Substituted quinoline-3-carboxamides as KCNQ2/3 modulators

Substituted quinoline-3-methamide as KCNQ2/3 regulator

The present invention relates to substituted quinoline-3-carboxamides, pharmaceutical compositions containing these compounds and the use of these compounds in the treatment and/or prevention of pain, and other diseases and/or disorders.

The treatment of pain, especially the treatment of pain caused by neuropathy, is of considerable importance in medicine. There is a demand for effective pain treatment all over the world. This urgent need for the treatment of patients and targeted chronic and non-chronic pain states is understood here as giving patients effective and satisfactory treatment of pain, and it has also been widely documented in the past in the application of analgesics Or in scientific papers in the field of basic research on pain perception.

The pathophysiological feature of chronic pain is the excessive stress of the nerve cell itself. The stress of nerve cell body is mainly affected by potassium ion (K⁺) The channel activity is affected, because these channels control the membrane potential of the cell when it is resting, and therefore also influence the threshold of stress. Heteropolymer potassium ion (K) with molecular subtype KCNQ2/3 (Kv.7.2/7.3)⁺) Channels are expressed in nerve cells in different regions of the central nervous system (hippocampal gyrus, brain amygdala) and peripheral nervous system (dorsal root ganglia), and regulate the stress of these cells. Activate KCNQ2/3 potassium ion (K⁺The) channel causes the cell membrane to be excessively polarized, and thus further reduces the electrical stress of the nerve cells. The dorsal root ganglion exhibits KCNQ2/3 nerve cells involved in transmitting the stimulation received by pain sensory receptors from the peripheral nerves to the spinal cord (Passmore et al., J Neurosci. 2003; 23(18): 7227-36).

Therefore, the agonist of KCNQ2/3, Retigabine, can be proven to have analgesic effects in preclinical neuropathology and inflammatory pain models (Blackburn-Munro and Jensen, Eur J Pharmacol. 2003:460(2-3): 109-16; Dost et al., Naunyn Schmiedebergs Arch Pharmacol 2004; 369(4):382-390).

KCNQ2/3 potassium ion (K⁺) Channel is therefore a suitable focus for the treatment of pain; especially for the treatment of pain (Nielsen et al., Eur J Pharmacol. 2004; 487(1-3):93-103); especially for the treatment of pain caused by neuropathy and pain caused by inflammation.

In addition, KCNQ2/3 potassium ion (K⁺) Channel is also a suitable target for the treatment of some other diseases, such as migraine (US2002/0128277), cognitive disorders (Gribkoff, Expert Opin Ther Targets 2003; 7(6): 737-748), anxiety states ( Korsgaard et al., J Pharmacol Exp Ther. 2005,14(1):282-92), epilepsy (Wickenden et al., Expert Opin Ther Pat 2004,14(4):457-469; Gribkoff, Expert Opin Ther Targets 2008;12(5):565-81 ; Micell et al., Curr Opin Pharmacol 2008, 8(1): 65-74), urinary incontinence (Streng et al., J Urol 2004; 172: 2054-2058), addiction (Hansen et al., Eur J Pharmacol 2007,570(1-3):77-88), bipolar disorder/bipolar disorder (Dencker et al., Epilepsy Behav 2008,12(1):49-53), related to dystonia Involuntary movement (Richter et al., Br. J Pharmacol 2006,149(6):747-53).

For example, it is known from the previous technical level (WO 2008/046582, WO 2010/046108) that the substituted compound has an effect on KCNQ2/3 potassium ion (K⁺) The channel has affinity. Regulating agents for melanin expression are, for example, known from WO 2008/121850 A2. The heterocyclic regulator of TGR5 is for example known from WO 2008/097976 A1. The 4-hydroxy-substituted quinol derivatives are, for example, learned from US Patent No. 4,450,167 and US Patent No. 4,518,775.

WO 2007/133637 discloses amide derivatives, which can alter the ion channels of mammals, such as the VR1 cation channel. These compounds help treat various mammalian diseases, including pain, inflammation, traumatic injury and others.

French patent FR 2532939 discloses that 2-substituted 4-hydroxy-quinoline-formamide has analgesic and anti-inflammatory effects.

WO 2010/094644 and WO 2010/094645 disclose substituted morpholinyl pyridine derivatives and 1,4-oxazepine cycloheptyl. Two compounds are described as voltage gate K_v7(KCNQ) Modulator of potassium ion channel. These compounds are helpful in the treatment of various diseases, including pain, epilepsy, schizophrenia, urinary incontinence and the like.

WO 2008/007211 discloses substituted N-bicycloalkylbicyclocarboxamide compounds and the use of these compounds in the treatment of mammalian diseases caused by excessive activation of VR1 receptors, such as pain. Similarly, WO 2008/050199 discloses substituted phenylmethylbicyclocarboxamide compounds, which are useful for treating diseases such as pain caused by excessive activation of VR1 receptors in mammals.

European patent EP 0 089 597 discloses sulfonylurea derivatives and the use of these derivatives as anti-diabetic drugs.

In addition, in addition to having affinity for KCNQ2/3, other compounds that are comparable or better in properties such as (strength, curative effect) are also required.

Therefore, it would be advantageous to improve the stability of metabolites, which is equal to the solubility in the aqueous vehicle or the permeability of the compounds. These factors can produce favorable results for oral bioavailability, or can change the quantitative curve of PK/PD (pharmacokinetics/pharmacodynamics), which can, for example, produce a more favorable effect time. At the same time, weak or no interaction with the transport molecules involved in the absorption and excretion of the pharmaceutical composition is also regarded as evidence of improved bioavailability and at least low interaction with the pharmaceutical composition. In addition, the interaction with the enzymes involved in the decomposition and excretion of the pharmaceutical composition should also be as small as possible, because the results of these tests also suggest that the pharmaceutical composition is expected to be at most low or no interaction. effect.

In addition, it would be advantageous if these compounds show a high degree of selectivity (specificity) for other receptors of the KCNQ group, such as KCNQ1, KCNQ3/5 or KCNQ4. A high degree of selectivity can produce favorable results for the quantitative curve of side effects: for example, compounds that are known to (also) bind to KCNQ1 have a high risk of cardiac side effects, because the high degree of selectivity to KCNQ1 can be expected. However, it would also be advantageous to have high selectivity for other receptors. For example, a low affinity with human ERG ion channels or with left-handed calcium ion channels (phenylalkylamine binding site, benzothiazepine binding site, dihydropyridine binding site) will also It is advantageous because these receptors are known to cause cardiac side effects. In addition, when the selectivity of binding to other endogenous proteins (ie, receptors or enzymes) is improved, the quantitative curve of side effects can be improved, and thus its tolerance can be improved.

The purpose of the present invention is therefore to provide novel compounds, which have more advantages than the compounds under the current state of the art. These compounds should be particularly suitable as pharmacologically active substances in pharmaceutical compositions, especially for the treatment and/or prevention of at least partly caused by KCNQ2/3 potassium ion (K⁺) The pharmacologically active substance in the medical composition of the disease or condition promoted by the channel.

This purpose is achieved by applying for the subject matter of the patent scope.

The present invention unexpectedly discovered that the substituted compound having the general formula (1) shown in the figure below is suitable for the treatment of pain. In addition, the present invention also unexpectedly discovered that the substituted compound with the general formula (1) shown in the figure below has the effect of KCNQ2/3 potassium ion (K⁺) Channel also has excellent affinity, so it is suitable to be used to treat and/or prevent at least partly caused by KCNQ2/3 potassium ion (K⁺) Diseases or illnesses promoted by the channel. The mode of action of these substituted compounds is KCNQ2/3 potassium ion (K⁺) Channel modulator, that is, agonist or antagonist.

The present invention therefore relates to substituted compounds of general formula (I),

<chemistry general="n"><img file="TW201210596A_D0001.tif" /></chemistry>

Where R¹Represents an aliphatic hydrocarbon residue containing 1 to 10 carbon atoms, which is unsubstituted or substituted once or several times; a cycloaliphatic hydrocarbon residue containing 3 to 10 carbon atoms or a cycloaliphatic hydrocarbon residue containing 3 to 10 rings Membered heterocyclic aliphatic hydrocarbon residues, each of which is unsubstituted or substituted once or several times, and each of them can optionally form a bond via an aliphatic hydrocarbon functional group containing 1 to 8 carbon atoms, and It can also be unsubstituted or substituted once or several times; aryl or heteroaromatic group, each of which is unsubstituted or substituted once or several times, and each of them can be optionally substituted by a containing 1 to 8 The aliphatic hydrocarbon functional group of three carbon atoms forms a bond, and it may be unsubstituted or substituted once or several times; R²Represents hydrogen, fluorine, chlorine, bromine, iodine and other atoms, cyano, trifluoromethyl, aldehyde, nitro, trifluoromethoxy, trifluoromethylthio, an aliphatic hydrocarbon containing 1 to 4 carbon atoms Residues, an aliphatic hydrocarbon residue carbonyl group containing 1 to 4 carbon atoms, an aliphatic hydrocarbon residue oxycarbonyl group containing 1 to 4 carbon atoms, an N- (aliphatic hydrocarbon residue containing 1 to 4 carbon atoms) Group) amide group, one N,N-di (aliphatic hydrocarbon residue containing 1 to 4 carbon atoms) amide group, wherein the aliphatic hydrocarbon residue containing 1 to 4 carbon atoms may be each unsubstituted Or it may be substituted once or several times; an aliphatic hydrocarbon residue oxy group containing 1 to 4 carbon atoms, an aliphatic hydrocarbon residue carbonyloxy group containing 1 to 4 carbon atoms, and an aliphatic hydrocarbon residue carbonyloxy group containing 1 to 4 carbon atoms Aliphatic hydrocarbon residue sulfur group, an aliphatic hydrocarbon residue sulfonyl group containing 1 to 4 carbon atoms, an aliphatic hydrocarbon residue oxysulfonyl group containing 1 to 4 carbon atoms, wherein the aliphatic hydrocarbon residue group contains 1 to 4 carbon atoms The aliphatic hydrocarbon residues of carbon atoms can each be unsubstituted or substituted once or several times; a cycloaliphatic hydrocarbon residue containing 3 to 6 carbon atoms or a heterocyclic aliphatic hydrocarbon residue containing 3 to 6 ring members Groups, each of which is unsubstituted or substituted once or several times, and each of them can optionally form a bond through an aliphatic hydrocarbon functional group containing 1 to 4 carbon atoms, and they can be unsubstituted Or replaced by one or several times; R³, R⁴, R⁵And R⁶Independently of each other, it represents hydrogen, fluorine, chlorine, bromine, iodine and other atoms, cyano, trifluoromethyl, aldehyde, carboxy, amide, trifluoromethylthio, hydroxysulfonyl, nitro, trifluoro Methoxy; an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, an aliphatic hydrocarbon residue carbonyl containing 1 to 4 carbon atoms, an aliphatic hydrocarbon residue oxycarbonyl containing 1 to 4 carbon atoms, One N- (aliphatic hydrocarbon residue containing 1 to 4 carbon atoms) amide group, one N,N-di (aliphatic hydrocarbon residue containing 1 to 4 carbon atoms) amide group, wherein the containing 1 to The aliphatic hydrocarbon residues of 4 carbon atoms may be unsubstituted or substituted once or several times; one is an aliphatic hydrocarbon residue oxy group containing 1 to 4 carbon atoms, and one is an aliphatic hydrocarbon containing 1 to 4 carbon atoms. Residual carbonyloxy group, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, a sulfur group, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, a sulfonyl group, an aliphatic hydrocarbon containing 1 to 4 carbon atoms The residue oxysulfonyl, wherein the aliphatic hydrocarbon residue containing 1 to 4 carbon atoms may be unsubstituted or substituted once or several times;-N- (aliphatic hydrocarbon containing 1 to 4 carbon atoms Residue) amine group, one N,N-two (aliphatic hydrocarbon residue containing 1 to 4 carbon atoms) amine group, one N- (aliphatic hydrocarbon residue containing 1 to 4 carbon atoms carbonyl) amine group, One N- (aliphatic hydrocarbon residue sulfonyl containing 1 to 4 carbon atoms) amine group, one N- (aliphatic hydrocarbon residue carbonyl containing 1 to 4 carbon atoms) -N- (containing 1 to 4 carbon atoms) Carbon atom aliphatic hydrocarbon residue) amino group or one N-(aliphatic hydrocarbon residue containing 1 to 4 carbon atoms sulfonyl)-N-(aliphatic hydrocarbon residue containing 1 to 4 carbon atoms) amino group , Wherein the aliphatic hydrocarbon residues containing 1 to 4 carbon atoms may each be unsubstituted or substituted once or several times; a cycloaliphatic hydrocarbon residue containing 3 to 6 carbon atoms or one containing 3 to 6 carbon atoms The heterocyclic aliphatic hydrocarbon residues of ring members are each unsubstituted or substituted once or several times, and each of them can optionally form a bond through an aliphatic hydrocarbon functional group containing 1 to 4 carbon atoms, And it can be unsubstituted or substituted once or several times; but its condition is: R³, R⁴, R⁵And R⁶At least one of the residues is not a hydrogen atom, R⁷Represents an aliphatic hydrocarbon residue containing 2 to 10 carbon atoms, which is unsubstituted or substituted once or several times; a cycloaliphatic hydrocarbon residue containing 3 to 10 carbon atoms or a cycloaliphatic hydrocarbon residue containing 3 to 10 rings Membered heterocyclic aliphatic hydrocarbon residues, each of which is unsubstituted or substituted once or several times, and each of them can optionally form a bond via an aliphatic hydrocarbon functional group containing 1 to 8 carbon atoms, and It can be unsubstituted or substituted once or several times; but its condition is: if R⁷When it represents a heterocyclic aliphatic hydrocarbon residue containing 3 to 10 ring members, the bonding is completed through one of the carbon atoms of the heterocyclic aliphatic hydrocarbon residue containing 3 to 10 ring members, in which one " "Aliphatic hydrocarbon functional group" and "aliphatic hydrocarbon residue" are each branched or unbranched, saturated or unsaturated, in which a "cycloaliphatic hydrocarbon residue" and a "heterocyclic aliphatic hydrocarbon residue" can each be saturated Or unsaturated, in which there are "one or several substitutions" of an "aliphatic hydrocarbon functional group" and an "aliphatic hydrocarbon residue". As far as each corresponding residue or functional group is concerned, it is related to one or more Each hydrogen atom is independently replaced by at least one substituent selected from the following group consisting of fluorine, chlorine, bromine, iodine and other atoms, nitro, amino, and one N- (containing Aliphatic hydrocarbon residues with 1 to 4 carbon atoms) amino groups, one N,N-di (aliphatic hydrocarbon residues containing 1 to 4 carbon atoms) amino groups, one N- (containing 1 to 4 carbon atoms) Aliphatic hydrocarbon residue carbonyl) amine group, one N- (aliphatic hydrocarbon residue sulfonyl containing 1 to 4 carbon atoms) amine group, pendant oxy group, hydroxyl group, trifluoromethoxy group, one containing 1 to 4 Aliphatic hydrocarbon residue oxy group of carbon atoms, aliphatic hydrocarbon residue containing 1 to 4 carbon atoms carbonyloxy group, mercapto group, trifluoromethylthio group, aliphatic hydrocarbon residue thio group containing 1 to 4 carbon atoms , Hydroxysulfonyl, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, oxysulfonyl, an N- (containing 1 to 4 Aliphatic hydrocarbon residues with three carbon atoms) sulfonamide, cyano, trifluoromethyl, aldehyde, carboxyl, aliphatic hydrocarbon residues containing 1 to 4 carbon atoms, and aliphatic hydrocarbon residues containing 1 to 4 carbon atoms Aliphatic hydrocarbon residue carbonyl, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms oxycarbonyl, a cycloaliphatic hydrocarbon residue containing 3 to 6 carbon atoms, a heterocyclic aliphatic containing 3 to 6 ring members Hydrocarbon residues, amide groups, one N- (aliphatic hydrocarbon residues containing 1 to 4 carbon atoms) amide groups, one N,N-di (aliphatic hydrocarbon residues containing 1 to 4 carbon atoms) It is composed of amine groups, etc.; there are "one or several substitutions" of a "cycloaliphatic hydrocarbon residue" and a "heterocyclic aliphatic hydrocarbon residue". As far as each corresponding residue is concerned, it is related to one Or several hydrogen atoms independently of each other are replaced by at least one substituent selected from the following group consisting of atoms such as fluorine, chlorine, bromine, iodine, nitro, amino, and one N- (Aliphatic hydrocarbon residues containing 1 to 4 carbon atoms) amine group, one N,N-two (aliphatic hydrocarbon residue containing 1 to 4 carbon atoms) amino group, one N- (aliphatic hydrocarbon residue containing 1 to 4 carbon atoms carbonyl) amino group, one N- (containing 1 to 4 carbon atoms) Aliphatic hydrocarbon residues of carbon atoms (sulfonyl) amine groups, pendant oxy groups, hydroxyl groups, trifluoromethoxy groups, an aliphatic hydrocarbon residue oxy group containing 1 to 4 carbon atoms, one containing 1 to 4 carbon atoms The aliphatic hydrocarbon residues are carbonyloxy, mercapto, trifluoromethylthio, aliphatic hydrocarbon residues containing 1 to 4 carbon atoms, thio, hydroxysulfonyl, and aliphatic hydrocarbon residues containing 1 to 4 carbon atoms Sulfonyl, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, oxysulfonyl, an N- (aliphatic hydrocarbon residue containing 1 to 4 carbon atoms) sulfonamide, cyano, three Fluoromethyl, aldehyde, carboxyl, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, a carbonyl group, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms Oxycarbonyl group, a cycloaliphatic hydrocarbon residue containing 3 to 6 carbon atoms, a heterocyclic aliphatic hydrocarbon residue containing 3 to 6 ring members, an amino group, an N- (containing 1 to 4 carbon atoms) Aliphatic hydrocarbon residues of atoms) amide groups, one N,N-di (aliphatic hydrocarbon residues containing 1 to 4 carbon atoms) amide groups, etc.; among them, there are information about an "aromatic group" and a " The "one or several substitutions" of "heteroaryl", for each corresponding residue, are related to one or several hydrogen atoms independently of each other being replaced by at least one substituent selected from the following groups Substitution, this group consists of fluorine, chlorine, bromine, iodine and other atoms, nitro groups, amino groups,N-di (aliphatic hydrocarbon residues containing 1 to 4 carbon atoms) amide groups, etc.; among them, there are "one or several substitutions" about an "aryl" and a "heteroaryl", just For each corresponding residue, it is related to the substitution of one or several hydrogen atoms independently of each other by at least one substituent selected from the following group consisting of fluorine, chlorine, bromine, and iodine Isoatoms, nitro groups, amine groups,N-di (aliphatic hydrocarbon residues containing 1 to 4 carbon atoms) amide groups, etc.; among them, there are "one or several substitutions" about an "aryl" and a "heteroaryl", just For each corresponding residue, it is related to the substitution of one or several hydrogen atoms independently of each other by at least one substituent selected from the following group consisting of fluorine, chlorine, bromine, and iodine Isoatoms, nitro groups, amine groups,<img file="TW201210596A_D0002.tif" />, One N- (aliphatic hydrocarbon residue containing 1 to 4 carbon atoms) amino group, one N, N-di (aliphatic hydrocarbon residue containing 1 to 4 carbon atoms) amino group, one N- (containing 1 Aliphatic hydrocarbon residues (carbonyl groups up to 4 carbon atoms) amine groups, hydroxyl groups, trifluoromethoxy groups, an aliphatic hydrocarbon residue oxygen groups containing 1 to 4 carbon atoms, an aliphatic hydrocarbon residues containing 1 to 4 carbon atoms Residual carbonyloxy group, mercapto group, trifluoromethylthio group, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, thio, hydroxysulfonyl group, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, sulfonyl Group, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, oxysulfonyl, an N- (aliphatic hydrocarbon residue containing 1 to 4 carbon atoms) sulfonamide, cyano, trifluoromethyl , Aldehyde group, carboxyl group, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms carbonyl, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, oxy Carbonyl, a cyclic aliphatic hydrocarbon residue containing 3 to 6 carbon atoms, a heterocyclic aliphatic hydrocarbon residue containing 3 to 6 ring members, benzyl, aromatic, heteroaromatic, amido, N -(Aliphatic hydrocarbon residues containing 1 to 4 carbon atoms) amide group, one N,N-di (aliphatic hydrocarbon residues containing 1 to 4 carbon atoms) amide group, etc.; its form is free Compounds, racemic isomers, enantiomers, diastereomers, or mixtures composed of enantiomers or diastereomers in any mixing ratio or in the form of a single type of enantiomers Or diastereomers; or its form is a salt formed by a physiologically acceptable acid or base, or its form is a solvate, especially a hydrate.

"Aliphatic hydrocarbon residues containing 1 to 10 carbon atoms", "Aliphatic hydrocarbon residues containing 1 to 8 carbon atoms", "Aliphatic hydrocarbon residues containing 1 to 6 carbon atoms", "Aliphatic hydrocarbon residues containing 1 to 4 The expressions such as aliphatic hydrocarbon residues containing 1 to 2 carbon atoms" and "aliphatic hydrocarbon residues containing 1 to 2 carbon atoms" in the definition of the present invention mean acyclic, saturated or unsaturated aliphatic hydrocarbon residues , Which can be bifurcated or unbranched, unsubstituted or substituted once or several times, containing 1 to 10, or 1 to 8, or 1 to 6, or 1 to 4, respectively , Or 1 to 2 carbon atoms, that is, an alkyl group containing 1 to 10 carbon atoms, an alkenyl group containing 2 to 10 carbon atoms, and an alkynyl group containing 2 to 10 carbon atoms, respectively, and a group containing 1 An alkyl group with to 8 carbon atoms, an alkenyl group with 2 to 8 carbon atoms, and an alkynyl group with 2 to 8 carbon atoms, and an alkyl group with 1 to 6 carbon atoms, containing 2 to 6 carbons -Atom alkenyl and alkynyl groups containing 2 to 6 carbon atoms, and are alkyl groups containing 1 to 4 carbon atoms, alkenyl groups containing 2 to 4 carbon atoms, and alkynyl groups containing 2 to 4 carbon atoms , And are alkyl groups containing 1 to 2 carbon atoms, alkenyl groups containing 2 carbon atoms, and alkynyl groups containing 2 carbon atoms. The alkenyl group contains at least one carbon-carbon double bond (ie C=C bond), and the alkynyl group contains at least one carbon-carbon triple bond (ie CC bond). Preferably, the aliphatic hydrocarbon residue is selected from the following group consisting of alkyl and alkenyl residues, more preferably alkyl residues. Preferably, the alkyl group containing 1 to 10 carbon atoms is selected from the following group consisting of methyl, ethyl, n-propyl, 2-propyl, n-butyl, isobutyl, di It is composed of grade-butyl, tertiary-butyl, n-pentyl, isopentyl, neopentyl, n-hexyl, n-heptyl, n-octyl, n-nonyl and n-decyl. Preferred alkyl residues containing 1 to 8 carbon atoms are selected from the following group consisting of methyl, ethyl, n-propyl, 2-propyl, n-butyl, isobutyl , Secondary-butyl, tertiary-butyl, n-pentyl, isopentyl, neopentyl, n-hexyl, n-heptyl and n-octyl. Preferred alkyl residues containing 1 to 6 carbon atoms are selected from the following group consisting of methyl, ethyl, n-propyl, 2-propyl, n-butyl, isobutyl , Secondary-butyl, tertiary-butyl, n-pentyl, isopentyl, neopentyl and n-hexyl. Preferred alkyl residues containing 1 to 4 carbon atoms are selected from the following group consisting of methyl, ethyl, n-propyl, 2-propyl, n-butyl, isobutyl , Secondary-butyl, tertiary-butyl, etc. Preferably contains 2 to 10 carbon sources₂CH=CH₂), prop-1-enyl (-CH=CH-CH₃), isopropenyl (-CH(=CH₂)-CH₃)], butenyl, pentenyl, hexenyl, heptenyl, octenyl, nonenyl and decenyl. Preferred alkenyl residues containing 2 to 8 carbon atoms are selected from the following group consisting of vinyl, propenyl [prop-2-enyl (-CH₂CH=CH₂), prop-1-enyl (-CH=CH-CH₃), isopropenyl (-CH(=CH₂)-CH₃)], butenyl, pentenyl, hexenyl, heptenyl and octenyl. The preferred alkenyl residues containing 2 to 6 carbon atoms are selected from the following group consisting of vinyl, propenyl [prop-2-enyl (-CH₂CH=CH₂), prop-1-enyl (-CH=CH-CH₃), isopropenyl (-CH(=CH₂)-CH₃)], butenyl, pentenyl and hexenyl. Preferred alkenyl residues containing 2 to 4 carbon atoms are selected from the following group consisting of vinyl, propenyl [prop-2-enyl (-CH₂CH=CH₂), prop-1-enyl (-CH=CH-CH₃), isopropenyl (-CH(=CH₂)-CH₃)] and butenyl. The preferred alkynyl residues containing 2 to 10 carbon atoms are selected from the following group consisting of ethynyl, propynyl [prop-2-ynyl (-CH-CCH), Prop-1-ynyl (-CC-CH₃)], butynyl, pentynyl, hexynyl, heptynyl, octynyl, nonynyl, and decynyl and other residues. The preferred alkynyl residues containing 2 to 8 carbon atoms are selected from the following group consisting of ethynyl, propynyl [prop-2-ynyl (-CH-CCH), Prop-1-ynyl (-CC-CH₃)], butynyl, pentynyl, hexynyl, heptynyl and octynyl. The preferred alkynyl residues containing 2 to 6 carbon atoms are selected from the following group consisting of ethynyl, propynyl [prop-2-ynyl (-CH-CCH), Prop-1-ynyl (-CC-CH₃)], butynyl, pentynyl and hexynyl. The preferred alkynyl residues containing 2 to 4 carbon atoms are selected from the following group consisting of ethynyl, propynyl [prop-2-ynyl (-CH-CCH), Prop-1-ynyl (-CC-CH₃)] and butynyl, etc.

"Cycloaliphatic hydrocarbon residues containing 3 to 6 carbon atoms" and "cyclic aliphatic hydrocarbon residues containing 3 to 10 carbon atoms" as defined in the present invention refer to containing 3, 4, 5 or 6 respectively Carbon atoms and cyclic aliphatic hydrocarbon hydrocarbons containing 3, 4, 5, 6, 7, 8, 9 or 10 carbon atoms, in which each of these hydrocarbons may be saturated or unsaturated (but not aromatic) , Unsubstituted or replaced once or several times. The bond between the cycloaliphatic hydrocarbon residue and each higher-order general structure can be achieved through any desired and possible ring members on the cycloaliphatic hydrocarbon residue. The cycloaliphatic hydrocarbon residues can also be condensed with other saturated, (partially) unsaturated, (hetero)cyclic, aromatic or heteroaromatic hydrocarbon ring systems, that is, with cycloaliphatic hydrocarbons, heterocyclic aliphatic hydrocarbons, aromatics Residues such as hydrocarbons or heteroaromatic hydrocarbons are condensed, and these residues may be unsubstituted or substituted once or several times. Cycloaliphatic hydrocarbon residues containing 3 to 10 carbon atoms can be bonded once or several times, such as adamantyl, bicyclo[2.2.1]heptyl or bicyclo[2.2.2]octyl, etc. The preferred cycloaliphatic hydrocarbon residues containing 3 to 10 carbon atoms are selected from the following groups, which are cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, Cyclononyl, cyclodecyl, adamantyl,<img file="TW201210596A_D0003.tif" />, Cyclopentenyl, cyclohexenyl, cycloheptenyl and cyclooctenyl residues. Preferred cycloaliphatic hydrocarbon residues containing 3 to 6 carbon atoms are selected from the following groups, which are cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclopentenyl and cyclohexene It is composed of base and so on.

