Granted Patent B2

US 8,389,547 · App. 12/298,394 · Granted Mar 5, 2013

Abstract

Claims (28)

1. A compound of formula I:

or a pharmaceutically acceptable salt thereof; wherein:

p is 0 or 1;

q is 0, 1, 2 or 3;

V represents a carbon atom whose remaining valencies are satisfied via bonding to H, R 2 or X-Z or to any combination thereof;

W represents a carbon atom whose remaining valencies are satisfied via bonding to H, R 2 or X-Z or to any combination thereof;

X represents a bond or C(R 1 ) 2 or CH 2 C(R 1 ) 2 ;

Y represents a bond or CH 2 or CH 2 CH 2 ;

Z represents CO 2 H or a tetrazole ring;

each R 1 independently represents H or a non-aromatic hydrocarbon group of up to 6 carbon atoms; or the two R 1 groups complete a C 3-6 alicyclic group;

R 2 represents a non-aromatic hydrocarbon group of up to 6 carbon atoms;

R 3 and R 4 each represents H, or when V and W each represents a carbon atom, R 3 and R 4 may together represent a CH 2 CH 2 bridge;

each R 5 independently represents halogen, C 1-6 alkyl bearing 0-3 fluorine substituents, C 1-6 alkoxy bearing 0-3 fluorine substituents, C 2-6 alkenyl or Si(C 1-4 alkyl) 3 ; and

R 6 and R 7 independently represent linear or branched hydrocarbon groups each containing up to 10 carbon atoms optionally bearing a substituent selected from perfluoroC 1-4 alkyl, C 3-6 alicyclic, hydroxyC 3-6 alicyclic, OH, C 1-4 alkoxy, phenyl or benzyloxy, where said C 1-4 alkoxy, phenyl and benzyloxy substituents themselves bear 0-3 substituents selected from halogen, C 1-4 alkyl, C 1-4 alkoxy and perfluoroC 1-4 alkyl.

2. A compound according to claim 1 or a pharmaceutically acceptable salt thereof wherein R 3 and R 4 both represent H.

3. A compound according to claim 1 or a pharmaceutically acceptable salt thereof wherein (R 5 ) q represents 2-CF 3 , 3-CF 3 , 4-CF 3 , 2,4-di(CF 3 ), 2-F-4-CF 3 , 4-OCF 3 , 4-allyl, 4-n-propyl, 4-isopropyl or 4-tert-butyl.

4. A compound according to claim 1 which is a compound of formula III:

or a pharmaceutically acceptable salt thereof; wherein:

Y is a bond and p is 0.

5. A compound according to claim 1 which is a compound of formula IV:

or a pharmaceutically acceptable salt thereof; wherein:

R a represents H, halogen or CF 3 .

6. A compound according to claim 5 or a pharmaceutically acceptable salt thereof wherein the substituted phenyl group attached to the 2-position of the piperidine ring and the CH 2 CO 2 H group attached in the 4-position are in the cis-configuration with respect to the piperidine ring.

7. A compound according to claim 1 or a pharmaceutically acceptable salt thereof wherein one or both of R 6 and R 7 represent unsubstituted hydrocarbon groups which may be the same or different.

8. A compound according to claim 7 or a pharmaceutically acceptable salt thereof wherein one or both of R 6 and R 7 are independently selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, t-butyl, 3-methylbutyl, 2-ethylbutyl, 4-methylpentyl, 3,3,-dimethylbutyl, 3-methyl-1-butenyl, 3-methyl-3-butenyl, 3-methyl-3-butene- 1-ynyl, 4-methyl-1-pentynyl and 3,3-dimethyl- 1-butynyl.

9. A compound according to claim 1 or a pharmaceutically acceptable salt thereof wherein one or both of R 6 and R 7 bears a substituent selected from perfluoroC 1-4 alkyl, C 3-6 alicyclic, hydroxyC 3-6 alicyclic, OH, C 1-4 alkoxy, phenyl or benzyloxy, where said C 1-4 alkoxy, phenyl and benzyloxy substituents themselves bear 0 to 3 substituents selected from halogen, C 1-4 alkyl, C 1-4 alkoxy and perfluoroC 1-4 alkyl.

10. A compound according to claim 9 or a pharmaceutically acceptable salt thereof wherein one or both of R 6 and R 7 is selected from 2,2,2-trifluoroethyl, 3,3,3-trifluoropropyl, 4,4,4-trifluorobutyl, 2-phenylethyl, 3-methoxyprop-1-ynyl, cyclohexylethynyl, 1-methyl-3,3,3-trifluoropopyl, 2,2,3,3,3-pentafluoropropyl, hydroxymethyl, isopropoxymethyl, difluoromethoxymethyl, 4-benzyloxy-3-methyl-l-butynyl, 4-hydroxy-3-methyl-l-butynyl, 4-benzyloxy-3-methylbutyl, 4-hydroxy-3-methylbutyl, 2-cyclopropylethyl, 2-cyclohexylethyl, 2-(cyclohexen-1-yl)ethyl, 2-(1-hydroxycyclopentyl)ethyl, 2-(1-hydroxycyclohexyl)ethyl, 2-(3-fluorophenyl)ethyl, 2-(2,4-difluorophenyl)ethyl, 2-(3-methylphenyl)ethyl, 2-(4-t-butylphenyl)ethyl, 2-[3-(trifluoromethyl)phenyl]ethyl and2-[4-(trifluoromethyl)phenyl]ethyl.

11. A pharmaceutical composition comprising a compound according to claim 1 or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier.

Assignments (8)