td><td>MH⁺found</td>

<td></td><td>(R) -l- {2- [5- (4-</td><td>(R) -l- {2- [5- (4-</td><td></td>

<td></td><td>Methoxy-phenyl) -2H-</td><td>Methoxy-phenyl) -2H-</td><td></td>

<td> 172</td><td>[1,2,4] triazol-3-yl] -</td><td>[1,2,4] triazol-3-yl] -</td><td> 408,4</td>

<td></td><td>4-methyl-piperazin-l-</td><td>piperazinl-il} -2-</td><td></td>

<td></td><td>il} -2-phenoxy-ethanone</td><td>phenoxy-ethanone</td><td></td>

<td></td><td>(R) -1- {2- [5- (4-</td><td>(R) -1- {2- [5- (4-</td><td></td>

<td></td><td>Fluoro-phenyl) -2H-</td><td>Fluoro-phenyl) -2H-</td><td></td>

<td> 173</td><td>[1,2,4] triazol-3-yl] -</td><td>[1,2,4] triazol-3-yl] -</td><td> 396, 4</td>

<td></td><td>4-methyl-piperazin-l-</td><td>piperazinl-il} -2-</td><td></td>

<td></td><td>il} -2-phenoxy-ethanone</td><td>phenoxy-ethanone</td><td></td>

<td></td><td>(R) -1- {2- [5- (4-</td><td>(R) -1- {2- [5- (4-</td><td></td>

<td></td><td>Methanesulfonyl-</td><td>Methanesulfonyl-</td><td></td>

<td></td><td>phenyl) -2H-</td><td>phenyl) -2H-</td><td></td>

<td> 174</td><td></td><td></td><td> 456, 4</td>

<td></td><td>[1,2,4] triazol-3-yl] -</td><td>[1,2,4] triazol-3-yl] -</td><td></td>

<td></td><td>4-methyl-piperazin-l-</td><td>piperazin-l-il} -2-</td><td></td>

<td></td><td>il} -2-phenoxy-ethanone</td><td>phenoxy-ethanone</td><td></td>

<td></td><td>Methyl acid ester</td><td>Methyl acid ester</td><td></td>

<td></td><td>(R) -4- {5- [4-Methyl-</td><td>(R) -4- {5- [1- (2-</td><td></td>

<td></td><td>1- (2-phenoxy-acetyl) -</td><td>phenoxy-acetyl) -</td><td></td>

<td> 175</td><td></td><td></td><td> 436, 5</td>

<td></td><td>piperazin-2-yl] -1H-</td><td>piperazin-2-yl] -1H-</td><td></td>

<td></td><td>[1,2,4] triazol-3-yl} -</td><td>[1,2,4] triazol-3-yl} -</td><td></td>

<td></td><td>benzoic</td><td>benzoic</td><td></td>

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<td>Example</td><td>Compound name</td><td>Starting material</td><td>MH⁺find auger</td>

<td> 176</td><td>(R) -N- (3- {5- [4-Methyl- 1- (2-phenoxy-acetyl) piperazin-2-yl] -1H [1,2,4] triazol-3-yl} phenyl) -acetamide</td><td>(R) -N- (3- {5- [1- (2- Phenoxy-acetyl) piperazin-2-yl] -1H- [1,2,4] triazol-3-yl} - phenyl) -acetamide</td><td> 435, 5</td>

<td> 177</td><td>(R) -N- (3- {5- [4-Methyl- 1- (2-phenoxy-acetyl) piperazin-2-yl] -1H [1,2,4] triazol-3-yl} phenyl) -methanesulfonamide</td><td>(R) -N- (3- {5-Γ1- (2- Phenoxy-acetyl) piperazin-2-yl] -1H- [1,2,4] triazol-3-yl} phenyl) -methanesulfonamide</td><td> 471,5</td>

<td> 178</td><td>(R) -4- {5- [4-Methyl-l- (2-phenoxy-acetyl) piperazin-2-yl] -1H [1,2,4] triazol-3-yl} benzamide</td><td>(R) -4- {5- [1- (2- Phenoxy-acetyl) piperazin-2-yl] -1H- [1,2,4] triazol-3-yl} - benzamide</td><td> 421,5</td>

Example 179

(R) -4- {5- [1- (2-phenoxy-acetyl) -piperidin-2-yl] [1,2,4] oxadiazol-3-yl} -benzoic acid

4 mmol of benzyl ester of (R) -4- {5- [1- (2-phenoxy-acetyl) -piperidin-2-yl] [1,2,4] oxadiazol-3-yl} - benzoic in MeOH and treated with Pd / C and washed with hydrogen (3 bar) and stirred for 30 minutes. The catalyst was REMo130 / 229 filtered and the solvent evaporated. After extraction from ethyl acetate / water, the resulting oil was purified by means of preparation HPLC. The corresponding alkyl esters were treated with 2N aqueous NaOH or LiOH in methanol at room temperature. The allyl ester can be cleaved using Pd (Ph3) 4 as a catalyst and morpholine as a nucleophile.

MS (ISO): 408.5 (MH +)

The following compounds were prepared in analogy:

Table 3

<td>Example</td><td>Compound name</td><td>Starting material</td><td>MH⁺found</td>

<td> 180</td><td>(R) —3— [5— [1- (2-phenoxy-acetyl) piperidin-2-yl] [1,2,4] oxadiazol-3yl} -benzoic acid</td><td>Methyl acid ester (R) -3- {5- [l- (2- phenoxy-acetyl) piperidin-2-yl] [1,2,4] oxadiazol-3yl} -benzoic</td><td> 408,5</td>

<td> 181</td><td>(R) -6- {5- [1- (2- phenoxy-acetyl) piperidin-2-yl] - [1,2,4] oxadiazole-3- il} -nicotinico</td><td>(R) -6- {5- [1- (2-phenoxy-acetyl) piperidin-2-yl] [1,2,4] oxadiazol-3yl} -nicotinic acid methyl ester</td><td> 409, 4</td>

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<td>Example</td><td>Compound name</td><td>Starting material</td><td>MH⁺found</td>

<td> 182</td><td>(R) -2-Fluoro-4 {5- [1- (2-phenoxyacetyl) -piperidin-2yl] - [1,2,4] oxadiazole- 3-il} -benzoic</td><td>Methyl acid ester (R) -2-Fluoro-4- {5- [1 (2-phenoxy-acetyl) piperidin-2-yl] [1,2,4] oxadiazol-3yl} -benzoic</td><td> 426, 5</td>

<td> 183</td><td>(R) -5- {5- [1 - (- 2-Phenoxy-acetyl) piperidin-2-yl] [1,2,4] oxadiazol-3yl} -pyridine-2carboxylic acid</td><td>(R) —5— {5— [1— (2 - Phenoxy-acetyl) piperidin-2-yl] [1,2,4] oxadiazol-3yl} -pyridine-2carboxylic acid methyl ester</td><td> 409, 4</td>

<td> 184</td><td>(R) -4- {5- [1- (2-phenoxy-acetyl) piperidin-2-yl] [1,2,4] oxadiazol-3yl} -pyridine-2-carboxylic acid</td><td>Ethyl acid ester (R) —4 - {5— [1— (2 - phenoxy-acetyl) piperidin-2-yl] [1,2,4] oxadiazol-3yl} -pyridine-2carboxylic</td><td> 409, 4</td>

<td> 185</td><td>(R) -3- {5- [1- (2- phenoxy-acetyl) piperidin-2-yl] -1H [1,2,4] triazol-3-yl} benzoic</td><td>(R) -3- {5- [1- (2-phenoxy-acetyl) piperidin-2-yl] -1H [1,2,4] triazol-3-yl} benzoic acid methyl ester</td><td> 407,4</td>

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<td>Example</td><td>Compound name</td><td>Starting material</td><td>MH⁺found</td>

<td></td><td>3- {5- [4- (2-</td><td>Methyl acid ester</td><td></td>

<td></td><td>phenoxy-acetyl) -</td><td>3- {5- [4- (2-phenoxy-</td><td></td>

<td> 186</td><td>morfolin-3-il] -</td><td>acetyl) -morpholin-3-</td><td> 410,5</td>

<td></td><td>[1,2,4] oxadiazole-3-</td><td>il] - [1,2,4] oxadiazole-</td><td></td>

<td></td><td>il} -benzoic</td><td>3-il} -benzoic</td><td></td>

<td></td><td>3- {5- [4- (2-</td><td>Methyl acid ester</td><td></td>

<td></td><td>Phenoxy-acetyl) -</td><td>3- {5- [4- (2-Phenoxy-</td><td></td>

<td> 187</td><td>morfolin-3-il] -</td><td>acetyl) -morpholin-3-</td><td> 410,5</td>

<td></td><td>[1,2,4] oxadiazole-3-</td><td>il] - [1,2,4] oxadiazole-</td><td></td>

<td></td><td>il} -benzoic</td><td>3-il} -benzoic</td><td></td>

<td></td><td>4- {5- [4- (2-Phenoxy-</td><td>4- {5- Methyl ester</td><td></td>

<td></td><td>acetyl) -tiomorfolin-</td><td>[4- (2-phenoxy-acetyl) -</td><td></td>

<td> 188</td><td>3-il] -</td><td>thiomorfolin-3-yl] -</td><td> 426, 4</td>

<td></td><td>[1,2,4] oxadiazole-3-</td><td>[1,2,4] oxadiazole-3-</td><td></td>

<td></td><td>il} -benzamide</td><td>il} -benzamide</td><td></td>

<td></td><td>4- {5- [4- (2-Phenoxy-</td><td>4— {5— methyl ester</td><td></td>

<td></td><td>acetyl) -tiomorfolin-</td><td>[4- (2-phenoxy-acetyl) -</td><td></td>

<td> 189</td><td>3-il] -</td><td>thiomorfolin-3-yl] -</td><td> 426, 4</td>

<td></td><td>[1,2,4] oxadiazole-4-</td><td>[1,2,4] oxadiazole-4-</td><td></td>

<td></td><td>il} -benzamide</td><td>il} -benzamide</td><td></td>

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<td>Example</td><td>Compound name</td><td>Starting material</td><td>MH⁺found</td>

<td> 190</td><td>3- {5- [4-acetyl- 1- (2-phenoxy-acetyl) piperazin-2-yl] [1,2,4] oxadiazol-3yl} -benzoic</td><td>Methyl acid ester 3- {5- [4-acetyl-1- (2-phenoxy-acetyl) piperazin-2-yl] [1,2,4] oxadiazole-3yl} -benzoic</td><td> 451,5</td>

<td> 191</td><td>4- {5- [4-acetyl- 1- (2-phenoxy-acetyl) piperazin-2-yl] [1,2,4] oxadiazol-3yl} -benzoic</td><td>Methyl acid ester 4— {5— [4-acetyl-l- (2-phenoxy-acetyl) piperazin-2-yl] [1,2,4] oxadiazol-3yl} -benzoic</td><td> 451,5</td>

<td> 192</td><td>Acid (R) —4— [5— [4— methyl-1- (2-phenoxyacetyl) -piperazin-2yl] -1H- [1,2,4] triazol-3-yl} - benzoic</td><td>(R) -4- {5- [1- (2-phenoxy-acetyl) piperazin-2-yl] -1H [1,2,4] triazol-3-yl} benzoic acid methyl ester</td><td> 422,5</td>

<td> 193</td><td>(R) -5- {5- [1- (2- phenoxy-acetyl) piperidin-2-yl] [1,2,4] oxadiazol-3yl} -nicotinic</td><td>(R) -5- {5- [1- (2Phenoxy-acetyl) piperidin-2-yl] [1,2,4] oxadiazol-3yl} -nicotinic acid ester</td><td> 409, 5</td>

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Example 194 (R) -1- (2- {3- [4- (Morpholine-4-carbonyl) -phenyl] [1,2,4] oxadiazol-5-yl} -piperidin-l-yl) -2- phenoxy-ethanone

(R) - 4— {5— [1— (2-phenoxy-acetyl) -piperidin-2-yl] - [1,2,4] oxadiazol-3yl} -benzoic acid was treated with 0.07 mmol 1 equivalent of TBTU / DIPEA in 1 ml of DMF for 10 minutes and 2 equivalents of morpholine were added. The reaction is subjected to stirring overnight at room temperature and the product isolated 10 by means of preparation HPLC.

MS (ISO): 477.6 (MH +)

In analogy, the following compounds were prepared:

Table 4

<td>Example</td><td>Compound name</td><td>Starting materials</td><td>MH⁺found</td>

<td> 195</td><td>(R) -1- (2- {3- [4- (3- Hydroxy-pyrrolidine-1carbonyl) -phenyl] [1,2,4] oxadiazol-5yl} -piperidin-1-yl) -2phenoxy-ethanone</td><td>(R) —4— {5— [1- (2-phenoxy-acetyl) piperidin-2-yl] [1,2,4] oxadiazol-3yl} -benzoic acid and pyrrolidin-3-ol</td><td> 477,6</td>

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<td>Example</td><td>Compound name</td><td>Starting materials</td><td>MH⁺found</td>

<td> 196</td><td>(R) -N, N-Diethyl-4- {5 [1- (2-phenoxy-acetyl) piperidin-2-yl] [1,2,4] oxadiazol-3yl} -benzamide</td><td>(R) —4— {5— [1- (2-phenoxy-acetyl) piperidin-2-yl] [1,2,4] oxadiazol-3yl} -benzoic acid and diethylamine</td><td> 463, 6</td>

<td> 197</td><td>(R) -N-Methyl-4- {5- [1 (2-phenoxy-acetyl) piperidin-2-yl] [1,2,4] oxadiazol-3yl} -benzamide</td><td>(R) -4- {5- [1- (2- phenoxy-acetyl) piperidin-2-yl] [1,2,4] oxadiazol-3yl] -benzoic acid and methylamine</td><td> 421,5</td>

<td> 198</td><td>(R) -N, N-Dimethyl-4- {5- [1- (2-phenoxy-acetyl) piperidin-2-yl] [1,2,4] oxadiazol-3yl} -benzamide</td><td>(R) -4- {5- [1- (2-phenoxy-acetyl) piperidin-2-yl] [1,2,4] oxadiazol-3yl] -benzoic acid and dimethylamine</td><td> 435,5</td>

<td> 199</td><td>(R) -N-Ethyl-4- {5- [1- (2- phenoxy-acetyl) piperidin-2-yl] [1,2,4] oxadiazol-3yl} -benzamide</td><td>(R) -4- {5- [1- (2- phenoxy-acetyl) piperidin-2-yl] [1,2,4] oxadiazol-3yl} -benzoic acid and ethylamine</td><td> 435, 5</td>

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<td>Example</td><td>Compound name</td><td>Starting materials</td><td>MH⁺found</td>

<td> 200</td><td>(R) -N-Cyclopropyl-4- {5- [1- (2-phenoxyacetyl) -piperidin-2yl] - [1,2,4] oxadiazole- 3-yl} -benzamide</td><td>(R) -4- {5- [1- (2-phenoxy-acetyl) piperidin-2-yl] [1,2,4] oxadiazol-3yl} -benzoic acid and cyclopropylamine</td><td> 447,5</td>

<td> 201</td><td>(R) -N- (2-Hydroxyethyl) -4- {5- [1- (2-phenoxy-acetyl) piperidin-2-yl] [1,2,4] oxadiazol-3yl} -benzamide</td><td>(R) —4— {5— [1- (2-phenoxy-acetyl) piperidin-2-yl] [1,2,4] oxadiazol-3yl} -benzoic acid and ethanolamine</td><td> 451,5</td>

<td> 202</td><td>(R) -N- (2-Methoxy-ethyl) - N-methyl-4- {5- [1- (2-phenoxy-acetyl) piperidin-2-yl] [1,2,4] oxadiazol-3yl} -benzamide</td><td>(R) -4- {5- [1- (2-phenoxy-acetyl) piperidin-2-yl] [1,2,4] oxadiazol-3yl} -benzoic acid and (2-methoxy-ethyl) -methylamine</td><td> 479, 5</td>

<td> 203</td><td>(R) -N-Methyl-3- {5- [1 (2-phenoxy-acetyl) piperidin-2-yl] [1,2,4] oxadiazol-3yl} -benzamide</td><td>Acid (R) —3— {5— [1— (2— phenoxy-acetyl) piperidin-2-yl] [1,2,4] oxadiazol-3yl} -benzoic acid and methylamine</td><td> 421,5</td>

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<td>Example</td><td>Compound name</td><td>Starting materials</td><td>MH⁺found</td>

<td> 204</td><td>(R) -N, N-Dimethyl-3- {5 [1- (2-phenoxy-acetyl) piperidin-2-yl] - [1,2,4] oxadiazol-3yl} -benzamide</td><td>(R) -3- {5- [1- (2-phenoxy-acetyl) piperidin-2-yl] [1,2,4] oxadiazol-3yl} -benzoic acid and dimethylamine</td><td> 435,5</td>

<td> 205</td><td>(R) -N-Ethyl-3- {5- [1- (2-phenoxy-acetyl) piperidin-2-yl] - [1,2,4] oxadiazole-3- il} -benzamide</td><td>(R) -3- {5- [1- (2-phenoxy-acetyl) piperidin-2-yl] [1,2,4] oxadiazol-3yl} -benzoic acid and ethylamine</td><td> 435, 5</td>

<td> 206</td><td>(R) -N-Cyclopropyl-3- {5 - [1- (2-phenoxyacetyl) -piperidin-2yl] - [1,2,4] oxadiazol3-yl} -benzamide</td><td>(R) —3— {5— [1- (2-phenoxy-acetyl) piperidin-2-yl] [1,2,4] oxadiazol-3yl} -benzoic acid and cyclopropylamine</td><td> 447,5</td>

<td> 207</td><td>(R) -N- (2-Hydroxyethyl) -3- {5- [1- (2-phenoxy-acetyl) piperidin-2-yl] [1,2,4] oxadiazol-3yl} -benzamide</td><td>(R) -3- {5- [1- (2- phenoxy-acetyl) piperidin-2-yl] [1,2,4] oxadiazol-3yl} -benzoic acid and ethanolamine</td><td> 451, 5</td>

138/229

<td>Example</td><td>Compound name</td><td>Starting materials</td><td>MH⁺found</td>

<td> 208</td><td>(R) -N- (2-Methoxy-ethyl) N-methyl-3- {5- [1- (2-phenoxy-acetyl) piperidin-2-yl] [1,2,4] oxadiazol-3yl} -benzamide</td><td>(R) -3- {5- [1- (2- phenoxy-acetyl) piperidin-2-yl] - [1,2,4] oxadiazole-311} -benzoic and (2methoxy-ethyl) -methylamine</td><td> 479, 5</td>

<td> 209</td><td>(R) -1- (2- {3- [3 (Morpholine-4carbonyl) -phenyl] [1,2,4] oxadiazol-5yl} -piperidin-1-yl) -2-phenoxy-ethanone</td><td>(R) -3- {5- [1- (2-phenoxy-acetyl) piperidin-2-yl] [1,2,4] oxadiazol-3yl} -benzoic acid and morpholine</td><td> 477,6</td>

<td> 210</td><td>(R) -1- (2- {3- [3- (3Hydroxy-pyrrolidine-1carbonyl) -phenyl] [1,2,4] oxadiazol-5yl} -piperidin-1-yl) -2-phenoxy-ethanone</td><td>(R) -3- {5- [1- (2-phenoxy-acetyl) piperidin-2-yl] [1,2,4] oxadiazol-3yl} -benzoic acid and pyrrolidin-3-ol</td><td> 477, 6</td>

<td> 211</td><td>(R) -N, N-Diethyl-3- {5- [1- (2-phenoxy-acetyl) piperidin-2-yl] [1,2,4] oxadiazol-3yl} -benzamide</td><td>(R) -3- {5- [1- (2-phenoxy-acetyl) piperidin-2-yl] [1,2,4] oxadiazol-3yl} -benzoic acid and diethylamine</td><td> 463, 6</td>

<td> 212</td><td>(R) —4— {5— [1— (2-phenoxyacetyl) -piperidin-2yl] - [1,2,4] oxadiazol3-yl} -pyridine-2-carboxylic acid methylamide</td><td>(R) —4— {5— [1- (2-phenoxy-acetyl) piperidin-2-yl] [1,2,4] oxadiazol-3yl} -pyridine-2-carboxylic acid and methylamine</td><td> 422,5</td>

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<td>Example</td><td>Compound name</td><td>Starting materials</td><td>MH⁺found</td>

<td> 213</td><td>acid dimethylamide (R) -4- {5- [1- (2-Phenoxyacetyl) -piperidin-2yl] - [1,2,4] oxadiazol3-yl} -pyridine-2carboxylic</td><td>(R) -4- {5- [1- (2-phenoxy-acetyl) piperidin-2-yl] [1,2,4] oxadiazol-3yl} -pyridine-2-carboxylic acid and dimethylamine</td><td> 436, 5</td>