Expressions such as "heterocyclic aliphatic hydrocarbon residues containing 3 to 6 ring members" and "heterocyclic aliphatic hydrocarbon residues containing 3 to 10 ring members", as defined in the present invention, mean that they contain 3 to 6 ring members, respectively. One, that is, containing 3, 4, 5, or 6 ring members, and containing 3 to 10, that is, containing 3, 4, 5, 6, 7, 8, 9 or 10 ring members of heterocyclic aliphatic hydrocarbons Saturated or unsaturated (but not aromatic hydrocarbon) residues, each of which has at least one, and if necessary, two or three carbon atoms can be composed of oxygen, sulfur, sulfonyl, nitrogen, imine Group and N-(alkyl containing 1 to 8 carbon atoms) imino group, preferably N-methyl imino group, etc. which are selected independently of each other in the group consisting of heteroatoms or heteroatoms A radical group is substituted, wherein the ring members may be unsubstituted or substituted once or several times. The bonding between the heterocyclic aliphatic hydrocarbon residue and the higher-order general structure can be achieved through any desired and possible ring member on the heterocyclic aliphatic hydrocarbon residue. And the heterocyclic aliphatic hydrocarbon residues can also be condensed with other saturated, (partial) unsaturated, (hetero)cyclic or aromatic or heteroaromatic hydrocarbon ring systems, that is, with cycloaliphatic hydrocarbon groups, heterocyclic aliphatic hydrocarbons Condensation of residues such as, aromatic hydrocarbons or heteroaromatic hydrocarbons, and these residues may be unsubstituted or substituted once or several times. The preferred heterocyclic aliphatic hydrocarbon residues are selected from the following group consisting of azetidinyl, aziridinyl, azepanyl, aza Azocanyl, diazepanyl, dithiolanyl, dihydroquinolinyl, dihydropyrrolyl, dioxanyl ), dioxolanyl, dioxepanyl, dihydroindenyl, dihydropyridinyl, dihydrofuranyl, dihydroisoquinolinyl (dihydroisoquinolinyl), dihydroindolinyl, dihydroisoindolyl, imidazolidinyl, isoxazolidinyl, morpholinyl, ethylene oxide Alkyl (ox

The expression "aromatic group" refers to aromatic hydrocarbon hydrocarbons containing 6 to 14 ring members, including benzene and naphthalene compounds in terms of the definition of the present invention. Each aryl residue may be unsubstituted or substituted once or several times, wherein the aryl substituents may be the same or different, and may appear in any desired and possible positions of the aromatic ring. The bond between the aromatic group and the higher-order general structure can be achieved through any desired and possible ring member on the aromatic residue. And these aromatic residues can also be condensed with other saturated, (partially) unsaturated, (hetero) rings, aromatic hydrocarbons or heteroaromatic hydrocarbon ring systems, that is, with monocyclic aliphatic hydrocarbon residues, heterocyclic aliphatic Residues such as hydrocarbon residues, aromatic groups or heteroaromatic groups are condensed, and these residues may be unsubstituted or substituted once or several times. Examples of aromatic residues after condensation are benzodioxolanyl and benzodioxanyl. Preferably, the aromatic group is selected from the group consisting of phenyl, 1-naphthyl, 2-naphthyl, fluorenyl and anthracenyl, among which Each residue can be individually unsubstituted or substituted once or several times. Among them, benzene is a particularly preferred aromatic group, which is unsubstituted or substituted once or several times.

The expression "heteroaromatic group" as defined in the present invention means a cyclic aromatic hydrocarbon residue containing 5 or 6 ring members, which contains at least one, and may contain 2, 3, 4 or 5 if necessary. Heteroatoms, selected from the group consisting of sulfur, nitrogen and oxygen atoms independently of each other, and the heteroaromatic residue may be unsubstituted or substituted once or several times ; If the substitution reaction is carried out on the heteroaromatic group, the substituents may be the same or different, and may appear in each desired and possible position of the heteroaromatic ring. The bond with the higher-order general structure can be achieved through any desired and possible ring member on the heteroaromatic residue. The heteroaromatic group can also be part of a bicyclic or polycyclic ring system containing up to 14 ring members, in which the ring system can be saturated, (partially) unsaturated, (hetero) ring, aromatic hydrocarbon or The heteroaromatic ring system is formed by a cycloaliphatic hydrocarbon residue, a heterocyclic aliphatic hydrocarbon residue, an aromatic group or a heteroaromatic group, etc. These residues can be unsubstituted or substituted once Or several times. The preferred heteroaromatic residues are composed of benzofuranyl, benzoimidazolyl, benzothienyl, benzothiadiazolyl, and benzothiazolyl. ), benzotriazolyl, benzooxazolyl, benzooxadiazolyl, quinazolinyl, quinoxalinyl, carbazolyl ( carbazolyl), quinolinyl (quinolinyl), dibenzofuranyl (dibenzofuranyl), dibenzothienyl (dibenzothienyl), furyl (furyl, furanyl, imidazolyl, imidazothiazolyl, indazolyl, indolizinyl, indolyl, isoquinolinyl, isoxazolyl (isoxazolyl), isothiazolyl, indolyl, naphthyridinyl, oxazolyl, oxadiazolyl, phenazinyl, phenothiazine Phenothiazinyl, phtalazinyl, pyrazolyl, pyridyl (2-pyridyl, 3-pyridyl, 4-pyridyl), pyrrolyl (pyrrolyl), pyridazinyl, pyrimidinyl, pyrazinyl, purinyl, phenazinyl, thienyl, thiophenyl, triazolyl ), tetrazolyl, thiazolyl, thiadiazolyl and triazinyl residues. Among them, furyl, pyridyl, oxazolyl, thiazolyl and thienyl are particularly preferred. thiophenyl, triazolyl, tetrazolyl, thiazolyl, thiadiazolyl and triazinyl residues are selected from the group consisting of residues. Among them, furyl, pyridyl, oxazolyl, thiazolyl and thienyl are particularly preferred. thiophenyl, triazolyl, tetrazolyl, thiazolyl, thiadiazolyl and triazinyl residues are selected from the group. Among them, furyl, pyridyl, oxazolyl, thiazolyl and thienyl are particularly preferred.

"Aromatic groups, heteroaromatic groups, heterocyclic aliphatic hydrocarbon residues or cycloaliphatic groups bonded via an aliphatic hydrocarbon functional group containing 1 to 4 carbon atoms or via an aliphatic hydrocarbon functional group containing 1 to 8 carbon atoms The expressions such as "hydrocarbon residue" in the present invention mean that the expressions such as "aromatic group, heteroaromatic group, heterocyclic aliphatic hydrocarbon residue or cycloaliphatic hydrocarbon residue" have the meanings defined above and are respectively Through an aliphatic hydrocarbon functional group containing 1 to 4 carbon atoms or an aliphatic hydrocarbon functional group containing 1 to 8 carbon atoms, it is connected to each higher-order general formula. The aliphatic hydrocarbon functional group containing 1 to 4 carbon atoms and the aliphatic hydrocarbon functional group containing 1 to 8 carbon atoms may each be branched or unbranched, unsubstituted or substituted one or several times. The aliphatic hydrocarbon functional group containing 1 to 4 carbon atoms may each be further saturated or unsaturated, that is, an alkylene group containing 1 to 4 carbon atoms, or an alkylene group containing 2 to 4 carbon atoms. Alkenyl, or an alkynylene group containing 2 to 4 carbon atoms. The same principle can be applied to an aliphatic hydrocarbon functional group containing 1 to 8 carbon atoms, that is, an aliphatic hydrocarbon functional group containing 1 to 8 carbon atoms can each be further saturated or unsaturated, that is, an aliphatic hydrocarbon functional group containing 1 An alkylene group having to 8 carbon atoms, or an alkenylene group having 2 to 8 carbon atoms, or an alkynylene group having 2 to 8 carbon atoms. Preferably, the aliphatic hydrocarbon functional group containing 1 to 4 carbon atoms is an alkylene group containing 1 to 4 carbon atoms, or an alkenylene group containing 2 to 4 carbon atoms, more preferably It is an alkylene group containing 1 to 4 carbon atoms. Preferably, the aliphatic hydrocarbon functional group containing 1 to 8 carbon atoms is an alkylene group containing 1 to 8 carbon atoms, or an alkenylene group containing 2 to 8 carbon atoms, more preferably It is an alkylene group containing 1 to 8 carbon atoms. Preferred alkylene groups containing 1 to 4 carbon atoms are selected from the following group, which is composed of methylene (-CH₂-), 1,2-ethylene (-CH₂-CH₂-), methylmethylene (-CH(CH₃)-), 1,3-propylene (-CH₂-CH₂-CH₂-), methyl-1,2-ethylene (-CH(CH₃)-CH₂-), ethylmethylene (-CH(CH₂CH₃)-), 1,4-Butylene (-CH₂-(CH₂)₂-CH₂-), 1-methyl-1,3-propylene (-CH(CH₃)-CH₂-CH₂-), 2-methyl-1,3-propylene (-CH₂-CH(CH₃)-CH₂-), 1,2-Dimethyl-1,2-ethylene (-CH(CH₃)-CH(CH₃)-), ethyl-1,2-ethylene (-CH(CH₂CH₃)-CH₂-), 1,2-isobutylene (-C(CH₃)₂-CH₂-), propylmethylene (-CH(CH₂CH₂CH₃)-) and methylethylmethylene (-C(CH₃)(CH₂CH₃)-) etc. Preferred alkenylene groups containing 2 to 4 carbon atoms are selected from the following group consisting of 1,2-vinylene (-CH=CH-) and 1,3-propenylene (-CH=CH-CH₂-), 1-methyl-1,2-vinylidene (-C(CH₃)=CH-), 1,4-butene-1-enyl (-CH=CH-CH₂-CH₂-), 1,4-Butylene-2-enyl (-CH₂-CH=CH-CH₂-), 1,4-Butylene-1,3-dienyl (-CH=CH-CH=CH-), 1-methyl-1,3-propenylene (-C(CH₃)=CH-CH₂-), 2-methyl-1,3-propenylene (-CH=C(CH₃)-CH₂-), 1,2-Dimethyl-1,2-vinylidene (-C(CH₃)=C(CH₃)-) and 1-ethyl-1,2-vinylidene (-C(CH₂CH₃)=CH-) and so on. The preferred alkynylene groups containing 2 to 4 carbon atoms are selected from the following group consisting of 1,2-ethynylene (-CC-), 1,3-propynylene Base (-CC-CH₂-), 1,4-Butylene-1-ynyl (-CC-CH₂-CH₂-), 3-methyl-1,3-propynylene (-CC-CH(CH₃)-), 1,4-Butylene-2-ynyl (-CH₂-CC-CH₂-) and 1,4-butane-1,3-diynyl (-CCCC-) and so on. Preferred alkylene groups containing 1 to 8 carbon atoms are selected from the following group, which is composed of methylene (-CH₂-), 1,2-ethylene (-CH₂-CH₂-), methylmethylene (-CH(CH₃)-), 1,3-propylene (-CH₂-CH₂-CH₂-), methyl-1,2-ethylene (-CH(CH₃)-CH₂-), ethylmethylene (-CH(CH₂CH₃)-), 1,4-Butylene (-CH₂-(CH₂)₂-CH₂-), 1-methyl-1,3-propylene (-CH(CH₃)-CH₂-CH₂-), 2-methyl-1,3-propylene (-CH₂-CH(CH₃)-CH₂-), 1,2-Dimethyl-1,2-ethylene (-CH(CH₃)-CH(CH₃)-), ethyl-1,2-ethylene (-CH(CH₂CH₃)-CH₂-), 1,2-isobutylene (-C(CH₃)₂-CH₂-), propylmethylene (-CH(CH₂CH₂CH₃)-), methyl ethyl methylene (-C(CH₃)(CH₂CH₃)-), 1,5-Pentylene (-CH₂-(CH₂)₃-CH₂-), 1-methyl-1,4-butylene (-CH(CH₃)-CH₂-CH₂-CH₂-), 2-methyl-1,4-butylene (-CH₂-CH(CH₃)-CH₂-CH₂-), 1,3-dimethyl-1,3-propylene (-CH(CH₃)-CH₂-CH(CH₃)-), 1,2-dimethyl-1,3-propylene (-CH(CH₃)-CH(CH₃)-CH₂-), 1,3-isopentylene (-C(CH₃)₂-CH₂-CH₂-), 2,2-Dimethyl-1,3-propylene (-CH₂-C(CH₃)₂-CH₂-), 1-ethyl-1,3-propylene (-CH(CH₂CH₃)-CH₂-CH₂-), 2-ethyl-1,3-propylene (-CH₂-CH(CH₂CH₃)-CH₂-), 1,1,2-trimethyl-1,2-ethylene (-C(CH₃)₂-CH(CH₃)-), 1-ethyl-2-methyl-1,2-ethylene (-CH(CH₂CH₃)-CH(CH₃)-), 1-methyl-1-ethyl-1,2-ethylene (-C(CH₃)(CH₂CH₃)-CH₂-), 1-propyl-1,2-ethylene (-CH(CH₂CH₂CH₃)-CH₂-), 1-propyl-1,2-ethylene (-CH(CH₂CH₂CH₃)-CH₂-), butylmethylene (-CH(CH₂CH₂CH₂-CH₃)-), Methylpropylmethylene (-C(CH₃)(CH₂CH₂CH₃)-), diethylmethylene (-C(CH₂CH₃)₂-) and 1,6-hexylene (-CH₂-(CH₂)₄-CH₂-) and so on. The preferred alkenylene groups containing 2 to 8 carbon atoms are selected from the following group consisting of 1,2-vinylene (-CH=CH-) and 1,3-propenylene (-CH=CH-CH₂-), 1-methyl-1,2-vinylidene (-C(CH₃)=CH-), 1,4-butene-1-enyl (-CH=CH-CH₂-CH₂-), 1,4-Butylene-2-enyl (-CH₂-CH=CH-CH₂-), 1,4-Butylene-1,3-dienyl (-CH=CH-CH=CH-), 1-methyl-1,3-propenylene (-C(CH₃)=CH-CH₂-), 2-methyl-1,3-propenylene (-CH=C(CH₃)-CH₂-), 1,2-Dimethyl-1,2-vinylidene (-C(CH₃)=C(CH₃)-), 1-ethyl-1,2-vinylidene (-C(CH₂CH₃)=CH-), 1,5-pentylene-1-enylene (-CH=CH-CH₂-CH₂-CH₂-), 1,5-Pentylene-2-enyl (-CH₂-CH=CH-CH₂-CH₂-), 1,5-Pentylene-1,2-dienyl (-CH=C=CH-CH₂-CH₂-) and 1,5-pentylene-1,4-dienyl (-CH=CH-CH₂-CH=CH-) and so on. The preferred alkynylene groups containing 2 to 8 carbon atoms are selected from the following group consisting of 1,2-ethynylene (-CC-), 1,3-propynylene Base (-CC-CH₂-), 1,4-Butylene-1-ynyl (-CC-CH₂-CH₂-), 3-methyl-1,3-propylene-1-ynyl (-CC-CH(CH₃)-), 1,4-Butylene-2-ynyl (-CH₂-CC-CH₂-), 1,4-butane-1,3-diynyl (-CCCC-), 3,3-dimethyl-1,3-propane-1-ynyl (-CC -CH(CH₃)₂-), 1,5-pentylene-1-ynyl (-CC-CH₂-CH₂-CH₂-), 1,5-Pentylene-2-ynyl (-CH₂-CC-CH₂-CH₂-), 1,5-Pentylene-1,3-diynyl (-CCCC-CH₂-) and 1,5-pentylene-1,4-diynyl (-CC-CH₂-CC-) and so on.

With regard to "aliphatic hydrocarbon residues" and "aliphatic hydrocarbon functional groups", the expression "one or several substitutions" in the definition of the present invention means one or several corresponding residues or functional groups. The hydrogen atoms are independently substituted by at least one substituent selected from the following groups once or several times, such as two, three or four times, the group consists of fluorine, chlorine, bromine, iodine, etc. Atom, nitro group, amine group, one N- (aliphatic hydrocarbon residue containing 1 to 4 carbon atoms) amine group, one N,N-di (aliphatic hydrocarbon residue containing 1 to 4 carbon atoms) amine group , One N- (aliphatic hydrocarbon residue carbonyl containing 1 to 4 carbon atoms) amino group, one N- (aliphatic hydrocarbon residue sulfonyl containing 1 to 4 carbon atoms) amino group, pendant oxygen group, hydroxyl group , Trifluoromethoxy, an aliphatic hydrocarbon residue oxygen containing 1 to 4 carbon atoms, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, carbonyloxy, mercapto, trifluoromethylthio, one containing Aliphatic hydrocarbon residues with 1 to 4 carbon atoms, sulfanyl, hydroxysulfonyl, aliphatic hydrocarbon residues containing 1 to 4 carbon atoms, sulfonyl group, aliphatic hydrocarbon residues containing 1 to 4 carbon atoms, oxygen Sulfonyl, one N- (aliphatic hydrocarbon residue containing 1 to 4 carbon atoms) sulfonamide, cyano, trifluoromethyl, aldehyde, carboxyl, one containing 1 to 4 carbon atoms Hydrocarbon residues, an aliphatic hydrocarbon residue carbonyl group containing 1 to 4 carbon atoms, an aliphatic hydrocarbon residue oxycarbonyl group containing 1 to 4 carbon atoms, a cycloaliphatic hydrocarbon residue containing 3 to 6 carbon atoms , A heterocyclic aliphatic hydrocarbon residue containing 3 to 6 ring members, an amide group, an N- (aliphatic hydrocarbon residue containing 1 to 4 carbon atoms) an amide group and a N,N-di (containing The aliphatic hydrocarbon residue of 1 to 4 carbon atoms) is composed of amide groups. With regard to residues and functional groups that have been substituted several times, the expression "substitution several times" includes several substitutions of these residues or functional groups on different or the same atoms, such as substitution on the same carbon atom Three times, as in the example trifluoromethyl or 2,2,2-trifluoroethyl, or three times with different atoms, as in the example 1-hydroxy-4,4-dichloro-but-2-ene (CH( OH)-CH=CH-CHCl₂). A replacement is based on the fact that it can be replaced one or several times when necessary. The multiple substitution reactions can be carried out with the same or different substituents.

Regarding "cycloaliphatic hydrocarbon residues" and "heterocyclic aliphatic hydrocarbon residues", the expression "one or several substitutions" in the definition of the present invention refers to one or several corresponding residues. The hydrogen atoms are independently substituted by at least one substituent selected from the following groups once or several times, such as two, three or four times, the group consists of fluorine, chlorine, bromine, iodine, etc. Atom, nitro group, amine group, one N- (aliphatic hydrocarbon residue containing 1 to 4 carbon atoms) amine group, one N,N-di (aliphatic hydrocarbon residue containing 1 to 4 carbon atoms) amine group , An aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, a carbonylamino group, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, a sulfonylamino group, a pendant oxygen group, a hydroxyl group, a trifluoromethoxy group, a An aliphatic hydrocarbon residue oxygen containing 1 to 4 carbon atoms, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms carbonyloxy, mercapto, trifluoromethylthio, a fatty hydrocarbon containing 1 to 4 carbon atoms Hydrocarbon residues thio, sulfonyl, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, oxysulfonyl, an N-( Aliphatic hydrocarbon residues containing 1 to 4 carbon atoms) sulfonamide groups, cyano groups, trifluoromethyl, aldehyde groups, carboxyl groups, aliphatic hydrocarbon residues containing 1 to 4 carbon atoms, one containing 1 to 4 Aliphatic hydrocarbon residue carbonyl group containing 1 to 4 carbon atoms, an aliphatic hydrocarbon residue oxycarbonyl group containing 1 to 4 carbon atoms, a cycloaliphatic hydrocarbon residue containing 3 to 6 carbon atoms, and a cycloaliphatic hydrocarbon residue containing 3 to 6 ring members Heterocyclic aliphatic hydrocarbon residues, amide groups, one N- (aliphatic hydrocarbon residues containing 1 to 4 carbon atoms) amide groups and one N,N-di (aliphatic hydrocarbons containing 1 to 4 carbon atoms) Residue) composed of amide groups. With regard to residues and functional groups that have been substituted several times, the expression "substitution several times" includes several substitutions of these residues or functional groups on different or the same atoms, such as the substitution of two on the same atom. Times, such as 1,1-difluorocyclohexyl (1,1-difluorocyclohexyl), or two substitutions on different atoms, such as 1-chloro-3-fluorocyclohexyl (1-chloro-3-fluorocyclohexyl) ). A substitution is based on the fact that it can be substituted one or several times when necessary. The multiple substitution reactions can be carried out with the same or different substituents.

The preferred substituents of "aliphatic hydrocarbon residue" and "aliphatic hydrocarbon functional group" are selected from the following groups, which are composed of fluorine, chlorine, bromine, iodine and other atoms, nitro groups, amino groups, and one N- (aliphatic hydrocarbon residues containing 1 to 4 carbon atoms) amino groups, one N,N-di (aliphatic hydrocarbon residues containing 1 to 4 carbon atoms) amino groups, pendant oxygen groups, hydroxyl groups, trifluoro Methoxy, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, oxy, mercapto, trifluoromethylthio, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, thio, cyano, trifluoromethyl Group, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, an aliphatic hydrocarbon residue carbonyl containing 1 to 4 carbon atoms, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, oxycarbonyl, amide Group, one N-(aliphatic hydrocarbon residue containing 1 to 4 carbon atoms) amide group and one N,N-di(aliphatic hydrocarbon residue containing 1 to 4 carbon atoms) amide group and so on.

The preferred substituents of "cycloaliphatic hydrocarbon residues" and "heterocyclic aliphatic hydrocarbon residues" are selected from the following group consisting of fluorine, chlorine, bromine, iodine and other atoms, nitro groups, and amines Group, one N-(aliphatic hydrocarbon residue containing 1 to 4 carbon atoms) amino group, one N,N-di(aliphatic hydrocarbon residue containing 1 to 4 carbon atoms) amino group, pendant oxygen group, hydroxyl group , Trifluoromethoxy, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, oxy, sulfhydryl, trifluoromethylthio, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, a sulfur group, one containing 1 Aliphatic hydrocarbon residues with to 4 carbon atoms sulfonyl, one N- (aliphatic hydrocarbon residues containing 1 to 4 carbon atoms) sulfonamide, cyano, trifluoromethyl, one containing 1 to 4 Aliphatic hydrocarbon residues of carbon atoms, aliphatic hydrocarbon residues containing 1 to 4 carbon atoms It is composed of aliphatic hydrocarbon residues up to 4 carbon atoms) amide group and one N,N-di (aliphatic hydrocarbon residues containing 1 to 4 carbon atoms) amide group.

Regarding "aryl" and "heteroaryl", the expression "one or several substitutions" in the definition of the present invention means one or more hydrogen atoms on different atoms if necessary Independently of each other, it is substituted once or several times by at least one substituent selected from the following groups, such as two, three or four times, and the group consists of atoms such as fluorine, chlorine, bromine, iodine, etc. Nitro, amine,<img file="TW201210596A_D0004.tif" /><img file="TW201210596A_D0005.tif" />, One N- (aliphatic hydrocarbon residue containing 1 to 4 carbon atoms) amino group, one N, N-di (aliphatic hydrocarbon residue containing 1 to 4 carbon atoms) amino group, one N- (containing 1 Aliphatic hydrocarbon residues (carbonyl groups up to 4 carbon atoms) amine groups, hydroxyl groups, trifluoromethoxy groups, an aliphatic hydrocarbon residue oxygen groups containing 1 to 4 carbon atoms, an aliphatic hydrocarbon residues containing 1 to 4 carbon atoms Residual carbonyloxy group, mercapto group, trifluoromethylthio group, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, a sulfanyl group, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, a sulfonyl group , An aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, oxysulfonyl, an N- (aliphatic hydrocarbon residue containing 1 to 4 carbon atoms) sulfonamide, cyano, trifluoromethyl, Aldehyde, carboxyl, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, an aliphatic hydrocarbon residue carbonyl containing 1 to 4 carbon atoms, an aliphatic hydrocarbon residue oxycarbonyl containing 1 to 4 carbon atoms , A cycloaliphatic hydrocarbon residue containing 3 to 6 carbon atoms, a heterocyclic aliphatic hydrocarbon residue containing 3 to 6 ring members, benzyl, aromatic, heteroaromatic, amido, N- (Aliphatic hydrocarbon residues containing 1 to 4 carbon atoms) Amino groups and a N,N-di (aliphatic hydrocarbon residues containing 1 to 4 carbon atoms) amide groups, one of which is substituted based on need The time itself can be replaced one or several times. The multiple substitution reactions can be carried out with the same or different substituents.

The preferred substituents of "aryl" and "heteroaryl" are selected from the following groups, which are composed of fluorine, chlorine, bromine, iodine and other atoms, nitro groups, amino groups,<img file="TW201210596A_D0006.tif" /><img file="TW201210596A_D0007.tif" />, One N- (aliphatic hydrocarbon residue containing 1 to 4 carbon atoms) amino group, one N, N-di (aliphatic hydrocarbon residue containing 1 to 4 carbon atoms) amino group, one N- (containing 1 Aliphatic hydrocarbon residues (carbonyl groups up to 4 carbon atoms) amine groups, hydroxyl groups, trifluoromethoxy groups, aliphatic hydrocarbon residues containing 1 to 4 carbon atoms, oxy groups, mercapto groups, trifluoromethylthio groups, one containing 1 Aliphatic hydrocarbon residues with up to 4 carbon atoms, sulfur groups, sulfonyl groups, aliphatic hydrocarbon residues containing 1 to 4 carbon atoms, sulfonyl groups, and N- (aliphatic hydrocarbon residues containing 1 to 4 carbon atoms) ) Sulfonamide group, cyano group, trifluoromethyl group, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, a carbonyl group, a containing 1 to 4 carbon atoms Aliphatic hydrocarbon residue oxycarbonyl group, a cycloaliphatic hydrocarbon residue containing 3 to 6 carbon atoms, a heterocyclic aliphatic hydrocarbon residue containing 3 to 6 ring members, an amino group, an N-(containing Aliphatic hydrocarbon residues with 1 to 4 carbon atoms) amide group and one N,N-di (aliphatic hydrocarbon residues with 1 to 4 carbon atoms) amide group, aromatic group, preferably phenyl group, Or benzyl, each of which is unsubstituted or substituted one or several times by at least one substituent selected from the following group, which is composed of atoms such as fluorine, chlorine, bromine, and iodine, and cyano , Trifluoromethyl, methyl, ethyl, isopropyl, tertiary-butyl, carboxy, methylcarbonyl, ethylcarbonyl, methoxycarbonyl and ethoxycarbonyl, methoxy, trifluoromethoxy Group, hydroxymethoxy, methoxymethoxy, mercapto, methylthio, trifluoromethylthio, nitro, amino, N,N-dimethylamino, N-methyl-N-ethyl Amino group and N,N-diethylamino group, heteroaromatic group, preferably composed of pyridyl, thienyl, furyl, thiazolyl or oxazolyl, etc., each of which is unsubstituted or via At least one substituent selected from the following group is substituted one or several times, the group is composed of fluorine, chlorine, bromine, iodine and other atoms, cyano, trifluoromethyl, methyl, ethyl, isopropyl Group, tertiary-butyl, carboxyl, methylcarbonyl, ethylcarbonyl, methoxycarbonyl and ethoxycarbonyl, methoxy, trifluoromethoxy, hydroxymethoxy, methoxymethoxy, Sulfhydryl, methylthio, trifluoromethylthio, nitro, amino, N,N-dimethylamino, N-methyl-N-ethylamino and N,N-diethylamino, etc. Constituted.

The compounds according to the present invention are composed of substituents, for example by R¹, R²And R³(First-generation substituent) is defined, and it is itself substituted when necessary (second-generation substituent). The substituents of these substituents can themselves be substituted again according to the definition (third-generation substituents). For example, if R¹= When an aliphatic hydrocarbon residue containing 1 to 10 carbon atoms (first-generation substituents), the aliphatic hydrocarbon residue containing 1 to 10 carbon atoms can itself be, for example, an N- (containing 1 to 4 The aliphatic hydrocarbon residue of the carbon atom) is substituted by an amine group (the second-generation substituent). This substitution produces a functional group R¹= (Aliphatic hydrocarbon residue containing 1 to 10 carbon atoms) -N- (aliphatic hydrocarbon residue containing 1 to 4 carbon atoms) amino group). The N- (aliphatic hydrocarbon residue containing 1 to 4 carbon atoms) amine base itself can then be replaced by, for example, a chlorine atom (third-generation substituent) again. Finally, a total of functional groups R are generated from this¹= Aliphatic hydrocarbon residues containing 1 to 10 carbon atoms -N- (aliphatic hydrocarbon residues containing 1 to 4 carbon atoms) amino groups, where the N- (aliphatic hydrocarbon residues containing 1 to 4 carbon atoms) ) The aliphatic hydrocarbon residue containing 1 to 4 carbon atoms of the amine group is replaced by a chlorine atom.

