2-(Benzimidazol-1-Yl)-N-(4-phenylthiazol-2-yl) acetamide derivatives
The invention relates 2-(benzimidazol-1-yl)-N-(4-phenylthiazol-2-yl)acetamide derivatives having the general Formula I wherein R 1 is H, (C 1-4 )alkyl, (C 1-4 )alkyloxy or halogen; R 2 represents 1-3 substituents selected from H, (C 1-4 )alkyl (optionally substituted with 1 or more halogens), (C 1-4 )alkyloxy (optionally substituted with 1 or more halogens), halogen, CF 3 or cyano; or a pharmaceutically acceptable salt thereof; to pharmaceutical compositions comprising the same and to the use of said 2-(benzimidazol-1-yl)-N-(4-phenylthiazol-2-yl)acetamide derivatives in the treatment of TRPV1 mediated disorders.
1 . A 2-(benzimidazol-1-yl)-N-(4-phenylthiazol-2-yl)acetamide derivatives having the general Formula I
wherein
R 1 is H, (C 1-4 )alkyl, (C 1-4 )alkyloxy or halogen;
R 2 represents 1-3 substituents selected from H, (C 1-4 )alkyl (optionally substituted with 1 or more halogens), (C 1-4 )alkyloxy (optionally substituted with 1 or more halogens), halogen, CF 3 or cyano; or a pharmaceutically acceptable salt thereof;
with the exclusion of
2-(benzimidazol-1-yl)-N-(4-phenylthiazol-2-yl)-acetamide;
2-(benzimidazol-1-yl)-N-[4-(4-chlorophenyl)thiazol-2-yl]-acetamide;
2-(benzimidazol-1-yl)-N-[4-(4-bromophenyl)thiazol-2-yl]-acetamide;
2-(benzimidazol-1-yl)-N-[4-(4-methylphenyl)thiazol-2-yl]-acetamide; and
2-(benzimidazol-1-yl)-N-[4-(4-methoxyphenyl)thiazol-2-yl]-acetamide.
2 . The 2-(benzimidazol-1-yl)-N-(4-phenylthiazol-2-yl)acetamide derivative of claim 1 , wherein R 1 is H.
3 . The 2-(benzimidazol-1-yl)-N-(4-phenylthiazol-2-yl)acetamide derivative of claim 1 , wherein R 2 represents 1-3 substituents selected from (C 1-4 )alkyl, CF 3 , methoxy, chloro and fluoro.
4 . The 2-(benzimidazol-1-yl)-N-(4-phenylthiazol-2-yl)acetamide derivative of claim 2 , wherein R 2 represents 1-3 substituents selected from (C 1-4 )alkyl, CF 3 , methoxy, chloro and fluoro.
5 . The 2-(benzimidazol-1-yl)-N-(4-phenylthiazol-2-yl)acetamide derivative of claim 1 , which is selected from:
2-benzimidazol-1-yl-N-[4-(3,5-dichloro-2-methoxy-phenyl)-thiazol-2-yl]-acetamide;
2-benzimidazol-1-yl-N-[4-(3,4-difluorophenyl)-thiazol-2-yl]-acetamide;
2-benzimidazol-1-yl-N-[4-(5-chloro-4-methyl-2-methoxy-phenyl)-thiazol-2-yl]-acetamide;
2-benzimidazol-1-yl-N-[4-(3-chlorophenyl)-thiazol-2-yl]-acetamide;
2-benzimidazol-1-yl-N-[4-(3,4-dichlorophenyl)-thiazol-2-yl]-acetamide;
2-benzimidazol-1-yl-N-[4-(4-t-butyl-phenyl)-thiazol-2-yl]-acetamide;
2-benzimidazol-1-yl-N-[4-(3-methyl-4-chlorophenyl)-thiazol-2-yl]-acetamide;
2-benzimidazol-1-yl-N-[4-(3-fluorophenyl)-thiazol-2-yl]-acetamide;
2-benzimidazol-1-yl-N-[4-(3-methyl-4-fluorophenyl)-thiazol-2-yl]-acetamide;
2-benzimidazol-1-yl-N-[4-(3-chloro-4-fluorophenyl)-thiazol-2-yl]-acetamide;
2-benzimidazol-1-yl-N-[4-(3,5-dichloro-2-methoxyphenyl)-thiazol-2-yl]-acetamide;
2-benzimidazol-1-yl-N-[4-(4-trifluoromethylphenyl)-thiazol-2-yl]-acetamide;
2-benzimidazol-1-yl-N-[4-(2,4-dichlorophenyl)-thiazol-2-yl]-acetamide;
2-benzimidazol-1-yl-N-[4-(2,4-dimethylphenyl)-thiazol-2-yl]-acetamide; and
-2-benzimidazol-1-yl-N-[4-(4-difluoromethoxyphenyl)-thiazol-2-yl]-acetamide,
or a pharmaceutically acceptable salt thereof.
6 . A pharmaceutical composition comprising a 2-(benzimidazol-1-yl)-N-(4-phenylthiazol-2-yl)acetamide derivative of claim 1 in admixture with pharmaceutically acceptable auxiliaries.
7 . A pharmaceutical composition comprising a 2-(benzimidazol-1-yl)-N-(4-phenylthiazol-2-yl)acetamide derivative of claim 2 in admixture with pharmaceutically acceptable auxiliaries.
8 . A pharmaceutical composition comprising a 2-(benzimidazol-1-yl)-N-(4-phenylthiazol-2-yl)acetamide derivative of claim 3 in admixture with pharmaceutically acceptable auxiliaries.
9 . A pharmaceutical composition comprising a 2-(benzimidazol-1-yl)-N-(4-phenylthiazol-2-yl)acetamide derivative of claim 4 in admixture with pharmaceutically acceptable auxiliaries.
10 . A pharmaceutical composition comprising a 2-(benzimidazol-1-yl)-N-(4-phenylthiazol-2-yl)acetamide derivative of claim 5 in admixture with pharmaceutically acceptable auxiliaries.
11 . A method for treating TRPV1 mediated disorders in a subject comprising administering to the subject an effective amount of a 2-(benzimidazol-1-yl)-N-(4-phenylthiazol-2-yl)acetamide derivative of claim 1 .
12 . A method for treating TRPV1 mediated disorders in a subject comprising administering to the subject an effective amount of a 2-(benzimidazol-1-yl)-N-(4-phenylthiazol-2-yl)acetamide derivative of claim 2 .
13 . A method for treating TRPV1 mediated disorders in a subject comprising administering to the subject an effective amount of a 2-(benzimidazol-1-yl)-N-(4-phenylthiazol-2-yl)acetamide derivative of claim 3 .
14 . A method for treating TRPV1 mediated disorders in a subject comprising administering to the subject an effective amount of a 2-(benzimidazol-1-yl)-N-(4-phenylthiazol-2-yl)acetamide derivative of claim 4 .
15 . A method for treating TRPV1 mediated disorders in a subject comprising administering to the subject an effective amount of a 2-(benzimidazol-1-yl)-N-(4-phenylthiazol-2-yl)acetamide derivative of claim 5 .
16 . The method of claim 11 , wherein the TRPV1 mediated disorders are selected from the group consisting of chronic pain disorders, acute and chronic neuropathic pain, acute and chronic inflammatory pain, and respiratory diseases.
17 . The method of claim 11 , wherein the subject is a human.