<td> 214</td><td>Acid ethylamide (R) —4 - {5— [1— (2-phenoxyacetyl) -piperidin-2yl] - [1,2,4] oxadiazol3-yl} -pyridine-2carboxylic</td><td>(R) —4— {5— [1- (2-phenoxy-acetyl) piperidin-2-yl] [1,2,4] oxadiazol-3yl} -pyridine-2-carboxylic acid and ethylamine</td><td> 436, 5</td>

<td> 215</td><td>(R) —4 - {5— [1— (2-phenoxyacetyl) -piperidin-2yl] - [1,2,4] oxadiazol3-yl} -pyridine-2carboxylic acid diethylamide</td><td>(R) —4— {5— [1- (2-phenoxy-acetyl) piperidin-2-yl] [1,2,4] oxadiazol-3yl} -pyridine-2-carboxylic acid and diethylamine</td><td> 464,5</td>

<td> 216</td><td>(R) -1- (2 - {3- [2- (Morpholine-4carbonyl) -pyridin-4yl] - [1,2,4] oxadiazol5-yl} -piperidin-1-yl) 2-phenoxy-ethanone</td><td>(R) -4- {5- [1- (2-phenoxy-acetyl) piperidin-2-yl] [1,2,4] oxadiazol-3yl} -pyridine-2-carboxylic acid and morpholine</td><td> 478,5</td>

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<td>Example</td><td>Compound name</td><td>Starting materials</td><td>MH⁺found</td>

<td> 217</td><td>(R) -1- (2- {3- [2- (3- Methanesulfonylpyrrolidine-1carbonyl) -pyridin-4yl] - [1,2,4] oxadiazol5-yl} -piperidin-1-yl) 2-phenoxy-ethanone</td><td>(R) -4- {5- [1- (2-phenoxy-acetyl) piperidin-2-yl] [1,2,4] oxadiazol-3yl} -pyridine-2-carboxylic acid and 3-methanesulfonylpyrrolidine</td><td> 540,5</td>

<td> 218</td><td>Acid methylamide (R) -5- {5- [1- (2-phenoxyacetyl) -piperidin-2yl] - [1,2,4] oxadiazol3-yl} -pyridine-2carboxylic</td><td>(R) -5- {5- [1- (2-phenoxy-acetyl) piperidin-2-yl] [1,2,4] oxadiazol-3yl} -pyridine-2-carboxylic acid and methylamine</td><td> 422,4</td>

<td> 219</td><td>(R) -N-Methyl-3- {5- [1 (2-phenoxy-acetyl) piperidin-2-yl] -1H [1,2,4] triazol-3-yl} benzamide</td><td>(R) -3- {5- [1- (2-phenoxy-acetyl) piperidin-2-yl] -1H [1,2,4] triazol-3-yl} benzoic acid and methylamine</td><td> 420,4</td>

<td> 220</td><td>1N, N-Diethyl-4- {5- [1 (2-phenoxy-acetyl) piperazin-2-yl] [1,2,4] oxadiazol-3yl} -benzamide</td><td>3- [3- (4carboxy-phenyl) [1,2,4] oxadiazole-5yl] -4- (2-phenoxyacetyl) -piperazine-1carboxylic acid tert-Butyl ester and diethylamine</td><td> 464,3</td>

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<td>Example</td><td>Compound name</td><td>Starting materials</td><td>MH⁺found</td>

<td> 221</td><td>1— (2— {3— [4— (Morpholine- 4-carbonyl) -phenyl] [1,2,4] oxadiazole-5- il} -piperazin-l-yl) -2phenoxy-ethanone</td><td>3- [3- (4-carboxy-phenyl) [1,2,4] oxadiazole-5yl] -4- (2-phenoxyacetyl) -piperazine-1-carboxylic acid tert-Butyl ester and morpholine</td><td> 478,0</td>

<td> 222</td><td>N-Methyl-4- {5- [1- (2-phenoxy-acetyl) piperazin-2-yl] [1,2,4] oxadiazol-3yl} -benzamide</td><td>3— [3— (4 - carboxy-phenyl) acid tert-Butyl ester [1,2,4] oxadiazol-5yl] -4- (2-phenoxyacetyl) -piperazine-1carboxylic and methylamine</td><td> 422,4</td>

<td> 223</td><td>(R) -N-Methyl-5- {5- [1- (2-phenoxy-acetyl) piperidin-2-yl] [1,2,4] oxadiazol-3yl} -nicotinamide</td><td>(R) -5- {5- [1- (2-phenoxy-acetyl) piperidin-2-yl] [1,2,4] oxadiazol-3yl} -nicotinic acid and methylamine</td><td> 422,4</td>

<td> 224</td><td>(R) -N-Ethyl-5- {5- [1- (2-phenoxy-acetyl) piperidin-2-yl] [1,2,4] oxadiazol-3yl} -nicotinamide</td><td>(R) —5— {5— [1- (2-phenoxy-acetyl) piperidin-2-yl] [1,2,4] oxadiazol-3yl} -nicotinic acid and ethylamine</td><td> 436, 5</td>

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<td>Example</td><td>Compound name</td><td>Starting materials</td><td>MH⁺found</td>

<td> 225</td><td>(R) -N-Diethyl-5- {5- [1- (2-phenoxy-acetyl) piperidin-2-yl] [1,2,4] oxadiazol-3yl} -nicotinamide</td><td>(R) -5- {5- [1- (2-phenoxy-acetyl) piperidin-2-yl] [1,2,4] oxadiazol-3yl} -nicotinic acid and diethylamine</td><td> 436, 5</td>

<td> 226</td><td>(R) -N-Diethyl-5- {5- [1- (2-phenoxy-acetyl) piperidin-2-yl] [1,2,4] oxadiazol-3yl} -nicotinamide</td><td>(R) —5— {5— [1- (2-phenoxy-acetyl) piperidin-2-yl] [1,2,4] oxadiazol-3yl} -nicotinic acid and diethylamine</td><td> 464,5</td>

<td> 227</td><td>(R) -N- (2-Hydroxyethyl) -5- {5- [1- (2-phenoxy-acetyl) piperidin-2-yl] [1,2,4] oxadiazol-3yl} -nicotinamide</td><td>(R) —5— {5— [1— (2-phenoxy-acetyl) piperidin-2-yl] [1,2,4] oxadiazol-3yl} -nicotinic acid and aminoethanol</td><td> 452,5</td>

<td> 228</td><td>(R) -N- (2-Methoxy-ethyl) N-methyl-5- {5- [1- (2-phenoxy-acetyl) piperidin-2-yl] [1,2,4] oxadiazol-3yl} -nicotinamide</td><td>(R) -5- {5- [1- (2phenoxy-acetyl) piperidin-2-yl] [1,2,4] oxadiazol-3yl} -nicotinic acid (2Methoxy-ethyl) -methylamine</td><td> 480, 6</td>

<td> 229</td><td>(R) -N-Cyclopropyl-5- {5- [1- (2-phenoxyacetyl) -piperidin-2yl] - [1,2,4] oxadiazol3-yl} -nicotinamide</td><td>(R) —5— {5— [1— (2— phenoxy-acetyl) piperidin-2-yl] [1,2,4] oxadiazol-3yl} -nicotinic acid and cyclopropylamine</td><td> 448,5</td>

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<td></td><td>Example</td><td>Compound name</td><td>Starting materials</td><td>MH⁺found</td>

<td></td><td></td><td>(R) -1- (2- {3- [5- (3-</td><td>(R) -5- {5- [1- (2-</td><td></td>

<td> *</td><td></td><td>Hydroxy-pyrrolidine-1-</td><td>phenoxy-acetyl) -</td><td></td>

<td></td><td></td><td>carbonyl) -pyridin-3-</td><td>piperidin-2-yl] -</td><td></td>

<td></td><td> 230</td><td></td><td></td><td> 478,5</td>

<td> •</td><td></td><td>il] - [1,2,4] oxadiazole-</td><td>[1,2,4] oxadiazole-3-</td><td></td>

<td></td><td></td><td>5-il} -piperidin-l-il) -</td><td>il} -nicotinico e Pir-</td><td></td>

<td></td><td></td><td>2-phenoxy-ethanone</td><td>rolidin-3-ol</td><td></td>

Example 231 (R) -4- {5- [1- (2-Phenoxy-acetyl) -piperidin-2-yl] - [1,2,4] oxadiazol-3-yl} -benzamide

34 mg (R) —4— {5— [1— (2— phenoxy-acetyl) -piperidin-2-yl] - [1,2,4] oxadiazol-3-yl} benzoic acid was treated with 1 equivalent of HATU / DIPEA in DMF and added to 1 equivalent of Rink resin. The reaction was subjected to stirring overnight at room temperature. The resin was washed with DMF, MeOH, DCM (3 x 10 times each) and then treated with TFA / DCM (1: 1) for 2 hours. The resulting yellow oil was purified by means of preparation HPLC.

MS (ISO): 407.5 (MH +) compounds:

In analogy, the following

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Table 5

<td>Example</td><td>Compound name</td><td>Starting materials</td><td>MH⁺Find auger</td>

<td> 232</td><td>(R) —3— {5— [1— (2-Phenoxyacetyl) -piperidin-2yl] - [1,2,4] oxadiazole- 3-yl} -benzamide</td><td>(R) —3— {5— [1— (2— phenoxy-acetyl) piperidin-2-yl] [1,2,4] oxadiazol-3yl} -benzoic acid and Rink resin</td><td> 407,4</td>

<td> 233</td><td>(R) -4 {5- [1- (2-phenoxyacetyl) -piperidin-2yl] - [1,2,4] oxadiazol3-yl} -pyridine-2-carboxylic acid amide</td><td>(R) -4- {5- [1- (2-phenoxy-acetyl) piperidin-2-yl] - acid [1,2,4] oxadiazol-3yl} -pyridine-2-carboxylic and Rink resin</td><td> 408,4</td>

<td> 234</td><td>(R) —3— {5— [1— (2-Phenoxy- acetyl) -piperidin-2- il] -1H- [1,2,4] triazole- 3-yl} -benzamide</td><td>(R) —3— {5— [1- (2-phenoxy-acetyl) piperidin-2-yl] -1H- acid [1,2,4] triazol-3-yl} benzoic and Rink resin</td><td> 406, 4</td>

<td> 235</td><td>4- {5- [4- (2-Phenoxyacetyl) -morpholin-3- il] - [1,2,4] oxadiazole- 3-yl} -benzamide</td><td>4- {5- [4- (2- phenoxy-acetyl) morpholin-3-yl] - [1,2,4] oxadiazol-3yl} -benzoic and Rink resin</td><td> 409, 5</td>

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<td>Example</td><td>Compound name</td><td>Starting materials</td><td>MH⁺Found</td>

<td> 236</td><td>4- {5- [4- (2-Phenoxyacetyl) -tiomorfolin-3 yl] - [1,2,4] oxadiazole- 3yl} -benzamide</td><td>Acid 4— [5— [4— (2— phenoxy-acetyl) thiomorpholin-3 yl] - [1,2,4] oxadiazole- 3il} -benzoic and Rink resin</td><td> 425,5</td>

<td> 237</td><td>4- {5- [1- (2-Phenoxyacetyl) -piperazin-2yl] - [1,2,4] oxadiazole- 3-yl} -benzamide</td><td>3- [3- (4carboxy-phenyl) [1,2,4] oxadiazole-5yl] -4- (2-phenoxyacetyl) -piperazine-1carboxylic acid tert-butyl ester and Rink resin</td><td> 408,3</td>

<td> 238</td><td>(R) —5— {5 - [1- (2-Phenoxyacetyl) -piperidin-2yl] - [1,2,4] oxadiazol3-yl} -nicotinamide</td><td>(R) -5- {5- [1- (2-phenoxy-acetyl) piperidin-2-yl] [1,2,4] oxadiazol-3yl} -nicotinic acid and Rink resin</td><td> 408,5</td>

Example 239 (R) -1- {2- [3- (3-Amino-phenyl) - [1,2,4] oxadiazol-5-yl] piperidin-1-yl} -2-phenoxy-ethanone

(R) —1— {2— [3- (3-Nitro-phenyl) 5 [1,2,4] oxadiazol-5-yl] -piperidin-1-yl} -2-phenoxy-ethanone was dissolved in 100 ml of MeOH. 50 ml of NH was added₄Saturated C1 and Zn powder. The suspension was briefly heated to reflux and subjected to stirring for 30 minutes.

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After filtering the MeOH was evaporated and the product was isolated by means of ethyl acetate / water extraction.

MS (ISO): 379.5 (MH +)

Example 240 (R) - l- {2- [3- (4-Amino-phenyl) - [1,2,4] oxadiazol-5-yl] piperidin-1-i}} -2-phenoxy-ethanone

(R) —1— {2— [3— (4-nitro-phenyl) - [1.2.4] oxadiazol-5-yl] -piperidin-l-yl} -2-phenoxy-ethanone was dissolved in 100 ml of MeOH. 50 ml of NH was added₄Saturated C1 and Zn powder. The suspension was briefly heated to reflux and subjected to stirring for 30 minutes. After filtering, the MeOH was evaporated and the product isolated by means of ethyl acetate / water extraction.

MS (ISO): 379, 5 (MH +)

Example 241 (R) -1- {2- [5- (3-Amino-phenyl) -2H- [1,2,4] triazol-3-yl] piperidin-1-yl] -2-phenoxy-ethanone

(R) —1— {2— [3- (4-nitro-phenyl) - [1.2.4] triazol-3-yl] -piperidin-l-yl} -2-phenoxy-ethanone was dissolved in 100 ml of MeOH. 50 ml of NH was added₄Saturated C1 and Zn powder. The suspension was briefly heated to reflux and subjected to stirring for 30 minutes. After filtering, the MeOH was evaporated and the product isolated by means of ethyl acetate / water extraction.

MS (ISO): 378.5 (MH +)

Example 242

147/229 (R) -N- (3— {5— [1- (2-Phenoxy-acetyl) -piperidin-2-yl] - [1,2,4] oxadiazol-3-yl} -phenyl) - acetamide

(R) -l- {2- [3- (3Amino-phenyl) - [1,2,4] oxadiazol-5-yl] -piperidin-l-yl} -25 phenoxy ethanone 1 mmol was dissolved in THF . 2 equivalents of DIPEA were added. The reaction was cooled to 0 ° C. 1 equivalent of acetylchloride in THF was added dropwise and the reaction was subjected to stirring for 30 minutes. The product was isolated by stripping from ethyl acetate / water and subsequent purification by means of preparation HPLC.

MS (ISO): 421.5 (MH +)

The compounds shown below were generated by analogy using either acetyl chloride, mesyl chloride, chloroform acid allyl ester or ethylisocyanate as a reagent:

Table 6

<td>Example</td><td>Compound name</td><td>Starting materials</td><td>MH⁺We found auger</td>

<td> 243</td><td>(R) -N- (4- [5- [l- (2- Phenoxy-acetyl) piperidin-2-yl] [1,2,4] oxadiazol-3yl] -phenyl) -acetamide</td><td>(R) —1— {2— [3— (4-Amino- phenyl) - [1,2,4] oxadiazole-5- il] -piperidin-l-yl} -2phenoxy-ethanone and acetyl chloride</td><td> 421,5</td>

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<td>Example</td><td>Compound name</td><td>Starting materials</td><td>MH⁺We found auger</td>

<td> 244</td><td>(R) -N- (5- {5- [1- (2- Phenoxy-acetyl) piperidin-2-yl] - [1,2,4] oxadiazol-3yl} -pyridin-2-yl) acetamide</td><td>(R) —1 - {2 - [3- (6-Aminopyridin-3-yl) - [1,2,4] oxadiazole-5- il] -piperidin-l-yl} -2phenoxy-ethanone and acetyl chloride</td><td> 422,5</td>

<td> 245</td><td>(R) -N- (3- {5- [1- (2- Phenoxy-acetyl) piperidin-2-yl] -1H [1,2,4] triazol-3-yl} phenyl) -acetamide</td><td>(R) -1- {2- [5- (3-Aminophenyl) -2H- [1,2,4] triazol-3-yl] piperidin-l-yl} -2phenoxy-ethanone and acetyl chloride</td><td> 420,5</td>

<td> 246</td><td>(R) -N- (3- {5- [1- (2- Phenoxy-acetyl) piperidin-2-yl] [1,2,4] oxadiazol-3yl} -phenyl) methanesulfonamide</td><td>(R) -1- {2- [3- (3-Aminophenyl) - [1,2,4] oxadiazole-5- il] -piperidin-lil} -2 phenoxy-ethanone and mesyl chloride</td><td> 457,4</td>

<td> 247</td><td>(R) -N- (4- {5- [1- (2- Phenoxy-acetyl) piperidin-2-yl] [1,2,4] oxadiazol-3yl} -phenyl) -methanesulfonamide</td><td>(R) -l- {2- [3- (4-Amino- phenyl) - [1,2,4] oxadiazole-5- il] -piperidin-l-yl} -2phenoxy-ethanone and monthylchloride</td><td> 457,4</td>

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<td>Example</td><td>Compound name</td><td>Starting materials</td><td>MH⁺We found auger</td>

<td> 248</td><td>Allyl acid ester (R) - (3- {5- [l- (2- phenoxy-acetyl) piperidin-2-yl] [1,2,4] oxadiazol-3yl} -phenyl) -carbamic</td><td>Allyl acid ester (R) —1— [2— [3— (3-amino- phenyl) - [1,2,4] oxadiazole-5- il] -piperidin-lil} -2 phenoxy-ethanone</td><td> 463, 5</td>

<td> 249</td><td>Allyl acid ester (R) - (4- {5- [1- (2-phenoxy-acetyl) piperidin-2-yl] [1,2,4] oxadiazol-3yl} -phenyl) -carbamic</td><td>(R) -1- {2- [3- (4-Aminophenyl) - [1,2,4] oxadiazole-5- il] -piperidin-l-yl} -2-phenoxy-ethanone and allyl ester of chloroformic acid</td><td> 463,5</td>

<td> 250</td><td>(R) -N- (3- {5- [1- (2- Phenoxy-acetyl) piperidin-2-yl] -1H- [1,2,4] triazol-3-yl} - phenyl) - methanesulfonamide</td><td>(R) -l- {2- [5- (3-Amino- phenyl) -2H- [1,2,4] triazol-3-yl] piperidin-l-yl} -2phenoxy-ethanone and mesyl chloride</td><td> 456, 5</td>

<td> 251</td><td>(R) -l-Ethyl-3- (3- {5- [1- (2-phenoxy-acetyl) piperidin-2-yl] -1H- [1,2,4] triazol-3-yl} phenyl) -urea</td><td>(R) —1— {2— [5- (3-Aminophenyl) -2H- [1,2,4] triazol-3-yl] -piperidinl-yl] -2-phenoxy-ethanone and ethylisocyanate</td><td> 449,5</td>

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Example 252 (R) -3- {5- [1- (2-Phenoxy-acetyl) -piperidin-2-yl] -1H- [1.2.4] triazol-3-yl} -benzonitrile

(R) —3— {5— [1— (2—

Phenoxy-acetyl) -piperidin-2-yl] -1H- [1,2,4] triazol-3-yl} benzamide with pure trifluoroacetic anhydride at room temperature overnight. The reaction was quenched with aqueous NaHCO3 and the product extracted with ethyl acetate twice. The organic layers were washed with water / NaCl, combined, dried over Na2SO4 and the solvent evaporated. The product was purified by means of preparation HPLC.

MS (ISO): 388.5 (MH +)

Example 253 (R) -5- {5- [1- (2-Phenoxy-acetyl) -piperidin-2-yl] - [1.2.4] oxadiazol-3-yl} -nicotinonitrile

0.15 mmol of 5- {5- [1- (2-Phenoxyacetyl) -piperidin-2-yl] - [1,2,4] oxadíazole-3-yl} nicotinamide is treated with trifluoroacetic anhydride at room temperature during the night. The reaction was quenched with aqueous NaHCO3 and the product extracted with ethyl acetate twice. The organic layers were washed with water / NaCl, combined, subjected to drying over Na2SO4 and the solvent evaporated. The product was purified by means of preparation HPLC.

MS (ISO): 390.4 (MH +)

Example 254

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1-tert-Butyl ester of 4-acetyl-piperazine-1,2-bicarboxylic acid

10 mmol of 1-tert-butyl ester 2-methyl ester of piperazine-1,2-bicarboxylic acid were dissolved in 20 ml of methylene chloride. 1.05 equivalent of DIPEA and acetichloride was added. The reaction mixture was stirred at room temperature for 30 minutes. The product was extracted from ethyl acetate / water. The crude material was re-dissolved in methanol and treated with 2N NaOH. The reaction mixture was stirred at room temperature for 2 hours. The mixture was neutralized with HCl and the product isolated by means of extraction from ethyl acetate / water.