However, in a preferred embodiment, the third-generation substituent cannot be substituted again, that is, there is no fourth-generation substituent after it.

In another preferred embodiment, the second-generation substituent can no longer be substituted, that is, there is no third-generation substituent after it. In other words, in this embodiment, if, for example, the general formula (I), the functional group R¹To R⁷Each can be replaced when needed, but their respective replacement basic bodies cannot be replaced again.

In some cases, the compounds according to the present invention are defined by substituents, which are or carry an aromatic or heteroaromatic residue each of which is unsubstituted or substituted one or several times, or Etc. and connected with it, as a ring member or as a ring member(s), the carbon atom(s) or heteroatom(s) together form a ring, such as an aryl or heteroaryl residue, each of which is not Replace or be replaced one or several times. These aromatic or heteroaromatic residues and the (hetero)aromatic hydrocarbon ring system formed in this way can be combined with a cyclic aliphatic hydrocarbon residue, preferably with a cyclic aliphatic containing 3 to 6 carbon atoms when necessary. Hydrocarbon residues or heterocyclic aliphatic hydrocarbon residues are preferably condensed with a heterocyclic aliphatic hydrocarbon residue containing 3 to 6 ring members, or with an aromatic or heteroaromatic group, for example, with a heterocyclic aliphatic hydrocarbon residue containing 3 to 6 ring members. A cycloaliphatic hydrocarbon residue of three carbon atoms, such as cyclopentyl, or a heterocyclic aliphatic hydrocarbon residue containing 3 to 6 ring members, such as morpholinyl, or an aromatic group, such as phenyl, or A heteroaromatic group, such as a pyridyl group, is condensed with each other, wherein the cycloaliphatic hydrocarbon residue or heterocyclic aliphatic hydrocarbon residue formed by the condensation in this way, the aromatic group or heteroaromatic residue, etc. may themselves be unsubstituted Or replaced one or several times.

In some cases, the compounds according to the present invention are defined by substituents, which are or carry a cycloaliphatic hydrocarbon residue or a heterocyclic aliphatic hydrocarbon residue that is unsubstituted or substituted one or several times. The group, or the like and connected thereto, as a ring member or as a ring member(s), the carbon atom(s) or heteroatom(s) together form a ring, such as a cyclic aliphatic hydrocarbon or a heterocyclic aliphatic hydrocarbon ring system. These cyclic aliphatic hydrocarbons or heterocyclic aliphatic hydrocarbon ring systems and the (hetero)cyclic aliphatic hydrocarbon ring systems formed in this way can be combined with aromatic or heteroaromatic groups, or with a cycloaliphatic hydrocarbon residue, preferably Condense with a cycloaliphatic hydrocarbon residue containing 3 to 6 carbon atoms, or with a heterocyclic aliphatic hydrocarbon residue, preferably with a heterocyclic aliphatic hydrocarbon residue containing 3 to 6 ring members, for example with An aromatic group, such as phenyl, or a heteroaromatic group, such as pyridyl, or a cycloaliphatic hydrocarbon residue, such as cyclohexyl, or a heterocyclic aliphatic hydrocarbon residue, such as morpholinyl, is condensed, wherein The aromatic or heteroaromatic residues, or cycloaliphatic hydrocarbon residues or heterocyclic aliphatic hydrocarbon residues condensed in this way may each be unsubstituted or substituted one or several times.

In the present invention, the symbols used in the general formula

<chemistry general="n"><img file="TW201210596A_D0008.tif" /></chemistry>

It means that a corresponding residue is connected to each higher order main general formula.

If a residue occurs several times in a molecule, the residue can have different meanings for various substituents: for example, if R²And R³When the two represent a heterocyclic aliphatic hydrocarbon residue containing 3 to 6 ring members, the heterocyclic aliphatic hydrocarbon residue containing 3 to 6 ring members, such as R²May represent morpholinyl, and R³May represent piperazinyl.

"Salts produced by physiologically acceptable acids" in the definition of the present invention means that each active substance and physiologically, especially when used in humans and/or other mammals, can be used Salts formed by accepted inorganic or organic acids. Among them, hydrochloride is particularly preferred. Examples of physiologically acceptable acids are hydrochloric acid (hydrochloric acid), bromine hydrochloride, sulfuric acid, methanesulfonic acid, p-toluenesulfonic acid, carbonic acid, formic acid, acetic acid (acetic acid), oxalic acid, succinic acid, tartaric acid , Mandelic acid, fumaric acid, maleic acid, lactic acid, citric acid, glutamic acid, glucaric acid, monomethyl sebacic acid, 5-oxo-proline, hexane-1-sulfonic acid Acid, nicotinic acid, 2-,3- or 4-aminobenzoic acid, 2,4,6-trimethylbenzoic acid, -lipoic acid, acetylglycine, hippuric acid, phosphoric acid, aspartic acid. Among them, citric acid and hydrochloric acid are particularly preferred.

"Salts formed from physiologically acceptable bases" in the definition of the present invention refers to each compound according to the present invention-as an anion when, for example, a suitable functional group is deprotonated-and At least one cation or base-preferably one and at least one inorganic cation-form a salt, which is physiologically acceptable-especially when used in humans or other mammals. Among them, the particularly preferred ones are the salts formed by alkali gold and alkaline earth metals, especially (mono) or (di) sodium salt, (mono) or (di) potassium salt, magnesium salt or calcium salt, etc., but also include Ammonium salt [NH_xR_4-x]⁺, Where x=0, 1, 2, 3 or 4, and R represents a branched or unbranched alkyl group containing 1 to 4 carbon atoms.

According to the preferred embodiments of the compound of general formula (I) of the present invention, the following figure shows (<b>Ia</b>)、(<b>Ib</b>)、(<b>Ic</b>)or(<b>Id</b>)：

<chemistry general="n"><img file="TW201210596A_D0009.tif" /></chemistry>

Another preferred embodiment of the present invention is a compound of general formula (I) according to the present invention, wherein R¹Represents an aliphatic hydrocarbon residue containing 1 to 10 carbon atoms, preferably represents an aliphatic hydrocarbon residue containing 1 to 8 carbon atoms, which is unsubstituted or at least one selected from the following groups Substituents are substituted one or several times. The group consists of fluorine, chlorine, bromine, iodine and other atoms, nitro groups, amino groups, one N- (aliphatic hydrocarbon residues containing 1 to 4 carbon atoms) amino groups, one N,N-two (aliphatic hydrocarbon residues containing 1 to 4 carbon atoms) amino groups, hydroxyl groups, pendant oxy groups, aliphatic hydrocarbon residues containing 1 to 4 carbon atoms, oxy groups, trifluoromethoxy, Sulfhydryl, trifluoromethylthio, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, thio, trifluoromethyl, cyano, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, carboxyl, etc. , Wherein each of the aliphatic hydrocarbon residues containing 1 to 4 carbon atoms may be unsubstituted or substituted one or several times with at least one substituent selected from the following groups, the group consisting of fluorine, chlorine, It is composed of bromine, iodine and other atoms, hydroxyl, trifluoromethoxy, trifluoromethyl and an unsubstituted aliphatic hydrocarbon residue oxygen containing 1 to 4 carbon atoms, or represents one containing 3 to 10 carbons A cycloaliphatic hydrocarbon residue of one atom, or a heterocyclic aliphatic hydrocarbon residue containing 3 to 10 ring members, each of which is unsubstituted or substituted with at least one substituent selected from the following groups Second, this group consists of fluorine, chlorine, bromine, iodine and other atoms, nitro groups, amino groups, one N- (aliphatic hydrocarbon residues containing 1 to 4 carbon atoms) amino groups, one N,N-two ( Aliphatic hydrocarbon residues containing 1 to 4 carbon atoms) amine groups, hydroxyl groups, pendant oxy groups, aliphatic hydrocarbon residues containing 1 to 4 carbon atoms, oxy groups, trifluoromethoxy, mercapto groups, trifluoromethyl sulfide Aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, sulfur group, trifluoromethyl, cyano group, aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, carboxyl group, one containing 3 to 6 carbon atoms The cycloaliphatic hydrocarbon residue and a heterocyclic aliphatic hydrocarbon residue containing 3 to 6 ring members, etc., wherein the aliphatic hydrocarbon residue containing 1 to 4 carbon atoms may be unsubstituted or at least one Substitute one or several times with the substituent selected from the following group, the group consists of fluorine, chlorine, bromine, iodine and other atoms, hydroxyl, trifluoromethoxy, trifluoromethyl and one unsubstituted The aliphatic hydrocarbon residues of 1 to 4 carbon atoms are composed of oxy groups, and the cycloaliphatic hydrocarbon residues containing 3 to 6 carbon atoms or the heterocyclic aliphatic hydrocarbon residues containing 3 to 6 ring members can be Each is unsubstituted or substituted one or several times with at least one substituent selected from the following groups, the group consisting of atoms such as fluorine, chlorine, bromine, iodine, nitro, amino, and one N-( Aliphatic hydrocarbon residues containing 1 to 4 carbon atoms) amine group, one N,N-di (aliphatic hydrocarbon residues containing 1 to 4 carbon atoms) amine groups, hydroxyl groups, pendant oxy groups, aliphatic hydrocarbon residues containing 1 to 4 carbon atoms, oxy groups, trifluoromethoxy, mercapto groups, Trifluoromethylthio, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, thio, trifluoromethyl, cyano, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms and carboxyl groups, etc., and Wherein, the cycloaliphatic hydrocarbon residue containing 3 to 10 carbon atoms or the heterocyclic aliphatic hydrocarbon residue containing 3 to 10 ring members can each be selected via an aliphatic hydrocarbon functional group containing 1 to 8 carbon atoms, Preferably, the bond is formed through an aliphatic hydrocarbon functional group containing 1 to 4 carbon atoms, which may be unsubstituted or substituted one or several times with at least one substituent selected from the following group. The group consists of fluorine, chlorine, bromine, iodine and other atoms, nitro groups, amino groups, one N- (aliphatic hydrocarbon residues containing 1 to 4 carbon atoms) amino groups, one N, N-di (containing 1 to Aliphatic hydrocarbon residues of 4 carbon atoms) amine groups, hydroxyl groups, pendant oxy groups, aliphatic hydrocarbon residues containing 1 to 4 carbon atoms, oxy groups, trifluoromethoxy groups, mercapto groups, trifluoromethylthio groups, one It is composed of aliphatic hydrocarbon residues containing 1 to 4 carbon atoms, sulfur, trifluoromethyl, cyano, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, and carboxyl groups, or represents an aromatic or heteroaromatic group Groups, each of which is unsubstituted or substituted one or several times with at least one substituent selected from the following group consisting of fluorine, chlorine, bromine, iodine and other atoms, nitro group, and amino group , One N- (aliphatic hydrocarbon residue containing 1 to 4 carbon atoms) amino group, one N,N-di (aliphatic hydrocarbon residue containing 1 to 4 carbon atoms) amino group, hydroxyl group, one containing 1 to Aliphatic hydrocarbon residues of 4 carbon atoms, oxy, trifluoromethoxy, mercapto, trifluoromethylthio, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, thio, trifluoromethyl, cyano, Aliphatic hydrocarbon residues containing 1 to 4 carbon atoms, carboxyl, methylcarbonyl, ethylcarbonyl, methoxycarbonyl and ethoxycarbonyl, a cycloaliphatic hydrocarbon residues containing 3 to 6 carbon atoms, and a Heterocyclic aliphatic hydrocarbon residues containing 3 to 6 ring members,N-di (aliphatic hydrocarbon residues containing 1 to 4 carbon atoms) amine groups, hydroxyl groups, aliphatic hydrocarbon residues containing 1 to 4 carbon atoms, oxy groups, trifluoromethoxy groups, mercapto groups, trifluoromethyl sulfide Group, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, thio, trifluoromethyl, cyano, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, carboxyl, methylcarbonyl, ethylcarbonyl, Methoxycarbonyl and ethoxycarbonyl, a cycloaliphatic hydrocarbon residue containing 3 to 6 carbon atoms and a heterocyclic aliphatic hydrocarbon residue containing 3 to 6 ring members,N-di (aliphatic hydrocarbon residues containing 1 to 4 carbon atoms) amine groups, hydroxyl groups, aliphatic hydrocarbon residues containing 1 to 4 carbon atoms, oxy groups, trifluoromethoxy groups, mercapto groups, trifluoromethyl sulfide Group, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, thio, trifluoromethyl, cyano, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, carboxyl, methylcarbonyl, ethylcarbonyl, Methoxycarbonyl and ethoxycarbonyl, a cycloaliphatic hydrocarbon residue containing 3 to 6 carbon atoms and a heterocyclic aliphatic hydrocarbon residue containing 3 to 6 ring members,N-di (aliphatic hydrocarbon residues containing 1 to 4 carbon atoms) amine groups, hydroxyl groups, aliphatic hydrocarbon residues containing 1 to 4 carbon atoms, oxy groups, trifluoromethoxy groups, mercapto groups, trifluoromethyl sulfide Group, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, thio, trifluoromethyl, cyano, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, carboxyl, methylcarbonyl, ethylcarbonyl, Methoxycarbonyl and ethoxycarbonyl, a cycloaliphatic hydrocarbon residue containing 3 to 6 carbon atoms and a heterocyclic aliphatic hydrocarbon residue containing 3 to 6 ring members,N-di (aliphatic hydrocarbon residues containing 1 to 4 carbon atoms) amine groups, hydroxyl groups, aliphatic hydrocarbon residues containing 1 to 4 carbon atoms, oxy groups, trifluoromethoxy groups, mercapto groups, trifluoromethyl sulfide Group, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, thio, trifluoromethyl, cyano, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, carboxyl, methylcarbonyl, ethylcarbonyl, Methoxycarbonyl and ethoxycarbonyl, a cycloaliphatic hydrocarbon residue containing 3 to 6 carbon atoms and a heterocyclic aliphatic hydrocarbon residue containing 3 to 6 ring members,N-di (aliphatic hydrocarbon residues containing 1 to 4 carbon atoms) amino groups, hydroxyl groups, pendant oxy groups, aliphatic hydrocarbon residues containing 1 to 4 carbon atoms, oxy groups, trifluoromethoxy, mercapto groups, Trifluoromethylthio, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, thio, trifluoromethyl, cyano, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms and a carboxyl group, or Represents an aromatic group or a heteroaromatic group, each of which is unsubstituted or substituted one or several times with at least one substituent selected from the following groups, the group consisting of fluorine, chlorine, bromine, iodine, etc. Atom, nitro group, amine group, one N- (aliphatic hydrocarbon residue containing 1 to 4 carbon atoms) amine group, one N,N-di (aliphatic hydrocarbon residue containing 1 to 4 carbon atoms) amine group , Hydroxyl, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, oxy, trifluoromethoxy, mercapto, trifluoromethylthio, aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, a sulfur group, three Fluoromethyl, cyano, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, carboxyl, methylcarbonyl, ethylcarbonyl, methoxycarbonyl and ethoxycarbonyl, a containing 3 to 6 carbon atoms Cycloaliphatic hydrocarbon residues and a heterocyclic aliphatic hydrocarbon residue containing 3 to 6 ring members,N-di (aliphatic hydrocarbon residues containing 1 to 4 carbon atoms) amino groups, hydroxyl groups, pendant oxy groups, aliphatic hydrocarbon residues containing 1 to 4 carbon atoms, oxy groups, trifluoromethoxy, mercapto groups, Trifluoromethylthio, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, thio, trifluoromethyl, cyano, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms and a carboxyl group, or Represents an aromatic group or a heteroaromatic group, each of which is unsubstituted or substituted one or several times with at least one substituent selected from the following groups, the group consisting of fluorine, chlorine, bromine, iodine, etc. Atom, nitro group, amine group, one N- (aliphatic hydrocarbon residue containing 1 to 4 carbon atoms) amine group, one N,N-di (aliphatic hydrocarbon residue containing 1 to 4 carbon atoms) amine group , Hydroxyl, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, oxy, trifluoromethoxy, mercapto, trifluoromethylthio, aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, a sulfur group, three Fluoromethyl, cyano, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, carboxyl, methylcarbonyl, ethylcarbonyl, methoxycarbonyl and ethoxycarbonyl, a containing 3 to 6 carbon atoms Cycloaliphatic hydrocarbon residues and a heterocyclic aliphatic hydrocarbon residue containing 3 to 6 ring members,<img file="TW201210596A_D0010.tif" />, Benzyl, phenyl, thienyl, pyridyl, furyl, thiazolyl and oxazolyl, etc., wherein the aliphatic hydrocarbon residues containing 1 to 4 carbon atoms may be unsubstituted or Substituting one or more times with at least one substituent selected from the following groups, the group consisting of fluorine, chlorine, bromine, iodine and other atoms, hydroxyl, trifluoromethoxy, trifluoromethyl and a It is composed of substituted aliphatic hydrocarbon residues containing 1 to 4 carbon atoms, oxy groups, etc., and wherein benzyl, phenyl, thienyl, pyridyl, furyl, thiazolyl and oxazolyl may each be unsubstituted or Substitute one or several times by at least one substituent selected from the following groups, which are composed of fluorine, chlorine, bromine, iodine and other atoms, nitro groups, amino groups, and one N- (containing 1 to 4 carbon atoms). Aliphatic hydrocarbon residues of atoms) amino groups, one N,N-di (aliphatic hydrocarbon residues containing 1 to 4 carbon atoms) amino groups, hydroxyl groups, an aliphatic hydrocarbon residues containing 1 to 4 carbon atoms, oxy , Trifluoromethoxy, hydroxymethoxy, methoxymethoxy, mercapto, trifluoromethylthio, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, thio, trifluoromethyl, cyano , An aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, carboxyl, methylcarbonyl, ethylcarbonyl, methoxycarbonyl and ethoxycarbonyl, etc., and the ring containing 3 to 6 carbon atoms The aliphatic hydrocarbon residue and the heterocyclic aliphatic hydrocarbon residue containing 3 to 6 ring members may each be unsubstituted or substituted one or several times with at least one substituent selected from the following group. It consists of fluorine, chlorine, bromine, iodine and other atoms, nitro, amino, one N- (aliphatic hydrocarbon residue containing 1 to 4 carbon atoms) amino, one N, N-di (containing 1 to 4 carbon Atom of aliphatic hydrocarbon residue) amine group, hydroxyl group, pendant oxy group, an aliphatic hydrocarbon residue oxy group containing 1 to 4 carbon atoms, trifluoromethoxy, mercapto group, trifluoromethylthio group, one containing 1 to Aliphatic hydrocarbon residues with 4 carbon atoms, thio, trifluoromethyl, cyano, an aliphatic hydrocarbon residue with 1 to 4 carbon atoms, and carboxyl groups, etc., and the aromatic group or heteroaromatic group can be individually Depending on the choice, the bond is formed via an aliphatic hydrocarbon residue containing 1 to 8 carbon atoms, preferably via an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, which in turn may be unsubstituted or through at least one Substitute one or several times with the substituent selected from the following group, the group is composed of fluorine, chlorine, bromine, iodine and other atoms, nitro group, amino group, one N- (fat containing 1 to 4 carbon atoms) Hydrocarbon residues) amino groups, one N,N-di (aliphatic hydrocarbon residues containing 1 to 4 carbon atoms) amino groups, hydroxyl groups, pendant oxygen groups, one aliphatic hydrocarbon residues containing 1 to 4 carbon atoms, oxygen R²Represents hydrogen, fluorine, chlorine, bromine, iodine and other atoms, cyano, trifluoromethyl, nitro, trifluoromethoxy, trifluoromethylthio, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, An aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, a thio group, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, an oxy group, wherein the aliphatic hydrocarbon residue containing 1 to 4 carbon atoms can each be Substituted or substituted one or several times; a cycloaliphatic hydrocarbon residue containing 3 to 6 carbon atoms or a heterocyclic aliphatic hydrocarbon residue containing 3 to 6 ring members, each of which is unsubstituted or substituted Substitution one or several times or each other depending on the choice is bonded via an aliphatic hydrocarbon functional group containing 1 to 4 carbon atoms, and the functional group may be unsubstituted or substituted one or several times, preferably Represents hydrogen, fluorine, chlorine, bromine, iodine and other atoms, cyano, trifluoromethyl, nitro, trifluoromethoxy, trifluoromethylthio, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, An aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, a thio group, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, an oxy group, wherein the aliphatic hydrocarbon residue containing 1 to 4 carbon atoms can each be Substituted or substituted one or several times with at least one substituent selected from the following groups, the group consisting of fluorine, chlorine, bromine, iodine and other atoms, pendant oxygen groups, hydroxyl groups and an unsubstituted one containing 1 Aliphatic hydrocarbon residues with to 4 carbon atoms are composed of oxy groups; a cycloaliphatic hydrocarbon residue with 3 to 6 carbon atoms or a heterocyclic aliphatic hydrocarbon residue with 3 to 6 ring members, each of which It is unsubstituted or substituted one or several times with at least one substituent selected from the following groups, the group consisting of atoms such as fluorine, chlorine, bromine, iodine, pendant oxygen groups, hydroxyl groups, and one containing 1 to 4 The aliphatic hydrocarbon residue containing 1 to 4 carbon atoms is composed of an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, etc., wherein the aliphatic hydrocarbon residue containing 1 to 4 carbon atoms may be unsubstituted or At least one substituent selected from the following group is substituted one or several times, the group is composed of fluorine, chlorine, bromine, iodine and other atoms, pendant oxygen groups, hydroxyl groups and an unsubstituted one containing 1 to 4 carbons And the cycloaliphatic hydrocarbon residue containing 3 to 6 carbon atoms or the heterocyclic aliphatic hydrocarbon residue containing 3 to 6 ring members can each be selected according to a The aliphatic hydrocarbon functional group containing 1 to 4 carbon atoms forms a bond, and it may be unsubstituted or substituted one or several times with at least one substituent selected from the following group, which is composed of fluorine , Chlorine, bromine, iodine and other atoms, pendant oxygen groups, hydroxyl groups, an unsubstituted aliphatic hydrocarbon residue containing 1 to 4 carbon atoms and an unsubstituted aliphatic hydrocarbon residue containing 1 to 4 carbon atoms Oxy group, etc., R³, R⁴, R⁵And R⁶Independently of each other, it represents atoms such as hydrogen, fluorine, chlorine, bromine, and iodine, cyano, trifluoromethyl, trifluoromethoxy, trifluoromethylthio, aldehyde, carboxy, amide, and hydroxysulfonyl , Nitro, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, an aliphatic hydrocarbon residue carbonyl containing 1 to 4 carbon atoms, an aliphatic hydrocarbon residue oxycarbonyl containing 1 to 4 carbon atoms, One N- (aliphatic hydrocarbon residue containing 1 to 4 carbon atoms) amide group, one N,N-di (aliphatic hydrocarbon residue containing 1 to 4 carbon atoms) amide group, one containing 1 to 4 Aliphatic hydrocarbon residue oxy group containing 1 to 4 carbon atoms, an aliphatic hydrocarbon residue carbonyloxy group containing 1 to 4 carbon atoms, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms thio group, one containing 1 to 4 carbon atoms Aliphatic hydrocarbon residues of carbon atoms sulfonyl, one N- (aliphatic hydrocarbon residues containing 1 to 4 carbon atoms) amine groups, one N,N-di (aliphatic hydrocarbon residues containing 1 to 4 carbon atoms) ) Amine group, one N-(aliphatic hydrocarbon residue carbonyl containing 1 to 4 carbon atoms) amine group and one N-(aliphatic hydrocarbon residue sulfonyl containing 1 to 4 carbon atoms) amine group, wherein the The aliphatic hydrocarbon residues containing 1 to 4 carbon atoms may each be unsubstituted or substituted one or several times with at least one substituent selected from the following group consisting of fluorine, chlorine, bromine, and iodine Consists of equal atoms, pendant oxy groups, hydroxyl groups and an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms; one containing 3 to 6 carbon atoms or a cycloaliphatic hydrocarbon residue containing 3 to 6 rings Member heterocyclic aliphatic hydrocarbon residues, each of which is unsubstituted or substituted one or several times with at least one substituent selected from the following group consisting of fluorine, chlorine, bromine, iodine and other atoms , Pendant oxy group, hydroxyl group, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms and an aliphatic hydrocarbon residue oxy group containing 1 to 4 carbon atoms, etc., and each of them is selected by an unsubstituted The aliphatic hydrocarbon residues containing 1 to 4 carbon atoms form a bond, but the condition is: R³, R⁴, R⁵And R⁶At least one of them is not a hydrogen atom, R⁷Represents an aliphatic hydrocarbon residue containing 2 to 10 carbon atoms, preferably represents an aliphatic hydrocarbon residue containing 2 to 8 carbon atoms, which is unsubstituted or at least one selected from the following groups Substituents are substituted one or several times. The group consists of fluorine, chlorine, bromine, iodine and other atoms, nitro groups, amino groups, one N- (aliphatic hydrocarbon residues containing 1 to 4 carbon atoms) amino groups, one N,N-two (aliphatic hydrocarbon residues containing 1 to 4 carbon atoms) amino groups, hydroxyl groups, pendant oxy groups, aliphatic hydrocarbon residues containing 1 to 4 carbon atoms, oxy groups, trifluoromethoxy, Sulfhydryl, trifluoromethylthio, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, thio, trifluoromethyl, cyano, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, carboxyl, etc. , Wherein the aliphatic hydrocarbon residues containing 1 to 4 carbon atoms may each be unsubstituted or substituted one or several times with at least one substituent selected from the following groups, the group consisting of fluorine, chlorine, Bromine, iodine and other atoms, hydroxyl, trifluoromethoxy, trifluoromethyl, and an unsubstituted aliphatic hydrocarbon residue oxygen containing 1 to 4 carbon atoms, etc., or represents a containing 3 to 10 A carbon atom cycloaliphatic hydrocarbon residue or a heterocyclic aliphatic hydrocarbon residue containing 3 to 10 ring members, each of which is unsubstituted or substituted with at least one substituent selected from the following groups Secondly, this group consists of fluorine, chlorine, bromine, iodine and other atoms, nitro groups, amino groups, one N- (aliphatic hydrocarbon residues containing 1 to 4 carbon atoms) amino groups, one N,N-di (aliphatic hydrocarbon residues containing 1 to 4 carbon atoms) amine groups, hydroxyl groups, pendant oxy groups, aliphatic hydrocarbon residues containing 1 to 4 carbon atoms, oxy groups, trifluoromethoxy, mercapto groups, Trifluoromethylthio, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, thio, trifluoromethyl, cyano, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms and a carboxyl group, etc. The aliphatic hydrocarbon residues containing 1 to 4 carbon atoms may each be unsubstituted or substituted one or several times with at least one substituent selected from the following groups, the group consisting of fluorine, chlorine, bromine, It is composed of iodine and other atoms, hydroxyl, trifluoromethoxy, trifluoromethyl, and an unsubstituted aliphatic hydrocarbon residue oxy group containing 1 to 4 carbon atoms, and which contains 3 to 10 carbon atoms The cycloaliphatic hydrocarbon residue or the heterocyclic aliphatic hydrocarbon residue containing 3 to 10 ring members can each be selected via an aliphatic hydrocarbon functional group containing 1 to 8 carbon atoms, preferably via an aliphatic hydrocarbon functional group containing 1 to 4 The aliphatic hydrocarbon functional group of three carbon atoms forms a bond, and it can be unsubstituted or substituted one or several times with at least one substituent selected from the following group, which is composed of fluorine, chlorine, bromine , Iodine and other atoms, nitro group, amino group, one N-(aliphatic hydrocarbon residue containing 1 to 4 carbon atoms) amino group, one N,N-di(aliphatic hydrocarbon residue containing 1 to 4 carbon atoms) ) Amino groups, hydroxyl groups, pendant oxygen groups, aliphatic hydrocarbon residues containing 1 to 4 carbon atoms, oxy groups, trifluoromethoxy groups, mercapto groups, trifluoromethylthio groups, and fatty acids containing 1 to 4 carbon atoms Hydrocarbon residues are composed of sulfur, trifluoromethyl, cyano, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, and carboxyl, but the condition is: if R⁷When it represents a heterocyclic aliphatic hydrocarbon residue containing 3 to 10 ring members, the heterocyclic aliphatic hydrocarbon residue containing 3 to 10 ring members is connected via a carbon atom.

