Nova Patents
IL150952A

Preparation of aqueous clear solution dosage forms with bile acids

Abstract

This record has no abstract on file.

IL150952A, drawing sheet 1
Sheet 1 of 46

Term

No projected expiry on record.

  1. Priority
  2. Filed
  3. Published
  4. Today

20 claims: 7 independent, 13 dependent

  1. 1
    Claims 1. A compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof:nr 2 r 3 (¢ in which: A is a group of formula (a) or (b): (b) R 1 represents a C3-C7 carbocyclic, 008-ן alkyl, C2-C8 alkenyl or C2־Cg alkynyl group, the latter four groups being optionally substituted by one or more substituent groups independently selected from halogen atoms, -OR 4 , -NR 5 R 6 , -CONRSR 6 , -COOR 7 , -NR 8 COR 9 , -SR 10 , -SO2R 10 , -SO2NR 5 R 6 , -NR°SO2R 10 , an aryl or heteroaryl group both of which can be optionally substituted by one or more substituents Independently selected from halogen atoms, cyano, nitro, -OR 4 , -NR S R 6 , -CONR 5 R B , -COOR 7 , -NR 8 COR 10 , -SR 10 , -SO2R 10 , -SO2NR 5 R 6 , -NR 8 SO2R 10 , 006-ן alkyl or trifluoromethyl groups;one of R 2 and R 3 is hydrogen and the other is C 3 -C 4 alkyl substituted by one or more hydroxy groups;R 4 represents hydrogen, C r C 6 alkyl or a phenyl group the latter two of which may be optionally substituted by one or more substituent groups independently selected from halogen atoms, phenyl, -OR 11 and -NR 12 R 13 ;R 5 and R 6 independently represent a hydrogen atom or a C-!-Cg alkyl or phenyl group the latter two of which may be optionally substituted by one or more substituent groups independently selected from halogen atoms, phenyl, -OR 14 and -NR 15 R 16 , -CONR 15 R 16 , -NR 15 COR 16 , -SO2NR 15 R 16 , NR 1s SO2R 16 or R 5 and R 6 together with the nitrogen atom to which they are attached form a 4- to 7-membered saturated heterocyclic ring system optionally comprising a further heteroatom selected from oxygen and nitrogen atoms, which ring system may be optionally substituted by one or more substituent groups independently selected from phenyl, -OR 14 , -COOR 14 , -NR 15 R 16 , -CONR 15 R 18 , -NR 15 COR 16 , -SO2NR 18 R1 8 , NR 18 SO2R 16 or C r C 6 151132/2 ‘ ___ .. — --י---נ . .־'.’ יי ' י.''. ־- . . . , —.,! v .> I . . ΐΐί® ׳ ׳:' Wfew 'י.'.'.:׳ .'>. י י > WiW . . ’ ־. ־: ־ י י. י י י * י י' : '.^;ί ־ יי יrfוי. 1 '־' .. . .' . . . alkyl, itself optionally substituted by one or more substituents independently selected from halogen atoms and / ( -NR 15 R 1B and-OR 1 ' 7 groups;R 10 represents a 0^,(¾ alkyl or a phenyl group, each of which may be optionally substituted by one or more substituent groups Independently selected from halogen atoms, phenyl, -OR 17 and -NR 15 R 16 ;. י''.!;׳',,.!' י''.? .־'.׳ יי׳.. 'י. ׳.'.‘י;XisO, SorNR 9 ;, . '.יי. י /:¾¾. YisCR 18 R 9 ־;Z is CR 20 where R 20 represents a CrC6 alkyl or a phenyl group, each of which may be optionally substituted by one or more substituent groups independently selected from halogen atoms, phenyl, -OR 21 and -NR 22 R 23 , or an acyl group selected from CO2R 21 or CONR 22 R 23 ;and each of R 7 , R 8 , R 9 , R 11 , R 12 , R 13 , R 14 R 15 , R 15 , R 17 . R 18 . R 19 . R 21 . R 22 and R 23 independently represent a hydrogen atom, C^Cg, alkyl, or a phenyl group.
  2. 4
    A compound according to any one of claims 1 to 3 wherein one of R 2 and R 3 is hydrogen and the other is CH(CH g ) CH 2 OH, CH(Et)CH 2 OH, C(CH 3 ) 2 CH 2 OH or CH(CH 2 OH) 2 .
  3. 5
    A compound according to .any one of claims 1 to 3 wherein one of R 2 and R 3 is hydrogen and the other is CH(CH 3 ) CH 2 OH.
  4. 6
    A compound according to any one of claims 3 to 5 in the form of the (R) isomer.
  5. 7
    A compound according to any one of claims 1 to 6 wherein A is a group of formula (b) and Z = CR 20 .