MS (ISO): 271.3 (M-H +)

Example 255

1-tert-Butyl ester of 4-methanesulfonyl-piperazine-1,2-bicarboxylic acid

10 mmol of 1-tert-butyl esters 20-piperazine-1,2-bicarboxylic acid 2-methyl ester were dissolved in 20 ml of methylene chloride. Then 1.05 equivalent of DIPEA and mesylchloride was added. The reaction mixture was stirred at room temperature for 30 minutes. The product was extracted at 25 ° C from ethyl acetate / water. The crude material was redissolved in methanol and treated with 2N NaOH. The reaction mixture was stirred at room temperature for 2 hours. The mixture was neutralized with

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HCI and the product isolated by extraction from ethyl acetate / water.

MS (ISO): 307.4 (M-H +)

Example 256

N-Hydroxy-4-sulfamoyl-benzamidine

1 mmol of 4-cyanobenzenesulfonamide is dissolved in a mixture of ethanol / water (7: 3) and 5 equivalents of hydroxylamine hydrochloride and 2.5 equivalents of Na2CO3 are added. The suspension was at 80 ° C for 2 hours. After evaporation of the solvent mixture, the resulting material is extracted from ethyl acetate / water. The product was no longer featured.

MS (ISO): 216.3 (MH +)

All of the following compounds were prepared by analogy:

Table 7

<td>Example</td><td>Compound name</td><td>Starting materials</td>

<td></td><td>3- Acid methyl ester</td><td>3- Acid methyl ester</td>

<td> 257</td><td>(N-hydroxy-</td><td>cyano-benzoic and hydro-</td>

<td></td><td>carbamimidoyl) -benzoic</td><td>xylamine</td>

<td></td><td>Ethyl ester of 4- (N-</td><td>Ethyl ester of 4- acid</td>

<td> 258</td><td>hydroxycarbamimidoyl) -</td><td>cyano-pyridine-2-</td>

<td></td><td>pyridine-2-carboxylic</td><td>carboxylic</td>

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<td>Example</td><td>Compound name</td><td>Starting materials</td>

<td> 259</td><td>3- Acid methyl ester fluoro-4- (N-hydroxycarbon- mimidoil) -benzoic</td><td>Methyl ester of 4-cyano-3-fluoro-benzoic acid</td>

<td> 260</td><td>N-Hydroxy-4-nitrobenzamidine</td><td>4-Nitro-benzonitrile and hydroxylamine</td>

<td> 261</td><td>N-Hydroxy-3-sulfamoyl- benzamidine</td><td>3-Cyano-benzenesulfone- mida and hydroxylamine</td>

<td> 262</td><td>N-Hydroxy-6-methoxy- nicotinamidine</td><td>6-Methoxy-nicotinonitrile and hydroxylamine</td>

<td> 263</td><td>N-Hydroxy-3-hydroxymethyl- benzamidine</td><td>3-Hydroxymethyl-benzoni- tryl and hydroxylamine</td>

<td> 264</td><td>N-Hydroxy-4-imidazole-l- il-benzamidine</td><td>4-Imidazol-1-yl-benzoni- tryl and hydroxylamine</td>

<td> 265</td><td>N-Hydroxy-6-morpholin-4- il-nicotinamidine</td><td>6-Morfolin-4-il- nicotine-nitrile and hy- droxylamine</td>

<td></td><td>N-Hydroxy-4-</td><td>4-Trifluoromethanesul-</td>

<td> 266</td><td>trifluoromethanesulfonyl-</td><td>fonyl-benzonitrile and hy-</td>

<td></td><td>benzamidine</td><td>droxylamine</td>

<td></td><td>N-Hydroxy-4-</td><td>4-Trifluoromethyl-</td>

<td> 267</td><td>trifluoromethyl-</td><td>benzonitrile and hydroxy-</td>

<td></td><td>benzamidine</td><td>blade</td>

<td> 268</td><td>4-Chlorine-N-hydroxy- benzamidine</td><td>4-Chloro-benzonitrile and hydroxylamine</td>

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<td>Example</td><td>Compound name</td><td>Starting materials</td>

<td></td><td>N- [4- (N-Hydroxycarbami-</td><td>N- (4-Cyano-2-trifluoro-</td>

<td> 269</td><td>midoyl) -2-trifluoromethyl-</td><td>romethyl-phenyl) -acetamide</td>

<td></td><td>phenyl] -acetamide</td><td>and hydroxylamine</td>

<td></td><td>N-Hydroxy-3-</td><td>3-Methanesulfonyl-</td>

<td> 270</td><td>methanesulfonyl-</td><td>benzonitrile and hydroxy-</td>

<td></td><td>benzamidine</td><td>blade</td>

<td> 271</td><td>N-Hydroxy-4-methyl-3- nitro-benzamidine</td><td>4-Methyl-3-nitro- benzonitrile and hydroxy- blade</td>

<td> 272</td><td>N-Hydroxy-4-methoxy-3- nitro-benzamidine</td><td>4-Methoxy-3-nitrobenzonitrile and hydroxylamine</td>

<td> 273</td><td>N-Hydroxy-2-oxo-1,2-dihydro-pyridine-4carboxamidine</td><td>2-Oxo-1,2-dihydro- pyridine-4-carbonitrile</td>

<td> 274</td><td>N-Hydroxy-6-oxo-1,6-dihydro-pyridine-3carboxamidine</td><td>6-Oxo-1,6-dihydro- pyridine-3-carbonitrile</td>

<td> 275</td><td>N-Hydroxy-4- (1H-tetrazole- 5-yl) -benzamidine</td><td>4- (1H-Tetrazol-5-yl) benzonitrile and hydroxylamine</td>

<td> 276</td><td>N-Hydroxy-1H-indazole-5- carboxamidine</td><td>lH-Indazol-5-carbonyl tryl and hydroxylamine</td>

<td> 277</td><td>N-Hydroxy-1H-indazole-6- carboxamidine</td><td>lH-Indazol-6-carbonyl tryl and hydroxylamine</td>

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<td>Example</td><td>Compound name</td><td>Starting materials</td>

<td></td><td>4-Fluoro-N-hydroxy-3-</td><td>4-Fluoro-3-trifluoro-</td>

<td> 278</td><td>trifluoromethyl-</td><td>methyl benzonitrile and</td>

<td></td><td>benzamidine</td><td>droxylamine</td>

<td></td><td>N-Hydroxy-2-oxo-2,3-</td><td>2-Oxo-2,3-dihydro-1H-</td>

<td> 279</td><td>dihydro-1H-indole-6-</td><td>indole-6-carbonitrile and</td>

<td></td><td>carboxamidine</td><td>hydroxylamine</td>

<td> 280</td><td>N-Hydroxy-2-oxo-2,3-dihydro-1H-benzoimidazole5-carboxamidine</td><td>2-Oxo-2,3-dihydro-1Hbenzoimidazole-5carbonitrile and hydroxylamine</td>

<td></td><td>N-Hydroxy-2-oxo-2,3-</td><td>2-Oxo-2,3-dihydro-1H-</td>

<td> 281</td><td>dihydro-1H-indole-5-</td><td>indole-5-carbonitrile and</td>

<td></td><td>carboxamidine</td><td>hydroxylamine</td>

<td> 282</td><td>N-Hydroxy-pyridine-2carboxamidine</td><td>Pyridine-2-carbonitrile and hydroxylamine</td>

<td> 283</td><td>N-Hydroxy-pyridine-3carboxamidine</td><td>Pyridine-3-carbonitrile and hydroxylamine</td>

<td> 284</td><td>4-Diethylamino-N-hydroxy- benzamidine</td><td>4-Diethylaminobenzonitrile and hydroxylamine</td>

<td></td><td>N- [4- (N-Hydroxycarbami-</td><td>N- (4-Cyano-2-trifluoro-</td>

<td> 285</td><td>midoyl) -2-trifluoromethyl-</td><td>romethyl-phenyl) -acetamide</td>

<td></td><td>phenyl] -acetamide</td><td>and hydroxylamine</td>

<td> 286</td><td>4-Chlorine-N-hydroxy-3- nitro-benzamidine</td><td>4-Chlorine-3-nitrobenzonitrile and hydroxylamine</td>

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<td>Example</td><td>Compound name</td><td>Starting materials</td>

<td> 287</td><td>N-Hydroxy-4-pyrrole-lil- benzamidine</td><td>4-Pyrrol-l-yl-benzoni- tryl and hydroxylamine</td>

<td> 288</td><td>2,4-Dichloro-N-hydroxy- benzamidine</td><td>2,4-Dichloro-benzonitrile and hydroxylamine</td>

<td></td><td>N-Hydroxy-3- (2-oxo-</td><td>3- (2-0xo-piperidin-l-</td>

<td> 289</td><td>piperidin-l-yl) -</td><td>il) -benzonitrile and hy-</td>

<td></td><td>benzamidine</td><td>droxylamine</td>

<td> 290</td><td>N-Hydroxy-1H-benzoimide- zol-5-carboxamidine</td><td>1H-Benzoimidazole-5- carbonitrile</td>

<td></td><td>Allyl ester of 6- (N-</td><td>6- Allyl acid ester</td>

<td> 291</td><td>hydroxy-carbamimidoyl) -</td><td>cyano-nicotinic and hy-</td>

<td></td><td>nicotinic</td><td>droxylamine</td>

<td> 292</td><td>Ethyl ester of 4- (Nhydroxycarbamimidoyl) pyridine-2-carboxylic acid</td><td>Ethyl ester of 4 cyano-pyridine-2-carboxylic acid and hydroxylamine</td>

<td> 293</td><td>3-Fluoro-4- (Nhydroxycarbamimidoyl) benzoic acid methyl ester</td><td>Methyl ester of 4-cyano-3-fluoro-benzoic acid and hydroxylamine</td>

<td> 294</td><td>N-Hydroxy-1H-benzotria- zol-5-carboxamidine</td><td>1H-Benzotriazole-5- carbonitrile</td>

<td> 294</td><td>6-Benzyloxy-N-hydroxy- nicotinamidine</td><td>6-Benzyloxy nicotinonitrile</td>

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<td>Example</td><td>Compound name</td><td>Starting materials</td>

<td> 295</td><td>N- [5- (N- Hydroxycarbamimidoil) - pyridin-2-yl] -acetamide</td><td>N- (5-Cyano-pyridin-2- il) -acetamide</td>

<td> 296</td><td>N- [4- (N- Hydroxycarbamimidoil) - pyridin-2-yl] -acetamide</td><td>N- (4-Cyano-pyridin-2- il) -acetamide</td>

Example 297

N-Hydroxy-4-methylsulfamoyl-benzamidine

5 mmol of 4-cyano-benzenesulfonyl chloride was dissolved in 10 ml of THF. Five 10 ml of a 2M methylamine / THF solution was added dropwise.

The reaction was subjected to stirring at room temperature overnight. The solvent was evaporated and the product extracted from ethyl acetate / water. The nitrile obtained was treated in a manner similar to the E10 example 231.

MS (ISO): 230.5 (MH +)

All of the following compounds were prepared by analogy:

Table 8

<td>Example</td><td>Compound name</td><td>Starting materials</td>

<td> 298</td><td>N-Hydroxy-4- (morpholine-4- sulfonyl) -benzamidine</td><td>4-Cyanobenzenesulfonyl chloride and morpholine</td>

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<td>Example</td><td>Compound name</td><td>Starting materials</td>

<td> 299</td><td>N-Hydroxy-4- (2-hydroxy- ethylsulfamoyl) -benzamidine</td><td>4-Cyanobenzenesulfonyl chloride and ethanolamine</td>

<td></td><td>N-Hydroxy-4 - [(2-methoxy-</td><td>4-cyano- chloride</td>

<td> 300</td><td>ethyl) -methyl-sulfamoyl] -</td><td>benzenesulfonyl and (2-</td>

<td></td><td>benzamidine</td><td>Methoxy-ethyl) -methylamine</td>

<td> 301</td><td>4-Dimethylsulfamoyl-N- hydroxy-benzamidine</td><td>4-Cyanobenzenesulfonyl chloride and dimethylamine</td>

<td> 302</td><td>4-Diethylsulfamoyl-N- hydroxy-benzamidine</td><td>4-Cyano-benzenesulfonyl chloride and diethylamine</td>

Example 303

6- (1,1-Dioxo-thiomorfolin-4-yl) -N-hydroxy-nicotinamidine

10 mmol of 6-Cl-4-CN-pyridine are dissolved in 10 ml of DMF. 20 mmol of morpholine are added and the reaction is heated to 120 ° C under microwave conditions for 20 minutes. The DMF is evaporated and the crude extracted from ethyl acetate / water. After evaporation the resulting solid was treated with 30 mmol of meta-chloroperbenzoic acid in DCM at room temperature overnight and the resulting precipitate removed by filtration and recrystallized from MeOH. The obtained nitrile was treated in a manner analogous to example 231.

MS (ISO): 271.5 (MH +)

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The following compounds were prepared in analogy.

Table 9

<td>Example</td><td>Compound name</td><td>Starting materials</td>

<td> 304</td><td>N-Hydroxy-2-morpholin-4- il-isonicotinamidine</td><td>2-Chlorisonicotinonitrile and morpholin</td>

<td> 305</td><td>N-Hydroxy-3,4,5,6tetrahydro-2H- [1,2 '] bipyridinyl-4' - carboxamidine</td><td>2-Chlorisonicotinonitrile and piperidine</td>

<td> 306</td><td>N-Hydroxy-2- tiomorfolin-4-il- isonicotinamidine</td><td>2-Chlorisonicotinonitrile and tiomorfolin</td>

<td> 307</td><td>2-Diethylamino-N- hydroxy- isonicotinamidine</td><td>2-Chlorisonicotinonitrile and diethylamine</td>

<td> 308</td><td>N-Hydroxy-6- (3-oxo- piperazin-l-il) - nicotinamidine</td><td>2-Chloronicotinonitrile and Piperazin-2-one</td>

<td> 309</td><td>6- (4-Acetyl-piperazin- 1-yl) -N-hydroxy- nicotinamidine</td><td>2-Chloronicotinonitrile and 1- acetylpiperazine</td>

<td> 310</td><td>N-Hydroxy-6- (3hydroxymethylpyrrolidin-1-yl) nicotinamidine</td><td>2-Chloronicotinonitrile and Pyrrolidin-3-yl-methanol</td>

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<td>Example</td><td>Compound name</td><td>Starting materials</td>

<td> 311</td><td>N-Hydroxy-6-morpholin-4- il-nicotinamidine</td><td>2-Chloronicotinonitrile and morpholine</td>

Example 312

4-Fluoro-N-amino-benzamidine hydrochloride

82 mmol of methyl ester of 3-cyano-benzoic acid were dissolved in 50 ml of a solution of HCl-saturated methylene chloride and 50 ml of methanol. Under refrigeration from an ice bath, HCI gas was bubbled through the solution to maintain the temperature under 20 ° C. The reaction mixture was stirred overnight at room temperature. 10 100 ml of diethyl ether was added and the resulting solid filtered off, washed with diethyl ether and subjected to vacuum drying. 0 The resulting imido-ether was extracted from ethyl acetate / aqueous sodium bicarbonate to result in an oily residue. This was collected in 15 ml of methanol and treated with 1 ml of hydrazine monohydrate at room temperature overnight. The solution was added slowly to a cold 4N HCl / dioxane solution. 80 ml of diethyl ether were added and the suspension was stirred at room temperature 20 ° C for 30 minutes. The solid was removed by filtration and washed with diethyl ether and subjected to vacuum drying. The product has been confirmed by MS.

MS (ISO): 194.4 (MH +)

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The following compounds were prepared in analogy:

Table 10

<td>Example</td><td>Compound name</td><td>Starting materials</td>

<td></td><td>4-fluoro-N- hydrochloride</td><td>4-Flu.oro-3-</td>

<td> 313</td><td>amino-3-trifluoromethyl-</td><td>trifluoromethyl-</td>

<td></td><td>benzamidine</td><td>benzonitrile and hydrazine</td>

<td> 314</td><td>N-Amino-4-methanesulfonylbenzamidine hydrochloride</td><td>4-Methanesulfonyl- benzonitrile and hydrazine</td>

<td> 315</td><td>N-amino-3- hydrochloride trifluoromethyl- benzamidine</td><td>m-Trifluoromethyl- benzonitrile and hydrazine</td>

<td> 316</td><td>N-Amino-4- Hydrochloride methyl benzamidine</td><td>p-Tolunitril and hydrazine</td>

<td> 317</td><td>N-Amino-4- Hydrochloride trifluoromethyl- benzamidine</td><td>p-Trifluoromethyl- benzonitrile and hydrazine</td>

<td> 318</td><td>N-Amino-4- Hydrochloride methoxy-benzamidine</td><td>4-Methoxybenzonitrile and hydrazine</td>

<td> 319</td><td>N-amino- hydrochloride 2,4-difluoro-benzamidine</td><td>2,4-Difluorobenzonitrile and hydrazine</td>

<td> 320</td><td>N-amino- hydrochloride 3,4-dimethoxy-benzamidine</td><td>3,4-Dimetoxybenzonitrile and hydrazine</td>

<td> 321</td><td>N-amino- hydrochloride 3,4-dichloro-benzamidine</td><td>3,4-Dichlorobenzonitrile and hydrazine</td>

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<td>Example</td><td>Compound name</td><td>Starting materials</td>

<td> 322</td><td>N-aminobenzamidine hydrochloride</td><td>Benzonitrile and hydrazine</td>

<td> 323</td><td>N-Amino-3- Hydrochloride Nitro-benzamidine</td><td>3-Nitrobenzonitrile and drazina</td>

<td> 324</td><td>N-Amino-3- Hydrochloride methylester-benzamidine</td><td>Methyl ester of 3-cyano-benzoic acid and hydrazine</td>

<td> 325</td><td>N-Amino-2-oxo-2,3-dihydro- lH-indole-6-carboxamidine</td><td>2-Oxo-2,3-dihydro-1Hindole-6-carbonitrile and hydrazine</td>

<td> 326</td><td>N-Amino-2-fluoro-benzamidine hydrochloride</td><td>2-Fluorobenzonitrile and hydrazine</td>

Example 327

Allyl ester of 6-cyano-nicotinic acid

4 mmol of 65 cyanonicotinic acid were dissolved in THF. 1.5 equivalents of Cs2CO3 were added and the reaction was stirred for 10 minutes. 1.5 equivalents of allylbromide and a catalytic amount of K1 were added and the reaction was heated to 100 ° C for 4 hours. Product 10 was isolated by extraction from ethyl acetate / water.

MS (ISO): 222.5 (MH +)

Example 328 1H-Benzotriazole-5-carbonitrile

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10 mmol of 3,4-diamine benzonitrile was suspended in water / acetic acid (4: 1) and cooled to 0 ° C. 1.05 NaNO equivalents were dissolved₂ in water and inert 30 minutes were added. The reaction was subjected to stirring at room temperature overnight. The precipitate was filtered off, washed with ether and dried under vacuum. The intermediate was no longer characterized.

Example 329

6-Benzyloxy-nicotinonitrile

20 mmol of 6-chloronicotinonitrile were dissolved in THF. 1.1 equivalents of benzyl alcohol were added. The reaction mixture was cooled to 0 ° C and washed with argon. 4 equivalents of NaH were added slowly. After 15 minutes the product was isolated by means of extraction from ethyl acetate / water.

MS (ISO): 211.5 (MH +)

Example 330

N- (5-Cyano-pyridin-2-yl) -acetamide

8 mmol of 6-aminonicotinonitrile were dissolved in THF. 2 equivalents of DIPEA were added. The reaction mixture was cooled to 0 ° C and 1.0 equivalent of acetylchloride in THF was added dropwise and the reaction stirred for hours. The product was isolated by extraction from ethyl acetate / water.

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MS (ISO): 162.2 (MH +)

Example 331

N- (4-Cyano-pyridin-2-yl) -acetamide

8 mmol of 2-amino5 isonicotinonitrile were dissolved in THF. 2 equivalents of DIPEA were added. The reaction mixture was cooled to 0 ° C and 1.0 equivalent of acetylchloride in THF was added dropwise and the reaction was stirred for 2 hours. The product was isolated by extraction 10 from ethyl acetate / water.