According to the general formula (<b>I</b>) In a preferred embodiment of the compound, the residue R¹Represents an aliphatic hydrocarbon residue containing 1 to 10 ring members, preferably represents an aliphatic hydrocarbon residue containing 1 to 8 ring members, which is unsubstituted or at least one selected from the following groups Substituents are substituted one or several times. The group consists of fluorine, chlorine, bromine, iodine and other atoms, nitro groups, amino groups, one N- (aliphatic hydrocarbon residues containing 1 to 4 carbon atoms) amino groups, one N,N-two (aliphatic hydrocarbon residues containing 1 to 4 carbon atoms) amino groups, hydroxyl groups, pendant oxy groups, aliphatic hydrocarbon residues containing 1 to 4 carbon atoms, oxy groups, trifluoromethoxy, Sulfhydryl, trifluoromethylthio, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, thio, trifluoromethyl, cyano, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, carboxyl, etc. , Wherein the aliphatic hydrocarbon residues containing 1 to 4 carbon atoms may each be unsubstituted or substituted one or several times with at least one substituent selected from the following groups, the group consisting of fluorine, chlorine, Bromine, iodine and other atoms, hydroxyl, trifluoromethoxy, trifluoromethyl, and an unsubstituted aliphatic hydrocarbon residue oxygen containing 1 to 4 carbon atoms, etc., or represents a containing 3 to 10 A carbon atom cycloaliphatic hydrocarbon residue or a heterocyclic aliphatic hydrocarbon residue containing 3 to 10 ring members, each of which is unsubstituted or substituted with at least one substituent selected from the following groups Second, this group consists of fluorine, chlorine, bromine, iodine and other atoms, nitro groups, amino groups, one N- (aliphatic hydrocarbon residues containing 1 to 4 carbon atoms) amino groups, one N,N-two ( Aliphatic hydrocarbon residues containing 1 to 4 carbon atoms) amine groups, hydroxyl groups, pendant oxygen groups, aliphatic hydrocarbon residues containing 1 to 4 carbon atoms, oxy groups, trifluoromethoxy groups, mercapto groups, trifluoromethyl sulfide Aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, sulfur group, trifluoromethyl, cyano group, aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, carboxyl group, one containing 3 to 6 carbon atoms The cycloaliphatic hydrocarbon residues and a heterocyclic aliphatic hydrocarbon residues containing 3 to 6 ring members, etc., wherein the aliphatic hydrocarbon residues containing 1 to 4 carbon atoms can each be unsubstituted or have at least one Substitute one or several times with the substituent selected from the following group, which consists of fluorine, chlorine, bromine, iodine and other atoms, hydroxyl, trifluoromethoxy, trifluoromethyl and one unsubstituted The aliphatic hydrocarbon residues of 1 to 4 carbon atoms are composed of oxy groups, and the cycloaliphatic hydrocarbon residues containing 3 to 6 carbon atoms or the heterocyclic aliphatic hydrocarbon residues containing 3 to 6 ring members can be Each is unsubstituted or substituted one or several times with at least one substituent selected from the following groups, the group consisting of atoms such as fluorine, chlorine, bromine, iodine, nitro, amino, and one N-( Aliphatic hydrocarbon residues containing 1 to 4 carbon atoms) amine group, -N,N-di (aliphatic hydrocarbon residues containing 1 to 4 carbon atoms) amino groups, hydroxyl groups, pendant oxy groups, aliphatic hydrocarbon residues containing 1 to 4 carbon atoms, oxy groups, trifluoromethoxy, mercapto groups, Trifluoromethylthio, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, thio, trifluoromethyl, cyano, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, carboxyl, etc., and Wherein the cycloaliphatic hydrocarbon residue containing 3 to 10 carbon atoms or the heterocyclic aliphatic hydrocarbon residue containing 3 to 10 ring members can each be selected via an aliphatic hydrocarbon functional group containing 1 to 8 carbon atoms, Preferably, the bond is formed through an aliphatic hydrocarbon functional group containing 1 to 4 carbon atoms, which may be unsubstituted or substituted one or several times with at least one substituent selected from the following group. The group consists of fluorine, chlorine, bromine, iodine and other atoms, nitro groups, amino groups, one N- (aliphatic hydrocarbon residues containing 1 to 4 carbon atoms) amino groups, one N, N-di (containing 1 to Aliphatic hydrocarbon residues of 4 carbon atoms) amine groups, hydroxyl groups, pendant oxy groups, aliphatic hydrocarbon residues containing 1 to 4 carbon atoms, oxy groups, trifluoromethoxy groups, mercapto groups, trifluoromethylthio groups, one It is composed of aliphatic hydrocarbon residues containing 1 to 4 carbon atoms, sulfur, trifluoromethyl, cyano, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, and carboxyl groups, or represents an aromatic or heteroaromatic group Groups, each of which is unsubstituted or substituted one or several times with at least one substituent selected from the following groups, the group consisting of atoms such as fluorine, chlorine, bromine, and iodine, nitro, amino, One N- (aliphatic hydrocarbon residue containing 1 to 4 carbon atoms) amino group, one N,N-di (aliphatic hydrocarbon residue containing 1 to 4 carbon atoms) amino group, hydroxyl group, one containing 1 to 4 Aliphatic hydrocarbon residues oxy, trifluoromethoxy, mercapto, trifluoromethylthio, aliphatic hydrocarbon residues containing 1 to 4 carbon atoms, thio, trifluoromethyl, cyano, one Aliphatic hydrocarbon residues containing 1 to 4 carbon atoms, carboxyl, methylcarbonyl, ethylcarbonyl, methoxycarbonyl and ethoxycarbonyl, one containing 3 to 6 carbon atoms cycloaliphatic hydrocarbon residues, one containing Heterocyclic aliphatic hydrocarbon residues of 3 to 6 ring members,N-di (aliphatic hydrocarbon residues containing 1 to 4 carbon atoms) amine groups, hydroxyl groups, aliphatic hydrocarbon residues containing 1 to 4 carbon atoms, oxy groups, trifluoromethoxy groups, mercapto groups, trifluoromethyl sulfide Group, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, thio, trifluoromethyl, cyano, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, carboxyl, methylcarbonyl, ethylcarbonyl, Methoxycarbonyl and ethoxycarbonyl, a cycloaliphatic hydrocarbon residue containing 3 to 6 carbon atoms, a heterocyclic aliphatic hydrocarbon residue containing 3 to 6 ring members,N-di (aliphatic hydrocarbon residues containing 1 to 4 carbon atoms) amine groups, hydroxyl groups, aliphatic hydrocarbon residues containing 1 to 4 carbon atoms, oxy groups, trifluoromethoxy groups, mercapto groups, trifluoromethyl sulfide Group, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, thio, trifluoromethyl, cyano, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, carboxyl, methylcarbonyl, ethylcarbonyl, Methoxycarbonyl and ethoxycarbonyl, a cycloaliphatic hydrocarbon residue containing 3 to 6 carbon atoms, a heterocyclic aliphatic hydrocarbon residue containing 3 to 6 ring members,N-di (aliphatic hydrocarbon residues containing 1 to 4 carbon atoms) amine groups, hydroxyl groups, aliphatic hydrocarbon residues containing 1 to 4 carbon atoms, oxy groups, trifluoromethoxy groups, mercapto groups, trifluoromethyl sulfide Group, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, thio, trifluoromethyl, cyano, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, carboxyl, methylcarbonyl, ethylcarbonyl, Methoxycarbonyl and ethoxycarbonyl, a cycloaliphatic hydrocarbon residue containing 3 to 6 carbon atoms, a heterocyclic aliphatic hydrocarbon residue containing 3 to 6 ring members,N-di (aliphatic hydrocarbon residues containing 1 to 4 carbon atoms) amine groups, hydroxyl groups, aliphatic hydrocarbon residues containing 1 to 4 carbon atoms, oxy groups, trifluoromethoxy groups, mercapto groups, trifluoromethyl sulfide Group, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, thio, trifluoromethyl, cyano, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, carboxyl, methylcarbonyl, ethylcarbonyl, Methoxycarbonyl and ethoxycarbonyl, a cycloaliphatic hydrocarbon residue containing 3 to 6 carbon atoms, a heterocyclic aliphatic hydrocarbon residue containing 3 to 6 ring members,N-di (aliphatic hydrocarbon residues containing 1 to 4 carbon atoms) amino groups, hydroxyl groups, pendant oxy groups, aliphatic hydrocarbon residues containing 1 to 4 carbon atoms, oxy groups, trifluoromethoxy, mercapto groups, Trifluoromethylthio, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, thio, trifluoromethyl, cyano, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms and a carboxyl group, or Represents an aromatic group or a heteroaromatic group, each of which is unsubstituted or substituted one or several times with at least one substituent selected from the following group consisting of fluorine, chlorine, bromine, iodine and other atoms , Nitro, amine group, one N- (aliphatic hydrocarbon residue containing 1 to 4 carbon atoms) amine group, one N,N-di (aliphatic hydrocarbon residue containing 1 to 4 carbon atoms) amine group, Hydroxyl, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, oxy, trifluoromethoxy, mercapto, trifluoromethylthio, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, thio, trifluoro Methyl, cyano, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, carboxyl, methylcarbonyl, ethylcarbonyl, methoxycarbonyl and ethoxycarbonyl, a ring containing 3 to 6 carbon atoms Aliphatic hydrocarbon residues, a heterocyclic aliphatic hydrocarbon residue containing 3 to 6 ring members,N-di (aliphatic hydrocarbon residues containing 1 to 4 carbon atoms) amino groups, hydroxyl groups, pendant oxy groups, aliphatic hydrocarbon residues containing 1 to 4 carbon atoms, oxy groups, trifluoromethoxy, mercapto groups, Trifluoromethylthio, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, thio, trifluoromethyl, cyano, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms and a carboxyl group, or Represents an aromatic group or a heteroaromatic group, each of which is unsubstituted or substituted one or several times with at least one substituent selected from the following group consisting of fluorine, chlorine, bromine, iodine and other atoms , Nitro, amine group, one N- (aliphatic hydrocarbon residue containing 1 to 4 carbon atoms) amine group, one N,N-di (aliphatic hydrocarbon residue containing 1 to 4 carbon atoms) amine group, Hydroxyl, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, oxy, trifluoromethoxy, mercapto, trifluoromethylthio, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, thio, trifluoro Methyl, cyano, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, carboxyl, methylcarbonyl, ethylcarbonyl, methoxycarbonyl and ethoxycarbonyl, a ring containing 3 to 6 carbon atoms Aliphatic hydrocarbon residues, a heterocyclic aliphatic hydrocarbon residue containing 3 to 6 ring members,<img file="TW201210596A_D0011.tif" />, Benzyl, phenyl, thienyl, pyridyl, furyl, thiazolyl and oxazolyl, etc., wherein the aliphatic hydrocarbon residues containing 1 to 4 carbon atoms may be unsubstituted or at least One or several times substituted by the substituent selected from the following group, the group consisting of fluorine, chlorine, bromine, iodine and other atoms, hydroxyl, trifluoromethoxy, trifluoromethyl and an unsubstituted Aliphatic hydrocarbon residues containing 1 to 4 carbon atoms are composed of oxy groups, and the benzyl, phenyl, thienyl, pyridyl, furyl, thiazolyl and oxazolyl groups may each be unsubstituted or Substitute one or several times by at least one substituent selected from the following groups, which are composed of fluorine, chlorine, bromine, iodine and other atoms, nitro groups, amino groups, and one N- (containing 1 to 4 carbon atoms). Aliphatic hydrocarbon residues of atoms) amino groups, one N,N-di (aliphatic hydrocarbon residues containing 1 to 4 carbon atoms) amino groups, hydroxyl groups, an aliphatic hydrocarbon residues containing 1 to 4 carbon atoms, oxy , Trifluoromethoxy, hydroxymethoxy, methoxymethoxy, mercapto, trifluoromethylthio, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, thio, trifluoromethyl, cyano , An aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, carboxyl, methylcarbonyl, ethylcarbonyl, methoxycarbonyl and ethoxycarbonyl, etc., and the ring containing 3 to 6 carbon atoms The aliphatic hydrocarbon residue and the heterocyclic aliphatic hydrocarbon residue containing 3 to 6 ring members may each be unsubstituted or substituted one or several times with at least one substituent selected from the following group. It consists of fluorine, chlorine, bromine, iodine and other atoms, nitro, amino, one N- (aliphatic hydrocarbon residue containing 1 to 4 carbon atoms) amino, one N, N-di (containing 1 to 4 carbon Atom of aliphatic hydrocarbon residue) amine group, hydroxyl group, pendant oxy group, an aliphatic hydrocarbon residue oxy group containing 1 to 4 carbon atoms, trifluoromethoxy, mercapto group, trifluoromethylthio group, one containing 1 to Aliphatic hydrocarbon residues with 4 carbon atoms, thio, trifluoromethyl, cyano, an aliphatic hydrocarbon residue with 1 to 4 carbon atoms, and carboxyl groups, etc., and the aromatic group or heteroaromatic group can be individually Depending on the choice, the bond is formed via an aliphatic hydrocarbon residue containing 1 to 8 carbon atoms, preferably via an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, which in turn may be unsubstituted or through at least one Substitute one or several times with the substituent selected from the following group, the group is composed of fluorine, chlorine, bromine, iodine and other atoms, nitro group, amino group, one N- (fat containing 1 to 4 carbon atoms) Hydrocarbon residue) amine group, -N,N-di (aliphatic hydrocarbon residues containing 1 to 4 carbon atoms) amino groups, hydroxyl groups, pendant oxy groups, aliphatic hydrocarbon residues containing 1 to 4 carbon atoms, oxy groups, trifluoromethoxy, mercapto groups, It is composed of trifluoromethylthio, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, thio, trifluoromethyl, cyano and carboxyl.

In another preferred embodiment of the compound of formula (I) according to the present invention, the residue R¹Representative part of the structure (<b>T1</b>)

<chemistry general="n"><img file="TW201210596A_D0012.tif" /></chemistry>

Wherein m represents 0, 1, 2, 3 or 4, preferably represents 0, 1 or 2, R^8aAnd R^8bIndependently of each other, it represents hydrogen, fluorine, chlorine, bromine, iodine and other atoms, nitro groups, amino groups, one N- (aliphatic hydrocarbon residues containing 1 to 4 carbon atoms) amino groups, one N, N-di ( Aliphatic hydrocarbon residues containing 1 to 4 carbon atoms) amine groups, hydroxyl groups, aliphatic hydrocarbon residues containing 1 to 4 carbon atoms, oxy groups, trifluoromethoxy groups, mercapto groups, trifluoromethylthio groups, one containing Aliphatic hydrocarbon residues of 1 to 4 carbon atoms, thio, trifluoromethyl, cyano, an aliphatic hydrocarbon residue or carboxyl group containing 1 to 4 carbon atoms, or together represent pendant oxy groups, etc., preferably Independently of each other, it represents hydrogen, fluorine, chlorine, bromine, iodine and other atoms, amino groups, one N- (aliphatic hydrocarbon residues containing 1 to 4 carbon atoms) amino groups, one N, N-di (containing 1 to Aliphatic hydrocarbon residues with 4 carbon atoms) amine groups, hydroxyl groups, an aliphatic hydrocarbon residues containing 1 to 4 carbon atoms, oxy groups, or an aliphatic hydrocarbon residues containing 1 to 4 carbon atoms, and more preferably each other Each independently represents atoms such as hydrogen, fluorine, chlorine, bromine, iodine, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, an oxy group, or an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, or even better It represents independently of each other atoms such as hydrogen and fluorine, an aliphatic hydrocarbon residue oxy group containing 1 to 4 carbon atoms, or an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, and R^8cRepresents an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, which is unsubstituted or substituted one or several times with at least one substituent selected from the following group consisting of fluorine, chlorine, and bromine , Iodine and other atoms, nitro group, amino group, one N-(aliphatic hydrocarbon residue containing 1 to 4 carbon atoms) amino group, one N,N-di(aliphatic hydrocarbon residue containing 1 to 4 carbon atoms) ) Amino groups, hydroxyl groups, pendant oxy groups, aliphatic hydrocarbon residues containing 1 to 4 carbon atoms, oxy groups, trifluoromethoxy groups, mercapto groups, trifluoromethylthio groups, and fatty acids containing 1 to 4 carbon atoms Hydrocarbon residues are composed of thio, trifluoromethyl, cyano, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms or carboxyl group, or represent a cycloaliphatic hydrocarbon residue containing 3 to 10 carbon atoms or A heterocyclic aliphatic hydrocarbon residue containing 3 to 10 ring members, preferably when m0, each of which is unsubstituted or substituted with at least one substituent selected from the following groups, or Several times, this group consists of fluorine, chlorine, bromine, iodine and other atoms, nitro groups, amino groups, one N- (aliphatic hydrocarbon residues containing 1 to 4 carbon atoms) amino groups, one N,N-two (Aliphatic hydrocarbon residues containing 1 to 4 carbon atoms) Amino groups, hydroxyl groups, pendant oxygen groups, an aliphatic hydrocarbon residues containing 1 to 4 carbon atoms, oxy groups, trifluoromethoxy, mercapto, trifluoromethyl Sulfur group, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, sulfur group, trifluoromethyl, cyano, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, a carboxyl group, one containing 3 to 6 carbons A cycloaliphatic hydrocarbon residue containing 3 to 6 ring members and a heterocyclic aliphatic hydrocarbon residue containing 3 to 6 ring members, etc., wherein the aliphatic hydrocarbon residue containing 1 to 4 carbon atoms may each be unsubstituted or at least One or several times substituted by the substituent selected from the following group, the group consisting of fluorine, chlorine, bromine, iodine and other atoms, hydroxyl, trifluoromethoxy, trifluoromethyl and an unsubstituted The aliphatic hydrocarbon residues containing 1 to 4 carbon atoms are composed of oxy groups, and the cycloaliphatic hydrocarbon residues containing 3 to 6 carbon atoms and the heterocyclic aliphatic hydrocarbon residues containing 3 to 6 ring members Each may be unsubstituted or substituted one or several times with at least one substituent selected from the following groups, the group consisting of atoms such as fluorine, chlorine, bromine, iodine, nitro, amino, and one N- (Aliphatic hydrocarbon residues containing 1 to 4 carbon atoms) amine group, one N,N-di (aliphatic hydrocarbon residues containing 1 to 4 carbon atoms) amine groups, hydroxyl groups, pendant oxy groups, aliphatic hydrocarbon residues containing 1 to 4 carbon atoms, oxy groups, trifluoromethoxy, mercapto groups, Trifluoromethylthio, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, thio, trifluoromethyl, cyano, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms and a carboxyl group, or Representative-preferably when m = 0-an aryl or heteroaromatic group, each of which is unsubstituted or substituted one or several times with at least one substituent selected from the following group, the group It is composed of fluorine, chlorine, bromine, iodine and other atoms, nitro group, amino group, one N- (aliphatic hydrocarbon residue containing 1 to 4 carbon atoms) amino group, one N, N-di (containing 1 to 4 Aliphatic hydrocarbon residues of carbon atoms) amine groups, hydroxyl groups, aliphatic hydrocarbon residues containing 1 to 4 carbon atoms, oxy groups, trifluoromethoxy, mercapto groups, trifluoromethylthio groups, one containing 1 to 4 carbons Aliphatic hydrocarbon residues of atoms thio, trifluoromethyl, cyano, aliphatic hydrocarbon residues containing 1 to 4 carbon atoms, carboxyl, methylcarbonyl, ethylcarbonyl, methoxycarbonyl and ethoxycarbonyl , A cycloaliphatic hydrocarbon residue containing 3 to 6 carbon atoms, a heterocyclic aliphatic hydrocarbon residue containing 3 to 6 ring members,<img file="TW201210596A_D0013.tif" /><img file="TW201210596A_D0014.tif" />, Benzyl, phenyl, thienyl, pyridyl, furyl, thiazolyl and oxazolyl, etc., wherein the aliphatic hydrocarbon residues containing 1 to 4 carbon atoms may be unsubstituted or at least One or several times substituted by the substituent selected from the following group, the group consisting of fluorine, chlorine, bromine, iodine and other atoms, hydroxyl, trifluoromethoxy, trifluoromethyl and an unsubstituted The aliphatic hydrocarbon residues containing 1 to 4 carbon atoms are composed of oxy groups, and the benzyl, phenyl, thienyl, pyridyl, furanyl, thiazolyl and oxazolyl groups may each be unsubstituted or At least one substituent selected from the following group is substituted one or several times, the group is composed of atoms such as fluorine, chlorine, bromine, iodine, nitro, amino, and one N- (containing 1 to 4 carbon atoms Aliphatic hydrocarbon residues) amino groups, one N,N-di (aliphatic hydrocarbon residues containing 1 to 4 carbon atoms) amino groups, hydroxyl groups, an aliphatic hydrocarbon residues oxygen containing 1 to 4 carbon atoms, Trifluoromethoxy, mercapto, trifluoromethylthio, aliphatic hydrocarbon residues containing 1 to 4 carbon atoms, thio, trifluoromethyl, cyano, and aliphatic hydrocarbon residues containing 1 to 4 carbon atoms Group, carboxyl group, methylcarbonyl group, ethylcarbonyl group, methoxycarbonyl group and ethoxycarbonyl group, etc., and the cycloaliphatic hydrocarbon residue containing 3 to 6 carbon atoms and the cycloaliphatic hydrocarbon residue containing 3 to 6 ring members The heterocyclic aliphatic hydrocarbon residues can each be unsubstituted or substituted one or several times with at least one substituent selected from the following groups, which are composed of fluorine, chlorine, bromine, iodine and other atoms, nitro , Amine group, one N- (aliphatic hydrocarbon residue containing 1 to 4 carbon atoms) amino group, one N,N-di (aliphatic hydrocarbon residue containing 1 to 4 carbon atoms) amino group, hydroxyl, side Oxygen, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, oxy, trifluoromethoxy, mercapto, trifluoromethylthio, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, thio, three It is composed of a fluoromethyl group, a cyano group, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, and a carboxyl group.

The better one is R¹Representative part of the structure (<b>T1</b>), where m represents 0, 1 or 2, R^8aAnd R^8bIndependently of each other, it represents atoms such as hydrogen, fluorine, chlorine, bromine, iodine, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, or an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, preferably It represents independently of each other atoms such as hydrogen, fluorine, etc., an aliphatic hydrocarbon residue oxy group containing 1 to 2 carbon atoms, or an aliphatic hydrocarbon residue containing 1 to 2 carbon atoms, and R^8cRepresents an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, which is unsubstituted or substituted one or several times with at least one substituent selected from the following group consisting of fluorine, chlorine, and bromine , Iodine and other atoms, hydroxyl, pendant oxygen, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, oxy, trifluoromethoxy, trifluoromethyl, and an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms Group and carboxyl group, etc., or represent a cycloaliphatic hydrocarbon residue containing 3 to 10 carbon atoms or a heterocyclic aliphatic hydrocarbon residue containing 3 to 10 ring members, each of which is unsubstituted or at least Substitute one or several times with a substituent selected from the following group, which consists of fluorine, chlorine, bromine, iodine and other atoms, hydroxyl groups, pendant oxygen groups, and aliphatic hydrocarbon residues containing 1 to 4 carbon atoms Oxy, trifluoromethoxy, trifluoromethyl, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, a carboxyl group, a cycloaliphatic hydrocarbon residue containing 3 to 6 carbon atoms, and a cycloaliphatic hydrocarbon residue containing 3 to 6 carbon atoms It is composed of 6 ring-membered heterocyclic aliphatic hydrocarbon residues, etc., wherein the aliphatic hydrocarbon residues containing 1 to 4 carbon atoms can be each unsubstituted or substituted with at least one substituent selected from the following groups One or several times, the group consists of fluorine, chlorine, bromine, iodine and other atoms, hydroxyl, trifluoromethoxy, trifluoromethyl and an unsubstituted aliphatic hydrocarbon residue containing 1 to 4 carbon atoms The cycloaliphatic hydrocarbon residue containing 3 to 6 carbon atoms and the heterocyclic aliphatic hydrocarbon residue containing 3 to 6 ring members may each be unsubstituted or at least one of the following Substituents selected from the group are substituted one or several times, the group is composed of fluorine, chlorine, bromine, iodine and other atoms, hydroxyl, pendant oxygen, and an aliphatic hydrocarbon residue oxygen containing 1 to 4 carbon atoms , Trifluoromethoxy, trifluoromethyl, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms and a carboxyl group, or represents-preferably when m=0-an aromatic or heteroaromatic group Groups, each of which is unsubstituted or substituted one or several times with at least one substituent selected from the following groups, the group consisting of atoms such as fluorine, chlorine, bromine, and iodine, hydroxyl groups, one containing 1 to Aliphatic hydrocarbon residues of 4 carbon atoms, oxy, trifluoromethoxy, mercapto, trifluoromethylthio, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, thio, trifluoromethyl, cyano, Aliphatic hydrocarbon residues containing 1 to 4 carbon atoms, carboxyl, methylcarbonyl, ethylcarbonyl, methoxycarbonyl and ethoxycarbonyl, a cycloaliphatic hydrocarbon residues containing 3 to 6 carbon atoms, a Containing 3 to 6 ring member heterocyclic aliphatic hydrocarbon residues, benzyl, phenyl, thienyl, pyridyl, furyl, thiazolyl and oxazolyl, etc., which contain 1 to 4 carbon atoms The aliphatic hydrocarbon residues can each be unsubstituted or at least one selected from the following groupsThe substituents are substituted one or several times. The group consists of fluorine, chlorine, bromine, iodine and other atoms, hydroxyl, trifluoromethoxy, trifluoromethyl and an unsubstituted one containing 1 to 4 carbon atoms Aliphatic hydrocarbon residues are composed of oxy groups, and among them, benzyl, phenyl, thienyl, pyridyl, furyl, thiazolyl, and oxazolyl may each be unsubstituted or at least one of the following groups The selected substituents are substituted one or several times, preferably unsubstituted or substituted one or two times. The group consists of atoms such as fluorine, chlorine, bromine, and iodine, hydroxyl groups, and one containing 1 to 4 carbon atoms. The aliphatic hydrocarbon residue oxy, trifluoromethoxy, trifluoromethyl, cyano, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, carboxyl, methylcarbonyl, ethylcarbonyl, methoxycarbonyl It is composed of ethoxycarbonyl, etc., preferably by at least one substituent selected from the following group, which is composed of fluorine, chlorine and other atoms, methyl, methoxy, and trifluoromethyl And trifluoromethoxy, etc., wherein the cycloaliphatic hydrocarbon residue containing 3 to 6 carbon atoms and the heterocyclic aliphatic hydrocarbon residue containing 3 to 6 ring members may each be unsubstituted or at least Substitute one or several times with a substituent selected from the following group, which consists of fluorine, chlorine, bromine, iodine and other atoms, hydroxyl groups, pendant oxygen groups, and aliphatic hydrocarbon residues containing 1 to 4 carbon atoms It is composed of oxy, trifluoromethoxy, trifluoromethyl, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms and a carboxyl group.It is composed of aliphatic hydrocarbon residue oxy group, trifluoromethoxy group, trifluoromethyl group, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms and carboxyl group.It is composed of aliphatic hydrocarbon residue oxy group, trifluoromethoxy group, trifluoromethyl group, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms and carboxyl group.