  6. 12
    14. A compound of formula (I), or a pharmaceutically-acceptable salt or solvate thereof, as claimed in any one of 30 claims 1 to 9 for use in therapy.
  7. 13
    15. Use of a compound of formula (I), or a pharmaceutically acceptable salt or solvate thereof, as claimed in any one of claims 1 to 9 in the manufacture of a medicament for use in therapy. 35
  8. 14
    16. A compound of formula (IA) for use in method of treating a chemokine mediated disease wherein the chemokine binds to one or more chemokine receptors, which comprises administering to a patient a therapeutically effective amount of a compound of formula (IA), or a pharmaceutically acceptable salt or solvate thereof.:nr 2 r 3 in which: A is a group of formula (a) or (b): (IA) (a) R 1 represents a C3-C7 carbocyclic, 008-ן alkyl, C2-C6 alkenyl or C2-C6 alkynyl group, the latter four groups being optionally substituted by one or more substituent groups independently selected from halogen atoms, -OR 4 , NR 5 R 8 , -CONR 5 R 6 , -COOR 7 , -NR 8 COR 9 , -SR 10 , -SO2R 10 , -SO2NR 5 R 6 , -NR 8 SO2R 10 , an aryl or het25 eroaryl group both of which can be optionally substituted by one or more substituents independently selected from halogen, atoms, cyano, nitro, -OR 4 , -NR 5 R 6 , -CONR 5 R 8 , -COOR 7 , -NR 8 COR 10 , -SR 10 , -SO2R 10 , -SO2NR 5 R 6 , -NR 8 SO2R 10 , 006-ן alkyl or trifluoromethyl groups;R 2 represents hydrogen or a C 3 -C 7 carbocyclic group, 00 8 -ן alkyl, C 2 -C 6 alkenyl or C 2 -C 6 alkynyl group, the 30 latter four groups may be optionally substituted by one or more substituent groups independently selected from halogen atoms, -OR 4 , -NR 5 R 8 -CONR 5 R 6 , -COOR 7 , -NR 8 COR 9 , -SR 10 , -SO2R 10 , -SO2NR 5 R 6 or -NR 8 SO 2 R 9 ;R 3 represents hydrogen or C 2 -C 6 alkyl optionally substituted by one or more substituent groups independently 35 selected from halogen atoms, phenyl, -OR 10 and -NR 11 R 12 ;or R 2 and R 3 represent a 3-8 membered ring optionally containing one or more atoms selected from 0, S, NR 8 and itself optionally substituted by C^-alkyl, halogen or OR 4 ;40 R 4 represents hydrogen, 00 6 -ן alkyl or a phenyl group the latter two of which may be optionally substituted by one or more substituent groups independently selected from halogen atoms, phenyl, -OR 11 and -NR 12 R 13 ;R 5 and R 6 independently represent a hydrogen atom or a Cj-Οθ alkyl or phenyl group the latter two of which may be optionally substituted by one or more substituent groups independently selected from halogen atoms, 45 phenyl, -OR 14 and -NR 15 R 16 , -CONR 15 R 16 , -NR 15 C0R 16 , -SO2NR 15 R 1e , NR 15 SO2R 1s or R 5 and R 8 together with the nitrogen atom to which they are attached form a 4- to 7-membered saturated heterocyclic ring system optionally comprising a further heteroatom selected from oxygen and nitrogen atoms, which ring system may be optionally substituted by one or more substituent groups independently selected so from phenyl, -OR 14 , -COOR 14 , -NR 15 R 16 , -CONR 15 R 16 , -NR 15 COR 18 -SO2NR 18 R 18 , NR 15 SO2R 16 or C^Ce alkyl, itself optionally substituted by one or more substituents independently selected from halogen atoms and -NR 15 R 16 and -OR 17 groups;R 10 represents a 00 6 -ן alkyl or a phenyl group, each of which may be optionally substituted by one or more S5 substituent groups independently selected from halogen atoms, phenyl, -OR 17 and -NR 15 R 1B ;X is 0, S or NR 8 ;YisCR 18 R 19 ;Z is CR 20 where R 20 represents a 006-ן alkyl or a phenyl group, each of which may be optionally substituted by one or more substituent groups independently selected from halogen atoms, phenyl, -OR 21 and -NR 22 R 23 , or an acyl group selected from CO2R 21 or CONR 22 R 2a ;and ;each of R 7 , R 8 , R 9 , R 11 , R 12 , R 13 , R 14 R 15 > R 18 , R 17 R 18 , R 19 , R 21 > R 22 and R 23 independently represent a hydrogen atom, C r C 6 , alkyl, or a phenyl group.