MS (ISO): 162.2 (MH +)

The following compounds were generated in analogy to example 1:

<td>Example</td><td>Compound Name</td><td>Starting materials</td><td>MH + en- con auger</td>

<td> 332</td><td>1- {2- [3- (2-Methyl-1Hbenzoimidazol-5-yl) [1,2,4] oxadiazol-5yl] -piperidin-l-yl} - 2- phenoxy-ethanone</td><td>Boc-DPipecolic acid, NHhydroxy-2-methyl-1Hbenzoimidazole-5carboxamidine and phenoxyacetyl chloride</td><td> 418,5</td>

<td> 333</td><td>1— {2— [3- (2-Aminopyridin-4-yl) [1,2,4] oxadiazol-5yl] -piperidin-l-yl} - 2- phenoxy-ethanone</td><td>Boc-D- Acid Pipecolic, 2-Amino- N-hydroxyisonicotinamidine and phenoxyacetic acid</td><td> 380, 5</td>

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<td>Example</td><td>Compound Name</td><td>Starting materials</td><td>MH + en- con auger</td>

<td> 334</td><td>1— {2— [3- (3-Hydroxyphenyl) - [1,2,4] oxadiazol-5yl] -piperidin-l-yl} - 2- phenoxy-ethanone</td><td>Boc-D- Acid Pipecolic, 3-NDhydroxy-benzamidine and phenoxyacetic acid</td><td> 380,5</td>

<td> 335</td><td>4- {5- [1- (2-Phenoxyacetyl) -piperidin-2yl] - [1,2,4] oxadiazol3-yl} -1H-pyridin-2one</td><td>Boc-D- Acid Pipecolic, 2, N- Dihydroxyisonicotinamidine and phenoxyacetyl chloride</td><td> 381,4</td>

<td> 336</td><td>1— {2— [3- (4-Hydroxyphenyl) - [1,2,4] oxadiazol-5yl] -piperidin-l-yl} - 2- phenoxy-ethanone</td><td>Boc-D- Acid Pipecolic, 4-NDhydroxy-benzamidine and phenoxyacetic acid</td><td> 379, 6</td>

<td> 337</td><td>Acid 3- {5- [l- (2- phenoxy-acetyl) piperidin-2-yl] [1,2,4] oxadiazol-3yl} -phenylboronic</td><td>Boc-DPipecolic acid, 3- (NHidroxicarbamidoil) phenylboronic and phenoxyacetyl chloride</td><td> 407,7</td>

<td> 338</td><td>4- (2-Oxo-2- {2- [3- (2oxo-2,3-dihydro-1Hindol-5-yl) - [1,2,4] oxadiazol-5yl] -piperidin-1-yl} ethoxy) -benzonitrile</td><td>Boc-DPipecolic acid, NHhydroxy-2-oxo-2,3-dihydro-1H-indole-5carboxamidine and 4-cyano phenoxyacetic acid</td><td> 443,7</td>

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<td>Example- plo</td><td>Compound Name</td><td>Starting materials</td><td>MH + en- con auger</td>

<td> 339</td><td>4— (2— {2— [3— (4-Methoxyphenyl) - [1,2,4] oxadiazol-5yl] -piperidin-1-yl} 2-oxo-ethoxy) benzonitrile</td><td>Boc-D- Acid Pipecolic, N- Hydroxy-4-methoxybenzamidine and 4-cyano phenoxyacetic acid</td><td> 419,3</td>

<td> 340</td><td>2-Methyl-5- {5- [1- (2fenoxi-acetyl) -piperidin-2-yl] [1,2,4] oxadiazol-3-yl} -3H-pirim IDIN-4-one</td><td>Boc-DPipecolic acid, 4, NDhydroxy-2-methylpyrimidine-5carboxamidine and phenoxyacetyl chloride</td><td> 396,2</td>

<td> 341</td><td>1 - [(R) -2- (3-Furan-2- il- [1,2,4] oxadiazole- 5-yl) -piperidin-l- il] -2-phenoxy-ethanone</td><td>Boc-DPipecolic acid, NHhydroxy-furan-2carboxamidine and phenoxyacetyl chloride</td><td> 354,2</td>

<td> 342</td><td>1- [(R) -2- (3- Imidazo [1,2- a] pyridin-2-yl- [1,2,4] oxadiazol-5yl) -piperidin-1-yl] - 2- phenoxy-ethanone</td><td>Boc-D- Acid Pipecolic, N- Hydroxy-imidazo [1,2a] pyridine-2carboxamidine and phenoxyacetyl chloride</td><td> 404,2</td>

<td> 343</td><td>l - {(R) -2- [3- (4-Methyl- [1,2,3] thiadiazole-5- il) - [1,2,4] oxadiazole- 5-yl] -piperidin-l- il} -2-phenoxy-ethanone</td><td>Boc-DPipecolic acid, NHhydroxy-4-methyl [1,2,3] thiadiazole-5carboxamidine and phenoxyacetyl chloride</td><td> 386,2</td>

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<td>Example- plo</td><td>Compound Name</td><td>Starting materials</td><td>MH + en- con auger</td>

<td> 344</td><td>l - {(R) -2- [3- (2,5Dimethyl-2H-pyrazol-3- il) - [1,2,4] oxadiazole- 5-yl] -piperidin-l- il} -2-phenoxy-ethanone</td><td>Boc-DPipecolic Acid, N- Hydroxy-2,5-dimethyl2H-pyrazol-3carboxamidine and phenoxyacetyl chloride</td><td> 382,2</td>

<td> 345</td><td>2-Phenoxy-l - {(R) -2- [3 (1H-pyrazol-4-yl) [1,2,4] oxadiazol-5yl] -piperidin-l-yl} ethanone</td><td>Boc-D- Acid Pipecolic, N- Hydroxy-1H-pyrazol-4carboxamidine and phenoxyacetyl chloride</td><td> 354,2</td>

<td> 346</td><td>1- {(R) -2- [3- (5-Methylisoxazol-3-yl) [1,2,4] oxadiazol-5yl] -piperidin-l-yl} - 2- phenoxy-ethanone</td><td>Boc-DPipecolic Acid, N- Hydroxy-5-methylisoxazole-3carboxamidine and phenoxyacetyl chloride</td><td> 369, 2</td>

<td> 347</td><td>2-Phenoxy-1 - {(R) -2- [3- (lH-pyrazol-3-yl) [1,2,4] oxadiazol-5yl] -piperidin-l-yl} ethanone</td><td>Boc-DPipecolic acid, NHhydroxy-1H-pyrazol-3carboxamidine and phenoxyacetyl chloride</td><td> 354,2</td>

<td> 348</td><td>5- {5 - [(R) -1- (2- Phenoxy-acetyl) piperidin-2-yl] [1,2,4] oxadiazol-3yl} -1H-pyrimidine- 2,4-dione</td><td>Boc-D- Acid Pipecolic, 2,4, NTrihydroxy-pyrimidine5-carboxamidine and phenoxyacetyl chloride</td><td> 398,2</td>

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<td>Example- plo</td><td>Compound Name</td><td>Starting materials</td><td>MH + found</td>

<td> 349</td><td>1— {(R) -2- [3- (6-Aminopyridin-3-yl) [1,2,4] oxadiazol-5yl] -piperidin-l-yl} - 2- phenoxy-ethanone</td><td>Boc-D- Acid Pipecolic, 6-Amino- N-hydroxynicotinamidine and phenoxyacetyl chloride</td><td> 380,5</td>

<td> 350</td><td>1- [(R) -2- (3- Imidazo [1,2- a] pyridin-6-il- [1,2,4] oxadiazol-5yl) -piperidin-1-yl] - 2- phenoxy-ethanone</td><td>Boc-DPipecolic Acid, N- Hydroxy-imidazo [1,2— a] pyridine-6carboxamidine and phenoxyacetyl chloride</td><td> 404,2</td>

<td> 351</td><td>6- {5 - [(R) -1- (2- Phenoxy-acetyl) piperidin-2-yl] [1,2,4] oxadiazol-3yl} -4H- benzo [1,4] oxazin-3one</td><td>Boc-DPipecolic Acid, N- Hydroxy-3-oxo-3,4dihydro-2H- benzo [1,4] oxazine-6carboxamidine and phenoxyacetyl chloride</td><td> 435,2</td>

<td> 352</td><td>6- {5 - [(R) -l- (2- Phenoxy-acetyl) piperidin-2-yl] [1,2,4] oxadiazol-3yl} -1,4-dihydrobenzo [d] [1,3] oxazin-2 one</td><td>Boc-DPipecolic acid, NHhydroxy-2-oxo-1,4-hydroxy-2Hbenzo [d] [1,3] oxazine6-carboxamidine and phenoxyacetyl chloride</td><td> 435,2</td>

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<td>Example</td><td>Compound Name</td><td>Starting materials</td><td>MH + found</td>

<td> 353</td><td>1- ((R) -2- {3- [3- (1,1DIOXO-1À6isothiazolidin-2-yl) phenyl] - [1,2,4] oxadiazol-5yl} -piperidin-1-yl) - 2- phenoxy-ethanone</td><td>Boc-D- Acid Pipecolic, 3- (1,1- Dioxo-ΐλβisothiazolidin-2-yl) N-hydroxy-benzamidine and phenoxyacetyl chloride</td><td> 483, 3</td>

<td> 354</td><td>1— (3— {5— [(R) -l- (2- Phenoxy-acetyl) piperidin-2-yl] [1,2,4] oxadiazol-3yl} -phenyl) pyrrolidin-2-one</td><td>Boc-D- Acid Pipecolic, NHidroxy-3- (2-oxopyrrolidin-1-yl) benzamidine and phenoxyacetyl chloride</td><td> 447,3</td>

<td> 355</td><td>1- (3- {5 - [(R) -l- (2- Phenoxy-acetyl) piperidin-2-yl] [1,2,4] oxadiazol-3yl} -phenyl) imidazolidine-2,4dione</td><td>Boc-D- Acid Pipecolic, 3- (2,4- Dioxo-imidazolidin-1yl) -N-hydroxybenzamidine and phenoxyacetyl chloride</td><td> 462,5</td>

<td> 356</td><td>4- (3- {5 - [(R) -1- (2- Phenoxy-acetyl) piperidin-2-yl] - [1.2.4] oxadiazol-3yl} -phenyl) -2,4 dihydro- [1.2.4] triazole-3-one</td><td>Boc-D- Acid Pipecolic, N- Hydroxy-3- (5-oxo-1,5, 5-hydro- [1,2,4] triazol-4-yl) benzamidine and phenoxyacetyl chloride</td><td> 447,5</td>

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<td>Example</td><td>Compound Name</td><td>Starting materials</td><td>MH + en- con auger</td>

<td> 357</td><td>1- (3-Fluoro-5- {5- [(R) -1- (2-phenoxyacetyl) -piperidin-2yl] - [1,2,4] oxadiazol3-yl} -phenyl) pyrrolidine-2,5-dione</td><td>Boc-DPipecolic Acid, 3- (2,5Dioxo-pyrrolidin-1- il) -5-fluoro-Nhydroxy-benzamidine and phenoxyacetyl chloride</td><td> 479,2</td>

<td> 358</td><td>5- {5 - [(R) -1- (2- Phenoxy-acetyl) piperidin-2-yl] -1H- [1,2,4] triazol-3-yl} - 1,3-dihydro-indole-2one</td><td>Boc-DPipecolic Acid, N-Amino2-Oxo-2,3-dihydro-1Hindol-5-carboxamidine and phenoxyacetic acid</td><td> 418,5</td>

<td> 359</td><td>l - {(R) -2- [5- (1H- Indazol-5-yl) -2H [1,2,4] triazol-3-yl] piperidin-l-yl} -2phenoxy-ethanone</td><td>Boc-D- Acid Pipecolic, N-Amino- 1H-Indazole-5- carboxamidine and acid phenoxyacetic</td><td> 403,5</td>

<td> 360</td><td>l - {(R) -2- [5- (lH- Indol-5-yl) -2H- [1,2,4] triazol-3-yl] piperidin-l-yl} -2phenoxy-ethanone</td><td>Boc-D- Acid Pipecolic, N-AminolH-Indole-5carboxamidine and phenoxyacetic acid</td><td> 402,5</td>

<td> 361</td><td>1- {(R) -2- [5- (3HBenzotriazol-5-yl) 2H- [1,2,4] triazol-3yl] -piperidin-l-yl} - 2- phenoxy-ethanone</td><td>Boc-D- Acid Pipecolic, N-Amino3H-Benzotriazole-5carboxamidine and phenoxyacetic acid</td><td>402.5 (M-H +)</td>

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<td>Example- plo</td><td>Compound Name</td><td>Starting materials</td><td>MH + en- con auger</td>

<td> 362</td><td>5- {5- [(R) —1— (2— Phenoxy-acetyl) piperidin-2-yl] -1H [1,2,4] triazol-3-yl} - 1,3-dihydrobenzoimidazole-2-one</td><td>Boc-DPipecolic acid, N-Amino2-Oxo-2,3-dihydro-1Hbenzoimidazole-5carboxamidine and phenoxyacetic acid</td><td> 419, 5</td>

<td> 363</td><td>l- {(R) -2- [5- (2-Methyl- 1H-benzoimidazole-5- il) -2H- [1,2,4] triazol-3-yl] piperidin-l-yl} -2phenoxy-ethanone</td><td>Boc-DPipecolic Acid, N-Amino- 2-Methyl-1Hbenzoimidazole-5carboxamidine and phenoxyacetic acid</td><td> 417,5</td>

<td> 364</td><td>1 - {(R) -2- [5- (2-Aminopyridin-4-yl) -2H- [1,2,4] triazol-3-yl] piperidin-l-yl} -2phenoxy-ethanone</td><td>Boc-D- Acid Pipecolic, N-Amino- 2-Aminoisonicotinamidine and phenoxyacetic acid</td><td> 379, 5</td>

<td> 365</td><td>5- (3- {5 - [(R) -1- (2- Phenoxy-acetyl) piperidin-2-yl] -1H- [1.2.4] triazol-3-yl} phenyl) -3H- [1.3.4] oxadiazole-2- ona</td><td>Boc-D- Acid Pipecolic, N-Amino3- (5-Oxo-4,5-dihydro [1,3,4] oxadiazol-2yl) -benzamidine and phenoxyacetic acid</td><td> 446, 7</td>

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<td>Example</td><td>Compound Name</td><td>Starting materials</td><td>MH + found</td>

<td> 366</td><td>l - {(R) -2- [5- (3- [1.3.4] Oxadíazol-2yl-phenyl) -2H- [1.2.4] triazol-3-yl] piperidin-l-yl} -2- phenoxyethanone</td><td>Boc-DPipecolic Acid, N-Amino3- [1,3,4] Oxadiazol-2yl-benzamidine and phenoxyacetic acid</td><td> 430,7</td>

<td> 367</td><td>Acid 3— {5— [l— (2— phenoxy-acetyl) piperidin-2-yl] -1H [1,2,4] triazol-3-yl} phenylboronic</td><td>Boc-D- Acid Pipecolic acid, NAmino-3-Carbamidoylphenylboronic acid and phenoxyacetic acid</td><td> 407,5</td>

Example 368:

6- {5- [(R) -1- (2-Phenoxy-acetyl) -piperidin-2-yl] -1H [1,2,4] triazol-3-yl} -4H-benzo [1,4] oxazin-3-one

Step 1:

2-hydrazinocarbonylpiperidine-1-carboxylic acid tert-butyl ester

3g of (R) -Piperidine-1,2-dicarboxylic acid 1-tert-butyl ester were dissolved in 30 ml of DMF. 5 g of HATU and 2.2 ml of DIPEA were added and the reaction mixture was cooled to 0 ° C. 4 equivalents of hydrazine monohydrate in 30 ml of DMF were added and the reaction was warmed to room temperature and stirred for 1 hour. The crude product was extracted from ethyl acetate / aqueous NaHC03.

MS (ISO): 244.3 (MH +)

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Step 2:

6- (5-Piperidin-2-yl-1H- [1,2,4] triazol-3-yl) -4Hbenzo [1,4] oxazin-3-one

1.5 mmol of 2-hydrazinocarbonyl-piperidine-1-carboxylic acid tert-butyl 5 ester was dissolved in 3 ml of DMF. 1 equivalent of 3-oxo-3,4-dihydro-2H-benzo [1,4] oxazine-6-carboxamidine and 90 µl of acetic acid were added and the reaction mixture was heated to 120 ° C overnight. The solvent was evaporated and the crude extracted from ethyl acetate / water.

The resulting oil was collected in 15 ml of DCM and treated with 3 ml of TFA. The reaction mixture was reduced to dryness.

Step 3:

6- {5- [(R) -1- (2-Phenoxy-acetyl) -piperidin-2-yl] -1H [1,2,4] triazol-3-yl} -4H-benzo [1,4] oxazin-3-one

The crude product from step 3 was collected in DMF and cooled to 0 ° C. 4 equivalents of DIPEA and 1 equivalent of phenoxyacetyl chloride 20 were added dropwise and the reaction mixture was warmed to room temperature and subjected to stirring for an additional 30 minutes. The product was isolated by means of preparation HPLC.

The following compounds were generated in analogy to example 368

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<td>Example</td><td>Compound name</td><td>Starting materials</td><td>MH + found</td>

<td> 369</td><td>l - [(R) -2- (5- Imidazo [1,2- a] pyridin-6-yl-2H- [1,2,4] triazol-3-yl) piperidin-l-yl] -2phenoxy-ethanone</td><td>Boc-D- Acid Pipecolic, Imidazo [1,2-a] pyridine-6carboxamidine and phenoxyacetic acid</td><td> 443,7</td>

<td> 370</td><td>1 - {(R) -2- [5- (6-Aminopyridin-3-yl) -2H [1,2,4] triazol-3-yl] piperidin-l-yl} -2phenoxy-ethanone</td><td>Boc-D- Acid Pipecolic, 6-Aminonicotinamidinaand phenoxyacetic acid</td><td> 379, 1</td>

<td> 371</td><td>1- {(R) -2- [5- (1H- Benzoimidazol-5-yl) 2H- [1,2,4] triazol-3yl] -piperidin-l-yl} - 2- phenoxy-ethanone</td><td>Boc-D- Acid Pipecolic, 1HBenzoimidazole-5carboxamidine and phenoxyacetic acid</td><td> 403,2</td>

<td> 372</td><td>2-Phenoxy-1 - [(R) -2- (5pyridin-3-yl-2H- [1,2,4] triazol-3-yl) piperidin-1-yl] ethanone</td><td>Boc-D- Acid Pipecolic, Nicotinamidine and phenoxyacetic acid</td><td> 364,2</td>

<td> 373</td><td>l - {(R) -2- [5- (3,5- Dimethyl-isoxazole-4- il) -2H- [1,2,4] triazol-3-yl] piperidin-l-yl} -2phenoxy-ethanone</td><td>Boc-D- Acid Pipecolic, 3,5Dimethyl-isoxazole-4carboxamidine and phenoxyacetic acid</td><td> 382,2</td>

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<td>Example</td><td>Compound name</td><td>Starting materials</td><td>MH + found</td>

<td> 374</td><td>2-Phenoxy-1 - [(R) -2- (5- thiophen-2-yl-2H [1,2,4] triazol-3-yl) piperidin-1-yl] ethanone</td><td>Boc-D- Acid Pipecolic, Thiophene- 2-carboxamidine and phenoxyacetic acid</td><td> 369, 1</td>

<td> 375</td><td>2-Phenoxy-1 - [(R) -2- (5pyrimidin-2-yl-2H [1,2,4] triazol-3-yl) piperidin-1-yl] ethanone</td><td>Boc-D- Acid Pipecolic, Pyrimidine-2-carboxamidine and phenoxyacetic acid</td><td> 365,1</td>

<td> 376</td><td>l - {(R) -2- [5- (4-Methyloxazol-5-yl) -2H- [1,2,4] triazol-3-yl] piperidin-l-yl} -2phenoxy-ethanone</td><td>Boc-D- Acid Pipecolic, 4-Methyloxazol-5carboxamidine and phenoxyacetic acid</td><td> 368,1</td>

<td> 377</td><td>2-Phenoxy-1 - [(R) -2- (5pyrazin-2-yl-2H- [1,2,4] triazol-3-yl) piperidin-1-yl] ethanone</td><td>Boc-DPipecolic Acid, Pyrazine2-carboxamidine and phenoxyacetic acid</td><td> 365, 1</td>

<td> 378</td><td>l - {(R) -2- [5- (2- Fluoro-phenyl) -2H [1,2,4] triazol-3-yl] piperidin-l-yl} -2phenoxy-ethanone</td><td>Boc-D- Acid Pipecolic, 2-Fluorobenzamidine and phenoxyacetic acid</td><td> 381,1</td>