The better one, R¹Representative part of the structure (<b>T1</b>), where m represents 0, 1 or 2, R^8aAnd R^8bIndependently of each other, it represents atoms such as hydrogen, fluorine, chlorine, bromine, iodine, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, or an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, preferably It represents independently of each other atoms such as hydrogen, fluorine, etc., an aliphatic hydrocarbon residue oxy group containing 1 to 2 carbon atoms, or an aliphatic hydrocarbon residue containing 1 to 2 carbon atoms, and R^8cRepresents an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, which is unsubstituted or substituted one or several times with at least one substituent selected from the following group consisting of fluorine, chlorine, and bromine , Iodine and other atoms, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, an oxy group, a trifluoromethyl group and an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, wherein the aliphatic hydrocarbon residue containing 1 to 4 carbon atoms The aliphatic hydrocarbon residues of the atoms may each be unsubstituted or substituted one or several times with at least one substituent selected from the following group consisting of fluorine, chlorine and other atoms, trifluoromethyl and a It is composed of substituted aliphatic hydrocarbon residues containing 1 to 4 carbon atoms, oxy groups, etc., or represents a cycloaliphatic hydrocarbon residue containing 3 to 10 carbon atoms or a heterocyclic aliphatic containing 3 to 10 ring members Hydrocarbon residues, each of which is unsubstituted or substituted one or several times with at least one substituent selected from the following groups, the group consisting of fluorine, chlorine, bromine, iodine and other atoms, one containing 1 to An aliphatic hydrocarbon residue with 4 carbon atoms, a trifluoromethyl group and an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, etc., wherein the aliphatic hydrocarbon residue containing 1 to 4 carbon atoms can be individually It is unsubstituted or substituted one or several times with at least one substituent selected from the following group, the group consisting of fluorine, chlorine and other atoms, trifluoromethyl and an unsubstituted one containing 1 to 4 Carbon atoms are composed of aliphatic hydrocarbon residues, oxy groups, etc., or represent-preferably when m=0-an aromatic or heteroaromatic group, each of which is unsubstituted or has at least one of the following groups The selected substituent is substituted one or several times. The group consists of fluorine, chlorine, bromine, iodine and other atoms, hydroxyl, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, oxy, trifluoromethoxy, Trifluoromethyl, cyano, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, methylcarbonyl, ethylcarbonyl, methoxycarbonyl and ethoxycarbonyl, a ring containing 3 to 6 carbon atoms Aliphatic hydrocarbon residues, a heterocyclic aliphatic hydrocarbon residue containing 3 to 6 ring members, benzyl, phenyl, thienyl or pyridyl, etc., including benzyl, phenyl, thienyl and pyridyl Each may be unsubstituted or substituted one or several times with at least one substituent selected from the following group, preferably unsubstituted or substituted one or two times, the group consisting of fluorine, chlorine, Bromine, iodine and other atoms, hydroxyl, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, oxy, trifluoromethoxy, trifluoromethyl, cyano, and an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms Group, methylcarbonyl group, ethylcarbonyl group, methoxycarbonyl group and ethoxycarbonyl group, etc., preferably substituted by at least one substituent selected from the following group, which group is composed of fluorine and chlorine Atoms, methyl, methoxy, trifluoromethyl and trifluoromethoxy, etc.And wherein the cycloaliphatic hydrocarbon residue containing 3 to 6 carbon atoms and the heterocyclic aliphatic hydrocarbon residue containing 3 to 6 ring members may each be unsubstituted or at least one of the following groups The selected substituents are substituted one or several times. The group consists of fluorine, chlorine, bromine, iodine and other atoms, hydroxyl, pendant oxygen, an aliphatic hydrocarbon residue oxygen containing 1 to 4 carbon atoms, trifluoromethyl It is composed of an oxy group, a trifluoromethyl group, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms and a carboxyl group.

In another preferred embodiment of the compound of formula (I) according to the present invention, the residue R¹Representative part of the structure (<b>T1</b>), where m represents 0, 1 or 2, and R^8aAnd R^8bIndependently of each other, it represents hydrogen, fluorine and other atoms, an aliphatic hydrocarbon residue oxy group containing 1 to 4 carbon atoms, or an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms; preferably, hydrogen, fluorine, etc. , Methyl or methoxy; R^8cRepresents an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, which is unsubstituted or substituted one or several times with at least one substituent selected from the following group consisting of fluorine, chlorine, and bromine , Iodine and other atoms, an unsubstituted aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, oxy, trifluoromethyl and an unsubstituted aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, Or represents a cycloaliphatic hydrocarbon residue containing 3 to 10 carbon atoms or a heterocyclic aliphatic hydrocarbon residue containing 3 to 10 ring members, each of which is unsubstituted or has at least one of the following groups The selected substituent is substituted one or several times. The group consists of fluorine, chlorine, bromine, iodine and other atoms, an unsubstituted aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, oxy, trifluoromethyl and An unsubstituted aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, etc., or where m represents 0, R⁸a and R^8bIndependently of each other, it represents hydrogen, fluorine and other atoms, an aliphatic hydrocarbon residue oxy group containing 1 to 4 carbon atoms, or an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms; preferably, hydrogen, fluorine, etc. , Methyl or methoxy; and R⁸c represents an aromatic group or a heteroaromatic group, each of which is unsubstituted or substituted one or several times with at least one substituent selected from the following groups, the group consisting of fluorine, chlorine, bromine, iodine, etc. Atom, hydroxyl, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, oxy, trifluoromethoxy, trifluoromethyl, cyano, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, methyl It is composed of carbonyl group, ethylcarbonyl group, methoxycarbonyl group, ethoxycarbonyl group and phenyl group, etc., wherein the phenyl group may be unsubstituted or substituted one or several times with at least one substituent selected from the following groups, Preferably, it is unsubstituted or substituted once or twice. The group consists of fluorine, chlorine, bromine, iodine and other atoms, hydroxyl, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, oxy, trifluoro It is composed of methoxy, trifluoromethyl, cyano, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, methylcarbonyl, ethylcarbonyl, methoxycarbonyl, ethoxycarbonyl, etc., preferably It is substituted by at least one substituent selected from the following group consisting of atoms such as fluorine and chlorine, methyl, methoxy, trifluoromethyl, and trifluoromethoxy.

A particularly preferred one is a compound of the general formula (I) according to the present invention, which has the general formula (Ie) shown in the following figure:

<chemistry general="n"><img file="TW201210596A_D0015.tif" /></chemistry>

In a preferred embodiment of the compound of general formula (I) according to the present invention, the residue R²Represents hydrogen, fluorine, chlorine, bromine, iodine and other atoms, cyano, trifluoromethyl, nitro, trifluoromethoxy, trifluoromethylthio, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, An aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, a thio group, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, an oxy group, wherein the aliphatic hydrocarbon residue containing 1 to 4 carbon atoms can each be Substituted or substituted one or several times; a cycloaliphatic hydrocarbon residue containing 3 to 6 carbon atoms or a heterocyclic aliphatic hydrocarbon residue containing 3 to 6 ring members, each of which is unsubstituted or substituted It is substituted one or several times, and each of them forms a bond through an aliphatic hydrocarbon functional group containing 1 to 4 carbon atoms according to the choice, and it may be unsubstituted or substituted one or several times.

The better one is R²Represents hydrogen, fluorine, chlorine, bromine, iodine and other atoms, cyano, trifluoromethyl, nitro, trifluoromethoxy, trifluoromethylthio, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, An aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, a thio group, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, an oxy group, wherein the aliphatic hydrocarbon residue containing 1 to 4 carbon atoms can each be Substituted or substituted one or several times with at least one substituent selected from the following groups, the group consisting of fluorine, chlorine, bromine, iodine and other atoms, pendant oxygen groups, hydroxyl groups and an unsubstituted one containing 1 It is composed of aliphatic hydrocarbon residues with to 4 carbon atoms, a cycloaliphatic hydrocarbon residue with 3 to 6 carbon atoms or a heterocyclic aliphatic hydrocarbon residue with 3 to 6 ring members, each of which It is unsubstituted or substituted one or several times with at least one substituent selected from the following groups, the group consisting of atoms such as fluorine, chlorine, bromine, iodine, pendant oxygen groups, hydroxyl groups, and one containing 1 to 4 The aliphatic hydrocarbon residue containing 1 to 4 carbon atoms is composed of an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, etc., wherein the aliphatic hydrocarbon residue containing 1 to 4 carbon atoms may be unsubstituted or At least one substituent selected from the following group is substituted one or several times, the group is composed of fluorine, chlorine, bromine, iodine and other atoms, pendant oxygen groups, hydroxyl groups and an unsubstituted one containing 1 to 4 carbons The aliphatic hydrocarbon residue is composed of oxy, etc., and the cycloaliphatic hydrocarbon residue containing 3 to 6 carbon atoms or the heterocyclic aliphatic hydrocarbon residue containing 3 to 6 ring members can be based on each Choose to form a bond through an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, which may be unsubstituted or substituted one or several times with at least one substituent selected from the following group. It is composed of fluorine, chlorine, bromine, iodine and other atoms, pendant oxygen groups, hydroxyl groups, an unsubstituted aliphatic hydrocarbon residue containing 1 to 4 carbon atoms and an unsubstituted fat containing 1 to 4 carbon atoms It is composed of hydrocarbon residues and oxygen groups.

The better one, R²Represents hydrogen, fluorine, chlorine, bromine, iodine and other atoms, cyano, trifluoromethyl, nitro, trifluoromethoxy, trifluoromethylthio, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, An aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, a thio group, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, an oxy group, wherein the aliphatic hydrocarbon residue containing 1 to 4 carbon atoms can each be Substituted or substituted one or several times with at least one substituent selected from the following groups, the group consisting of fluorine, chlorine, bromine, iodine and other atoms, pendant oxygen groups, hydroxyl groups and an unsubstituted one containing 1 It is composed of aliphatic hydrocarbon residues with up to 4 carbon atoms, such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, pyrrolidinyl, piperazinyl, 4-methylpiperazinyl, morpholinyl Or piperidinyl, preferably representing cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, each of which is unsubstituted or substituted one or several times with at least one substituent selected from the following groups , This group consists of fluorine, chlorine, bromine, iodine and other atoms, pendant oxygen groups, hydroxyl groups, an unsubstituted aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, and an unsubstituted aliphatic hydrocarbon residue containing 1 to 4 Carbon atoms of aliphatic hydrocarbon residues are composed of oxy groups, and among them cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, pyrrolidinyl, piperazinyl, 4-methylpiperazinyl, morpholinyl or The piperidinyl groups can each form a bond via an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms according to choice, and they can be unsubstituted or substituted with at least one substituent selected from the following groups, or Several times, the group consists of fluorine, chlorine and other atoms, hydroxyl, an unsubstituted aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, and an unsubstituted aliphatic hydrocarbon residue containing 1 to 4 carbon atoms. It is composed of oxy-group and so on.

Or even better, R²Represents hydrogen, fluorine, chlorine, bromine, iodine and other atoms, cyano, trifluoromethyl, nitro, trifluoromethoxy, trifluoromethylthio, methyl, ethyl, n-propyl, isopropyl, N-butyl, secondary-butyl, tertiary-butyl, methoxy, ethoxy, methoxyethoxy, hydroxyethoxy, methylthio, ethylthio, cyclopropyl, cyclobutyl Group, cyclopentyl and cyclohexyl, etc.

The better one, R²It is selected from the following group consisting of hydrogen, fluorine, chlorine and other atoms, trifluoromethyl, cyano, trifluoromethylthio, trifluoromethoxy, methyl, ethyl, n- It is composed of propyl, isopropyl, tertiary-butyl, cyclopropyl, methoxy and ethoxy.

Especially, R²It is selected from the following group, which consists of atoms such as hydrogen, fluorine, chlorine, trifluoromethyl, methyl, ethyl, isopropyl, cyclopropyl and methoxy; The best one is selected from the following group consisting of atoms such as hydrogen, fluorine, and chlorine, trifluoromethyl, methyl, and methoxy.

In one particularly preferred embodiment of the compound of general formula (I) according to the present invention, the residue R² hydrogen atom.

In one particularly preferred embodiment of the compound of general formula (I) according to the present invention, the residue R³, R⁴, R⁵And R⁶Independently of each other, it represents atoms such as hydrogen, fluorine, chlorine, bromine, and iodine, cyano, trifluoromethyl, trifluoromethoxy, trifluoromethylthio, aldehyde, carboxy, amide, and hydroxysulfonyl , Nitro, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, an aliphatic hydrocarbon residue carbonyl containing 1 to 4 carbon atoms, an aliphatic hydrocarbon residue oxycarbonyl containing 1 to 4 carbon atoms, One N- (aliphatic hydrocarbon residue containing 1 to 4 carbon atoms) amide group, one N,N-di (aliphatic hydrocarbon residue containing 1 to 4 carbon atoms) amide group, one containing 1 to 4 Aliphatic hydrocarbon residue oxy group containing 1 to 4 carbon atoms, an aliphatic hydrocarbon residue carbonyloxy group containing 1 to 4 carbon atoms, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms thio group, one containing 1 to 4 carbon atoms Aliphatic hydrocarbon residues of carbon atoms, amine groups, one N- (aliphatic hydrocarbon residues containing 1 to 4 carbon atoms) amino groups, one N,N-di (aliphatic hydrocarbon residues containing 1 to 4 carbon atoms) ) Amine group, one N-(aliphatic hydrocarbon residue carbonyl containing 1 to 4 carbon atoms) amine group and one N-(aliphatic hydrocarbon residue sulfonyl containing 1 to 4 carbon atoms) amine group, wherein the The aliphatic hydrocarbon residues containing 1 to 4 carbon atoms may each be unsubstituted or substituted one or several times with at least one substituent selected from the following group consisting of fluorine, chlorine, bromine, and iodine Consists of equal atoms, pendant oxy groups, hydroxyl groups, and an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms; one containing 3 to 6 carbon atoms or a cycloaliphatic hydrocarbon residue containing 3 to 6 rings The heterocyclic aliphatic hydrocarbon residues, each of which is unsubstituted or substituted one or several times with at least one substituent selected from the following group consisting of fluorine, chlorine, bromine, iodine and other atoms , Pendant oxy group, hydroxy group, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, and an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms. The substituted aliphatic hydrocarbon functional group containing 1 to 4 carbon atoms forms a bond, but the condition is: R³, R⁴, R⁵And R⁶At least one of them a hydrogen atom.

The better one is R³, R⁴, R⁵And R⁶Independently of each other, it represents atoms such as hydrogen, fluorine, chlorine, bromine, and iodine, cyano, trifluoromethyl, trifluoromethoxy, trifluoromethylthio, aldehyde, carboxyl, amide, and hydroxysulfonyl , Nitro, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, an aliphatic hydrocarbon residue carbonyl containing 1 to 4 carbon atoms, an aliphatic hydrocarbon residue oxycarbonyl containing 1 to 4 carbon atoms, An aliphatic hydrocarbon residue oxy group containing 1 to 4 carbon atoms, an aliphatic hydrocarbon residue carbonyloxy group containing 1 to 4 carbon atoms, an aliphatic hydrocarbon residue thio group containing 1 to 4 carbon atoms, a An aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, amide group, wherein the aliphatic hydrocarbon residue containing 1 to 4 carbon atoms may each be unsubstituted or with at least one substituent selected from the following groups Substitution one or several times, the group consists of fluorine, chlorine, bromine, iodine and other atoms, pendant oxygen groups, hydroxyl groups, and an aliphatic hydrocarbon residue oxygen group containing 1 to 4 carbon atoms; one containing 3 to A cycloaliphatic hydrocarbon residue of 6 carbon atoms or a heterocyclic aliphatic hydrocarbon residue containing 3 to 6 ring members, each of which is unsubstituted or substituted with at least one substituent selected from the following groups Or several times, the group consists of fluorine, chlorine, bromine, iodine and other atoms, pendant oxygen groups, hydroxyl groups, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, and an aliphatic hydrocarbon containing 1 to 4 carbon atoms The residue is composed of oxy groups, and each of them forms a bond through an unsubstituted aliphatic hydrocarbon functional group containing 1 to 4 carbon atoms according to the choice, but the condition is: R³, R⁴, R⁵And R⁶At least one of them a hydrogen atom.

The better one, R³, R⁴, R⁵And R⁶Independently of each other, it represents hydrogen, fluorine, chlorine, bromine, iodine and other atoms, cyano, trifluoromethyl, trifluoromethoxy, trifluoromethylthio, aldehyde, nitro, one containing 1 to 4 carbons Aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, an aliphatic hydrocarbon residue carbonyl group containing 1 to 4 carbon atoms, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms oxycarbonyl, an aliphatic hydrocarbon containing 1 to 4 carbon atoms The residue oxy group, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, a thio group, wherein the aliphatic hydrocarbon residue containing 1 to 4 carbon atoms may be each unsubstituted or at least one of the following groups The selected substituents are substituted one or several times. The group is composed of fluorine, chlorine, bromine, iodine and other atoms, pendant oxygen groups, hydroxyl groups, and an aliphatic hydrocarbon residue oxygen group containing 1 to 4 carbon atoms. ; A cycloaliphatic hydrocarbon residue containing 3 to 6 carbon atoms, which is unsubstituted or substituted one or several times with at least one substituent selected from the following groups, the group consisting of fluorine, chlorine, Bromine, iodine and other atoms, pendant oxygen groups, hydroxyl groups, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, and an aliphatic hydrocarbon residue oxygen containing 1 to 4 carbon atoms, etc., and each of them is based on Choose to form a bond via an unsubstituted aliphatic hydrocarbon functional group containing 1 to 4 carbon atoms, but the condition is: R³, R⁴, R⁵And R⁶At least one of them a hydrogen atom.

In another preferred embodiment of the present invention, R³, R⁴, R⁵And R⁶Independently of each other, it is selected from the following group, which consists of hydrogen, fluorine, chlorine, bromine, iodine and other atoms, nitro, trifluoromethyl, cyano, trifluoromethoxy, trifluoromethyl Sulfur group, an aliphatic hydrocarbon residue carbonyl group containing 1 to 4 carbon atoms, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, an aliphatic hydrocarbon residue oxy group containing 1 to 4 carbon atoms, and an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms. It is composed of aliphatic hydrocarbon residues of 1 to 4 carbon atoms, sulfide groups, etc., wherein the aliphatic hydrocarbon residues of 1 to 4 carbon atoms may each be unsubstituted or substituted with at least one selected from the following groups The group is substituted one or several times, the group is composed of fluorine, chlorine and other atoms and methoxy groups; but the condition is: R³, R⁴, R⁵And R⁶At least one of them a hydrogen atom.

The better one is R³, R⁴, R⁵And R⁶Independently of each other, it is selected from the following group, which consists of hydrogen, fluorine, chlorine, bromine, iodine and other atoms, nitro, trifluoromethyl, cyano, trifluoromethoxy, trifluoromethyl Thio, methyl, ethyl, n-propyl, isopropyl, n-butyl, 2-butyl, tertiary-butyl, cyclopropyl, methylcarbonyl, ethylcarbonyl, isopropylcarbonyl, Consists of tertiary-butylcarbonyl, methoxy, ethoxy, isopropyloxy, tertiary-butyloxy, methoxyethoxy, methylthio, ethylthio, etc.; but its conditions Yes: R³, R⁴, R⁵And R⁶At least one of them a hydrogen atom.

Especially, R³, R⁴, R⁵And R⁶Independently of each other, they are selected from the following groups, which consist of atoms such as hydrogen, fluorine, chlorine, bromine, iodine, nitro, trifluoromethyl, cyano, methylcarbonyl, ethylcarbonyl, iso Propylcarbonyl, tertiary-butylcarbonyl, methyl, ethyl, isopropyl, tertiary-butyl, methoxy, ethoxy, isopropyloxy, tertiary-butyloxy, tri Fluoromethoxy, methylthio, ethylthio and trifluoromethylthio, etc.; but the condition is: R³, R⁴, R⁵And R⁶At least one of them a hydrogen atom.

More special line, R³, R⁴, R⁵And R⁶Independently of each other, it is selected from the following groups, which are composed of hydrogen, fluorine, chlorine, bromine and other atoms, methyl, trifluoromethyl, cyano, trifluoromethoxy and nitro, etc. ; But its condition is: R³, R⁴, R⁵And R⁶At least one of them a hydrogen atom.

The best line, R³, R⁴And R⁶Independently of each other, they are selected from the following groups, which are composed of hydrogen and fluorine atoms, etc., and R⁵Represents atoms such as fluorine, chlorine, bromine, methyl, trifluoromethyl, trifluoromethoxy, cyano or nitro; preferably represents atoms such as fluorine, bromine, trifluoromethyl or cyano.

In one particularly preferred embodiment of the compound of general formula (I) according to the present invention, R³, R⁴, R⁵And R⁶At least one of the residues a hydrogen atom.

In a preferred embodiment of the compound of general formula (I) according to the present invention, the residue R⁷Represents an aliphatic hydrocarbon residue containing 2 to 10 carbon atoms, preferably represents an aliphatic hydrocarbon residue containing 2 to 8 carbon atoms, which is unsubstituted or at least one selected from the following groups Substituents are substituted one or several times. The group consists of fluorine, chlorine, bromine, iodine and other atoms, nitro groups, amino groups, one N- (aliphatic hydrocarbon residues containing 1 to 4 carbon atoms) amino groups, one N,N-two (aliphatic hydrocarbon residues containing 1 to 4 carbon atoms) amino groups, hydroxyl groups, pendant oxy groups, aliphatic hydrocarbon residues containing 1 to 4 carbon atoms, oxy groups, trifluoromethoxy, Sulfhydryl, trifluoromethylthio, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, thio, trifluoromethyl, cyano, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, one containing 1 to 4 carbon atoms The aliphatic hydrocarbon residues with 4 carbon atoms are composed of oxycarbonyl and carboxyl groups, among which the aliphatic hydrocarbon residues with 1 to 4 carbon atoms may be unsubstituted or at least one selected from the following groups Substituents are substituted one or several times. The group consists of fluorine, chlorine, bromine, iodine and other atoms, hydroxyl, trifluoromethoxy, trifluoromethyl and an unsubstituted fat containing 1 to 4 carbon atoms Hydrocarbon residues, oxy groups, etc., or represent a cycloaliphatic hydrocarbon residue containing 3 to 10 carbon atoms or a heterocyclic aliphatic hydrocarbon residue containing 3 to 10 ring members, each of which is unsubstituted or Substitute one or several times by at least one substituent selected from the following groups, which are composed of fluorine, chlorine, bromine, iodine and other atoms, nitro groups, amino groups, and one N- (containing 1 to 4 carbon atoms). Aliphatic hydrocarbon residue of atom) amine group, -N,N-di (aliphatic hydrocarbon residues containing 1 to 4 carbon atoms) amine groups, hydroxyl groups, pendant oxy groups, aliphatic hydrocarbon residues containing 1 to 4 carbon atoms, oxy groups, trifluoromethoxy, mercapto groups, Trifluoromethylthio, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, thio, trifluoromethyl, cyano, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, a carboxyl group, a containing 1 to 4 The aliphatic hydrocarbon residue containing 4 carbon atoms is composed of oxycarbonyl group, etc., wherein the aliphatic hydrocarbon residue containing 1 to 4 carbon atoms may be unsubstituted or substituted with at least one substituent selected from the following groups Substitute one or several times, the group consists of fluorine, chlorine, bromine, iodine and other atoms, hydroxyl, trifluoromethoxy, trifluoromethyl and an unsubstituted aliphatic hydrocarbon residue containing 1 to 4 carbon atoms And the cycloaliphatic hydrocarbon residues containing 3 to 10 carbon atoms or the heterocyclic aliphatic hydrocarbon residues containing 3 to 10 ring members can each be selected according to the choice of one containing 1 to 8 The aliphatic hydrocarbon residue of three carbon atoms is preferably bonded via an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, and it may be unsubstituted or at least one selected from the following group Substituents are substituted one or several times. The group consists of fluorine, chlorine, bromine, iodine and other atoms, nitro groups, amino groups, one N- (aliphatic hydrocarbon residues containing 1 to 4 carbon atoms) amino groups, one N,N-di (aliphatic hydrocarbon residue containing 1 to 4 carbon atoms) amino group, hydroxyl group, pendant oxygen group, one containing 1 to 4 carbon atoms aliphatic hydrocarbon residue oxygen group, one containing 1 to 4 Aliphatic hydrocarbon residues of carbon atoms, oxycarbonyl, trifluoromethoxy, mercapto, trifluoromethylthio, aliphatic hydrocarbon residues containing 1 to 4 carbon atoms, thio, trifluoromethyl, cyano, one Containing 1 to 4 carbon atoms of aliphatic hydrocarbon residues and carboxyl groups, etc., but the condition is: if R⁷When it represents a heterocyclic aliphatic hydrocarbon residue containing 3 to 10 ring members, the heterocyclic aliphatic hydrocarbon residue containing 3 to 10 ring members is connected via a carbon atom.

In a preferred embodiment of the compound of general formula (I) according to the present invention, the residue R⁷Represents an aliphatic hydrocarbon residue containing 2 to 10 carbon atoms, preferably represents an aliphatic hydrocarbon residue containing 2 to 8 carbon atoms, which is unsubstituted or at least one selected from the following groups Substituents are substituted one or several times. The group consists of atoms such as fluorine, chlorine, bromine, and iodine, nitro, one N- (aliphatic hydrocarbon residue containing 1 to 4 carbon atoms) amino, one N,N-di (aliphatic hydrocarbon residues containing 1 to 4 carbon atoms) amino groups, hydroxyl groups, pendant oxy groups, aliphatic hydrocarbon residues containing 1 to 4 carbon atoms, oxy groups, trifluoromethoxy, mercapto groups, Trifluoromethylthio, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, oxycarbonyl, trifluoromethyl, cyano, and one containing 1 It is composed of aliphatic hydrocarbon residues with to 4 carbon atoms, etc., wherein the aliphatic hydrocarbon residues with 1 to 4 carbon atoms may be each unsubstituted or substituted with at least one substituent selected from the following groups Or several times, the group consists of fluorine, chlorine, bromine, iodine and other atoms, hydroxyl, trifluoromethoxy, trifluoromethyl and an unsubstituted aliphatic hydrocarbon residue oxygen containing 1 to 4 carbon atoms. Groups, etc., or represent a cycloaliphatic hydrocarbon residue containing 3 to 10 carbon atoms or a heterocyclic aliphatic hydrocarbon residue containing 3 to 10 ring members, each of which is unsubstituted or has at least one Substituents selected from the following groups are substituted one or several times. The group consists of fluorine, chlorine, bromine, iodine and other atoms, nitro groups, hydroxyl groups, pendant oxygen groups, and an aliphatic hydrocarbon containing 1 to 4 carbon atoms Residue oxy group, trifluoromethoxy group, mercapto group, trifluoromethylthio group, aliphatic hydrocarbon residue thio group containing 1 to 4 carbon atoms, an aliphatic hydrocarbon residue oxy group containing 1 to 4 carbon atoms Carbonyl, trifluoromethyl, cyano, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, etc., wherein the aliphatic hydrocarbon residue containing 1 to 4 carbon atoms may each be unsubstituted or at least One or several times substituted by the substituent selected from the following group, the group consisting of fluorine, chlorine, bromine, iodine and other atoms, hydroxyl, trifluoromethoxy, trifluoromethyl and an unsubstituted The aliphatic hydrocarbon residue containing 1 to 4 carbon atoms is composed of oxy groups, and the cycloaliphatic hydrocarbon residue containing 3 to 10 carbon atoms or the heterocyclic aliphatic hydrocarbon residue containing 3 to 10 ring members The groups can each be bonded via an aliphatic hydrocarbon residue containing 1 to 8 carbon atoms, preferably via an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, and it can be unsubstituted or Substitute one or more times with at least one substituent selected from the following groups, the group consisting of fluorine, chlorine, bromine, iodine and other atoms, nitro groups, hydroxyl groups, pendant oxygen groups, one containing 1 to 4 carbons Aliphatic hydrocarbon residue oxy group containing 1 to 4 carbon atoms, an aliphatic hydrocarbon residue containing oxycarbonyl, trifluoromethoxy, mercapto, trifluoromethylthio group, a fat containing 1 to 4 carbon atoms Hydrocarbon residues thio, trifluoromethyl, cyano and an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, etc., but the condition is: if R, Trifluoromethyl, cyano and an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, etc., but the condition is: if R, Trifluoromethyl, cyano and an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, etc., but the condition is: if R⁷When it represents a heterocyclic aliphatic hydrocarbon residue containing 3 to 10 ring members, the heterocyclic aliphatic hydrocarbon residue containing 3 to 10 ring members is connected via a carbon atom.

