Heteroaryl and benzyl amide compounds
Compounds of formula I wherein R 1 , R 2 , R 4 , R 5 , A, B, D and n are as defined, and pharmaceutically acceptable salts thereof, processes for their preparation, their use as pharmaceuticals and pharmaceutical compositions comprising them.
1. A compound of formula I:
or pharmaceutically acceptable salts thereof, wherein:
R 1 is C 1 -C 6 alkyl, halo-C 1 -C 6 alkyl, halo-C 1 -C 6 alkoxy, C 3 -C 8 cycloalkyl, halo-C 3 -C 8 cycloalkyl or tri-C 1 -C 6 alkylsilyl;
R 2 is a group:
wherein:
R 6 and R 7 are independently hydrogen, C 1 -C 6 alkyl, halo-C 1 -C 6 alkyl, halogen, C 3 -C 8 cycloalkyl, OH or halo-C 1 -C 6 alkoxy;
R 8 and R 9 are independently hydrogen, C 1 -C 6 alkyl, halo-C 1 -C 6 alkyl, halogen, C 3 -C 8 cycloalkyl, OH or halo-C 1 -C 6 alkoxy;
X is CR 12 ;
Y is CH;
R 12 is halo-C 1 -C 6 alkyl, halogen, C 3 -C 8 cycloalkyl, OH or halo-C 1 -C 6 alkoxy;
R 5 is halo-C 1 -C 6 alkyl, halogen, C 3 -C 8 cycloalkyl, OH or halo-C 1 -C 6 alkoxy;
R 4 is hydrogen, C 1 -C 6 alkyl, halo-C 1 -C 6 alkyl, halogen, C 3 -C 8 cycloalkyl, OH or halo-C 1 -C 6 alkoxy;
A is CR 10 or N; wherein R 10 is hydrogen, C 1 -C 6 alkyl, halo-C 1 -C 6 alkyl, halogen, C 3 -C 8 cycloalkyl, OH or halo-C 1 -C 6 alkoxy;
B is CR 11 or N; wherein R 11 is hydrogen; or R 11 is C 1 -C 6 alkyl, halo-C 1 -C 6 alkyl, halogen, C 3 -C 8 cycloalkyl, OH or halo-C 1 -C 6 alkoxy, when at least two of R 3 , R 4 , R 5 and R 10 are not hydrogen;
D is CR 3 or N; wherein R 3 is hydrogen, C 1 -C 6 alkyl, halo-C 1 -C 6 alkyl, halogen, C 3 -C 8 cycloalkyl, OH or halo-C 1 -C 6 alkoxy;
wherein -B=A- and -A=D- are not —N═N—; and at least two of R 3 , R 4 , R 5 , R 10 and R 11 are not hydrogen; and
n is 1, 2 or 3.
2. A compound according to claim 1 wherein R 1 is C 1 -C 6 alkyl, halo-C 1 -C 6 alkyl, C 3 -C 8 cycloalkyl, halo-C 3 -C 8 cycloalkyl or tri-C 1 -C 6 alkylsilyl.
3. A compound according to claim 1 wherein R 2 is a group (a).
4. A compound according to claim 1 wherein R 2 is a group (b).
5. A compound according to claim 1 wherein A is CR 10 .
6. A compound according to claim 1 wherein:
A is N;
B is CR 11 ; and
D is CR 3 .
7. A compound according to claim 1 wherein:
A is CR 10 ;
B is CR 11 or N; and
D is CR 3 .
8. A compound according to claim 1 wherein:
R 1 is C 1 -C 6 alkyl;
R 2 is a group:
wherein:
R 8 and R 9 are independently hydrogen, halo-C 1 -C 6 alkyl, halogen, C 3 -C 8 cycloalkyl or halo-C 1 -C 6 alkoxy;
X is CR 12 , wherein R 12 is halogen or C 3 -C 8 cycloalkyl; and Y is CH;
R 5 is halogen;
R 4 is C 1 -C 6 alkyl, halo-C 1 -C 6 alkyl or halogen;
A is CR 10 ;
B is CR 11 or N;
D is CR 3 ;
R 3 is hydrogen;
R 10 is halo-C 1 -C 6 alkyl or halogen; and
R 11 is hydrogen.
9. A compound of claim 5 wherein R 2 is
10. A compound of claim 5 wherein R 2 is
11. A compound of claim 6 wherein R 2 is
12. A compound of claim 6 wherein R 2 is
13. A compound of claim 7 wherein R 2 is
14. A compound of claim 7 wherein R 2 is
15. A pharmaceutical composition comprising a compound according to claim 1 and a pharmaceutically acceptable carrier or adjuvant or mixture thereof.
16. N-(4-tert-Butyl-benzyl)-3-chloro-N-[2-(4-chloro-3-ethyl-phenyl)-ethyl]-2-fluoro-5-trifluoromethyl-benzamide or a pharmaceutically acceptable salt thereof.
17. N-(4-tert-Butyl-benzyl)-3-chloro-N-[2-(4-chloro-3-ethyl-phenyl)-ethyl]-2-fluoro-5-trifluoromethyl-benzamide.