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<td>Example</td><td>Compound name</td><td>Starting materials</td><td>MH + found</td>

<td> 379</td><td>l - {(R) -2- [5- (3,5- Difluoro-phenyl) -2H- [1,2,4] triazol-3-yl] piperidin-l-yl} -2phenoxy-ethanone</td><td>Boc-D- Acid Pipecolic, 3.5- Difluoro-benzamidine and phenoxyacetic acid</td><td> 399,1</td>

<td> 380</td><td>l - {(R) -2- [5- (2-Methylpyridin-4-yl) -2H- [1,2,4] triazol-3-yl] piperidin-l-yl} -2phenoxy-ethanone</td><td>Boc-D- Acid Pipecolic, 2-Methylisonicotinamidine and phenoxyacetic acid</td><td> 378,1</td>

<td> 381</td><td>l- {(R) -2- [5- (3- Fluoro-phenyl) -2H [1,2,4] triazol-3-yl] piperidin-l-yl} -2phenoxy-ethanone</td><td>Boc-D- Acid Pipecolic, 3-Fluorobenzamidine and phenoxyacetic acid</td><td> 381,1</td>

<td> 382</td><td>l - {(R) -2- [5- (3,4- Difluoro-phenyl) -2H [1,2,4] triazol-3-yl] piperidin-l-yl} -2phenoxy-ethanone</td><td>Boc-D- Acid Pipecolic, 3,4- Difluoro-benzamidine and phenoxyacetic acid</td><td> 399, 1</td>

<td> 383</td><td>6- {5 - [(R) -1- (2- Phenoxy-acetyl) piperidin-2-yl] -1H- [1,2,4] triazol-3-yl} - 1,4-dihydrobenzo [d] [1,3] oxazin2-one</td><td>Boc-D- Acid Pipecolic, 2-Oxo- 1,4-dihydro-2Hbenzo [d] [1,3] oxazine6-carboxamidine and phenoxyacetic acid</td><td> 434,5</td>

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<td>Example</td><td>Compound name</td><td>Starting materials</td><td>MH + found</td>

<td> 384</td><td>7— {5 - [(R) -1- (2- Phenoxy-acetyl) piperidin-2-yl] -1H- [1,2,4] triazol-3-yl} - 3,4-dihydro-1Hquinazolin-2-one</td><td>Boc-D- Acid Pipecolic, 2-0xo1,2,3,4-tetrahydroquinazoline-7carboxamidine and phenoxyacetic acid</td><td> 433,5</td>

<td> 385</td><td>1- (3- {5 - [(R) -l- (2- Phenoxy-acetyl) piperidin-2-yl] -1H- [1,2,4] triazol-3-yl} phenyl) -imidazolidine2,4-dione</td><td>Boc-DPipecolic acid, 3- (2,4Dioxo-imidazolidin-1yl) -benzamidine and phenoxyacetic acid</td><td> 461,3</td>

The following compounds were generated in analogy to example 1

<td></td><td>Example</td><td>Compound name</td><td>Starting materials</td><td>MH + found</td>

<td></td><td></td><td></td><td>tert-Butyl-ester of</td><td></td>

<td> *</td><td></td><td>1 - {(R) -3- [3- (2-Amino-</td><td>(R) -morpholine- acid</td><td></td>

<td> *</td><td></td><td>pyridin-4-yl) -</td><td>3,4-dicarboxylic, 2-</td><td></td>

<td>r</td><td> 386</td><td>[1,2,4] oxadiazole-5-</td><td>Amino-N-hydroxy-</td><td> 381, 6</td>

<td></td><td></td><td>il] -morfolin-4-il} -2-</td><td>isonicotinamidine and</td><td></td>

<td></td><td></td><td>phenoxyethanone</td><td>phenoxyacloride chloride</td><td></td>

<td></td><td></td><td></td><td>tilde</td><td></td>

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<td>Example</td><td>Compound name</td><td>Starting materials</td><td>MH + found</td>

<td> 387</td><td>l - {(R) -3- [3- (1H- Benzoimidazol-5-yl) [1,2,4] oxadiazol-5yl] -morpholin-4-yl} -2phenoxy-ethanone</td><td>4-tert-Butyl acid ester (R) —Morphole— 3,4-dicarboxylic acid, NHhydroxy-1Hbenzoimidazole-5carboxamidine and phenoxyacetyl chloride</td><td> 406,2</td>

<td> 388</td><td>1- {(R) -2- [3- (1H- Benzoimidazol-5-yl) [1,2,4] oxadiazol-5yl] -piperazin-l-yl} - 2- phenoxy-ethanone</td><td>1-tert-Butyl ester of piperazine-1,3-dicarboxylic acid, NHhydroxy-1Hbenzoimidazole-5carboxamidine and phenoxyacetic acid</td><td> 405, 4</td>

<td> 389</td><td>5- {5 - [(R) -1- (2- Phenoxy-acetyl) piperazin-2-yl] [1,2,4] oxadiazol-3yl} -1,3-dihydro-indol2-one</td><td>1-tert-Butyl ester of piperazine-1,3-dicarboxylic acid, NHhydroxy-2-oxo-2,3-dihydro-1H-indole-5carboxamidine and phenoxyacetic acid</td><td> 420,4</td>

<td> 390</td><td>1- {(R) -2- [3- (2-Aminopyridin-4-yl) [1,2,4] oxadiazol-5yl] -piperazin-l-yl} - 2- phenoxy-ethanone</td><td>1-tert-Butyl ester of piperazine-1,3-dicarboxylic acid, 2Amino-N-hydroxyisonicotinamidine and phenoxyacetic acid</td><td> 380,6</td>

Example 391

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(3- {5 - [(R) -1- (2-phenoxy-acetyl) -piperidin-2-yl] [1,2,4] oxadiazol-3-yl} -phenoxy) -acetic acid was the title compound prepared in analogy to example 180 from 5 (3- {5 - [(R) —1- (2-phenoxy-acetyl) -piperidin-2-yl] - [1,2,4] oxadiazole methylester- 3-yl} -phenoxy) -acetic.

MS: 436.5 (M-H +)

The following compounds were generated in analogy to example 194

<td>Example</td><td>Compound name</td><td>Starting materials</td><td>MH + found</td>

<td> 392</td><td>2-Phenoxy-1 - ((R) -2- {5 [3- (piperidine-1carbonyl) -phenyl] -2H [1,2,4] triazol-3-yl} piperidin-l-yl) ethanone</td><td>Acid 3- {5- [l- (2- phenoxy-acetyl) piperidin-2-yl] -1H- [1,2,4] triazol-3-yl} benzoic and piperidine</td><td> 474,6</td>

<td> 393</td><td>l - ((R) -2- {5- [3 (Morpholine-4carbonyl) -phenyl] -2H [1,2,4] triazol-3-yl} piperidin-l-yl) -2phenoxy-ethanone</td><td>3— {5— [1— (2— phenoxy-acetyl) piperidin-2-yl] -1H [1,2,4] triazol-3-yl] benzoic acid and morpholine</td><td> 476, 6</td>

<td> 394</td><td>l - ((R) -2- {5- [3- (4- Methyl-piperazine-1carbonyl) -phenyl] -2H [1,2,4] triazol-3-yl} piperidin-1-yl) -2phenoxy-ethanone</td><td>3— {5— [l— (2— phenoxy-acetyl) piperidin-2-yl] -1H [1,2,4] triazol-3-yl} benzoic acid and Nmethylpiperazine</td><td> 489, 7</td>

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<td>Example</td><td>Compound name</td><td>Starting materials</td><td>MH + found</td>

<td> 395</td><td>4- (3- {5 - [(R) -1- (2- Phenoxy-acetyl) piperidin-2-yl] -1H [1,2,4] triazol-3-yl} benzoyl) -piperazin-2one</td><td>Acid 3— {5— [l— (2— phenoxy-acetyl) piperidin-2-yl] -1H [1,2,4] triazol-3-yl} benzoic and Piperazin2-one</td><td> 489, 6</td>

<td> 396</td><td>N- (2-Methoxy-ethyl) -Nmethyl-3- {5 - [(R) -1- (2-phenoxy-acetyl) piperidin-2-yl] -1H [1,2,4] triazol-3-yl} benzamide</td><td>3— {5— [l— (2— phenoxy-acetyl) piperidin-2-yl] -1H [1,2,4] triazol-3-yl] benzoic acid and (2-methoxyethyl) -methyl-amine</td><td> 478,6</td>

<td> 397</td><td>l - ((R) —2— {5— [3— (4— Acetyl-piperazine-1carbonyl) -phenyl] -2H- [1,2,4] triazol-3-yl} piperidin-l-yl) -2phenoxy-ethanone</td><td>3- {5- [1- (2-phenoxy-acetyl) piperidin-2-yl] -1H- acid [1,2,4] triazol-3-yl} benzoic and 1Piperazin-l-ylethanone</td><td> 517,7</td>

<td> 398</td><td>1- (3- {5 - [(R) -1 (2-phenoxy-acetyl) piperidin-2-yl] -1H [1,2,4] triazol-3-yl] benzoyl) -piperidine4-carboxylic acid</td><td>3— {5— [l— (2— phenoxy-acetyl) piperidin-2-yl] -1H [1,2,4] triazol-3-yl} benzoic acid and piperidine-4- carboxylic</td><td> 518,6</td>

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<td>Example</td><td>Compound name</td><td>Starting materials</td><td>MH + found</td>

<td> 399</td><td>1— (3— {5 - [(R) -1- (2-phenoxyacetyl) -piperidin-2yl] -lH- acid amide [1,2,4] triazol-3-yl} benzoyl) -piperidine4-carboxylic</td><td>3— [5— [1— (2— phenoxy-acetyl) piperidin-2-yl] -1H [1,2,4] triazol-3-yl] benzoic acid and piperidine-4-carboxylic acid amide</td><td> 517,7</td>

<td> 400</td><td>2-Phenoxy-1 - ((R) -2- {5 [3- (thiazolidine-3carbonyl) -phenyl] -2H [1,2,4] triazol-3-yl} piperidin-l-yl) ethanone</td><td>3— {5— [1— (2— phenoxy-acetyl) piperidin-2-yl] -1H [1,2,4] triazol-3-yl} benzoic acid and Thiazolidine</td><td> 478, 6</td>

<td> 401</td><td>N- (2-Dimethylaminoethyl) -N-methyl-3- {5 [(R) -1- (2-phenoxyacetyl) -piperidin-2yl] -HH- [1,2,4] triazol-3-yl} benzamide</td><td>Acid 3— {5— [l— (2— phenoxy-acetyl) piperidin-2-yl] -1H [1,2,4] triazol-3-yl} benzoic and Ν, Ν, Ν'Trimethyl-ethane-1,2diamine</td><td> 491,7</td>

<td> 402</td><td>2-Phenoxy-l - ((R) -2- {5 [3- (thiomorpholine-4carbonyl) -phenyl] -2H [1,2,4] triazol-3-yl} piperidin-l-yl) ethanone</td><td>3- {5- [1- (2-phenoxy-acetyl) piperidin-2-yl] -1H [1,2,4] triazol-3-yl} benzoic acid and thiomorpholine</td><td> 492,8</td>

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<td>Example</td><td>Compound name</td><td>Starting materials</td><td>MH + found</td>

<td> 403</td><td>Ethyl acid ester 4- (3- {5 - [(R) -l- (2- phenoxy-acetyl) piperidin-2-yl] -1H- [1,2,4] triazol-3-yl} benzoyl) -piperazine1-carboxylic</td><td>3- {5- [1- (2-phenoxy-acetyl) piperidin-2-yl] -1H- acid [1,2,4] triazol-3-yl} benzoic and ethyl ester of piperazine1-carboxylic acid</td><td> 547,7</td>

<td> 404</td><td>N- (2-Hydroxy-ethyl) -3 {5 - [(R) -1- (2-phenoxyacetyl) -piperidin-2yl] -lH- [1,2,4] triazol-3-yl} - benzamide</td><td>3— [5— [1— (2— phenoxy-acetyl) piperidin-2-yl] -1H- acid [1,2,4] triazol-3-yl} benzoic and aminoethanol</td><td> 450,6</td>

<td> 405</td><td>N-Methyl-3- {5 - [(R) -1 (2-phenoxy-acetyl) piperidin-2-yl] -1H [1,2,4] triazol-3-yl} N- (2-pyridin- 2-ylethyl) -benzamide</td><td>Acid 3- {5- [l- (2- Phenoxy-acetyl) piperidin-2-yl] -1H [1,2,4] triazol-3-yl} benzoic and methyl- (2pyridin-2-yl-ethyl) amine</td><td> 525,7</td>

<td> 406</td><td>N- (2-Cyano-ethyl) -Ncyclopropyl-3- {5 [(R) -1- (2-phenoxyacetyl) -piperidin-2yl] -lH- [1,2,4] triazol-3-yl} benzamide</td><td>3— {5— [l— (2— phenoxy-acetyl) piperidin-2-yl] -1H- acid [1,2,4] triazol-3-yl} benzoic and 3cyclopropylaminopropionitrile</td><td> 499, 6</td>

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<td>Example</td><td>Compound name</td><td>Starting materials</td><td>MH + found</td>

<td> 407</td><td>1- (3- {5 - [(R) -1- (2- Phenoxy-acetyl) piperidin-2-yl] -1H- [1,2,4] triazol-3-yl} benzoyl) -4-phenylpiperidine-4carbonitrile</td><td>Acid 3— [5— [1— (2 - phenoxy-acetyl) piperidin-2-yl] -1H- [1,2,4] triazol-3-yl} benzoic and 4-phenylpiperidine-4carbonitrile</td><td> 575,7</td>

<td> 408</td><td>l - ((R) —2— {5— [3— (4— Hydroxy-piperidine-1carbonyl) -phenyl] -2H [1,2,4] triazol-3-yl} piperidin-1-yl) -2phenoxy-ethanone</td><td>Acid 3— {5— [1— (2— phenoxy-acetyl) piperidin-2-yl] -1H- [1,2,4] triazol-3-yl} benzoic and Piperidin4-ol</td><td> 490, 6</td>

<td> 409</td><td>8- (3- {5 - [(R) -1- (2- Phenoxy-acetyl) piperidin-2-yl] -1H [1,2,4] triazol-3-yl} benzoyl) -1,3,8triazaospiro [4.5] decan- 2,4-dione</td><td>3— [5— [1 ~ (2— phenoxy-acetyl) piperidin-2-yl] -1H- acid [1,2,4] triazol-3-yl} benzoic and 1,3,8Triaza- spiro [4.5] dean- 2,4-dione</td><td> 558,6</td>

<td> 410</td><td>1— (2— {5— [3— (Spiro (1- Phtalan) -piperidine-4carbonyl) -phenyl] -2H [1,2,4] triazol-3-yl} piperidin-l-yl) -2phenoxy-ethanone</td><td>Acid 3— {5— [l— (2— phenoxy-acetyl) piperidin-2-yl] -1H- [1,2,4] triazol-3-yl} - benzoic and 4- Spiro (1-Ftalan) piperidine</td><td> 578,7</td>

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<td>Example</td><td>Compound name</td><td>Starting materials</td><td>MH + found</td>

<td> 411</td><td>2-Phenoxy-1 - ((R) -2- {5 [3- (3-pyridin-4-ylpyrrolidine-1carbonyl) -phenyl] -2H [1,2,4] triazol-3-yl} piperidin-l -il) ethanone</td><td>Acid 3— {5— [1— (2 - phenoxy-acetyl) piperidin-2-yl] -1H- [1,2,4] triazol-3-yl} benzoic and 4- Pyrrolidin-3-ylpyridine</td><td> 537,7</td>

<td> 412</td><td>l - ((R) -2- {5- [3- (3- Methanesulfonylpyrrolidine-1carbonyl) -phenyl] -2H- [1,2,4] triazol-3-yl} piperidin-l-yl) -2phenoxy-ethanone</td><td>3— {5— [1— (2— phenoxy-acetyl) piperidin-2-yl] -1H- acid [1,2,4] triazol-3-yl} benzoic and 3- Methanesulfonylpyrrolidine</td><td> 538,6</td>

<td> 413</td><td>l - ((R) -2- {5- [3 - ((S) 3-Ethoxy-pyrrolidine- 1-carbonyl) -phenyl] 2H- [1,2,4] triazole-3yl} -piperidin-1-yl) - 2- phenoxy-ethanone</td><td>3— {5— [l— (2— phenoxy-acetyl) piperidin-2-yl] -1H [1,2,4] triazol-3-yl} benzoic acid and (S) —3— Ethoxy-pyrrolidine</td><td> 504,6</td>

<td> 414</td><td>l - ((R) —2— {5— [3 - ((S) - 3-Hydroxypyrrolidine-1carbonyl) -phenyl] -2H- [1,2,4] triazol-3-yl} piperidin-l-yl) -2phenoxy-ethanone</td><td>Acid 3— {5— [1— (2— phenoxy-acetyl) piperidin-2-yl] -1H [1,2,4] triazol-3-yl} benzoic and (S) —3— Hydroxy-pyrrolidine</td><td> 476, 6</td>

The following compounds were generated in analogy to example 231

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<td>Example</td><td>Compound name</td><td>Starting materials</td><td>MH + We found auger</td>

<td> 415</td><td>5— {5 - [(R) -1- (2- Phenoxy-acetyl) piperidin-2-yl] -1H- [1,2,4] triazol-3-yl} nicotinamide</td><td>5— {5— [l— (2— phenoxy-acetyl) piperidin-2-yl] -1H- [1,2,4] triazol-3-yl} - nicotinic and Rink resin</td><td> 407,5</td>

<td> 416</td><td>2— (3— [5— [1— (2-Phenoxyacetyl) -piperidin-2yl] - [1,2,4] oxadiazole- 3-yl} -phenoxy) acetamide</td><td>Acid (3— {5— [1— (2— phenoxy-acetyl) piperidin-2-yl] [1,2,4] oxadiazol-3yl} -phenoxy) -acetic and Rink resin</td><td> 437,5</td>

The following compounds were generated in analogy to example 242

<td>Example</td><td>Compound name</td><td>Starting materials</td><td>MH + found</td>

<td> 417</td><td>N- (3-Fluoro-5- {5- [(R) -1- (2-phenoxyacetyl) -piperidin-2yl] - [1,2,4] oxadiazol3-yl} -phenyl) acetamide</td><td>1- {2- [3- (3-Amino-5fluoro-phenyl) [1,2,4] oxadiazol-5yl] -piperidin-l-yl} - 2- phenoxy-ethanone and acetyl chloride</td><td> 439,1</td>

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<td> 418</td><td>N- (2-Fluoro-5- {5- [(R) -1- (2-phenoxyacetyl) -piperidin-2yl] - [1,2,4] oxadiazol3-yl} -phenyl) acetamide</td><td>Boc-D- Acid Pipecolic, N- [2- Fluoro-5- (Nhydroxycarbamidoyl) phenyl] -acetamide and phenoxyacetyl chloride</td><td> 439,1</td>

<td> 419</td><td>N- (3- {5 - [(R) -1- (2- Phenoxy-acetyl) piperidin-2-yl] -1H [1,2,4] triazol-3-yl} phenyl) -propionamide</td><td>1— {2— [5- (3-Aminophenyl) -2H- [1,2,4] triazol-3-yl] piperidin-l-yl} -2phenoxy-ethanone and propionic acid chloride</td><td> 434,5</td>

<td> 420</td><td>N- (3- {5 - [(R) -1- (2- Phenoxy-acetyl) piperidin-2-yl] -1H [1,2,4] triazol-3-yl} phenyl) -isobutyramide</td><td>1- {2- [5- (3-Aminophenyl) -2H [1,2,4] triazol-3-yl] piperidin-l-yl} -2phenoxy-ethanone and isobutyric acid chloride</td><td> 448,6</td>

The following compounds were generated in analogy to example 1:

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<td>Example</td><td>Compound name</td><td>Starting materials</td><td>MH + found</td>

<td> 421</td><td>N- (4-Fluoro-3- {5- [(R) -1- (2-phenoxy- acetyl) -piperidin-2- il] -1H- [1,2,4] triazol-3-yl} - phenyl) -acetamide</td><td>tert-Butyl-ester of -2hydrazinocarbonylpiperidine-1-carboxylic acid, N- (3- Carbamidoyl-4-fluorophenyl) -acetamide and phenoxyacetic acid</td><td> 438,5</td>

<td> 422</td><td>N- (3-Fluoro-5- {5- [(R) -1- (2-phenoxyacetyl) -piperidin-2yl] -lH- [1,2,4] triazol-3-yl} - phenyl) -acetamide</td><td>2-hydrazinocarbonylpiperidine-1-carboxylic acid tert-Butyl ester, N- (3Carbamimidoyl-5fluoro-phenyl) acetamide and phenoxyacetic acid</td><td> 348,5</td>

<td> 423</td><td>N- (2-Fluoro-5- {5- [(R) -1- (2-phenoxy- acetyl) -piperidin-2- il] -1H- [1,2,4] triazol-3-yl} phenyl) -acetamide</td><td>2-hydrazinocarbonylpiperidine-1-carboxylic acid tert-Butyl ester, N- (3Carbamimidoyl-6fluoro-phenyl) acetamide and phenoxyacetic acid</td><td> 348,5</td>

Example 424

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Ν- (4- {5 - [(R) -1- (2-Phenoxy-acetyl) -piperidin-2-yl] -1H- [1.2.4] triazol-3-yl} -pyridin-2-yl) -acetamide

The title compound was generated in analogy to example 242 from 1- [2- [5- (2-aminopyridin-4-yl) -2H- [1,2,4] triazol-3-yl] -piperidine- 1-yl} 2-phenoxy-ethanone and acetyl chloride.