The better one is R⁷Represents an aliphatic hydrocarbon residue containing 2 to 8 carbon atoms, which is unsubstituted or substituted one or several times with at least one substituent selected from the following groups, the group consisting of fluorine, chlorine, bromine , Iodine and other atoms, hydroxyl, pendant oxygen, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, oxy, trifluoromethoxy, and a N- (aliphatic hydrocarbon residue containing 1 to 4 carbon atoms) Amino, one N,N-di (aliphatic hydrocarbon residues containing 1 to 4 carbon atoms) amine groups, sulfhydryl groups, trifluoromethylthio groups, aliphatic hydrocarbon residues containing 1 to 4 carbon atoms, sulfur groups, and 1 to 4 aliphatic hydrocarbon residues The aliphatic hydrocarbon residue of carbon atoms is composed of oxycarbonyl, trifluoromethyl and an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, etc., wherein the aliphatic hydrocarbon residue containing 1 to 4 carbon atoms may be each Unsubstituted or substituted one or several times with at least one substituent selected from the following group consisting of fluorine, chlorine, bromine, iodine and other atoms, hydroxyl, trifluoromethyl and an unsubstituted It is composed of aliphatic hydrocarbon residues containing 1 to 4 carbon atoms, or represents a cycloaliphatic hydrocarbon residue containing 3 to 10 carbon atoms or a heterocyclic aliphatic hydrocarbon residue containing 3 to 10 ring members , Each of them is unsubstituted or substituted one or several times with at least one substituent selected from the following group, which consists of fluorine, chlorine, bromine, iodine and other atoms, hydroxyl, pendant oxygen, one Aliphatic hydrocarbon residues containing 1 to 4 carbon atoms, oxy, trifluoromethoxy, trifluoromethylthio, one containing 1 to 4 carbon atoms, aliphatic hydrocarbon residues, oxycarbonyl, one containing 1 to 4 The aliphatic hydrocarbon residues of carbon atoms, thio, trifluoromethyl, and an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, etc., wherein the aliphatic hydrocarbon residues containing 1 to 4 carbon atoms may be independently Substituted or substituted one or several times by at least one substituent selected from the following groups, the group consisting of atoms such as fluorine, chlorine, bromine, iodine, hydroxyl, trifluoromethoxy, trifluoromethyl and An unsubstituted aliphatic hydrocarbon residue containing 1 to 4 carbon atoms is composed of oxy groups, and the cycloaliphatic hydrocarbon residue containing 3 to 10 carbon atoms or the cycloaliphatic hydrocarbon residue containing 3 to 10 ring members The heterocyclic aliphatic hydrocarbon residues can each be bonded via an aliphatic hydrocarbon residue containing 1 to 8 carbon atoms, preferably via an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, which can be It is unsubstituted or substituted one or several times with at least one substituent selected from the following group, the group consisting of atoms such as fluorine, chlorine, bromine, iodine, hydroxyl, pendant oxygen, and one containing 1 to 4 Aliphatic hydrocarbon residues oxy, trifluoromethoxy, mercapto, trifluoromethylthio, one containing 1 to 4 carbon atoms, aliphatic hydrocarbon residues containing 1 to 4 carbon atoms, and one containing 1 to 4 carbon atoms Aliphatic hydrocarbon residues are composed of oxycarbonyl, trifluoromethyl, cyano and an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, but the condition is: if R⁷When it represents a heterocyclic aliphatic hydrocarbon residue containing 3 to 10 ring members, the heterocyclic aliphatic hydrocarbon residue containing 3 to 10 ring members is connected via a carbon atom.

The better one, R⁷Represents an aliphatic hydrocarbon residue containing 2 to 8 carbon atoms, preferably represents an aliphatic hydrocarbon residue containing 2 to 6 carbon atoms, which is unsubstituted or at least one selected from the following groups Substituents are substituted one or several times. The group consists of fluorine, chlorine, bromine, iodine and other atoms, hydroxyl, pendant oxygen, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, oxygen, and trifluoromethoxy , One N- (aliphatic hydrocarbon residue containing 1 to 4 carbon atoms) amino group, one N,N-di (aliphatic hydrocarbon residues containing 1 to 4 carbon atoms) amine groups, mercapto groups, trifluoromethylthio groups, aliphatic hydrocarbon residues containing 1 to 4 carbon atoms, sulfur groups, trifluoromethyl groups, one An aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, an oxycarbonyl group, and an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, etc., wherein the aliphatic hydrocarbon residue containing 1 to 4 carbon atoms may be each Unsubstituted or substituted one or several times with at least one substituent selected from the following group consisting of fluorine, chlorine, bromine, iodine and other atoms, hydroxyl, trifluoromethyl and an unsubstituted It is composed of aliphatic hydrocarbon residues containing 1 to 4 carbon atoms, oxy groups, etc., or represents a cycloaliphatic hydrocarbon residue containing 3 to 10 carbon atoms or a heterocyclic aliphatic hydrocarbon residue containing 3 to 10 ring members , Each of them is unsubstituted or substituted one or several times with at least one substituent selected from the following group, which consists of fluorine, chlorine, bromine, iodine and other atoms, hydroxyl, pendant oxygen, one Aliphatic hydrocarbon residues containing 1 to 4 carbon atoms, oxy, trifluoromethoxy, trifluoromethylthio, one containing 1 to 4 carbon atoms, aliphatic hydrocarbon residues containing thio, one containing 1 to 4 carbons The aliphatic hydrocarbon residue oxycarbonyl group, trifluoromethyl group and an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, etc., wherein the aliphatic hydrocarbon residue containing 1 to 4 carbon atoms may be Substituted or substituted one or several times by at least one substituent selected from the following groups, the group consisting of atoms such as fluorine, chlorine, bromine, iodine, hydroxyl, trifluoromethoxy, trifluoromethyl and An unsubstituted aliphatic hydrocarbon residue containing 1 to 4 carbon atoms is composed of oxy groups, and the cycloaliphatic hydrocarbon residue containing 3 to 10 carbon atoms or the heterocyclic aliphatic hydrocarbon residue containing 3 to 10 ring members The cycloaliphatic hydrocarbon residues can each be bonded via an aliphatic hydrocarbon residue containing 1 to 8 carbon atoms, preferably via an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, and it can be Unsubstituted or substituted one or several times with at least one substituent selected from the following groups, the group consisting of fluorine, chlorine, bromine, iodine and other atoms, hydroxyl, pendant oxygen, and one containing 1 to 4 Aliphatic hydrocarbon residues of carbon atoms, oxy, trifluoromethoxy, mercapto, trifluoromethylthio, aliphatic hydrocarbon residues containing 1 to 4 carbon atoms, sulfur groups, and aliphatic hydrocarbon residues containing 1 to 4 carbon atoms Hydrocarbon residues oxycarbonyl, trifluoromethyl, cyano and an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, etc., but the condition is: if R⁷When it represents a heterocyclic aliphatic hydrocarbon residue containing 3 to 10 ring members, the heterocyclic aliphatic hydrocarbon residue containing 3 to 10 ring members is connected via a carbon atom.

Or even better, R⁷Represents an aliphatic hydrocarbon residue containing 2 to 8 carbon atoms, preferably represents an aliphatic hydrocarbon residue containing 2 to 6 carbon atoms, which is unsubstituted or at least one selected from the following groups Substituents are substituted one or several times. The group consists of fluorine, chlorine, bromine, iodine and other atoms, hydroxyl groups, pendant oxygen groups, an aliphatic hydrocarbon residue oxygen containing 1 to 4 carbon atoms, and trifluoromethoxy , One N- (aliphatic hydrocarbon residue containing 1 to 4 carbon atoms) amino group, one N,N-di (aliphatic hydrocarbon residue containing 1 to 4 carbon atoms) amino group, mercapto group, trifluoromethyl sulfide Group, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, a sulfur group, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, oxycarbonyl, a trifluoromethyl group, and a fat containing 1 to 4 carbon atoms The aliphatic hydrocarbon residues containing 1 to 4 carbon atoms can each be unsubstituted or substituted one or several times with at least one substituent selected from the following groups. It is composed of fluorine, chlorine, bromine, iodine and other atoms, hydroxyl, trifluoromethyl and an unsubstituted aliphatic hydrocarbon residue oxygen containing 1 to 4 carbon atoms, or represents a containing 3 to 10 A carbon atom cycloaliphatic hydrocarbon residue or a heterocyclic aliphatic hydrocarbon residue containing 3 to 10 ring members, each of which is unsubstituted or substituted with at least one substituent selected from the following groups Second, the group consists of fluorine, chlorine, bromine, iodine and other atoms, hydroxyl, pendant oxygen, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, oxygen, trifluoromethoxy, trifluoromethylthio , An aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, sulfur group, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, oxycarbonyl, trifluoromethyl, and an aliphatic hydrocarbon containing 1 to 4 carbon atoms The aliphatic hydrocarbon residues containing 1 to 4 carbon atoms can each be unsubstituted or substituted one or several times with at least one substituent selected from the following groups. It is composed of fluorine, chlorine, bromine, iodine and other atoms, hydroxyl, trifluoromethoxy, trifluoromethyl, and an unsubstituted aliphatic hydrocarbon residue oxy group containing 1 to 4 carbon atoms, and the The cycloaliphatic hydrocarbon residues containing 3 to 10 carbon atoms or the heterocyclic aliphatic hydrocarbon residues containing 3 to 10 ring members can each be selected via an unsubstituted aliphatic hydrocarbon function containing 1 to 8 carbon atoms Group, preferably through an unsubstituted aliphatic hydrocarbon functional group containing 1 to 4 carbon atoms to form a bond, but the condition is: if R⁷When it represents a heterocyclic aliphatic hydrocarbon residue containing 3 to 10 ring members, the heterocyclic aliphatic hydrocarbon residue containing 3 to 10 ring members is connected via a carbon atom.

The better one, R⁷Represents an aliphatic hydrocarbon residue containing 2 to 6 carbon atoms, which is unsubstituted or substituted one or several times with at least one substituent selected from the following group consisting of fluorine, chlorine , and bromine , Iodine and other atoms, hydroxyl, pendant oxygen, an aliphatic hydrocarbon residue oxygen containing 1 to 4 carbon atoms, an N- (aliphatic hydrocarbon residue containing 1 to 4 carbon atoms) amino group, a N, N-di (aliphatic hydrocarbon residue containing 1 to 4 carbon atoms) amine group, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms oxycarbonyl, trifluoromethoxy, mercapto, trifluoromethylthio , An aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, sulfur group, trifluoromethyl group, and an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, etc., wherein the fat containing 1 to 4 carbon atoms The hydrocarbon residues may each be unsubstituted or represent a cycloaliphatic hydrocarbon residue containing 3 to 10 carbon atoms, preferably a cycloaliphatic hydrocarbon residue containing 3 to 6 carbon atoms, or a cycloaliphatic hydrocarbon residue containing 3 to 6 carbon atoms, or A heterocyclic aliphatic hydrocarbon residue of 3 to 10 ring members, preferably represents a heterocyclic aliphatic hydrocarbon residue containing 3 to 6 carbon atoms, each of which is unsubstituted or has at least one of the following groups The selected substituents are substituted one or several times. The group consists of fluorine, chlorine, bromine, iodine and other atoms, hydroxyl groups, pendant oxygen groups, an aliphatic hydrocarbon residue oxygen containing 1 to 4 carbon atoms, and trifluoro Methoxy, trifluoromethylthio, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, oxycarbonyl, trifluoromethyl, and one containing It is composed of aliphatic hydrocarbon residues with 1 to 4 carbon atoms, etc., wherein the aliphatic hydrocarbon residues with 1 to 4 carbon atoms can be unsubstituted or hydroxyl or an unsubstituted one with 1 to 4 carbons. The oxy group of the aliphatic hydrocarbon residue is substituted one or several times, and the cycloaliphatic hydrocarbon residue containing 3 to 10 carbon atoms or the heterocyclic aliphatic hydrocarbon residue containing 3 to 10 ring members can be selected according to each A bond is formed through an unsubstituted aliphatic hydrocarbon functional group containing 1 to 4 carbon atoms, but the condition is: if R⁷When it represents a heterocyclic aliphatic hydrocarbon residue containing 3 to 10 ring members, the heterocyclic aliphatic hydrocarbon residue containing 3 to 10 ring members is connected via a carbon atom.

Especially, R⁷Represents an aliphatic hydrocarbon residue containing 2 to 6 carbon atoms, the preferred ones are selected from the following groups, which are ethyl, n-propyl, 2-propyl, n-butyl, Isobutyl, 2-butyl, tertiary-butyl, n-pentyl, isopentyl, neopentyl, n-hexyl, vinyl and propenyl [prop-2-enyl (-CH₂CH=CH₂), prop-1-enyl (-CH=CH-CH₃), isopropenyl (-C(=CH₂)-CH₃)] etc., which are unsubstituted or substituted one or several times with at least one substituent selected from the following groups, which are composed of fluorine, chlorine, bromine, iodine and other atoms, hydroxyl, pendant oxygen Group, an aliphatic hydrocarbon residue oxy group containing 1 to 4 carbon atoms, an N- (aliphatic hydrocarbon residue containing 1 to 4 carbon atoms) amine group, a N,N-di (containing 1 to 4 Aliphatic hydrocarbon residues of carbon atoms) amine groups, aliphatic hydrocarbon residues containing 1 to 4 carbon atoms, oxycarbonyl, trifluoromethoxy, mercapto, trifluoromethylthio, and one containing 1 to 4 carbon atoms The aliphatic hydrocarbon residue is composed of sulfur group, trifluoromethyl group and an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms. Preferably, each is unsubstituted or at least one selected from the following group Substituents are substituted one or several times, the group consists of fluorine, chlorine and other atoms, hydroxyl, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, oxygen, and a N- (containing 1 to 4 carbon atoms) Aliphatic hydrocarbon residues) amino groups, one N,N-di (aliphatic hydrocarbon residues containing 1 to 4 carbon atoms) amino groups, trifluoromethyl groups, and one aliphatic hydrocarbon residues containing 1 to 4 carbon atoms, etc. More preferably, each is unsubstituted or substituted one or several times with at least one substituent selected from the following groups, the group consisting of atoms such as fluorine and chlorine, hydroxyl groups, and one containing 1 to 4 An aliphatic hydrocarbon residue oxy group with three carbon atoms and an N,N-di (aliphatic hydrocarbon residue containing 1 to 4 carbon atoms) amino group, etc., and even more preferably are each unsubstituted or at least A substituent selected from the following group is substituted one or several times, the group is composed of methoxy, hydroxyl and N,N-dimethylamino group, etc., wherein the aliphatic hydrocarbon residue containing 1 to 4 carbon atoms may be unsubstituted, or represent a cycloaliphatic hydrocarbon residue containing 3 to 6 carbon atoms, which The preferred one is selected from the following group consisting of cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl, or represents a heterocyclic aliphatic containing 3 to 6 ring members Hydrocarbon residues, the preferred ones are selected from the following group, the group is based on, each of which is unsubstituted or substituted one or several times with at least one substituent selected from the following groups , This group consists of piperidinyl (preferably piperidin-4-yl or piperidin-3-yl), tetrahydrofuranyl and tetrahydropyranyl, etc., each of which is unsubstituted or at least Substitute one or several times with a substituent selected from the following group, which consists of fluorine, chlorine, bromine, iodine and other atoms, hydroxyl groups, pendant oxygen groups, and aliphatic hydrocarbon residues containing 1 to 4 carbon atoms Oxy, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, oxycarbonyl, trifluoromethoxy, mercapto, trifluoromethylthio, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, a thio group , Trifluoromethyl and an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, etc., preferably each is unsubstituted or substituted by at least one substituent selected from the following groups Second, the group consists of fluorine, chlorine and other atoms, hydroxyl, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, oxy, trifluoromethyl, and an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, etc. More preferably, each is unsubstituted or substituted one or several times with at least one substituent selected from the following groups, the group consisting of fluorine, chlorine and other atoms and a group containing 1 to 4 carbons The oxy group of the aliphatic hydrocarbon residue is preferably composed of a methoxy group, etc., wherein the aliphatic hydrocarbon residue containing 1 to 4 carbon atoms may be unsubstituted, and the aliphatic hydrocarbon residue containing 3 to 6 carbon atoms The cycloaliphatic hydrocarbon residue or the heterocyclic aliphatic hydrocarbon residue containing 3 to 6 ring members can each be selected via an unsubstituted aliphatic hydrocarbon functional group containing 1 to 4 carbon atoms, preferably via An unsubstituted aliphatic hydrocarbon functional group containing 1 to 2 carbon atoms forms a bond, but the condition is: if RAnd an aliphatic hydrocarbon residue oxy group containing 1 to 4 carbon atoms, preferably composed of a methoxy group, etc., wherein the aliphatic hydrocarbon residue containing 1 to 4 carbon atoms may each be unsubstituted, and Wherein the cycloaliphatic hydrocarbon residues containing 3 to 6 carbon atoms or the heterocyclic aliphatic hydrocarbon residues containing 3 to 6 ring members can each be selected via an unsubstituted aliphatic containing 1 to 4 carbon atoms The hydrocarbon functional group is preferably bonded via an unsubstituted aliphatic hydrocarbon functional group containing 1 to 2 carbon atoms, but the condition is: if RAnd an aliphatic hydrocarbon residue oxy group containing 1 to 4 carbon atoms, preferably composed of a methoxy group, etc., wherein the aliphatic hydrocarbon residue containing 1 to 4 carbon atoms may each be unsubstituted, and Wherein the cycloaliphatic hydrocarbon residues containing 3 to 6 carbon atoms or the heterocyclic aliphatic hydrocarbon residues containing 3 to 6 ring members can each be selected via an unsubstituted aliphatic containing 1 to 4 carbon atoms The hydrocarbon functional group is preferably bonded via an unsubstituted aliphatic hydrocarbon functional group containing 1 to 2 carbon atoms, but the condition is: if R⁷When it represents a heterocyclic aliphatic hydrocarbon residue containing 3 to 6 ring members, the heterocyclic aliphatic hydrocarbon residue containing 3 to 6 ring members is connected via a carbon atom.

The best line, R⁷Represents ethyl, n-propyl, 2-propyl, n-butyl, isobutyl, secondary-butyl, tertiary-butyl, n-pentyl, isopentyl, neopentyl, n-hexyl, vinyl Or propenyl [prop-2-enyl (-CH₂CH=CH₂), prop-1-enyl (-CH=CH-CH₃), isopropenyl (-C(=CH₂)-CH₃)] etc., which are unsubstituted or substituted one or several times with at least one substituent selected from the following groups, which are composed of fluorine, chlorine and other atoms, hydroxyl, methoxy, and trifluoromethyl And N,N-dimethylamino group, etc., preferably each is unsubstituted or substituted one or several times with at least one substituent selected from the following groups, the group consisting of fluorine, It is composed of chlorine and other atoms, hydroxyl, methoxy and N,N-dimethylamino groups, and more preferably each is unsubstituted or substituted by at least one substituent selected from the following groups. Second, this group is composed of methoxy, hydroxyl and N,N-dimethylamino groups, or represents cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl, piperidinyl (preferably Piperidin-4-yl or piperidin-3-yl), tetrahydrofuranyl or tetrahydropyranyl, etc., each of which is unsubstituted or substituted with at least one substituent selected from the following groups, or Several times, the group consists of fluorine, chlorine and other atoms, hydroxyl, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, oxy, trifluoromethyl, and an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms Preferably, each is unsubstituted or substituted one or several times with at least one substituent selected from the following groups, the group consisting of fluorine, chlorine and other atoms and one containing 1 to 4 The aliphatic hydrocarbon residue oxy group of carbon atoms is preferably composed of methoxy group, etc., wherein the aliphatic hydrocarbon residue containing 1 to 4 carbon atoms may be unsubstituted, and the cyclopropyl and cyclobutyl Group, cyclopentyl and cyclohexyl, piperidinyl (preferably piperidin-4-yl or piperidin-3-yl), tetrahydrofuranyl and tetrahydropyranyl can be selected according to their respective Unsubstituted aliphatic hydrocarbon functional group containing 1 to 4 carbon atoms, preferably through an unsubstituted aliphatic hydrocarbon functional group containing 1 to 2 carbon atoms to form a bond, but the condition is: if R⁷When it represents piperidinyl, tetrahydrofuranyl or tetrahydropyranyl, each residue of piperidinyl, tetrahydrofuranyl or tetrahydropyranyl is connected via a carbon atom.

It is also particularly preferred that there is a compound according to the general formula (I), wherein R¹Representative part of the structure (<b>T1</b>)，

<chemistry general="n"><img file="TW201210596A_D0016.tif" /></chemistry>

Where m represents 0, 1 or 2, and R^8aAnd R^8bIndependently of each other, it represents hydrogen, fluorine and other atoms, an aliphatic hydrocarbon residue oxy group containing 1 to 4 carbon atoms, or an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms; preferably, hydrogen, fluorine, etc. , Methyl or methoxy; R^8cRepresents an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, which is unsubstituted or substituted one or several times with at least one substituent selected from the following group consisting of fluorine, chlorine, and bromine , Iodine and other atoms, an unsubstituted aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, oxy, trifluoromethyl and an unsubstituted aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, Or represents a cycloaliphatic hydrocarbon residue containing 3 to 10 carbon atoms or a heterocyclic aliphatic hydrocarbon residue containing 3 to 10 ring members, each of which is unsubstituted or has at least one of the following groups The selected substituent is substituted one or several times. The group consists of fluorine, chlorine, bromine, iodine and other atoms, an unsubstituted aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, oxy, trifluoromethyl and An unsubstituted aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, etc., or where m represents 0, R^8aAnd R^8bIndependently of each other, it represents hydrogen, fluorine and other atoms, an aliphatic hydrocarbon residue oxy group containing 1 to 4 carbon atoms, or an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms; preferably, hydrogen, fluorine, etc. , Methyl or methoxy; and R^8cRepresents an aromatic group or a heteroaromatic group, each of which is unsubstituted or substituted one or several times with at least one substituent selected from the following group consisting of fluorine, chlorine, bromine, iodine and other atoms , Hydroxyl, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, oxy, trifluoromethoxy, trifluoromethyl, cyano, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, methylcarbonyl , Ethylcarbonyl, methoxycarbonyl, ethoxycarbonyl, phenyl, etc., wherein the phenyl group may be unsubstituted or substituted one or several times with at least one substituent selected from the following groups. Preferably, it is unsubstituted or substituted once or twice. The group consists of fluorine, chlorine, bromine, iodine and other atoms, hydroxyl, aliphatic hydrocarbon residues containing 1 to 4 carbon atoms, oxy, trifluoromethoxy Group, trifluoromethyl, cyano, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, methylcarbonyl, ethylcarbonyl, methoxycarbonyl and ethoxycarbonyl, etc., preferably at least One is substituted by a substituent selected from the following group, which is composed of fluorine, chlorine and other atoms, methyl, methoxy, trifluoromethyl and trifluoromethoxy, etc., R²It is selected from the following group, which consists of atoms such as hydrogen, fluorine, chlorine, trifluoromethyl, methyl, ethyl, isopropyl, cyclopropyl and methoxy; R³, R⁴, R⁵And R⁶Independently of each other, they are selected from the following groups, which are composed of atoms such as hydrogen, fluorine, chlorine, trifluoromethyl, cyano, trifluoromethoxy, and nitro; but the conditions are : R³, R⁴, R⁵And R⁶At least one of them a hydrogen atom.

R⁷Represents ethyl, n-propyl, 2-propyl, n-butyl, isobutyl, secondary-butyl, tertiary-butyl, n-pentyl, isopentyl, neopentyl, n-hexyl, vinyl Or propenyl [prop-2-enyl (-CH₂CH=CH₂), prop-1-enyl (-CH=CH-CH₃), isopropenyl (-C(=CH₂)-CH₃)] etc., which are unsubstituted or substituted one or several times with at least one substituent selected from the following groups, which are composed of fluorine, chlorine and other atoms, hydroxyl, methoxy, trifluoro Methyl group and N,N-dimethylamino group, etc., preferably are each unsubstituted or substituted one or several times with at least one substituent selected from the following group, which group is composed of It is composed of fluorine, chlorine and other atoms, hydroxyl, methoxy and N,N-dimethylamino groups, and more preferably each is unsubstituted or substituted with at least one substituent selected from the following groups Or several times, this group is composed of methoxy, hydroxyl and N,N-dimethylamino groups, or represents cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl, piperidinyl (more Preferably, piperidin-4-yl or piperidin-3-yl), tetrahydrofuranyl or tetrahydropyranyl, each of which is unsubstituted or substituted with at least one substituent selected from the following groups Or several times, the group consists of fluorine, chlorine and other atoms, hydroxyl, an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms, oxy, trifluoromethyl, and an aliphatic hydrocarbon residue containing 1 to 4 carbon atoms. The preferred ones are each unsubstituted or substituted one or several times with at least one substituent selected from the following groups, the group consisting of atoms such as fluorine and chlorine and one containing 1 to 4 The oxy group of the aliphatic hydrocarbon residue containing 1 to 4 carbon atoms is preferably composed of a methoxy group, etc., wherein the aliphatic hydrocarbon residue containing 1 to 4 carbon atoms may be unsubstituted, and the cyclopropyl and cyclopropyl residues Butyl, cyclopentyl and cyclohexyl, piperidinyl (preferably piperidin-4-yl or piperidin-3-yl), tetrahydrofuranyl and tetrahydropyranyl can each be selected via an unsubstituted The aliphatic hydrocarbon functional group containing 1 to 4 carbon atoms is preferably bonded via an unsubstituted aliphatic hydrocarbon functional group containing 1 to 2 carbon atoms, but the condition is: if R⁷When representing piperidinyl, tetrahydrofuranyl, or tetrahydropyranyl, each of these residues is connected via a carbon atom.

