IP Library › Granted Patent US 7,671,080
Granted Patent B2
US 7,671,080 · App. 11/908,640 · Granted Mar 2, 2010

1-benzylindole-2-carboxamide derivatives

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Quick Facts
Patent No.
US 7,671,080
App. No.
11/908,640
Granted
Mar 2, 2010
Kind
B2
Abstract

The present invention relates to i-benzylindole-2-carboxamide derivatives of formula I, or a pharmaceutically acceptable salt or solvate thereof. The invention also relates to pharmaceutical compositions comprising said 1-benzylindole-2-carboxamide derivatives and to their use in therapy, particularly for the treatment of obesity or nicotine dependence.

Claims (38)

1. A 1-benzylindole-2-carboxamide compound of formula I,

wherein

R 1 is H or F;

R 2 is H, halogen, C 1-4 alkyl, C 1-4 alkyloxy, C 3-6 cycloalkyl or C 3-6 cycloalkylC 1-2 alkyl, said C 1-4 alkyl and C 1-4 alkyloxy being optionally substituted with one to three halogens or R 2 is a five or six membered heteroaryl ring comprising one or two heteroatoms selected from N and O or R 2 is a five or six membered saturated heterocyclic ring comprising one or two heteroatomic moieties selected from O and NR 8 ;

R 3 is H or F;

R 4 is H, halogen, CH 3 , OCH 3 or CF 3 or together with R 5 and the phenyl ring R 4 forms an indol-4-yl or a quinolin-5-yl;

R 5 is H, halogen, C 1-4 alkyl, CF 3 , C 1-4 alkyloxy, OCF 3 or together with R 4 and the phenyl ring R 5 forms an indol-4-yl or a quinolin-5-yl;

provided that one to three of R 1 -R 5 are not H;

R 6 is one or two substituents selected from Cl, Br and CN;

R 7 is C 1-6 alkyl optionally substituted with one to three halogens, C 3-6 cycloalkyl or C 3-6 cycloalkylC 1-2 alkyl each being substituted with 1-2 substituents selected from hydroxy, hydroxyC 1-2 alkyl, C 1-4 alkyloxy and C 1-2 thioalkyloxy, or R 7 is C 4-6 oxacycloalkylC 1-2 alkyl, said C 1-2 alkyl being optionally substituted with hydroxy or hydroxyC 1-2 alkyl or R 7 is C 4-6 oxacycloalkyl and

R 8 is H, C 1-4 alkyl or C 1-4 acyl

or a pharmaceutically acceptable salt thereof.

2. The 1-benzylindole-2-carboxamide compound according to claim 1 , wherein R 1 , R 3 and R 4 are H.

3. The 1-benzylindole-2-carboxamide compound according to claim 1 , wherein R 2 is CH 3 , CH(CH 3 ) 3 , CF 3 , OCH 3 , OCH(CH 3 ) 2 , OCHF 2 , OCF 3 , Br, Cl or F.

4. The 1-benzylindole-2-carboxamide compound according to claim 1 , wherein R 5 is H, CH 3 , OCH 3 , OCF 3 , Cl or F.

5. The 1-benzylindole-2-carboxamide compound according to claim 1 , wherein R 6 is CN.

6. The 1-benzylindole-2-carboxamide compound according to claim 1 , wherein NHR 7 is a group selected from

7. A 1-benzylindole-2-carboxamide compound selected from:

5-chloro-1-(2,5-dimethylbenzyl)-1H-indole-2-carboxylic acid (3-hydroxy-2,2-dimethylpropyl)amide;

5-chloro-1-(2,5-bis-trifluoromethylbenzyl)-1H-indole-2-carboxylic acid (3-hydroxy-2,2-dimethylpropyl)amide;

5-chloro-1-(2-methoxy-5-trifluoromethoxybenzyl)-1H-indole-2-carboxylic acid (3-hydroxy-2,2-dimethylpropyl)amide;

5-cyano-1-(2-methoxy-5-trifluoromethoxybenzyl)-1H-indole-2-carboxylic acid (3-hydroxy-2,2-dimethylpropyl)amide;

5-cyano-1-(3-trifluoromethoxybenzyl)-1H-indole-2-carboxylic acid (3-hydroxy-2,2-dimethylpropyl)amide;

trans-5-cyano-1-(3-trifluoromethoxybenzyl)-1H-indole-2-carboxylic acid (2-hydroxy-cyclohexylmethyl)amide;

5-cyano-1-(5-bromo-2-methoxybenzyl)-1H-indole-2-carboxylic acid (3-hydroxy-2,2-dimethylpropyl)amide;

5-cyano-1-(5-tert-butyl-2-methoxybenzyl)-1H-indole-2-carboxylic acid (3-hydroxy-2,2-dimethylpropyl)amide;

5-cyano-1-(2-methoxy-5-methylbenzyl)-1H-indole-2-carboxylic acid (3-hydroxy-2,2-dimethylpropyl)amide;

5-cyano-1-(5-chloro-2-methoxybenzyl)-1H-indole-2-carboxylic acid (3-hydroxy-2,2-dimethylpropyl)amide;

5-cyano-1-(2-methyl-5-trifluoromethylbenzyl)-1H-indole-2-carboxylic acid (3-hydroxy-3-methylbutyl)amide;

5-cyano-1-(3-trifluoromethoxybenzyl)-1H-indole-2-carboxylic acid (1-hydroxymethylcyclopentylmethyl)amide; and

5-cyano-1-(3-trifluoromethoxybenzyl)-1H-indole-2-carboxylic acid (1-hydroxymethylcyclobutyl-methyl)amide,

or a pharmaceutically acceptable salt thereof.

8. A pharmaceutical composition comprising a 1-benzylindole-2-carboxamide compound according to claim 1 or a pharmaceutically acceptable salt thereof in admixture with one or more pharmaceutically acceptable excipients.

9. A method for the treatment or prevention of obesity, the method comprising administering to a subject in need thereof an effective amount of the 1-benzylindole-2-carboxamide compound according to claim 1 or a pharmaceutically acceptable salt thereof.

10. A method for the treatment or prevention of nicotine dependence, the method comprising administering to a subject in need thereof an effective amount of the 1-benzylindole-2-carboxamide compound according to claim 1 or a pharmaceutically acceptable salt thereof.

11. A method for the treatment or prevention of obesity, the method comprising administering to a subject in need thereof an effective amount of the 1-benzylindole-2-carboxamide compound according to claim 1 or a pharmaceutically acceptable salt thereof.

12. A method for the treatment or prevention of nicotine dependence, the method comprising administering to a subject in need thereof an effective amount of the 1-benzylindole-2-carboxamide compound according to claim 7 or a pharmaceutically acceptable salt thereof.

13. A pharmaceutical composition comprising a 1-benzylindole-2-carboxamide compound according to claim 7 or a pharmaceutically acceptable salt thereof in admixture with one or more pharmaceutically acceptable excipients.

Assignments (1)
MERGER Recorded Dec 1, 2011
From: N.V. ORGANON
To: MSD OSS B.V.
Reel/Frame 027307/0482 →