MS 421.5 (MH +)

Example 425

1- (3- {5 - [(R) -1- (2-Phenoxy-acetyl) -piperidin-2-yl] -1H- [1.2.4] triazol-3-yl] -phenyl) -azetidin-2 -one

75 mg of 1- {2- [5- (3-aminophenyl) -2H- [1,2,4] triazol-3-yl] -piperidin-l-yl} -2phenoxy-ethanone were dissolved in MDF and added 40 µl of DIPEA is used. 34 mg of 3-bromo-propionyl chloride was added at 0 ° C and the reaction was warmed to room temperature and stirred for another 30 minutes. The reaction mixture was heated to 120 ° C using microwave heating and the product was isolated by means of preparation HPLC.

MS (ISO): 432.5 (MH +)

Example 426

1- (3- {5- [1- (2-Phenoxy-acetyl) -piperidin-2-yl] -1H- [1,2,4] triazol-3-yl} -phenyl) -pyrrolidine-2,5 -diona

0.1- [2- [5- (3-Aminophenyl) -2H- [1, 2.4] triazol-3-yl] -piperidin-l-yl} -2phenoxy-ethanone 0.1 mmol ml of DMF and 1 equivalent of succinic anhydride was added. The reaction was subjected to

189/229 stirring overnight and the intermediate (N- (3 {5- [1- (2-phenoxy-acetyl) -piperidin-2-yl] - [1,2,4] oxadiazol-3-yl} -phenyl) -succinamic) isolated by means of preparation HPLC. The isolated material was redissolved in DMF and 1 equivalent of HATU was added. The reaction mixture was heated to 120 ° C using microwave heating. The product was isolated by means of preparation HPLC.

MS (ISO): 460.5 (MH +)

Example 427

2-Phenoxy-1 - [(R) -2- (5-pyridazin-4-yl- [1,2,4] oxadiazol-3yl) -piperidin-1-yl] -ethanone

Step 1:

(R) -2- (N-hydroxycarbamidoyl) tert-Butyl ester 15 piperidine-1-carboxylic acid

3 g of (R) -N-Boc-2-cyanopiperidine (14 mmol) were treated with 70 mmol of hydrazine hydrochloride and 35 mmol of sodium carbonate in an ethanol / water mixture (7: 3) and heated to 50 ° C during the night. The solvent was evaporated and the crude extracted from ethyl acetate / water. The organic layer was dried over sodium sulfate. After evaporation, a white solid was obtained in quantitative yield.

MS (ISO): 244.5 (MH +)

Step 2:

(R) -2- (5-pyridazin-4-yl- [1,2,4] oxadiazol-3-yl) -piperidine-1-carboxylic acid tert-butyl ester

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0.2 mmol of pyridazine-4-carboxylic acid, HATU and diisopropylethylamine were dissolved in 1 ml of DMF and stirred for 15 minutes. 0.2 mmol (R) 2- (N-Hydroxycarbamidoyl) -piperidine-1-carboxylic acid tert-butyl ester was added. The reaction was heated to 80 ° C and stirred overnight. The DMF was evaporated and the crude extracted from ethyl acetate / water. The crude product was no longer characterized.

Step 3:

(R) 4- (3-Piperidin-2-yl- [1,2,4] oxadiazol-5-yl) -pyridazine trifluoroacetate

Crude material from step 3 was treated with pure TFA at room temperature for 1 h. The solvent was evaporated. The crude product was no longer characterized.

Step 4:

2-Phenoxy-1 - [(R) -2- (5-pyridazin-4-yl- [1,2,4] oxadiazol-3yl) -piperidin-1-yl] -ethanone

Crude material from step 3 was dissolved in 1 ml of DMF and 0.1 mmol of DIPEA. Either 0.1 mmol of phenoxyacetyl chloride was added and the reaction was stirred at room temperature for 30 minutes, or the corresponding phenoxyacetic acid derivatives were pre-activated with HATU / DIPEA in DMF for 10 minutes and added to the crude material from step 3. The product was isolated by in

191/229 high performance liquid chromatography (HPLC) preparation.

MS (ISO): 366, 5 (MH +)

The following compounds were generated in analogy to example 427

<td>Example</td><td>Compound name</td><td>Starting materials</td><td>MH + found</td>

<td> 428</td><td>4 - {3 - [(R) -1- (2-Phenoxyacetyl) -piperidin-2yl] - [1,2,4] oxadiazol5-yl} -benzonitrile</td><td>(R) -2- (N hydroxycarb-amidoyl) piperidine-1-carboxylic acid tert-Butyl ester, 4-cyanobenzoic acid and Phenoxyacetyl chloride</td><td> 389,3</td>

<td> 429</td><td>1 - {(R) -2- [5- (3-Amino- pyrazin-2-yl) - [1,2,4] oxadiazole-3- il] -piperidin-l-yl} -2phenoxy-ethanone</td><td>(R) -2- (N Hydroxycarb-amidoyl) piperidine-1-carboxylic acid tert-Butyl ester, 3-Amino-pyrazine-2-carboxylic acid and phenoxyacetyl chloride</td><td> 381,3</td>

<td> 430</td><td>3— {3 - [(R) -l- (2-Phenoxyacetyl) -piperidin-2yl] - [1,2,4] oxadiazol5-yl} -benzonitrile</td><td>(R) -2- (N Hydroxycarb-amidoyl) piperidine-1-carboxylic acid tert-Butyl ester, 3Cyanobenzoic acid and phenoxyacetyl chloride</td><td> 389, 3</td>

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<td>Example</td><td>Compound name</td><td>Starting materials</td><td>MH + found</td>

<td> 431</td><td>l - {(R) —2— [5— (2 - Hydroxy-pyridin-3-yl) [1,2,4] oxadiazol-3yl] -piperidin-l-yl} -2phenoxy-ethanone</td><td>(R) -2- (N Hydroxycarb-amidoyl) piperidine-1-carboxylic acid tert-Butyl ester, 2-Hydroxy-nicotinic and phenoxyacetyl chloride</td><td>379, 4 (M-H +)</td>

<td> 432</td><td>1 - {(R) -2- [5- (5-Amino- pyridin-3-yl) - [1,2,4] oxadiazole-3- il] -piperidin-l-yl} -2phenoxy-ethanone</td><td>(R) -2- (N Hydroxycarb-amidoyl) piperidine-1-carboxylic acid tert-Butyl ester, 5Amino-nicotinic acid and phenoxyacetyl chloride</td><td> 380, 3</td>

<td> 433</td><td>l- {(R) —2— [5— (2— Hydroxy-pyridin-4-yl) [1,2,4] oxadiazol-3yl] -piperidin-l-yl} -2phenoxy-ethanone</td><td>(R) -2- (N Hydroxycarb-amidoyl) piperidine-1-carboxylic acid tert-Butyl ester, 2-Hydroxy-isonicotinic acid and phenoxyacetyl chloride</td><td> 381,2</td>

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<td>Example</td><td>Compound name</td><td>Starting materials</td><td>MH + found</td>

<td> 434</td><td>l - {(R) -2- [5- (2- Hydroxy-6-methylpyridin-4-yl) [1,2,4] oxadiazol-3yl] -piperidin-l-yl} -2phenoxy-ethanone</td><td>(R) -2- (N Hydroxycarb-amidoyl) piperidine-1-carboxylic acid tert-Butyl ester, 2-Hydroxy-6-methylisonicotinic acid and phenoxyacetyl chloride</td><td> 395,2</td>

<td> 435</td><td>l - {(R) -2- [5- (4- Hydroxy-pyridin-2-yl) [1,2,4] oxadiazol-3yl] -piperidin-l-yl} -2phenoxy-ethanone</td><td>(R) -2- (N Hydroxycarb-amidoyl) piperidine-1-carboxylic acid tert-Butyl ester, 4-Hydroxy-pyridine-2-carboxylic acid and phenoxyacetyl chloride</td><td> 381,2</td>

<td> 436</td><td>1— {(R) -2- [5- (2-Amino5-chloro-pyrimidin-4yl) - [1,2,4] oxadiazole- 3 — il] -piperidin-l-il} - 2- phenoxy-ethanone</td><td>(R) -2- (N Hydroxycarb-amidoyl) piperidine-1-carboxylic acid tert-Butyl ester, 2-Amino-5-chloropyrimidine-4-carboxylic acid and phenoxyacetyl chloride</td><td> 415,2</td>

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<td>Example</td><td>Compound name</td><td>Starting materials</td><td>MH + find auger</td>

<td> 437</td><td>2-Phenoxy-1 - [(R) -2- (5pyrazin-2-yl- [1,2,4] oxadiazole-3- il) -piperidin-1-yl] ethanone</td><td>(R) -2- (N Hydroxycarb-amidoyl) piperidine-1carboxylic acid tert-Butyl ester, Pyrazine-2carboxylic acid and phenoxyacetyl chloride</td><td> 366,2</td>

<td> 438</td><td>2-Phenoxy-1 - {(R) -2- [5- (4- [1,2,4] triazole-1- il-phenyl) - [1,2,4] oxadiazole-3- il] -piperidin-l-il} ethanone</td><td>(R) -2- (N Hydroxycarb-amidoyl) piperidine-1-carboxylic acid tert-Butyl ester, 4- [1,2,4] Triazol-l-ylbenzoic and phenoxyacetyl chloride</td><td> 431,2</td>

<td> 439</td><td>2-Phenoxy-l - {(R&gt; —2— [5 - (4-tetrazol-l-ylphenyl) - [1,2,4] oxadiazol-3yl] -piperidin-l-yl} ethanone</td><td>(R) -2- (N Hydroxycarb-amidoyl) piperidine-1-carboxylic acid tert-Butyl ester, 4Tetrazol-l-ylbenzoic acid and phenoxyacetyl chloride</td><td> 432,2</td>

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<td>Example</td><td>Compound name</td><td>Starting materials</td><td>MH + found</td>

<td> 440</td><td>l - {(R) -2- [5- (1H- Benzoimidazol-4-yl) [1,2,4] oxadiazol-3yl] -piperidin-l-yl} -2phenoxy-ethanone</td><td>(R) -2- (N Hydroxycarb-amidoyl) piperidine-1-carboxylic acid tert-Butyl ester, 1H-Benzoimidazole-4-carboxylic acid and phenoxyacetyl chloride</td><td> 404,2</td>

<td> 441</td><td>l - {(R) -2- [5- (4-Acetyl- phenyl) - [1,2,4] oxadiazole-3- il] -piperidin-l-yl} -2phenoxy-ethanone</td><td>(R) -2- (N Hydroxycarb-amidoyl) piperidine-1-carboxylic acid tert-Butyl ester, 4-Acetyl-benzoic acid and phenoxyacetyl chloride</td><td> 406, 2</td>

<td> 442</td><td>l - {(R) —2— [5— (6— Hydroxy-pyridin-2-yl) [1,2,4] oxadiazol-3yl] -piperidin-l-yl} -2phenoxy-ethanone</td><td>(R) -2- (N Hydroxycarb-amidoyl) piperidine-1-carboxylic acid tert-Butyl ester, 6-Hydroxy-pyridine-2-carboxylic acid and phenoxyacetyl chloride</td><td> 381,2</td>

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<td>Example</td><td>Compound name</td><td>Starting materials</td><td>MH + found</td>

<td> 443</td><td>l - {(R) -2- [5- (5-Methyl- pyrazin-2-yl) - [1,2,4] oxadiazole-3- il] -piperidin-l-yl} -2phenoxy-ethanone</td><td>(R) -2- (N Hydroxycarb-amidoyl) piperidine-1-carboxylic acid tert-Butyl ester, 5-Methyl-pyrazine-2-carboxylic acid and phenoxyacetyl chloride</td><td> 380,2</td>

<td> 444</td><td>2-Phenoxy-1 - [(R) -2- (5quinoxalin-2-yl [1,2,4] oxadiazol-3yl) -piperidin-1-yl] ethanone</td><td>(R) -2- (N Hydroxycarb-amidoyl) piperidine-1-carboxylic acid tert-Butyl ester, Quinoxaline-2-carboxylic acid and phenoxyacetyl chloride</td><td> 416,2</td>

<td> 445</td><td>l - {(R) -2- [5- (3- Methanesulfonyl- phenyl) - [1,2,4] oxadiazole-3- il] -piperidin-l-yl} -2phenoxy-ethanone</td><td>(R) -2- (N Hydroxycarb-amidoyl) piperidine-1-carboxylic acid tert-Butyl ester, 3Methanesulfonylbenzoic acid and phenoxyacetyl chloride</td><td> 442,2</td>

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<td>Example</td><td>Compound name</td><td>Starting materials</td><td>MH + found</td>

<td> 446</td><td>l - {(R) -2- [5- (6-Chloro- pyridin-3-yl) - [1,2,4] oxadiazole-3- il] -piperidin-l-yl} -2phenoxy-ethanone</td><td>(R) —2— (N Hydroxycarb-amidoyl) piperidine-1-carboxylic acid tert-Butyl ester, 6-Chloro-nicotinic acid and phenoxyacetyl chloride</td><td> 399,1</td>

<td> 447</td><td>l - [(R) -2- (5- Benzothiazol-6-il- [1,2,4] oxadiazole-3- il) -piperidin-l-yl] -2phenoxy-ethanone</td><td>(R) -2- (N Hydroxycarb-amidoyl) piperidine-1-carboxylic acid tert-Butyl ester, Benzothiazol-6-carboxylic acid and phenoxyacetyl chloride</td><td> 421,2</td>

<td> 448</td><td>2-Phenoxy-1 - {(R) -2- [5- (2,4,5-trifluorophenyl) - [1,2,4] oxadiazol-3yl] -piperidin-l-yl} ethanone</td><td>(R) -2- (N Hydroxycarb-amidoyl) piperidine-1-carboxylic acid tert-Butyl ester, acid 2,4,5-Trifluorobenzoic and phenoxyacetyl chloride</td><td> 418,2</td>

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<td>Example</td><td>Compound name</td><td>Starting materials</td><td>MH + found</td>

<td> 449</td><td>2-Phenoxy-l - {(R) -2- [5 (6-trifluoromethylpyridin-3-yl) [1,2,4] oxadiazol-3yl] -piperidin-l-yl} ethanone</td><td>(R) -2- (N Hydroxycarb-amidoyl) piperidine-1-carboxylic acid tert-Butyl ester, 6Trifluoromethylnicotinic acid and phenoxyacetyl chloride</td><td> 433,2</td>

<td> 450</td><td>1- [(R) -2- (5- Benzo [1,2,3] thiadiazol5-yl- [1,2,4] oxadiazol3-yl) -piperidin-1-yl] - 2- phenoxy-ethanone</td><td>(R) -2- (N Hydroxycarb-amidoyl) piperidine-1-carboxylic acid tert-Butyl ester, Benzo [1,2,3] thiadiazole-5-carboxylic acid and phenoxyacetyl chloride</td><td> 422,2</td>

<td> 451</td><td>l - [(R) -2- (5- [1.8] Naftidirin-2-yl- [1,2,4] oxadiazole-3- il) -piperidin-l-yl] -2phenoxy-ethanone</td><td>(R) -2- (N Hydroxycarb-amidoyl) piperidine-1-carboxylic acid tert-Butyl ester, [1,8] Naphthyridine-2-carboxylic acid and phenoxyacetyl chloride</td><td> 416,2</td>

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<td>Example</td><td>Compound name</td><td>Starting materials</td><td>MH + found</td>

<td> 452</td><td>l - [(R) -2- (5- [1.6] Naftidirin-2-yl- [1,2,4] oxadiazole-3- il) -piperidin-l-yl] -2phenoxy-ethanone</td><td>(R) -2- (N Hydroxycarb-amidoyl) piperidine-1-carboxylic acid tert-Butyl ester, [1,6] Naphthidirine-2-carboxylic acid and phenoxyacetyl chloride</td><td> 416, 2</td>

<td> 453</td><td>l^-[(R)^-2- (5-Cinolin-4il- [1,2,4] oxadiazol-3yl) -piperidin-1-yl] -2-phenoxy-ethanone</td><td>(R) -2- (N Hydroxycarb-amidoyl) piperidine-1-carboxylic acid tert-Butyl ester, Cinoline-4-carboxylic acid and phenoxyacetyl chloride</td><td> 416,2</td>

<td> 454</td><td>l- {(R) -2- [5- (lH- Benzotriazol-5-yl) [1,2,4] oxadiazol-3yl] -piperidin-l-yl} -2phenoxy-ethanone</td><td>(R) -2- (N Hydroxycarb-amidoyl) piperidine-1-carboxylic acid tert-Butyl ester, 1H-Benzotriazole-5carboxylic acid and phenoxyacetyl chloride</td><td> 405,2</td>

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<td>Example</td><td>Compound name</td><td>Starting materials</td><td>MH + found</td>

<td> 455</td><td>l - {(R) -2- [5- (1H- Benzoimidazol-5-yl) [1,2,4] oxadiazol-3yl] -piperidin-l-yl} -2phenoxy-ethanone</td><td>(R) -2- (N Hydroxycarb-amidoyl) piperidine-1-carboxylic acid tert-Butyl ester, 1H-Benzoimidazole-5carboxylic acid and phenoxyacetyl chloride</td><td> 404,2</td>

<td> 456</td><td>1- {(R) -2- [5- (3,6- Dichloro-pyridazin-4- il) - [1,2,4] oxadiazole- 3-il] -piperidin-l-il} - 2- phenoxy-ethanone</td><td>(R) -2- (N Hydroxycarb-amidoyl) piperidine-1-carboxylic acid tert-Butyl ester, acid 3,6-Dichloropyridazine-4-carboxylic acid and phenoxyacetyl chloride</td><td> 435,2</td>

<td> 457</td><td>6- {3 - [(R) -1- (2-Phenoxyacetyl) -piperidin-2yl] - [1,2,4] oxadiazol5-yl} -4H-benzo [1,4] oxazin-3-one</td><td>(R) -2- (N Hydroxycarb-amidoyl) piperidine-1carboxylic acid tert-Butyl ester, 3Oxo-3,4-dihydro-2Hbenzo [1,4] oxazine-6carboxylic acid and phenoxyacetyl chloride</td><td> 435,2</td>

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<td>Example</td><td>Compound name</td><td>Starting materials</td><td>MH + found</td>

<td> 458</td><td>l - {(R) -2- [5- (3H- Imidazo [4,5-b] pyridin- 6 — il) - [1,2,4] oxadiazole-3- il] -piperidin-l-yl} -2phenoxy-ethanone</td><td>(R) -2- (N Hydroxycarb-amidoyl) piperidine-1-carboxylic acid tert-Butyl ester, 3H-Imidazo [4,5b] pyridine-6-carboxylic acid and phenoxyacetyl chloride</td><td> 405,1</td>

<td> 459</td><td>N- (4- {3 - [(R) -1- (2- Phenoxy-acetyl) piperidin-2-yl] [1,2,4] oxadiazol-5yl} -pyridin-2-yl) acetamide</td><td>(R) -2- (N Hydroxycarb-amidoyl) piperidine-1-carboxylic acid tert-Butyl ester, 2Acetylaminoisonicotinic acid and phenoxyacetic acid</td><td> 422,2</td>

<td> 460</td><td>1- {(R) -2- [5- (6-Chloro- 3-hydroxy-pyridazin-4- il) - [1,2,4] oxadiazole- 3-il] -piperidin-l-il} - 2- phenoxy-ethanone</td><td>(R) -2- (N Hydroxycarb-amidoyl) piperidine-1-carboxylic acid tert-Butyl ester, 6-Chloro-3-hydroxypyridazine-4-carboxylic acid and phenoxyacetyl chloride</td><td> 416,1</td>