  9. 16
    18. A compound according to claim 16 in a method according to claim 16 or 17 in which the chemokine receptor Is the CXCR2 receptor.
  10. 17
    19. A compound according to claims 1 to 9 or a pharmaceutically acceptable salt or solvate thereof in a method of treating an inflammatory disease in a patient suffering from, or at risk of, said disease, which comprises administering to the patient a therapeutically effective amount of a compound of formula (I), or a pharmaceutically acceptable salt or solvate thereof, as claimed in any one of claims 1 to 9.
  11. 19
    21. A method according to claim 19, wherein the disease is psoriasis.
  12. 20
    22. Use of a compound of formula (IA):nr 2 r 3 in which: A is a group of formula (a) or (b): R1 ™□resents benzvl optionally substituted by one or more substituent groups independently selected from X״ XXC“. OR<,NR־״־.CONRW -COOff. NR<COR<־. SRI־, -SO״״־, SO ־N RW. -NR 8 SO 2 R 10 , C^Cg alkyl or trifluoromethyl groups: R2 represents hydrogen or a C 3 ־C 7 carbocyclic group, C r C 8 alkyl, C 2 -C 6 alkenyl or C 2 rC 6 alkynyl group,,the latter four groups may be optionally substituted by one or more substituent groups irfdependently selected from halogen atoms, -OR 4 , -NR 5 R 6 -CONR 8 R 8 -COOR 7 , -NR 8 COR 9 , -SR™, -SO2R 10 , -SO2NR R or -NR 8 SO 2 R 9 ;r3 represents hydrogen or C 2 -C 6 alkyl optionally substituted by one or more substituent groups independently selected from halogen atoms, phenyl, -OR 10 and -NR 11 R 12 ;R 2 and R 3 represent a 3-8 membered ring optionally containing one or more atoms selected from O, S., NR 8 and itself optionally substituted by C^-alkyl, halogen or OR 4 ;R 4 represents hydrogen, C r C 6 alkyl or a phenyl group the latter two of which may be optionally by one or more substituent groups independently selected from halogen atoms, phenyl, -OR and -NR , R s and R 6 independently represent a hydrogen atom or a C^Cg alkyl or phenyl group the latter two of which may be optionally substituted by one or more substituent groups independently selected from halogen atoms, phenyl, ־OR™ and -NR 15 R 18 , -CONR 1B R 16 , -NR 15 COR™, -SO2NR' B R 18 , NR™SO2R 1b R B and R B together with the nitrogen atom to which they are attached form a 4- to 7-membered saturated in atoms, selected 071” ^'ס^י^ס״ן™, -COOR™, -NRW e , .CONR 18 R 18 , -NR 1B COR 16 , -SO2NR 15 R 16 , NR 1b SO2R 18 or C r Cg alkyl, itself optionally substituted by one or more substituents independently selected from halogen atoms and -NR15R16 anc j -OR 17 groups;R 10 represents a 00 6 - ר alkyl or a phenyl group, each of which may be optionally substituted by one or more substituent groups independently selected from halogen atoms, phenyl, -OR 17 and -NR R ;X is 0, S or NR 8 ;Y is CR 18 R 19 ;Z is CR 20 where R 2Q represents a CrCe alkyl or a phenyl group, each ,Of which may be optionally. 8 ^®Wuted by one or more substituent groups independently selected from halogen atoms, phenyl, -OR and -N or an acyl group selected from CO2R 21 or GCNR^R 23 ;and each of R 7 , R 8 , R 9 , R 11 , R 12 , R 13 . R 14 r15 . r16 > r17 ׳ r18 ׳ r19 ׳ r21 ׳ r22 and R23 iride P ender ' tl y re P reser1t a hydrogen atom, C r C e , alkyl, or a phenyl group, heterocyclic ring system optionally comprising a further heteroatom selected from oxygen and mtroge c־״tcm mav he nntinnailv substituted bv one or more substituent groups independently In the manufacture of a medicament for the treatment of a chemokine mediated disease.
Independent claims12