Particularly preferred ones are based on the compounds of general formula (I), which are selected from the following groups, which include:

<b>1</b>4-Methyl-2-propyl-N-(thiophen-2-yl-methyl)-7-(trifluoromethyl)-quinoline-3-carboxamide;

<b>2</b>N-(cycloheptyl-methyl)-4-methyl-2-propyl-7-(trifluoromethyl)-quinoline-3-carboxamide;

<b>3</b>N-[(4-Fluorophenyl)-methyl]-4-methyl-2-propyl-7-(trifluoromethyl)-quinoline-3-carboxamide;

<b>4</b>N-[(3-Fluorophenyl)-methyl]-4-methyl-2-propyl-7-(trifluoromethyl)-quinoline-3-carboxamide;

<b>5</b>2-Ethyl-N-[(4-fluorophenyl)-methyl]-4-methyl-7-(trifluoromethyl)-quinoline-3-carboxamide;

<b>6</b>2-Ethyl-N-[(3-fluorophenyl)-methyl]-4-methyl-7-(trifluoromethyl)-quinoline-3-carboxamide;

<b>7</b>N-[(4-fluorophenyl)-methyl]-2-isopropyl-4-methyl-7-(trifluoromethyl)-quinoline-3-carboxamide;

<b>8</b>N-[(3-Fluorophenyl)-methyl]-2-isopropyl-4-methyl-7-(trifluoromethyl)-quinoline-3-carboxamide;

<b>9</b>2-Cyclopropyl-N-[(4-fluorophenyl)-methyl]-4-methyl-7-(trifluoromethyl)-quinoline-3-carboxamide;

<b>10</b>2-Cyclopropyl-N-[(3-fluorophenyl)-methyl]-4-methyl-7-(trifluoromethyl)-quinoline-3-carboxamide;

<b>11</b>N-[(3-Fluorophenyl)-methyl]-2-isopropyl-7-(trifluoromethyl)-quinoline-3-carboxamide;

<b>12</b>N-[(4-fluorophenyl)-methyl]-2-isopropyl-7-(trifluoromethyl)-quinoline-3-carboxamide;

<b>13</b>2-tertiary-butyl-N-[(3-fluorophenyl)-methyl]-7-(trifluoromethyl)-quinoline-3-carboxamide;

<b>14</b>2-tertiary-butyl-N-[(4-fluorophenyl)-methyl]-7-(trifluoromethyl)-quinoline-3-carboxamide;

<b>15</b>N-[(3-fluorophenyl)-methyl]-2-(methoxymethyl)-4-methyl-7-(trifluoromethyl)-quinoline-3-carboxamide;

<b>16</b>N-[(4-fluorophenyl)-methyl]-2-(methoxymethyl)-4-methyl-7-(trifluoromethyl)-quinoline-3-carboxamide;

<b>17</b>N-[(3-fluorophenyl)-methyl]-2-(hydroxymethyl)-4-methyl-7-(trifluoromethyl)-quinoline-3-methanamide;

<b>18</b>2-(2,2-Dimethyl-propyl)-N-[(3-fluorophenyl)-methyl]-4-methyl-7-(trifluoromethyl)-quinoline-3-methyl Amide

<b>19</b>2-(2,2-Dimethyl-propyl)-N-[(4-fluorophenyl)-methyl]-4-methyl-7-(trifluoromethyl)-quinoline-3-methyl Amide

<b>20</b>2-Cyclopentyl-N-[(3-fluorophenyl)-methyl]-4-methyl-7-(trifluoromethyl)-quinoline-3-carboxamide;

<b>21</b>2-Cyclopentyl-N-[(4-fluorophenyl)-methyl]-4-methyl-7-(trifluoromethyl)-quinoline-3-carboxamide;

<b>22</b>N-(4,4-Dimethyl-pentyl)-4-methyl-2-propyl-7-(trifluoromethyl)-quinoline-3-carboxamide;

<b>23</b>N-[(3-Fluorophenyl)-methyl]-4-methyl-2-[(<i>E</i>)-Pro-1-enyl]-7-(trifluoromethyl)-quinoline-3-carboxamide;

<b>24</b>N-[(3-Fluorophenyl)-methyl]-4-methyl-2-(2-methyl-prop-1-enyl)-7-(trifluoromethyl)-quinoline-3- Formamide;

<b>2</b><b>5</b>7-bromo-2-ethyl-N-[(3-fluorophenyl)-methyl]-4-methyl-quinoline-3-carbamide;

<b>26</b>7-bromo-2-ethyl-N-[(4-fluorophenyl)-methyl]-4-methyl-quinoline-3-carbamide;

<b>27</b>7-bromo-2-cyclopropyl-N-[(3-fluorophenyl)-methyl]-4-methyl-quinoline-3-carbamide;

<b>28</b>7-bromo-2-cyclopropyl-N-[(4-fluorophenyl)-methyl]-4-methyl-quinoline-3-carbamide;

<b>29</b>7-bromo-N-[(3-fluorophenyl)-methyl]-2-isopropyl-4-methyl-quinoline-3-carbamide;

<b>30</b>7-bromo-N-[(4-fluorophenyl)-methyl]-2-isopropyl-4-methyl-quinoline-3-carbamide;

<b>31</b>2-(Dimethylaminomethyl)-N-[(3-fluorophenyl)-methyl]-4-methyl-7-(trifluoromethyl)-quinoline-3-methanamide;

<b>32</b>2-Ethyl-N-[(4-fluoro-3-methyl-phenyl)-methyl]-4-methyl-7-(trifluoromethyl)-quinoline-3-methamide;

<b>33</b>7-cyano-2-ethyl-N-[(3-fluorophenyl)-methyl]-4-methyl-quinoline-3-carbamide;

<b>34</b>2-Ethyl-N-[(3-fluoro-4-methyl-phenyl)-methyl]-4-methyl-7-(trifluoromethyl)-quinoline-3-methamide;

<b>35</b>7-cyano-2-ethyl-N-[(4-fluorophenyl)-methyl]-4-methyl-quinoline-3-carbamide;

<b>36</b>N-[(3-fluorophenyl)-methyl]-4-methyl-2-(2-methyl-propyl)-7-(trifluoromethyl)-quinoline-3-methamide;

<b>37</b>7-cyano-2-cyclopropyl-N-[(3-fluorophenyl)-methyl]-4-methyl-quinoline-3-carboxamide;

<b>38</b>7-cyano-2-cyclopropyl-N-[(4-fluorophenyl)-methyl]-4-methyl-quinoline-3-carboxamide;

<b>39</b>7-cyano-N-[(3-fluorophenyl)-methyl]-2-isopropyl-4-methyl-quinoline-3-carbamide; and

<b>40</b>7-cyano-N-[(4-fluorophenyl)-methyl]-2-isopropyl-4-methyl-quinoline-3-carboxamide; their respective forms are free compounds; racemic Isomers; mixtures of enantiomers, diastereomers, enantiomers or diastereomers in any mixing ratio or a single species of enantiomers or diastereomers; or forms thereof It is a salt formed by a physiologically acceptable acid or base; or its form is a solvate, especially a hydrate.

According to the present invention, the substituted compounds of the aforementioned general formula (I), their corresponding stereoisomers, and their corresponding salts and solvates all have toxicological safety and are therefore suitable As a pharmaceutical active substance in a pharmaceutical composition.

The present invention therefore relates to a pharmaceutical composition, which contains at least one compound according to the general formula (I), each of which is a pure stereoisomer when necessary, especially an enantiomer or non- One of the enantiomers is in the form, in the form of its racemic isomer, or in the form of a stereoisomer, especially a mixture of enantiomers or diastereomers in any desired mixing ratio In the form of, or each in the form of a physiologically acceptable salt, or each in the form of a corresponding solvate, and may optionally contain at least one pharmaceutically acceptable adjuvant and/or may be selected according to Contains at least another active substance.

The pharmaceutical compositions according to the present invention are particularly suitable for the regulation of KCNQ2/3 potassium channels, preferably for the inhibition of KCNQ2/3 potassium channels, and/or for the stimulation of KCNQ2/3 potassium channels, That is to say, these pharmaceutical compositions have agonistic or antagonistic effects.

The preferred pharmaceutical compositions according to the present invention are also suitable for the prevention and/or treatment of diseases and/or disorders that are at least partly promoted by the KCNQ2/3 potassium ion channel. The medical composition according to the present invention is suitable for administering to adults and children, including toddlers and babies who are learning to walk. The pharmaceutical composition according to the present invention can be prepared in the form of liquid, semi-solid or solid pharmaceutical dosage forms, such as injections, drops, juices, syrups, sprays, suspensions, tablets, patches, capsules, tapes, etc. Suppositories, ointments, creams, detergents, gels, emulsions, aerosols, etc., or in the form of multi-particulates, such as pills or granules, which can be compressed into tablets and filled when needed It is encapsulated or suspended in a liquid, and can also be administered as described above.

Except for at least one of the substituted compounds of the general formula (I) shown above, the pure stereoisomers, especially the mirror image isomers and/or the non-mirror mirror isomers, are used when necessary. One of the structures is in the form, in the form of its racemic isomers, or in the form of a group of stereoisomers, especially from the enantiomers and/or the diastereomers in any way In the form of a mixture composed of the desired mixing ratio, or in the form of a corresponding salt when necessary, or each in the form of a corresponding solvate, the pharmaceutical composition according to the present invention can usually further contain a physiologically Accepted pharmaceutical adjuvants, for example, can be selected from the following groups, which are composed of excipients, fillers, solvents, diluents, surface active substances, pigments, preservatives, disintegrating agents, and enhancing agents. It is composed of lubricants, lubricants, fragrances and adhesives. The choice of physiologically acceptable adjuvants and their dosages depends on whether the pharmaceutical composition is oral, subcutaneous, parenteral, intravenous, intraperitoneal, intradermal, intramuscular, nasal, or oral. , Rectal or topical use, such as skin, mucous membrane or eye infections. Tablets, dragees, capsules, granules, pills, drops, juices and syrups are preferably suitable for oral administration, while solutions, suspensions, dry prescriptions and sprays that can be easily reconstituted are suitable for oral administration. Parenteral, topical and inhalation administration. The compound substituted according to the present invention used in the pharmaceutical composition according to the present invention contained in the dissolving type reservoir dosage form or the medicated tape dosage form of the agent that promotes penetration of the skin is added as needed. All are suitable for transdermal administration. Medicine prescription. Where it can be used in oral or transdermal forms, the formulation can also release various compounds substituted according to the present invention in a delayed manner.

The pharmaceutical composition according to the present invention is prepared by common techniques, devices, methods and processes known to the current state of the art, such as those described in ",, Remington's Pharmaceutical Sciences", AR Gennaro (Editor), 17^th edition, Mack Publishing Company, Easton, Pa, 1985, especially in Unit 8, Chapter 76 to Chapter 93". Therefore, the relevant narratives in this document are cited as references and regarded as part of the disclosure content of the case. The dosage of various substituted compounds of general formula I as shown above in the present invention can be changed, which depends on the weight or age of the patient, and also depends on the method of administration, the indication and the severity of the disease. Spend. Usually, 0.001 to 100 mg, preferably 0.05 to 75 mg, and particularly preferably 0.05 to 50 mg of at least one compound according to the present invention are administered per kilogram of the patient's body weight. The pharmaceutical composition according to the present invention is preferably suitable for the treatment and/or prevention of one or several diseases and/or diseases, which are selected from the following groups, which are composed of pain, especially acute Pain, chronic pain, pain caused by neuropathy, muscular pain, visceral pain, and inflammatory pain selected from the group; epilepsy; urinary incontinence; anxiety; addiction; bipolar disorder; two-stage Disorders; migraine; cognitive disorders; involuntary movements related to dystonia.

The pharmaceutical composition according to the present invention is particularly suitable for the treatment of pain, and more particularly suitable for the treatment of acute pain, chronic pain, pain caused by neuropathy, visceral pain, inflammatory pain and muscular pain, etc., most particularly Those are suitable for the treatment of pain caused by neuropathy. The pharmaceutical composition according to the present invention is also preferably suitable for the treatment and/or prevention of epilepsy. The present invention therefore relates to at least one compound according to the general formula (I), and when necessary, it also includes one or several pharmaceutically acceptable adjuvants for modulating the KCNQ2/3 potassium ion channel, preferably with To inhibit and/or stimulate KCNQ2/3 potassium channels. The present invention therefore relates to at least one compound according to the general formula (I), and when necessary, also includes one or several pharmaceutically acceptable adjuvants for prevention and/or treatment at least partly due to KCNQ2/3 Diseases and/or disorders caused by potassium channels. Preferably, at least one compound according to the general formula (I) is used, and one or several pharmaceutically acceptable adjuvants can be used according to the choice to prevent and/or treat diseases and/or disorders, which are as follows The group is selected from the group consisting of pain, especially pain caused by acute pain, chronic pain, neuropathy, muscular pain, visceral pain, and inflammatory pain. Epilepsy; Urinary incontinence; Anxiety state; Addiction disorder; Bipolar disorder; Bi-stage disorder; Migraine; Cognitive disorders; Involuntary movements related to dystonia.

Particularly preferred is the use of at least one compound according to the general formula (I), and one or several pharmaceutically acceptable adjuvants may be used according to the choice for the prevention and/or treatment of diseases and/or disorders, which are caused by Selected from the following group, which is selected from the group consisting of pain, especially acute pain, chronic pain, pain caused by neuropathy, muscular pain, visceral pain and inflammatory pain, etc. Pain, most particularly pain caused by neuropathy. Particularly preferably, at least one compound according to the general formula (I) is also used, and one or several pharmaceutically acceptable adjuvants can be used according to the choice for the prevention and/or treatment of epilepsy. The present invention therefore relates to at least one compound according to the general formula (I), and when necessary, it also includes one or several pharmaceutically acceptable adjuvants for the regulation of the KCNQ2/3 potassium ion channel, preferably It is used to inhibit and/or stimulate KCNQ2/3 potassium channels. The present invention therefore relates to at least one compound according to the general formula (I), and when necessary, also includes one or several pharmaceutically acceptable adjuvants for prevention and/or treatment at least partly due to KCNQ2/3 Diseases and/or disorders caused by potassium channels. Preferably, at least one compound according to the general formula (I) is used, and one or several pharmaceutically acceptable adjuvants may be used according to the choice for the prevention and/or treatment of diseases and/or disorders, which are caused by Selected from the following group, which is selected from the group consisting of pain, especially acute pain, chronic pain, pain caused by neuropathy, muscular pain, visceral pain and inflammatory pain, etc. Pain; epilepsy; urinary incontinence; anxiety; addiction; bipolar disorder; bipolar disorder; migraine; cognitive disorders; involuntary movements related to dystonia.

Particularly preferred is the use of at least one compound according to the general formula (I), and one or several pharmaceutically acceptable adjuvants may be used according to the choice for the prevention and/or treatment of diseases and/or disorders, which are caused by Selected from the following group, which is selected from the group consisting of pain, especially acute pain, chronic pain, pain caused by neuropathy, muscular pain, visceral pain and inflammatory pain, etc. Pain, most particularly pain caused by neuropathy. Particularly preferably, at least one compound according to the general formula (I) is also used, and one or several pharmaceutically acceptable adjuvants can be used according to the choice for the prevention and/or treatment of epilepsy. Another aspect of the present invention is a method for treating and/or preventing diseases and/or disorders caused at least in part by KCNQ2/3 potassium ion channels in mammals, preferably treating and/or preventing diseases and / Or symptoms, which are selected from the following groups, which are pain, preferably acute pain, chronic pain, pain caused by neuropathy, muscular pain, visceral pain, and inflammation Pain selected from the group consisting of sexual pain; epilepsy; urinary incontinence; anxiety state; addiction disorder; bipolar disorder; bipolar disorder; migraine; cognitive disorders; involuntary movements related to dystonia, etc. The composition contains at least one compound of general formula (I) in a therapeutically effective amount administered to a mammal.

By flash tail test (e.g. according to D'Amour und Smith (J. Pharm. Exp. Ther. 72, 7479 (1941)) or by formalin test (e.g. according to D. Dubuisson et al., Pain 1977, 4, 161-174) For example, it can be used in Bennetts model or Chungs model (Bennett., GJ and Xie, YK, a rats peripheral neuropathy is similar to humans, Pain 1988, 33(1), 87-107; Kim , SH and Chung, JM; A peripheral neuropathy caused by ligation of spinal cord nerves in a rat experimental model, Pain 1992, 50(3), 355-363 (Bennett., GJ and Xie, YK, A peripheral mononeuropathyl in rat that produces disorders of pain sensation like those seen in man,Pain 1988,33(1),87-107; Kim,SH and Chung, JM, An Experimental model for peripheral neuropathy produced by seg mental spinal nerve ligation in the rat), Pain 1992, 50(3), 355-363)) showed an anti-pain effect. For example, the anti-epileptic effect can be demonstrated in the DAB/2 mouse model (De Sarro et al., Naunyn-Schmiedeberg's Arch. Pharmacol. 2001, 363, 330-336). The preferred compound according to the present invention has EC₅₀The value does not exceed 10000 nM or 8000 nM, preferably does not exceed 7000 nM or does not exceed 6000 nM, more preferably does not exceed 5000 nM or does not exceed 3000 nM, even more preferably does not exceed 2000 nM or does not exceed 1000 nM, and even better, no more than 800 nM or no more than 700 nM, better no more than 600 nM or no more than 500 nM, still better no more than 400 nM or no more than 300 nM, the best More than 200 nM or not more than 150 nM and especially not more than 120 nM or not more than 100 nM. Determination of EC₅₀The methods of value are all known to those who are acquainted with knowledge and skills. EC₅₀The better value is measured by fluorescence measurement method, especially the better value is measured by "<b>Pharmacology experiment</b>Measured by the method described in ". The present invention also provides methods for preparing substituted compounds according to the present invention. The chemicals and reactants used in the reactions and flowcharts described in the following are all purchased or can be prepared according to common methods that are known to those skilled in the art.

The various reactions described above can be carried out under traditional conditions known to those skilled in the art, for example, in terms of pressure and the order of reaction components to be added. If necessary, those skilled in the art can determine the most suitable reaction steps by simple preliminary tests under various reaction conditions. The intermediate products and final products obtained by the various reactions described above can be purified and/or separated individually, and if desired and/or necessary, traditional methods known to those skilled in the art can be used. Suitable purification methods include, for example, extraction and chromatography, such as column chromatography or preparative chromatography. All the method steps described below, and the purification and/or separation of various intermediate products or final products can be carried out partially or completely under an inert gas blowing, preferably under a nitrogen blowing. If the compounds substituted according to the present invention having the general formula (I) shown above are in the form of a mixture of their stereoisomers after their preparation, preferably they are racemic When the form of structure, or other forms of mixtures of various enantiomers and/or diastereoisomers are prepared, these compounds can be separated according to the traditional methods known to those skilled in the art, and if It can be purified when needed. Examples of purification and separation include chromatographic separation methods, especially liquid chromatography under normal pressure or elevated pressure, preferably medium pressure liquid chromatography (MPLC) or high pressure liquid chromatography Method (HPLC), and fractional crystallization method. These methods allow individual enantiomers to be formed by, for example, asymmetric stationary phase HPLC or by combining with asymmetric acids such as (+)-tartaric acid, (-)-tartaric acid or (+)-10-camphorsulfonic acid The way of crystallization produces diastereoisomeric salts which are separated from each other.<i>General reaction flow chart I (Synthesis of precursors HA-1, HA-2 and HA-3):</i>

<chemistry general="n"><img file="TW201210596A_D0017.tif" /></chemistry>

It is known from the current professional literature that many kinds of synthesis have general formulas<b>HA-1, HA-2</b>and<b>HA-3</b>, Which contains residue R², R³, R⁴, R⁵, R⁶And R⁷A very wide range of substitution models, such as quinoline-3-carboxylate and its synthetic pathways. For example, with general formula<b>HA-1</b>For example, the quinoline-3-carboxylate can have the general formula<b>AN-1</b>Aniline with the general formula<b>ES-1</b>The β-hydroxy-formate reaction is produced. General<b>HA-2</b>The 2-hydroxy-quinoline-3-carboxylate can, for example, have the general formula<b>AN-1</b>Aniline with the general formula<b>ES-2</b>The malonic acid derivatives are produced by the reaction. General<b>HA-3</b>The 4-hydroxy-quinoline-3-carboxylate can, for example, have the general formula<b>AN-2</b>Aniline with the general formula<b>ES-3</b>The malonic acid derivatives are produced by the reaction. Previously unknown, with residue R², R³, R⁴, R⁵, R⁶And R⁷Similar to the general formula of the replacement model<b>HA-1</b>、<b>HA-2</b>and<b>HA-3</b>The intermediate products, which are shown below and whose synthesis is not described in detail, can be synthesized by those skilled in the art according to these known methods or by a combination of these known methods.<i>General reaction flow chart II</i>

<chemistry general="n"><img file="TW201210596A_D0018.tif" /></chemistry>

At stage<b>01</b>,stage<b>05</b>And stage<b>08</b>According to the methods known to those skilled in the art, for example, using an alkali, such as lithium hydroxide, will have the general formula<b>HA-1</b>、<b>HA-6</b>or<b>HA-8</b>The quinoline-3-carboxylate is transformed into a general formula<b>HA-4</b>The acid compound. At stage<b>03</b>And stage<b>06</b>According to the methods known to those skilled in the art, such as using trifluoromethanesulfonate chloride or phosphatidyl chloride, the general formula<b>HA-2</b>Of 2-hydroxy-quinoline-3-carboxylate or with general formula<b>HA-3</b>The 4-hydroxy-quinoline formate is transformed into a general formula<b>HA-7</b>or<b>HA-5</b>Compounds where X each represents a leaving group, such as trifluoromethanesulfonate or chlorine. At stage<b>07</b>According to the methods known to those skilled in the art, for example, cross-coupling reactions, such as Suzuki coupling, Stille coupling, or Buchwald-Hartwig coupling, can be used, which will have the general formula<b>HA-7</b>The quinoline-3-carboxylate, where X represents a leaving group, such as trifluoromethanesulfonate or chlorine, is transformed into a general formula<b>HA-8</b>The compound. At stage<b>04</b>It can be based on methods known to those skilled in the art, such as substitution with the corresponding amine, or substitution with the corresponding alcohol, or through cross-coupling reactions, such as Suzuki coupling, Stille coupling, or Buchwald-Hartwig coupling. , Will have the general formula<b>HA-5</b>The quinoline-3-carboxylate, where X represents a leaving group, such as trifluoromethanesulfonate or chlorine, is transformed into a general formula<b>HA-6</b>The compound. At stage<b>02</b>According to the methods known to those skilled in the art, for example, using an appropriate coupling agent, such as HATU, will have the general formula<b>HA-4</b>The acid has the general formula R¹-(CH₂)-NH₂The amine reacts to be converted into an amide of general formula (I). The general formula (<b>I</b>The compounds of) can undergo simple derivatization reactions known to those skilled in the art, such as esterification, ester formation, amide formation, etherification, ether decomposition, reduction, substitution, or cross-coupling reactions, etc. , Is further transformed into introducing and/or replacing one or several substituents R¹, R², R³, R⁴, R⁵, R⁶And R⁷. The present invention will be explained below with the help of some examples. This description is for illustrative purposes only, and does not limit the overall concept of the present invention.

<b>example</b>"Equivalent" ("eq.") means molar equivalent, "RT" means room temperature (23±7°C), "M" means concentration, the unit is mol/liter, "aq." means aqueous solution, "sat "." means saturated, "sol." means solution, and "conc." means concentrated.

List of other abbreviations:

AcOH acetic acid (acetic acid)

d days

dba dibenzylidene acetone (dibenzylidene acetone)

brine saturated sodium chloride aqueous solution (NaCl aqueous solution)

CC silica gel column chromatography

DCM Dichloromethane (dichloromethane)

DIPEA N,N-diisopropylethylamine (N,N-diisopropylethylamine)

DMF N,N-dimethylformamide (N,N-dimethylformamide)

DMSO dimethyl sulfoxide

EtOAc (ethyl acetate)

ether diethyl ether

EtOH ethanol

h hours

H₂O water

HATU O-(7-Aza-benzotriazol-1-yl)-N,N,N',N'-tetramethylurea hexafluorophosphate

m/z mass to charge ratio

MeOH methanol (methanol)

MeCN acetonitrile

min minutes

MS mass spectroscopy

MW microwave

N/A Not available

NEt₃Triethylamine

RS reaction solution

THF Tetrahydrofuran (tetrahydrofuran)

TMEDA N,N,N',N'-tetramethylethylenediamine (N,N,N',N'-tetramethyl-ethylenediamine)

Xantphos 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene

The yield of the prepared compound has not been optimized.

All temperatures are uncorrected.

All unspecified starting compounds were obtained through purchase (detailed information of the supplier, such as Acros, Avocado, Aldrich, Bachem, Fluka, Lancaster, Maybridge, Merck, Sigma, TCI, Oakwood, etc., available for example in the United States, San Ramon, the MDL company<img file="TW201210596A_D0019.tif" /> Available Chemicals Database, or in the United States, District of Columbia, Washington, ACS<img file="TW201210596A_D0020.tif" /> Database), or its synthesis has been accurately described in the professional literature (experimental methods can be found in the Elsevier company in Amsterdam, the Netherlands, for example.<img file="TW201210596A_D0021.tif" />In the database, or search in the SciFinder database in the United States, District of Columbia, Washington, ACS), or it can be synthesized according to common methods known to those skilled in the art. The stationary phase used as the column chromatography is Silica 60 (0.040-0.063 mm) from E. Merck in Darmstadt, Germany. The mixing ratio of the solvent or the mobile phase solvent used in the chromatographic analysis test is expressed by volume/volume respectively. All intermediate products and example compounds are used¹H-NMR spectroscopy measurement method for analysis and identification. In addition, mass spectrometry tests (MS, data m/z represent [M+H] for all sample compounds and specially selected intermediate products)⁺)。

<b>Synthesis of Example 3: Synthesis of Example 3:</b>N-[(4-Fluorophenyl)-methyl]-4-methyl-2-propyl-7-(trifluoromethyl)-quinoline-3-carboxamide

a) Synthesis of 4-methyl-2-propyl-7-(trifluoromethyl)-quinoline-3-carboxylic acid ethyl ester -(Trifluoromethyl)phenyl)ethanone is hydrated with 2.6 ml (24.6 mmol) of 3-oxy-hexanoic acid ethyl ester and 5.6 g (24.6 mmol) of stannous chloride dihydrate The mixture was stirred at room temperature for 3 hours. The mixture was then heated to 80°C for 16 hours. After cooling to room temperature, the mixture was diluted with ethanol (25 mL), ice was added, and the mixture was heated at room temperature for 10 minutes. The solution was filtered and washed with ethyl acetate. The two phases were separated, and the aqueous portion was extracted with ethyl acetate. Then the organic phases were combined and washed with EDTA-disodium salt aqueous solution, water and saturated sodium chloride aqueous solution, then dried with magnesium sulfate to remove water, and then concentrated under vacuum. After the residue was purified by column chromatography (dichloromethane/hexane 2:1), 4.3 g (13.7 mmol, yield: 56%) of 4-methyl-2-propyl were obtained. -7-(Trifluoromethyl)-quinoline-3-carboxylic acid ethyl ester.

b) Synthesis of 4-methyl-2-propyl-7-(trifluoromethyl)-quinoline-3-carboxylic acid Add a 2M aqueous lithium hydroxide solution (44 ml) to a mixture of 4.3 g (13.7 ml) Mol) of 4-methyl-2-propyl-7-(trifluoromethyl)-quinoline-3-carboxylic acid ethyl ester dissolved in a methanol/tetrahydrofuran mixture (44 ml each), and then The mixture was heated to 60°C for 72 hours. The organic solvent was removed as much as possible under vacuum, and the resulting aqueous solution was washed with ether, adjusted to pH 2 with 2M hydrochloric acid, and then diluted with ethyl acetate. The organic phase was separated and collected, washed with a saturated aqueous sodium chloride solution, then dried with magnesium sulfate to remove water, and then concentrated under vacuum. As a result, 3.6 g (12.0 mmol, yield: 88%) of the residue, 4-methyl-2-propyl-7-(trifluoromethyl)-quinoline-3-carboxylic acid was obtained. This crude product was further converted into other compounds without additional purification.

c) Synthesis of N-[(4-fluorophenyl)-methyl]-4-methyl-2-propyl-7-(trifluoromethyl)-quinoline-3-carbamide

Add 311 microliters (2.7 millimoles) of 4-fluorobenzylamine, 941 milligrams (2.5 millimoles) of HATU and 1 milliliter (7.2 millimoles) of triethylamine to a mixture of 740 milligrams ( 2.5 millimoles) 4-methyl-2-propyl-7-(trifluoromethyl)-quinoline-3-carboxylic acid was dissolved in a solution consisting of tetrahydrofuran (19 ml), and then the mixture was mixed in 50 Stir at °C for 72 hours. Then the mixture was diluted with ethyl acetate, and washed with 4N aqueous ammonium chloride solution, 1M sodium carbonate aqueous solution and saturated sodium chloride aqueous solution. The organic phase is then dried with magnesium sulfate to remove water, filtered through silica gel, and then concentrated under vacuum. After the residue was purified by column chromatography (ethyl acetate/hexane 1:1), 770 mg (1.9 mmol, yield: 76%) of N-[(4-fluorophenyl) was obtained. )-Methyl)-4-methyl-2-propyl-7-(trifluoromethyl)-quinoline-3-carboxamide (<b>Example 3</b>). MS: m/z 405.2[M+H]⁺。

<b>Synthesis of example compound 15:</b>N-[(3-Fluorophenyl)-methyl]-2-(methoxymethyl)-4-methyl-7-(trifluoromethyl)-quinoline-3-methanamide

a) The synthesis of 2-(methoxymethyl)-4-methyl 7-(trifluoromethyl)-quinoline-3-carboxylic acid methyl ester will consist of 4.0 g (19.7 mmol) of 1-( 2-Amino-4-(trifluoromethyl)phenyl)ethanone, 11.5ml (98.5mmol) of 4-chloro-diethyl acetate and 1.7ml (19.7mmol) of concentrated hydrochloric acid The mixture was heated to 75°C in a sealed container with microwave (50 watts) for 6 minutes. This mixture was then diluted with ethyl acetate and water. The organic phase was separated and collected, washed with 1M aqueous sodium bicarbonate solution, dried with magnesium sulfate to remove water, and then concentrated under vacuum. The residue was purified by column chromatography (ethyl acetate/hexane 3:17) to obtain the crude product (7.47 g dissolved in methanol (76 ml), and then 35.3 ml (70.6 mmol) 2M aqueous lithium hydroxide solution was added to the mixture. Then the mixture was stirred at room temperature for 16 hours and heated to 60°C for 24 hours. After cooling to room temperature, the mixture was mixed with water and ethyl acetate The ester is diluted. The organic phase is separated and collected, then dried with magnesium sulfate to remove water, and then concentrated under vacuum. The residue is purified by column chromatography (ethyl acetate/hexane 1:3), and the result is obtained 985 mg (3.1 mmol, yield: 16%) of 2-(methoxymethyl)-4-methyl 7-(trifluoromethyl)-quinoline-3-carboxylic acid methyl ester.