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<td>Example</td><td>Compound name</td><td>Starting materials</td><td>MH + found</td>

<td> 461</td><td>6— {3 - [(R) -1- (2-Phenoxyacetyl) -piperidin-2yl] - [1,2,4] oxadiazol5-yl}-1,4-dihydroquinoxaline-2,3-dione</td><td>(R) -2- (N Hydroxycarb-amidoyl) piperidine-1-carboxylic acid tert-Butyl ester, 2,3-Dioxo-1,2,3,4tetrahydroquinoxaline-6-carboxylic acid and phenoxyacetyl chloride</td><td> 448,1</td>

<td> 462</td><td>l - {(R) -2- [5- (6- Hydroxy-pyridin-3-yl) [1,2,4] oxadiazol-3yl] -piperidin-l-yl} -2phenoxy-ethanone</td><td>(R) -2- (N Hydroxycarb-amidoyl) piperidine-1-carboxylic acid tert-Butyl ester, 6-Hydroxy-nicotinic acid and phenoxyacetyl chloride</td><td> 381,1</td>

<td> 463</td><td>7 - {3 - [(R) -1- (2-Phenoxyacetyl) -piperidin-2yl] - [1,2,4] oxadiazol5-yl} -3,4-dihydro-1Hquinoxalin-2-one</td><td>(R) -2- (N Hydroxycarb-amidoyl) piperidine-1carboxylic acid tert-Butyl ester, 3Oxo-1,2,3,4tetrahydroquinoxaline-6carboxylic acid and phenoxyacetic acid</td><td> 434,2</td>

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<td>Example</td><td>Compound name</td><td>Starting materials</td><td>MH + found</td>

<td> 464</td><td>1 - {(R) -2- [5- (6-Amino- pyridin-2-yl) - [1,2,4] oxadiazole-3- il] -piperidin-l-yl} -2phenoxy-ethanone</td><td>(R) -2- (N Hydroxycarb-amidoyl) piperidine-1-carboxylic acid tert-Butyl ester, 6Amino-pyridine-2-carboxylic acid and phenoxyacetic acid</td><td> 380,2</td>

<td> 465</td><td>6- {3 - [(R) -1- (2-Phenoxyacetyl) -piperidin-2yl] - [1,2,4] oxadiazol5-yl} -nicotinonitrile</td><td>(R) -2- (N Hydroxycarb-amidoyl) piperidine-1-carboxylic acid tert-Butyl ester, 5-Cyano-pyridine-2-carboxylic acid and phenoxyacetic acid</td><td> 390,1</td>

<td> 466</td><td>5— {3 - [(R) -1- (2-Phenoxyacetyl) -piperidin-2yl] - [1,2,4] oxadiazol5-yl} -pyridine-2carbonitrile</td><td>(R) -2- (N Hydroxycarb-amidoyl) piperidine-1-carboxylic acid tert-Butyl ester, 6Ciano-nicotinic acid and phenoxyacetic acid</td><td> 390, 1</td>

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<td>Example</td><td>Compound name</td><td>Starting materials</td><td>MH + found</td>

<td> 467</td><td>4 - {3 - [(R) -1- (2-Phenoxyacetyl) -piperidin-2yl] - [1,2,4] oxadiazol5-yl} -1,2-dihydroindazole-3-one</td><td>(R) -2- (N Hydroxycarb-amidoyl) piperidine-1-carboxylic acid tert-Butyl ester, 3Oxo-2,3-dihydro-1Hindazole-4-carboxylic acid and phenoxyacetic acid</td><td> 420,2</td>

<td> 468</td><td>1 - {(R) -2- [5- (2-Aminopyridin-4-yl) - [1,2,4] oxadiazole-3- il] -piperidin-l-yl} -2phenoxy-ethanone</td><td>(R) —2— (N Hydroxycarb-amidoyl) piperidine-1-carboxylic acid tert-Butyl ester, 2Amino-isonicotinic acid and phenoxyacetic acid</td><td> 380,1</td>

<td> 469</td><td>1- {(R) —2— [5— (6— Hydroxy-pyrimidin-4il) - [1,2,4] oxadiazol3-yl] -piperidin-l-yl} - 2- phenoxy-ethanone</td><td>(R) -2- (N Hydroxycarb-amidoyl) piperidine-1-carboxylic acid tert-Butyl ester, 6-Hydroxy-pyrimidine-4-carboxylic acid and phenoxyacetic acid</td><td> 382,1</td>

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<td>Example</td><td>Compound name</td><td>Starting materials</td><td>MH + find auger</td>

<td> 470</td><td>4- (3- {3 - [(R) -1- (2- Phenoxy-acetyl) piperidin-2-yl] - [1.2.4] oxadiazole-5- il} -phenyl) -2,4-dihydro- [1.2.4] triazole-3-one</td><td>(R) -2- (N Hydroxycarb-amidoyl) piperidine-1-carboxylic acid tert-Butyl ester, 3 (5-Oxo-1,5-dihydro [1,2,4] triazol-4-yl) benzoic acid and phenoxyacetic acid</td><td> 447,2</td>

<td> 471</td><td>1- (3- {3 - [(R) —1— (2— Phenoxy-acetyl) piperidin-2-yl] [1,2,4] oxadiazol-5yl} -phenyl) imidazolidine-2,4dione</td><td>(R) -2- (N Hydroxycarb-amidoyl) piperidine-1-carboxylic acid tert-Butyl ester, 3 (2,4-Dioxoimidazolidin-1-yl) benzoic acid and phenoxyacetic acid</td><td> 462,2</td>

<td> 472</td><td>l - ((R) —2— {5— [3— (1,1— Dioxo-ΐλβisothiazolidin-2-yl) phenyl] - [1,2,4] oxadiazol-3yl} -piperidin-l-yl) -2phenoxy-ethanone</td><td>(R) -2- (N Hydroxycarb-amidoyl) piperidine-1-carboxylic acid tert-Butyl ester, 3 (1,1-Dioxo-1Ã6isothiazolidin-2-yl) benzoic acid and phenoxyacetic acid</td><td> 483,2</td>

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<td>Example</td><td>Compound name</td><td>Starting materials</td><td>MH + found</td>

<td> 473</td><td>1- (3- {3 - [(R) -1- (2- Phenoxy-acetyl) piperidin-2-yl] [1,2,4] oxadiazol-5yl} -phenyl) -pyrrolidin- 2- one</td><td>(R) -2- (N Hydroxycarb-amidoyl) piperidine-1-carboxylic acid tert-Butyl ester, 3 (2-Oxo-pyrrolidin-lil) -benzoic acid and phenoxyacetic acid</td><td> 447,2</td>

<td> 474</td><td>1- (3- {3 - [(R) -l- (2- Phenoxy-acetyl) piperidin-2-yl] [1,2,4] oxadiazole-5- yl] -phenyl) -1,3-dihydro- imidazole-2-one</td><td>(R) -2- (N Hydroxycarb-amidoyl) piperidine-carboxylic acid tert-Butyl ester, 3-. (2-Oxo-2,3-dihydroimidazol-1-yl) benzoic and phenoxyacetic acid</td><td> 446,2</td>

<td> 475</td><td>3- (3— {3 - [(R) -1- (2Fenoxy-acetyl) piperidin-2-yl] [1,2,4] oxadiazol-5yl} -phenyl) imidazolidine-2,4dione</td><td>(R) -2- (N Hydroxycarb-amidoyl) piperidine-1-carboxylic acid tert-Butyl ester, 3 (2,5-Dioxoimidazolidin-1-yl) benzoic acid and phenoxyacetic acid</td><td> 462,2</td>

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<td>Example</td><td>Compound name</td><td>Starting materials</td><td>MH + find auger</td>

<td> 476</td><td>l - {(R) -2- [5- (1-MethylH-pyrazol-3-yl) [1,2,4] oxadiazole-3- il] -piperidin-l-yl} -2phenoxy-ethanone</td><td>(R) -2- (N Hydroxycarb-amidoyl) piperidine-1-carboxylic acid tert-Butyl ester, 1-Methyl-1H-pyrazol-3-carboxylic acid and phenoxyacetic acid</td><td> 368,2</td>

<td> 477</td><td>2-Phenoxy-l - {(R) -2- [5 (1H-pyrazol-3-yl) [1,2,4] oxadiazol-3yl] -piperidin-l-yl} ethanone</td><td>(R) -2- (N Hydroxycarb-amidoyl) piperidine-1-carboxylic acid tert-Butyl ester, 1H-Pyrazol-3-carboxylic acid and phenoxyacetic acid</td><td> 354,1</td>

<td> 478</td><td>l - {(R) -2- [5- (5-Methyl- isoxazol-3-yl) - [1,2,4] oxadiazole-3- il] -piperidin-l-yl} -2phenoxy-ethanone</td><td>(R) -2- (N Hydroxycarb-amidoyl) piperidine-1-carboxylic acid tert-Butyl ester, 5-Methyl-isoxazol-3-carboxylic acid and phenoxyacetic acid</td><td> 369, 1</td>

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<td>Example</td><td>Compound name</td><td>Starting materials</td><td>MH + found</td>

<td> 479</td><td>1- {(R) —2— [5— (2.5— Dimethyl-2H-pyrazol-3- il) - [1,2,4] oxadiazole- 3 — il] -piperidin-l-il} - 2- phenoxy-ethanone</td><td>(R) -2- (N Hydroxycarb-amidoyl) piperidine-1-carboxylic acid tert-Butyl ester, acid 2,5-Dimethyl-2Hpyrazol-3-carboxylic and phenoxyacetic acid</td><td> 382,2</td>

<td> 480</td><td>l - {(R) -2- [5- (5-Methyl- 2H-pyrazol-3-yl) [1,2,4] oxadiazole-3- il] -piperidin-l-yl} -2phenoxy-ethanone</td><td>(R) -2- (N Hydroxycarb-amidoyl) piperidine-1-carboxylic acid tert-Butyl ester, 5-Methyl-2H-pyrazol-3-carboxylic acid and phenoxyacetic acid</td><td> 368,2</td>

<td> 481</td><td>l - {(R) -2- [5- (3-Methyl- isoxazol-5-yl) [1,2,4] oxadiazol-3- il] -piperidin-l-yl} -2phenoxy-ethanone</td><td>(R) -2- (N Hydroxycarb-amidoyl) piperidine-1-carboxylic acid tert-Butyl ester, 3-methyl-isoxazol-5-carboxylic acid and phenoxyacetic acid</td><td> 369,1</td>

The following compounds were generated in analogy to example 256:

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<td>Example</td><td>Broker name</td><td>Starting materials</td>

<td> 482</td><td>N-Hydroxy-2-imidazole-l- il-isonicotinamidine</td><td>2-Imidazol-l-il- isonicotinonitrile and droxylamine</td>

<td> 483</td><td>N-Hydroxy-4- (3H-imidazole- 4-yl) -benzamidine</td><td>4- (3H-Imidazol-4-yl) benzonitrile and hydroxylamine</td>

<td> 484</td><td>N-Hydroxy-4- (2-methyl- imidazol-l-yl) - benzamidine</td><td>4- (2-Methyl-imidazole-l- il) -benzonitrile and hydroxylamine</td>

<td> 485</td><td>N-Hydroxy-2-pyrazol-1-ylisonicotinamidine</td><td>2-Pyrazol-l-il- isonicotinonitrile and droxylamine</td>

<td> 486</td><td>Ethyl ester of 5- (Nhydroxycarbamidoyl) nicotinic acid</td><td>Ethyl ester of 5 cyano-nicotinic acid and hydroxylamine</td>

<td> 487</td><td>N-Hydroxy-4-piperidin-lil-benzamidine</td><td>4-Piperidin-l-ylbenzonitrile and hydroxylamine</td>

<td> 488</td><td>N-Hydroxy-4-morpholin-l- il-benzamidine</td><td>4-Morfolin-l-ylbenzonitrile and hydroxylamine</td>

<td> 489</td><td>N-Hydroxy-6-imidazole-l- il-nicotinamidine</td><td>6-Imidazol-l-il- nicotinonitrile and hydro- xylamine</td>

<td> 490</td><td>N- [3- (N- Hydroxycarbamidoyl) phenyl] -acetamide</td><td>N- (3-Cyano-phenyl) acetamide and hydroxylamine</td>

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<td>Example</td><td>Broker name</td><td>Starting materials</td>

<td> 491</td><td>Benzyl ester of benzoic acid 4 (N-hydroxycarbamidoyl)</td><td>Benzyl ester of N (3-cyano-phenyl) -4-cyanobenzoic acid and hydroxylamine</td>

<td> 492</td><td>5 (N-hydroxycarbamidoyl) pyridine-2-carboxylic acid methyl ester</td><td>Methyl ester of 5 cyano-pyridine-2-carboxylic acid and hydroxylamine</td>

<td> 493</td><td>Ethyl ester of 2-fluoro-4- (N-hydroxycarbamidoyl) -benzoic acid</td><td>Ethyl ester of 4-cyano-2-fluoro-benzoic acid and hydroxylamine</td>

<td> 494</td><td>Methyl ester of benzoic acid 4 (N-hydroxycarbamidoyl)</td><td>Methyl ester of 4Cano-benzoic acid and hydroxylamine</td>

<td> 495</td><td>[3 (N-hydroxycarbamidoyl) phenoxy] -acetic acid methyl ester</td><td>Methyl ester of (3-cyano-phenoxy) -acetic acid and hydroxylamine</td>

<td> 496</td><td>N-Hydroxy-2-methyl-1Hbenzoimidazole-5carboxamidine</td><td>2-Methyl-1H-benzoimidazole-5-carbonitrile and hydroxylamine</td>

<td> 497</td><td>2-Amino-N-hydroxyisonicotinamidine</td><td>2-Amino- isonicotinonitrile and hy- droxylamine</td>

<td> 498</td><td>3, N-Dihydroxy-benzamidine</td><td>3-Hydroxy-benzonitrile and hydroxylamine</td>

<td> 499</td><td>4, N-Dihydroxy-benzamidine</td><td>4-Hydroxy-benzonitrile and hydroxylamine</td>

<td> 500</td><td>4- (N-hydroxycarbamimidoyl) -benzoic acid</td><td>4-Cyano-phenylboronic acid and hydroxylamine</td>

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<td>Example</td><td>Broker name</td><td>Starting materials</td>

<td> 501</td><td>N-Hydroxy-furan-2carboxamidine</td><td>Furan-2-carbonitrile and hydroxylamine</td>

<td> 502</td><td>N-Hydroxy-4-methyl- [1,2,3] thiadiazole-5carboxamidine</td><td>4-Methyl- [1,2,3] thiadiazole-5-carbonitrile and hydroxylamine</td>

<td> 503</td><td>N-Hydroxy-2,5-dimethyl-2Hpyrazol-3-carboxamidine</td><td>2,5-Dimethyl-2H-pyrazole- 3-carbonitrile and hydroxylamine</td>

<td> 504</td><td>N-Hydroxy-1H-pyrazol-4carboxamidine</td><td>lH-Pyrazol-4-carbonitrile and hydroxylamine</td>

<td> 505</td><td>N-Hydroxy-5-methyl- isoxazole-3-carboxamidine</td><td>5-Methyl-isoxazole-3carbonitrile and hydroxylamine</td>

<td> 506</td><td>N-Hydroxy-1H-pyrazol-3carboxamidine</td><td>lH-Pyrazol-3carbonitrile and hydroxylamine</td>

<td> 507</td><td>N-Hydroxy-2,4-dioxo- 1,2,3,4-tetrahydro-pyrimi- dine-5-carboxamidine</td><td>2,4-Dioxo-1, 2,3,4- tetrahydro-pyrimidine-5carbonitrile and hydroxylamine</td>

<td> 508</td><td>6-Amino-N-hydroxy- nicotinamidine</td><td>6-Amino-nicotinonitrile and hydroxylamine</td>

<td> 509</td><td>N-Hydroxy-imidazo [1,2- a] pyridine-6carboxamidine</td><td>Imidazo [1,2-a] pyridine- 6-carbonitrile and hydroxylamine</td>

<td> 510</td><td>N- [4-Fluoro-3- (Nhydroxycarbamimidoyl) phenyl] -acetamide</td><td>N- (3-Cyano-4-fluorophenyl) -acetamide and hydroxylamine</td>

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<td>Example</td><td>Broker name</td><td>Starting materials</td>

<td> 511</td><td>N- [5-Fluoro-3- (Nhydroxycarbamimidoyl) phenyl] -acetamide</td><td>N- (3-Cyano-5-fluorophenyl) -acetamide and hydroxylamine</td>

<td> 512</td><td>N- [6-Fluoro-3- (Nhydroxycarbamimidoyl) phenyl] -acetamide</td><td>N- (3-Cyano-6-fluorophenyl) -acetamide and hydroxylamine</td>

<td> 513</td><td>N-Hydroxy-3-oxo-3,4-dihydro-2H- benzo [1,4] oxazine-6carboxamidine</td><td>3-Oxo-3,4-dihydro-2Hbenzo [1,4] oxazine-6carbonitrile and hydroxylamine</td>

<td> 514</td><td>N-Hydroxy-2-oxo-1,4-hydroxy-2Hbenzo [d] [1,3] oxazine-6carboxamidine</td><td>2-Oxo-1,4-dihydro-2Hbenzo [d] [1,3] oxazine-6carbonitrile and hydroxylamine</td>

<td> 515</td><td>N-Hydroxy-2-oxo-1,2,3,4tetrahydro-quinazoline-7carboxamidine</td><td>2-Oxo-1,2,3,4-tetrahydroquinazoline-7carbonitrile and hydroxylamine</td>

<td> 516</td><td>3- (1, l-Dioxo-Ιλβisothiazolidin-2-yl) -Nhydroxy-benzamidine</td><td>3- (1,1-Dioxo-1À6isothiazolidin-2-yl) benzonitrile and hydroxylamine</td>

<td> 517</td><td>N-Hydroxy-3- (2-oxopyrrolidin-1-yl) benzamidine</td><td>3- (2-0xo-pyrrolidin-lil) -benzonitrile and hydroxylamine</td>

<td> 518</td><td>3- (2,4-Dioxoimidazolidin-1-yl) -Nhydroxy-benzamidine</td><td>3- (2,4-Dioxoimidazolidin-1-yl) benzonitrile and hydroxylamine</td>

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<td>Example</td><td>Broker name</td><td>Starting materials</td>

<td> 519</td><td>N-Hydroxy-3- (5-oxo-1,5, 5-hydro- [1,2,4] triazol-4yl) -benzamidine</td><td>3- (5-Oxo-1,5-dihydro- [1,2,4] triazol-4-yl) - benzonitrile and hydroxylamine</td>

The following compounds were generated in analogy to example 312

<td>Example</td><td>Broker name</td><td>Starting materials</td>

<td> 520</td><td>N-Amino-2- Hydrochloride Oxo-2,3-dihydro-1H-indole- 5-carboxamidine</td><td>2-Oxo-2,3-dihydro-1Hindol-5-carbonitrile and hydrazine</td>

<td> 521</td><td>N-Amino-1H- Hydrochloride Indazol-5-carboxamidine</td><td>1H-Indazole-5- carbonitrile and hydrazine</td>

<td> 522</td><td>N-Amino-1H- Hydrochloride Indol-5-carboxamidine</td><td>lH-Indole-5-carbonitrile and hydrazine</td>

<td> 523</td><td>N-Amino-1H- Hydrochloride Benzotriazole-5- carboxamidine</td><td>lH-Benzotriazole-5carbonitrile and hydrazine</td>

<td> 524</td><td>N-Amino-2Oxo-2,3-dihydro-1Hbenzoimidazole-5carboxamidine hydrochloride</td><td>2-Oxo-2,3-dihydro-1Hbenzoimidazole-5carbonitrile and hydrazine</td>

<td> 525</td><td>N-Amino-NHhydroxy-2-methyl-1Hbenzoimidazole-5carboxamidine hydrochloride</td><td>2-Methyl-1Hbenzoimidazole-5carbonitrile and hydrazine</td>

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<td>Example</td><td>Broker name</td><td>Starting materials</td>

<td> 526</td><td>N-Amino-2- Hydrochloride Amino-isonicotinamidine</td><td>2-Amino-isonicotinoni- trila and hydrazine</td>

<td> 527</td><td>N-Amino-3- Hydrochloride (5-Oxo-4,5-dihydro- [1,3,4] oxadiazol-2-yl) benzamidine</td><td>3- (5-Oxo-4,5-dihydro- [1,3,4] oxadiazol-2-yl) benzonitrile and hydrazine</td>

<td> 528</td><td>N-Amino-3- Hydrochloride [1,3,4] Oxadiazol-2-ylbenzamidine</td><td>3- [1,3,4] Oxadiazol-2-ylbenzonitrile and hydrazine</td>

<td> 529</td><td>N- acid hydrochloride Amino-3-Carbamidoyl- phenylboronic</td><td>3-Cyano-phenylboronic acid and hydrazine</td>

<td> 530</td><td>N-Amino-2fluoro-benzamidine hydrochloride</td><td>2-Fluorobenzonitrile and hydrazine and hydrazine</td>

<td> 531</td><td>N-Amino-6- Hydrochloride Amino-nicotinamidine</td><td>6-Amino-nicotinonitrile and hydrazine</td>

<td> 532</td><td>N-Amino-4Carbamimidoyl-benzoic acid methyl ester hydrochloride</td><td>4- Acid methyl ester Cyano-benzoic and hydrazine</td>

<td> 533</td><td>N-Amino-4- Hydrochloride Fluoro-benzamidine</td><td>4-Fluoro-benzonitrile and hydrazine</td>

<td> 534</td><td>N-Amino-3- Hydrochloride Fluoro-benzamidine</td><td>3-Fluoro-benzonitrile and hydrazine</td>

Example 535

N- (5-Cyano-2-fluoro-phenyl) -acetamide

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10 mmol of 3-amino-4-fluoro-benzonitrile were dissolved in 30 ml of THF. 1.5 equivalents of DIPEA were added and the reaction mixture was cooled to 0 ° C. 1.2 equivalents of 5 acetylchloride were added dropwise, the reaction was warmed to room temperature and subjected to stirring for an additional 30 minutes. The solvent was evaporated and the product isolated by extraction from ethyl acetate and saturated NaHCCb solution.