b) Synthesis of 2-(methoxymethyl)-4-methyl-7-(trifluoromethyl)-quinoline-3-carboxylic acid 980 mg (3.1 mmol) of 2-(methoxymethyl)-4-methyl7-(trifluoromethyl)-quinoline-3-carboxylic acid methyl ester dissolved in tetrahydrofuran (25ml) Then the mixture was heated to 60°C for 16 hours. The tetrahydrofuran was removed as much as possible under vacuum, and the resulting aqueous solution was washed with ether, adjusted to pH 2 with 2M hydrochloric acid, and then diluted with ethyl acetate. The organic phase was separated and collected, washed with a saturated aqueous sodium chloride solution, then dried with magnesium sulfate to remove water, and then concentrated under vacuum. As a result, 612 mg (2.0 millimoles, yield: 66%) of the residue was obtained, 2-(methoxymethyl)-4-methyl-7-(trifluoromethyl)-quinoline-3-carboxylic acid . This crude product was further converted into other compounds without additional purification.

c) N-[(3-Fluorophenyl)-methyl]-2-(methoxymethyl)-4-methyl-7-(trifluoromethyl)-quinoline-3-methanamide synthesis

Convert 2-(methoxymethyl)-4-methyl-7-(trifluoromethyl)-quinoline-3-carboxylic acid to N-[(3-fluorophenyl)-methyl]-2- (Methoxymethyl)-4-methyl-7-(trifluoromethyl)-quinoline-3-carboxamide (<b>Example 15</b>The reaction of) is carried out according to the method described in the example compound 3, c). MS: m/z 407.1[M+H]⁺。

<b>Synthesis of Example 17:</b>N-[(3-fluorophenyl)-methyl]-2-(hydroxymethyl)-4-methyl-7-(trifluoromethyl)-quinoline-3-carboxamide will contain 220 mg (0.54 mmol) of N-((3-fluorophenyl)-methyl)-2-(methoxymethyl)-4-methyl-7-(trifluoromethyl)-quinoline-3 -Formamide (<b>Example compound 15</b>) A solution composed of dichloromethane (5 mL) was cooled to -78°C, and then 5.4 mL (5.4 mmol, 2M dichloromethane solution) of boron tribromide was added to the mixture. After heating to 0°C, the mixture was stirred at this temperature for 16 hours. The reaction was terminated by adding 1M aqueous sodium bicarbonate solution (15 ml) and 10% strength sodium thiosulfate aqueous solution. The mixture was then diluted with methanol and dichloromethane. The organic phase was separated and collected, dried with magnesium sulfate to remove water, and then concentrated under vacuum. The residue was purified by column chromatography (ethyl acetate/hexane 1:1ethyl acetate/dichloromethane 1:1), and the result was 110 mg (0.28 mmol, yield: 52%) The N-[(3-fluorophenyl)-methyl]-2-(hydroxymethyl)-4-methyl-7-(trifluoromethyl)-quinoline-3-methanamide(<b>Example 17</b>). MS: m/z 393.1[M+H]⁺。

<b>Synthesis of Example 18:</b>2-(2,2-Dimethyl-propyl)-N-[(3-fluorophenyl)-methyl]-4-methyl-7-(trifluoromethyl)-quinoline-3-methyl Amide

a) Synthesis of 4-methyl-2-neopentyl-7-(trifluoromethyl)-quinoline-3-carboxylic acid ethyl ester Ethyl) ethyl ketone and ethyl 5,5-dimethyl-3-oxyhexanoate react to form 4-methyl-2-neopentyl-7-(trifluoromethyl)-quinoline-3-carboxylic acid ethyl ester The ester is carried out according to the method described in the example compound 3, paragraph a).

b) Synthesis of 4-methyl-2-neopentyl-7-(trifluoromethyl)-quinoline-3-carboxylic acid Add a 2M aqueous lithium hydroxide solution (10 ml) to a mixture of 1.1 g (3.0 Millimoles) 4-methyl-2-neopentyl-7-(trifluoromethyl)-quinoline-3-carboxylic acid ethyl ester dissolved in a methanol/1,4-dioxane mixture (each 10ml), then the mixture was heated to 80°C for 72 hours. The organic solvent was removed as much as possible under vacuum, and the resulting aqueous solution was washed with ether, adjusted to pH 2 with 2M hydrochloric acid, and then diluted with ethyl acetate. The organic phase was separated and collected, washed with a saturated aqueous sodium chloride solution, then dried with magnesium sulfate to remove water, and then concentrated under vacuum. As a result, 0.8 g (2.5 millimoles, yield: 82%) of the residue was obtained, the synthesis of 4-methyl-2-neopentyl-7-(trifluoromethyl)-quinoline-3-carboxylic acid. This crude product was further converted into other compounds without additional purification.

c) 2-(2,2-Dimethyl-propyl)-N-[(3-fluorophenyl)-methyl]-4-methyl-7-(trifluoromethyl)-quinoline-3 -The synthesis of methamide converts 4-methyl-2-neopentyl-7-(trifluoromethyl)-quinoline-3-carboxylic acid into 2-(2,2-dimethyl-propyl)- N-[(3-Fluorophenyl)-methyl]-4-methyl-7-(trifluoromethyl)-quinoline-3-carbamide(<b>Example 18</b>) Is carried out according to the method described in the example compound 3, c). MS: m/Z 433.2[M+H]⁺。

<b>Synthesis of Example 23:</b>N-[(3-Fluorophenyl)-methyl]-4-methyl-2-[(<i>E</i>)-Pro-1-enyl)-7-(trifluoromethyl)-quinoline-3-methanamide

a) Synthesis of 2-hydroxy-4-methyl-7-(trifluoromethyl)-quinoline-3-carboxylic acid ethyl esterAdd 12.6 ml (0.09 mol) of triethylamine to a mixture of 16.6 g ( 0.08 mol) of 1-(2-amino-4-(trifluoromethyl)phenyl)ethanone was dissolved in a solution of dichloromethane (170 ml), and then cooled to 0°C. Then, 13.4 ml (0.11 mol) of 3-chloro-3-oxy-propionic acid ethyl ester was added to the mixture in a trickle manner, and the mixture was stirred at room temperature for 16 hours. The mixture was then diluted with water and extracted with dichloromethane (3x). The combined organic phases were then dried with sodium sulfate to remove water, and then concentrated under vacuum. After the residue was purified by column chromatography (ethyl acetate/hexane 2:3), 18.1 g (0.07 mol, yield: 87%) of 2-hydroxy-4-methyl-7- (Trifluoromethyl)-quinoline-3-carboxylic acid ethyl ester.

b) Synthesis of 4-methyl-7-(trifluoromethyl)-2-(trifluoromethylsulfonyloxy)-quinoline-3-carboxylic acid ethyl ester Trifluoromethanesulfonic anhydride was added to a 1.0 g (3.3 mmol) of 2-hydroxy-4-methyl-7-(trifluoromethyl)-quinoline-3 in a trickle at 0°C -Ethyl formate and 930 microliters (6.7 millimoles) of triethylamine were dissolved in a solution of dichloromethane (30 mL). After stirring for 4 hours at room temperature, the mixture was diluted with dichloromethane (30 mL), and then washed with water, saturated aqueous sodium bicarbonate solution and saturated aqueous sodium chloride solution. The organic phase is then dried with sodium sulfate to remove water, and then concentrated under vacuum. As a result, 1.32 g (3.1 millimoles, yield: 92%) of the residue was obtained, 4-methyl-7-(trifluoromethyl)-2-(trifluoromethylsulfonyloxy)-quinoline- Synthesis of ethyl 3-formate. This crude product was further converted into other compounds without additional purification.

c) (<i>E</i>)-4-methyl-2-(prop-1-enyl)-7-(trifluoromethyl)-quinoline-3-carboxylic acid ethyl ester is synthesized by 1.8 g (5.6 millimoles) of cesium carbonate and 210 mg (0.2 millimoles) of tetrakis (triphenylphosphine) palladium is added to 800 mg (1.9 millimoles) of 4-methyl-7-(trifluoromethyl)-2-(trifluoromethyl) Sulfonyloxy)-quinoline-3-carboxylic acid ethyl ester and 320 mg (3.7 mmol) of (E)-propen-1-yl-boronic acid dissolved in ethanol/toluene mixture (1:9vv, 20ml) In the composed solution, the mixture was heated to 110°C for 1 hour. The mixture was then concentrated under vacuum, and the residue was dissolved in ethyl acetate (20 mL) and water (20 mL). The organic phase was separated and collected, washed with water and saturated aqueous sodium chloride solution, then dried with sodium sulfate to remove water, and then concentrated under vacuum. After the residue was purified by column chromatography (ethyl acetate/hexane 1:9), 450 mg (1.4 mmol, yield: 75%) of (<i>E</i>)-4-Methyl-2-(prop-1-enyl)-7-(trifluoromethyl)-quinoline-3-carboxylic acid ethyl ester.

d) (<i>E</i>)-4-methyl-2-(prop-1-enyl)-7-(trifluoromethyl)-quinoline-3-carboxylic acid synthesis The substance is added at 0 °C to 450 mg (1,4 millimoles) of (<i>E</i>)-4-methyl-2-(prop-1-enyl)-7-(trifluoromethyl)-quinoline-3-carboxylic acid ethyl ester dissolved in water/ethanol mixture (21 ml each) middle. The mixture was then heated to 90°C for 16 hours. It was then concentrated under vacuum, and the residue was dissolved in water (20 mL) and washed with ethyl acetate. The aqueous phase was then adjusted to pH~2 with 2M hydrochloric acid, and then extracted with ethyl acetate. The organic phase is then dried with sodium sulfate to remove water, and then concentrated under vacuum. As a result, 350 mg (1.2 millimoles, yield: 85%) of residue was obtained, (<i>E</i>) Synthesis of -4-methyl-2-(prop-1-enyl)-7-(trifluoromethyl)-quinoline-3-carboxylic acid. This crude product was further converted into other compounds without additional purification.

e) N-[(3-Fluorophenyl)-methyl]-4-methyl-2-[(<i>E</i>)-Pro-1-enyl)-7-(trifluoromethyl)-quinoline-3-methanamide will be synthesized (<i>E</i>)-4-methyl-2-(prop-1-enyl)-7-(trifluoromethyl)-quinoline-3-carboxylic acid is converted to N-[(3-fluorophenyl)-methyl]- 4-methyl-2-[(<i>E</i>)-Pro-1-enyl)-7-(trifluoromethyl)-quinoline-3-methanamide (<b>Example 23</b>) Is based on the example<i>Compound</i>3. Carry out the method described in paragraph c). MS: m/z 403.1[M+H]⁺。

<b>Synthesis of Example 24:</b>N-[(3-Fluorophenyl)-methyl]-4-methyl-2-(2-methyl-prop-1-enyl)-7-(trifluoromethyl)-quinoline-3- Formamide

a) Synthesis of 4-methyl-7-(trifluoromethyl)-2-(trifluoromethylsulfonyloxy)-quinoline-3-carboxylic acid ethyl ester

The synthesis of 4-methyl-7-(trifluoromethyl)-2-(trifluoromethylsulfonyloxy)-quinoline-3-carboxylic acid ethyl ester is as described in Exemplary Compound 23, paragraph a)+b) .

b) Synthesis of 4-methyl-2-(2-methylprop-1-enyl)-7-(trifluoromethyl)-quinoline-3-carboxylic acid ethyl ester

Add 5.6 ml (2.8 millimoles, 2M tetrahydrofuran solution) of (2-methylprop-1-enyl)magnesium bromide in a trickle at 0°C to 600 mg (1.4 millimoles) ) Of 4-methyl-7-(trifluoromethyl)-2-(trifluoromethylsulfonyloxy)-quinoline-3-carboxylic acid ethyl ester and 75 mg (0.1 mmol) of 1,3 -<b>pair</b>(Diphenylphosphine propane) nickel dichloride was dissolved in a solution of tetrahydrofuran (10 ml). The mixture was then stirred at room temperature for 16 hours, and then the reaction was terminated with a saturated aqueous ammonium chloride solution at 0°C. The mixture was extracted with ethyl acetate, the organic phase was then washed with water and a saturated aqueous sodium chloride solution, then dried over sodium sulfate to remove water, and then concentrated under vacuum. After the residue was purified by column chromatography (ethyl acetate/hexane 1:19), 200 mg (0.6 mmol, yield: 43%) of 4-methyl-2-(2- Methylprop-1-enyl)-7-(trifluoromethyl)-quinoline-3-carboxylic acid ethyl ester.

c) Synthesis of 4-methyl-2-(2-methylprop-1-enyl)-7-(trifluoromethyl)-quinoline-3-carboxylic acid

Convert 4-methyl-2-(2-methylprop-1-enyl)-7-(trifluoromethyl)-quinoline-3-carboxylic acid ethyl ester to 4-methyl-2-(2- The reaction of methylprop-1-enyl)-7-(trifluoromethyl)-quinoline-3-carboxylic acid is based on<b>Example 23</b>, The method described in paragraph d) is carried out.

d) N-[(3-Fluorophenyl)-methyl]-4-methyl]-2-(2-methyl-prop-1-enyl)-7-(trifluoromethyl)-quinoline Synthesis of -3-formamide

Convert 4-methyl-2-(2-methylprop-1-enyl)-7-(trifluoromethyl)-quinoline-3-carboxylic acid to N-[(3-fluorophenyl)-methyl Yl)-4-methyl)-2-(2-methyl-prop-1-enyl)-7-(trifluoromethyl)-quinoline-3-carboxamide (<b>Example 24</b>) Is based on<b>Example 3</b>, The method described in paragraph c) is carried out. MS: m/z 417.2[M+H]⁺。

<b>Synthesis of Example 28:</b>7-bromo-2-cyclopropyl-N-[(4-fluorophenyl)-methyl]-4-methyl-quinoline-3-methanamide

a) Synthesis of 7-bromo-2-cyclopropyl-4-methyl-quinoline-3-carboxylic acid ethyl ester

This reaction is carried out according to the synthesis method described in Paragraph 3, a) of the example compound.

b) Synthesis of 7-bromo-2-cyclopropyl-N-[(4-fluorophenyl)-methyl]-4-methyl-quinoline-3-carbamide

10.5 ml (2M toluene solution, 20.9 millimoles) of trimethylaluminum was added to a stirring at room temperature, from 1.0 grams (2.99 millimoles) of 7-bromo-2-cyclopropyl-4 -Methyl-quinoline-3-carboxylic acid ethyl ester was dissolved in a solution of toluene (10 ml), and then 3.74 g (29.9 mmol) of 4-fluorobenzylamine was added to the mixture. The reaction mixture was heated at 120°C for 16 hours. Then water (15 mL) was added to stop the reaction, and the mixture was extracted with ethyl acetate (3 x 30 mL). The combined organic layer was washed with 2N hydrochloric acid aqueous solution and saturated sodium chloride aqueous solution, then dried with magnesium sulfate to remove water, and then concentrated under vacuum. After the residue was purified by column chromatography (ethyl acetate/cyclohexane 1:2), 900 mg (2.2 mmol, yield: 73%) of 7-bromo-2-cyclopropyl was obtained. -N-[(4-Fluorophenyl)-methyl]-4-methyl-quinoline-3-carboxamide (<b>Example 28</b>). MS: m/z 413.1[M+H]⁺。

<b>Synthesis of Example 31:</b>2-(Dimethylaminomethyl)-N-[(3-fluorophenyl)-methyl]-4-methyl-7-(trifluoromethyl)-quinoline-3-methanamide

a) Synthesis of 2-((dimethylamino)methyl)-4-methyl-7-(trifluoromethyl)-quinoline-3-carboxylic acid ethyl ester

A mixture of 1.0 g (5.0 millimoles) of 1-(2-amino-4-(trifluoromethyl)phenyl)ethanone and 3.4 milliliters (25.0 millimoles) of 3-chloro-3-oxy A mixture of ethyl propionate and 435 microliters (5.0 millimoles) of concentrated hydrochloric acid was heated to 100°C in a microwave in a sealed container for 30 minutes. This mixture was then diluted with ethyl acetate and water. The organic phase was separated and collected, washed with 1M aqueous sodium bicarbonate solution, dried with magnesium sulfate to remove water, and then concentrated under vacuum. The residue was purified by column chromatography (ethyl acetate/cyclohexane 3:17) and the resulting crude product (1.14 g) was dissolved in acetonitrile (6 ml), and 2.7 ml (15.5 mmol) Ear) N,N-diisopropylethylamine and 838 mg (10.3 mmol) of dimethylammonium chloride were added to the mixture. The mixture was then stirred at room temperature for 16 hours. After cooling to room temperature, the mixture was diluted with water and extracted with ethyl acetate. The organic phase was then extracted twice with 2N aqueous hydrochloric acid and water. The combined aqueous phase was alkalized with sodium carbonate, and then extracted with ethyl acetate. The organic layer was washed with a saturated aqueous sodium chloride solution, then dried over magnesium sulfate to remove water, and then concentrated under vacuum. As a result, 776 mg (2.3 mmol, yield: 46%) of the residue was obtained, 2-((dimethylamino)methyl)-4-methyl-7-(trifluoromethyl)-quinoline- Ethyl 3-formate.

b) 2-(Dimethylaminomethyl)-N-[(3-fluorophenyl)-methyl]-4-methyl 7-(trifluoromethyl)-quinoline-3-methanamide synthesis

5.5 ml (2M toluene solution, 10.9 millimoles) of trimethylaluminum was added to a stirring at room temperature, from 530 milligrams (1.56 millimoles) of 2-((dimethylamino)methyl )-4-methyl-7-(trifluoromethyl)-quinoline-3-carboxylic acid ethyl ester was dissolved in toluene (33 ml), and then 1.77 g (15.6 mmol) was added to the mixture. Ear) 3-fluorobenzylamine. The reaction mixture was heated at 120°C for 2 days. Then water was added to stop the reaction, and the mixture was acidified to pH~2 with concentrated hydrochloric acid aqueous solution. After washing with ethyl acetate, the aqueous layer was basified to pH~11 with sodium hydroxide. Then the solution was extracted twice with ethyl acetate. The combined organic layer was washed with water and saturated aqueous sodium chloride solution, then dried with magnesium sulfate to remove water, and then concentrated under vacuum. After the residue was purified by column chromatography (ethyl acetate/hexane 1:1ethyl acetate/methanol 9:1), the result was 60 mg (0.14 mmol, yield: 9%) of 2 -(Dimethylaminomethyl)-N-[(3-fluorophenyl)-methyl]-4-methyl-7-(trifluoromethyl)-quinoline-3-methanamide(<b>Example 3</b>1). MS: m/z 420.2[M+H]⁺。

<b>Synthesis of Example 38:</b> 7-cyano-2-cyclopropyl-N-[(4-fluorophenyl)-methyl]-4-methyl-quinoline-3-carboxamide

Mix 70 microliters (0.47 millimoles) of TMEDA, 152 milligrams (1.28 millimoles) of zinc cyanide, 4 mg (0.007 millimoles) of three (dibenzylidene acetone) dipalladium and 25 mg ( 0.040 millimoles) of Xantphos is added to a mixture of 880 milligrams (2.13 millimoles) of 7-bromo-2-cyclohexyl-N-[(4-fluorophenyl)-methyl)-4-methyl-quine The morpholino-3-formamide (Exemplary Compound 28) was dissolved in a solution of dimethylformamide (3 mL). The reaction solution was degassed and filled with nitrogen three times, and then heated to 160° C. in a microwave for 4 minutes. After cooling to room temperature, the mixture was filtered through Celite and washed with dichloromethane. The combined organic layer was concentrated under vacuum. After the residue was purified by column chromatography (ethyl acetate/cyclohexane 1:2), 325 mg (0.90 mmol, yield: 42%) of 7-cyano-2-cyclopropane was obtained. -N-[(4-Fluorophenyl)-methyl]-4-methyl-quinoline-3-methanamide (<b>Example 38</b>). MS: m/z 360.1[M+H]⁺。

<b>Synthesis of other examples</b>

The synthesis of other exemplary compounds was carried out according to the methods already described. Table 1 shows which compound was prepared by which method. For those skilled in the art, the reactants and reagents used in various situations are clear.

<tables><img file="TW201210596A_D0022.tif" /></tables>

<tables><img file="TW201210596A_D0023.tif" /></tables>

<tables><img file="TW201210596A_D0024.tif" /></tables>

<b>Pharmacological test</b>

<b>Method I. Fluorescence test using a pair of voltage-sensitive infectious agents (fluorescence measurement method)</b>

The Chinese hamster ovary (CHO)-K1- cells expressing human KCNQ2/3 channels were placed at 37°C, 5% carbon dioxide (CO₂) And 95% air humidity in an ad hoc manner in DMEM-high glucose medium (Sigma Aldrich D7777) containing 10% fetal calf serum (FCS) (PAN Biotech, such as 3302-P270521) or containing 10% fetal cattle Serum (Invitrogen, #10270-106, heated to remove activity) and MEM Alpha medium (1x, liquid, Invitrogen, #22571) necessary for selection of antibiotics in cell culture flasks (for example, Nuncs 80 cm² TC flask) .

Before collecting the cells for measurement, divide the cells to 1x without Ca⁺²/Mg⁺²Wash with DPBS buffer (for example, Invitrogen, #14190-094), and then use Accutase hydrolase (PAA Laboratories, #L11-007) to separate the cells from the bottom of the cell culture flask (the cell culture solution and Accutase hydrolase Incubate at 37°C for 15 minutes). Followed by a CASY^TMCell counter (TCC type, Sch<img file="TW201210596A_D0025.tif" />rfe system) to determine the number of cells. According to the optimal concentration of each individual cell line, 20,000 to 30,000 cells/well/100 microliters are seeded into 96-well Corning^TM CellBIND^TMType measuring dish (light transparent black polystyrene microporous cell culture dish, #3340). Place the freshly seeded cells at room temperature for 1 hour, and then place them at 37°C, 5% carbon dioxide (CO₂) And incubate for 24 hours under 95% humidity.

The membrane potential test kit (Red^TM Bulk format part R8123 for FlIPR,MDS Analytical Technologies^TM) To prepare voltage-sensitive fluorescent dyes, the method is to dissolve the contents of the red component A bottle of a membrane potential test kit in 200 ml of extracellular buffer solution (ES-buffer solution, 120 mM chlorinated Sodium, 1 mM potassium chloride, 10 mM HEPES, 2 mM calcium chloride, 2 mM magnesium chloride, 10 mM glucose; pH 7.4). After removing the nutrient base, the cells were washed once with 200 μl of ES-buffer solution, and then 100 μl of the dye solution was added to the cells, and then the cells were incubated at room temperature and protected from light for 45 minutes.

Fluorescence measurement is based on BMG Labtech FLUOstar^TM, BMG Labtech NOVOstar^TMOr BMG Labtech POLARstar^TMPerform it with the instrument (excitation wavelength 525 nm, emission wavelength 560 nm, bottom reading mode). After incubating with a dye, add 50 microliters of the test substance of the desired concentration or 50 microliters of ES buffer solvent used as a control to the individual small holes of the measuring plate, and then place it at room temperature and protected from light Incubate for 30 minutes. Then measure the fluorescence intensity of the dye for 5 minutes, and measure the fluorescence value F of each hole at a specific constant time point₁. Then add 15 microliters of potassium chloride solution (potassium ion concentration 92 mM) into each hole. Then continue to monitor the changes in fluorescence intensity until all relevant measurement values are measured (the measurement time is mainly 5 to 30 minutes). The fluorescence value F is measured at a specific time point after adding potassium chloride₂, This is the time point when the fluorescence peak appears.

In the calculation, the fluorescence intensity F₂According to fluorescence intensity F₁Perform comparison and calibration, and measure the activity (ΔF/F) of the target compound on potassium channels as follows:

<maths><img file="TW201210596A_D0026.tif" /></maths>

To determine whether a substance has agonistic activity, for example,<img file="TW201210596A_D0027.tif" />Compared with control cells<img file="TW201210596A_D0028.tif" />Compare.<img file="TW201210596A_D0029.tif" />The measurement method is to add only the buffer solution, not the test substance, to the small hole, and determine the fluorescence intensity value F_1k, Add potassium ions as described above, and measure the fluorescence intensity value F_2k. Then calculate F as described below_2kAnd F_1k：

<maths><img file="TW201210596A_D0030.tif" /></maths>

if<img file="TW201210596A_D0031.tif" />more than the<img file="TW201210596A_D0032.tif" />When, a substance has agonistic activity on potassium ion channels:

<maths><img file="TW201210596A_D0033.tif" /></maths>

Divide the comparison<img file="TW201210596A_D0034.tif" />and<img file="TW201210596A_D0035.tif" />In addition, it can be concluded that a target compound has a stimulating effect, and when the target compound increases with the dose, it can be observed<img file="TW201210596A_D0036.tif" />The value also increases.

EC₅₀And IC₅₀Values are based on Prism v4.0<i>'</i>Software (GraphPad Soft-ware^TM) Calculated.

<b>Method II. Low-intensity flash tail test (rat)</b>

In the low-intensity flash tail test, the anti-pain effect of the compounds of the present invention on acute noxious thermal stimuli was determined according to the method described by D'Amour and Smith (J. Pharm. Exp. Ther. 72, 7479 (1941)) It is carried out by measuring the retraction and reflection action (flashing tail) of the rat's tail against a radiant heat beam (pain tester; Germany, Hofheim, Rhema Labortechnik model 2011). During the experiment, the rat was placed in a plexiglass holder, and a low-intensity radiant heat beam (48°C) was focused on the back of the rats tail root. The intensity of the stimulation is adjusted to produce an average value of the control flash tail latency before application, which is about 7 seconds. Therefore, the acute pain reflex induced by the spinal cord can also be adjusted on the spinal cord. The application of the 30-second cut-off time is to avoid damage to the organization. In this experiment, male Sprague-Dawly rats (Janvier, Le Genest St. Isle, France). Each group uses 10 rats. Before administering the compound according to the present invention, the rats were subjected to a pre-test twice in a time course of 5 minutes, and the average of these measured values was calculated as the average of the pre-test. Then, the anti-pain effect was measured 20 minutes, 40 minutes, and 60 minutes after the compound was administered orally. The anti-pain effect is characterized by a longer latency when the tail is removed. It is calculated according to the following formula and expressed as the percentage of the maximum possible effect (MPE[%]):

MPE=[(T₁-T₀)/(T₂-T₀)]*100

In it: T₀: Latent time of the control group before administration of the compound, T₁:Incubation time of control group after administration of compound, T₂: Deadline, MPE: The greatest possible effect. The analysis of variance (repeated measures ANOVA) can be used to test whether there is a statistically significant difference between the group administered with the compound according to the present invention and the group administered with the blank control. The level of significance is set at<img file="TW201210596A_D0037.tif" />0.05. To measure the dependence of the dose, administer the specific compound according to the present invention in a 3 to 5 times logarithmic increase in the dose, including a threshold dose and a maximum therapeutic dose, and then measure the ED by regression analysis₅₀value. ED₅₀Calculated based on the time of maximum therapeutic effect (usually 20 minutes after administration of the compound).

<b>Pharmacological data</b>

The pharmacological effects of the compounds according to the present invention are based on the methods described above (respectively<b>Pharmacology experiment</b>, Method I and Method II) determination.

The relevant pharmacological data are summarized in<i>Table 2</i>Among.

<tables><img file="TW201210596A_D0038.tif" /></tables>