MS (ISO): 179.2 (MH +)

Example 536

N- (3-Cyano-5-fluoro-phenyl) -acetamide

The title compound was prepared in analogy to example 535 from 3-Amino-5-Fluoro15 benzonitrile. MS (ISO): 179.2 (MH +)

Example 537

N- (3-Cyano-4-fluoro-phenyl) -acetamide

The title compound was prepared in analogy to example 535 from 5-Amino-2-Fluoro20 benzonitrile. MS (ISO): 179.2 (MH +) · “Example 538

3-Oxo-3,4-dihydro-2H-benzo [1,4] oxazine-6-carbonitrile

24 mmol of 4-hydroxy-3-nitrobenzonitrile were dissolved in DMF. 1.1 equiva25 C lenses were added₂CO₃ and the reaction was subjected to stirring at room temperature for 15 minutes. 1.5 equivalents of ethylbromo acetate were added and the mixture

The reaction was heated to 50 ° C for 2 hours. The intermediate was isolated by extraction from ethyl acetate / water. The organic layer was separated and dried over Na₂ONLY₄. After evaporation, the resulting solid was redissolved in MeOH and saturated NH₄C1 (1: 1). 8 g of Zn powder was added and the suspension was stirred at room temperature for 2 hours. The solid was filtered off and the organic layer evaporated. Ethyl acetate was added and the organic layer washed with NaHCO₃ saturated. The organic layer was separated again, subjected to drying over Na₂ONLY₄ and reduced, resulting in a light brown solid.

MS (ISO): 175.2 (MH +)

Example 539

2-Oxo-1,4-dihydro-2H-benzo [d] [1,3] oxazine-6-carbonitrile 20 mmol of 4-amino-3hydroxymethyl-benzonitrile were dissolved in THF. 1.2 equivalents of DIPEA were added and the reaction cooled to 0 ° C.

3.5 equivalents of ethyl chloroformate were added dropwise and the reaction warmed to room temperature and subjected to stirring for another 15 minutes. The crude material was extracted from ethyl acetate and NaHCO₃ saturated. After separation, and drying the organic layer, the solvent was evaporated and the crude was collected in toluene. 2.5 ml of DBU were added and the reaction mixture was refluxed for 4

217/229 hours. The organic layer was extracted with water and the organic layer separated and reduced resulting in a yellow oil. The raw material was no longer characterized.

Example 540

2-Oxo-1,2,3,4-tetrahydro-quinazoline-7-carbonitrile

24 mmol of hydrochloride were dissolved

2-nitro-4-chloro-benzylamine in THF. 2.2 equivalents of DIPEA were added and the reaction mixture cooled to 0 ° C. 3.5 equivalents of ethyl chloroformate were added dropwise and the reaction was stirred for 15 minutes. After extraction from saturated ethyl acetate / NaHCCb and evaporation of the organic layer, a light brown solid resulted. This was collected in saturated MeOH / NH4Cl (1: 1). 15 6 g of Zn were added and the suspension was stirred at room temperature for 4 hours. The solid was removed by filtration, methanol reduced and the product isolated by means of extraction with ethyl acetate. After evaporation, a light yellow solid was obtained.

MS (ISO): 174.2 (MH +)

Example 541

3- (5-Oxo-1,5-dihydro- [1,2,4] triazol-4-yl) -benzonitrile

2 g of 3-aminobenzonitrile were dissolved in 20 ml of MeOH. 1.8 ml of trimethyl 25 orthoformate, methyl ester of hydrazinecarboxylic acid and para-toluenesulfonic acid catalyst were added. The reaction mixture was heated to 65 ° C for 3 hours.

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The suspension was cooled to room temperature and 9 ml of NaOMe solution was added and the reaction mixture was stirred at room temperature for 2 hours. Water was added and the pH was set at 5 to 1 using aqueous HCl (25%). The resulting suspension was removed by filtration and subjected to vacuum drying. MS (ISO): 187.2 (MH +)

Example 542

3- (2,4-Dioxo-imidazolidin-1-yl) -benzonitrile

1 g of 3-aminobenzonitrile was dissolved in ml of Dioxan and 0.8 ml of chloroacetyl isocyanate was added. The reaction mixture was stirred at room temperature for 2 hours. 2.5 ml of DBU was added and the reaction mixture was stirred at room temperature for 40 hours. The product was extracted with DCM. MS (ISO): 202.2 (MH +)

Example 543

3- (1,1-Dioxo-lÀ6-isothiazolidin ~ 2-yl) -benzonitrile

1 g of 3-aminobenzonitrile was dissolved in ml of DCM and 2.2 ml of DIPEA. 1.3 ml of 3-chloro-propane-1-sulfonyl chloride was added and the reaction mixture was stirred at room temperature overnight. The organic layer was evaporated, the crude product collected in DMF and 1.5 ml of

DBU. The reaction mixture was stirred at room temperature overnight. DCM was added

219/229 and the organic phase was washed with water. The organic layer was separated, subjected to drying over Na₂ONLY₄ and evaporated. MS (ISO): 232.2 (MH +)

Example 544

3- (2-0xo-pyrrolidin-l-yl) -benzonitrile

2 g of 3-aminobenzonitrile were dissolved in 20 ml of DMF and 4.4 ml of DIPEA. The reaction mixture was cooled to 0 ° C and 2 ml of 4-chloro-butyryl chloride was added. The reaction mixture was stirred at room temperature for 1 hour. 5 ml of DBU was added and the reaction mixture was stirred at room temperature overnight. DCM was added and the organic phase was washed with IN HCL and water. The organic layer was separated, subjected to drying over Na₂ONLY₄ and evaporated.

MS (ISO): 187.2 (MH +)

Example 545

6-Chloro-3-hydroxy-pyridazine-4-carboxylic acid

2 mmol of 3,620 dichloropyridazine-4-carboxylic acid were treated with 8 ml of 2N aqueous NaOH and refluxed for 1 hour. The reaction mixture was acidified to pH = 1. The resulting white solid was removed by filtration and subjected to vacuum drying.

MS (ISO): 173.2 (M-H +)

Example 546

3- (5-oxo-1,5-dihydro- [1,2,4] triazol-4-yl) -benzoic acid

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13 mmol of methyl-3aminobenzoate was dissolved in 20 ml of MeOH. 12 mmol of trimethylortoformate, 12 mmol of methyl hydrazinecarboxylate and 50 mg of p-toluenesulfonic acid were added. The suspension was heated for 48 hours to 65 ° C. 37 mmol of sodium methanolate were added and stirred for an additional 2 hours. The organic layer was reduced and water was added. The solution was acidified to pH = 1 and the resulting solid removed by filtration to give 5.7 mmol of the product.

MS (ISO): 204.2 (M-H +)

Example 547

3- (2,4-Dioxo-imidazolidin-1-yl) -benzoic acid

12 mmol of ethyl-3aminobenzoate was dissolved in 120 ml of Dioxane. 1 equivalent of chloroacetyl isocyanate was added. The reaction mixture was stirred at room temperature for 1 hour and then heated to 120 ° C for an additional 2 hours. The reaction was cooled to room temperature, 2 equivalents of DBU were added and stirred again at room temperature overnight. The solvent was evaporated and the crude extracted from DCM. The crude material was dissolved in 20 ml of MeOH and 4 ml of 4N NaOH were added. The reaction mixture was stirred at room temperature for 20 hours. After evaporation of the organic layer, the aqueous phase was

221/229 citrated to pH = the resulting white solid oil was removed by filtration and subjected to vacuum drying. MS (ISO): 219.2 (M-H +)

Example 548 _{__}__5 3- (1, l-dioxo-l6- [1,2,5] thiadiazolidin-2-yl) -benzoic acid

13 mmol of methyl-3aminobenzoate were dissolved in 20 ml of DCM and 3 ml of TEA were added. 1.6 ml of 310 chloropropanesulfonyl chloride was added slowly under an argon atmosphere. The reaction mixture was stirred at room temperature overnight and washed with IN HCI. The organic layer was separated, dried over Na2SO4 and reduced in vacuo. The resulting crude was taken up in 16 ml of DMF and 2.4 ml of DBU was added. The reaction mixture was stirred at room temperature for 2 hours and washed with IN HCI. The crude material was dissolved in 20 ml of MeOH and 4 ml of 2N NaOH was added. The reaction mixture was stirred at room temperature for 72 hours and acidified with HCl to pH = 1. The resulting white solid was removed by filtration and subjected to vacuum drying. MS (ISO): 241.3 (M-H +)

Example 549

3- (2-Oxo-2,3-dihydro-imidazol-1-yl) -benzoic acid

12 mmol of ethyl-3aminobenzoate was dissolved in 20 ml of DCM and 2 ml of

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TEA. The reaction mixture was cooled to ° C and 1.5 ml of Diphosgen was added slowly. The reaction mixture was warmed to room temperature and subjected to stirring for an additional 1 hour under up to 5 argon. The reaction mixture was poured into ice and the organic layer separated, subjected to drying over Na₂ONLY₄ and reduced under vacuum. The crude material was collected in 30 ml of DCM and 1.3 ml of dimethylacetal aminoacetaldehyde was added. Reaction mixture 10 was stirred for 3 hours at room temperature. The organic layer was washed with NaHCO₃saturated, separated and dried over Na₂ONLY₄. After evaporation of the solvent, the resulting crude material was purified by means of 15 Kieselgel chromatography. 200 mg of the product were dissolved in 5 ml of

MeOH and 2 ml of 2N NaOH were added. The reaction mixture was stirred at room temperature for 2 hours, acidified with HCI to pH = the resulting white solid oil was removed by filtration.

MS (ISO): 203.2 (M-H +)

Example 550

3- (2,5-Dioxo-imidazolidin-1-yl) -benzoic acid

13 mmol of methyl-3aminobenzoate were dissolved in 20 ml of DCM and 1.7 ml 25 of ethyl isocyanate acetate were added. The reaction mixture was stirred at room temperature for 1 hour. The solvent was evaporated and the resulting crude was taken up in 50 ml of acetone. 50 ml of

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Aqueous HCl (25%) and heated to reflux for 8 hours. After evaporation of the organic layer, the resulting solid was removed by filtration, washed with water and subjected to vacuum drying.

MS (ISO): 219.2 (M-H +)

Example 551

3-Oxo-3,4-dihydro-2H-benzo [1,4] oxazine-6-carboxamidine

8.7 mmol of N-Hydroxy-3oxo-3,4-dihydro-2H-benzo [1,4] oxazine-6-carboxamidine were dissolved in 10 ml of acetic acid. 5 equivalents of ammonium formate and 0.05 equivalents of Pd / C (10%) were added and the reaction mixture heated to reflux overnight. The reaction mixture was concentrated, cooled to 0 ° C and the pH adjusted to 8 using aqueous NaOH 15 (28%). The resulting solid was removed by filtration and washed with water.

MS (ISO): 192.2 (M-H +)

The following intermediate compounds were generated in analogy to example 551

<td>Example</td><td>Broker name</td><td>Starting material</td>

<td> 552</td><td>&gt; Imidazo [1,2-a] pyridine-6carboxamidine</td><td>N-Hydroxy-imidazo [1,2a] pyridine-6carboxamidine</td>

<td> 553</td><td>1H-Benzoimidazole-5carboxamidine</td><td>N-Hydroxy-1H-benzoimide- zol-5-carboxamidine</td>

<td> 554</td><td>Nicotinamidine</td><td>N-Hydroxy-nicotinamidine</td>

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<td>Example</td><td>Broker name</td><td>Starting material</td>

<td> 555</td><td>3,5-Dimethyl-isoxazole-4carboxamidine</td><td>N-Hydroxy-3,5-dimethyl- isoxazole-4-carboxamidine</td>

<td> 556</td><td>Thiophene-2-carboxamidine</td><td>N-Hydroxy-thiophene-2carboxamidine</td>

<td> 556</td><td>Pyrimidine-2carboxamidine</td><td>N-Hydroxy-pyrimidine-2carboxamidine</td>

<td> 557</td><td>4-Methyl-oxazole-5- carboxamidine</td><td>N-Hydroxy-4-methyl- oxazoi-5-carboxamidine</td>

<td> 558</td><td>Pyrazine-2-carboxamidine</td><td>N-Hydroxy-pyrazine-2carboxamidine</td>

<td> 559</td><td>2-Methyl-isonicotinamidine</td><td>N-Hydroxy-2-methylisonicotinamidine</td>

<td> 560</td><td>2-Oxo-1,4-dihydro-2Hbenzo [d] [1,3] oxazine-6carboxamidine</td><td>N-Hydroxy-2-oxo-1,4-hydroxy-2H- benzo [d] [1,3] oxazine-6- carboxamidine</td>

<td> 561</td><td>2-Oxo-1,2,3,4-tetrahydroquinazoline-6carboxamidine</td><td>N-Hydroxy-2-oxo-1,2,3,4tetrahydro-quinazoline-6carboxamidine</td>

<td> 562</td><td>3- (2,4-Dioxoimidazolidin-1-yl) benzamidine</td><td>3- (2,4-Dioxoimidazolidin-1-yl) -Nhydroxy-benzamidine</td>

<td> 563</td><td>N- (3-Carbamidoyl-4- fluoro-phenyl) -acetamide</td><td>N- [4-Fluoro-3- (Nhydroxycarbamidoyl) phenyl] -acetamide</td>

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<td>Example</td><td>Broker name</td><td>Starting material</td>

<td> 564</td><td>N- (3-Carbamidoyl-5fluoro-phenyl) -acetamide</td><td>N- [5-Fluoro-3- (Nhydroxycarbamidoyl) phenyl] -acetamide</td>

<td> 565</td><td>N- (3-Carbamidoyl-6fluoro-phenyl) -acetamide</td><td>N- [6-Fluoro-3- (Nhydroxycarbamidoyl) phenyl] -acetamide</td>

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Example A

Film-coated tablets

<td colspan="5">containing the ingredients shown below can</td><td rowspan="2">to be</td>

<td> *</td><td>manufactured in a way</td><td colspan="3">conventional:</td>

<td>yo</td><td>Ingredients</td><td>Per</td><td></td><td></td><td></td>

<td></td><td></td><td>Tablet</td><td></td><td></td><td></td>

<td></td><td>Core:</td><td></td><td></td><td></td><td></td>

<td></td><td>Compound of formula (I)</td><td>10.0 mg</td><td></td><td> 200,0</td><td>mg</td>

<td></td><td>Microcrystalline cellulose</td><td>23.5 mg</td><td></td><td> 43,5</td><td>mg</td>

<td></td><td>Water lactose</td><td>60.0 mg</td><td></td><td> 70,0</td><td>mg</td>

<td></td><td>Povidone K30</td><td>12.5 mg</td><td></td><td> 15,0</td><td>mg</td>

<td></td><td>Sodium starch glycolate</td><td>12.5 mg</td><td></td><td> 17,0</td><td>mg</td>

<td></td><td>Magnesium stearate</td><td>1.5 mg</td><td></td><td> 4,5</td><td>mg</td>

<td></td><td>(Core Weight)</td><td>120.0 mg</td><td></td><td> 350,0</td><td>mg</td>

<td></td><td>Film coating:</td><td></td><td></td><td></td><td></td>

<td></td><td>Hydroxypropyl methyl cellulose</td><td>3.5 mg</td><td></td><td> 7,0</td><td>mg ·</td>

<td></td><td>Polyethylene glycol 6000</td><td>0.8 mg</td><td></td><td> 1,6</td><td>mg</td>

<td></td><td>Baby powder</td><td>1.3 mg</td><td></td><td> 2, 6</td><td>mg</td>

<td></td><td>Iron oxide (yellow)</td><td>0.8 mg</td><td></td><td> 1,6</td><td>mg</td>

<td rowspan="2">li</td><td>Titanium dioxide</td><td>0.8 mg</td><td></td><td> 1,6</td><td>mg</td>

<td>5 0 ingredient</td><td>active is</td><td colspan="2">sifted</td><td>and</td>

<td> 0·</td><td colspan="2">mixed with microcrystalline cellulose and</td><td>The</td><td colspan="2">mixture is</td>

granulated with a solution of polyvinylpyrrolidone in water. The granulate is mixed with sodium starch glycolate and magnesium stearate and compressed to provide 120 or 350 mg cores, respectively. The cores are lacquered with a

227/229 aforementioned film coating solution / suspension.

Example B

Capsules containing the following ingredients can be manufactured in a conventional manner:

Ingredients

Per capsule

Compound of formula (I)

25.0 mg

Lactose

150.0 mg

Maize starch

20.0 mg

Baby powder

5.0 mg

The components are sieved and mixed and filled in size capsules

2.

Example C

Can injection solutions have a?

composition shown below:

Compound of formula (I)

Polyethylene Glycol 400

Acetic Acid

Water for injection solutions

3,0

150.0 mg mg to a final pH of 5.0 aj. 1.0 ml

The active ingredient is dissolved in a mixture of Polyethylene glycol 400 and water for injection (part). The pH is adjusted to 5.0 by adding 15 acetic acid. The volume is adjusted to 1.0 ml by adding the residual amount of water. The solution is

228/229 filtered, poured into bottles using appropriate surplus and sterilized.

Example D

Soft gelatin capsules that contain the following ingredients can be manufactured in a conventional manner:

Capsule contents

<td>Compound of formula (I)</td><td> 5,0</td><td>mg</td>

<td>Yellow wax</td><td> 8,0</td><td>mg</td>

<td>Hydrogenated soybean oil</td><td> 8,0</td><td>mg</td>

<td>Hydrogenated partial vegetable oils</td><td> 34,0</td><td>mg</td>

<td>Soy oil</td><td> 110,0</td><td>mg</td>

<td>Weight of capsule contents</td><td> 165,0</td><td>mg</td>

Gelatin capsule

<td>Gelatine</td><td>75.0 mg</td>

<td>Glycerol 85%</td><td>32.0 mg</td>

<td>Karion 83</td><td>8.0 mg (mat</td>

<td></td><td>dry)</td>

<td>Titanium dioxide</td><td>0.4 mg</td>

<td>Yellow iron oxide</td><td>1.1 mg</td>

<td>0 active ingredient</td><td>is dissolved in a</td>

warm melt from the other ingredients and the mixture is poured into soft gelatin capsules of the appropriate size. The filled soft gelatin capsules are treated according to usual procedures.

Example E

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Sachets containing the following ingredients can be manufactured in a conventional manner:

Compound of formula (I)

Milky, fine powder

Microcrist cellulose. (AVICEL PH 102)

Sodium carboxymethyl cellulose

Polyvinylpyrrolidone K 30

Magnesium stearate

Flavoring additives

<td> 50,0</td><td>mg</td>

<td> 1015,0</td><td>mg</td>

<td> 1400,0</td><td>mg</td>

<td> 14,0</td><td>mg</td>

<td> 10, 0</td><td>mg</td>

<td> 10,0</td><td>mg</td>

<td> 1,0</td><td>mg</td>

active ingredient is mixed with lactose, microcrystalline cellulose and sodium carboxymethyl cellulose and then granulated with a mixture of polyvinylpyrrolidone in water. The granules are mixed with magnesium stearate and flavoring additives and poured into sachets.

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