US 2003/0195212 A1Published application

Novel melanocortin receptor agonists and antagonists

OwnerTorbjorn Lundstedt, Anna Skottner +6inventors

InventorsTorbjorn Lundstedt, Anna Skottner, Elisabeth Seifert, Igor Starchenkov, Peteris Trapencieris, Valerjans Kauss, Ivars Kalvins, Arne Boman

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Abstract

The present invention relates to novel aromatic amines of general formula (I) and to the use of these amines for the treatment of obesity, anorexia, inflammation, mental disorders an other diseases associated with the melanocortin receptors or related systems, e.g. the melanocyte stimulating hormones.

Claims45

Dependent claims

A compound of general formula (I):

9
wherein E and F are independently a saturated or unsaturated, acyclic hydrocarbon group having 1, 2, 3, 4 or 5 carbon atoms;
wherein X and Y are independently methylene;
one of X and Y are absent (i.e. a single bond);
or X can be:
10
and/or Y can be:
11
wherein M and Q are independently a saturated or unsaturated straight or branched chain acyclic hydrocarbon group having 1, 2, 3, 4, 5 or 6 carbon atoms;
or M and/or Q are absent (i.e. M and/or Q are single bonds);
R8, R9 and R10 are selected independently from hydrogen and the following:
12
wherein P and D are independently a saturated or unsaturated, straight or branched chain acyclic hydrocarbon group having 1, 2, 3, 4, 5 or 6 carbon atoms, preferably 1, 2, 3, 4 or 5 carbon atoms;
or D is absent (i.e. D is a single bond);
R4 is hydroxy, methyl, cyclohexyl, cyclopentyl, aminoguanidine, guanidine, carboxylic,
or R4 is selected from:
13
wherein R4 in R8, R9 and R10 may be the same or different.
R5 and R6 are the same or different and are selected from hydrogen, lower alkyl such as methyl, ethyl, propyl, iso-propyl, butyl, t-butyl, pentyl, t-pentyl, iso-pentyl, cyclopropyl, cyclobutyl, cyclopentyl cyclohexyl and hexyl;
R7 is selected from:
14
or R7 may be any one of R5 and R6;
A and B are the same or different and are selected from the following:
15
wherein R1, R2 and R3 are the same or different and are selected from hydrogen, halogen, alkyl having 1 to 5 carbon atoms, electron donor groups such as alkoxy having 1-5 carbon atoms or hydroxy, electron acceptor groups selected from cyano. nitro, trifluoroalkyl or amide;
and a pharmacologically active salt thereof.

23 more elements

A compound having one of the following formulae:

1:2 N-Cyclohexyl-2-[[2-(1H-indol-3-yl)-ethyl]-(2-naphthalen-1-yl-acetyl)-amino]-2-naphthalen-1-yl-acetamide
1:3 1H-Indole-2-carboxylic acid [(4-cyano-phenyl)-cyclohexylcarbamoyl-methyl]-[2-(1H-indol-3-yl)-ethyl]-amide
1:4 N-Cyclohexyl-2-{(2-1H-indol-3-yl-acetyl)-[2-(1H-indol-3-yl)-ethyl]-amino}-2-pyridin-3-yl-acetamide
1:5 2-(4-Chloro-phenyl)-N-cyclohexyl-2-[[2-(1H-indol-3-yl)-ethyl]-(2-naphthalen-2-yl-acetyl)-amino]-acetamide
1:6 N-(3-Amino-propyl)-3-(1H-indol-3-yl)-2-(2-naphthalen-1-yl-acetylamino)-propionamide
1:7 N-(3-Amino-propyl)-3-(1H-indol-3-yl)-2-(2-naphthalen-2-yl-acetylamino)-propionamide
1:8 N-(3-Amino-propyl)-3-(1H-indol-3-yl)-2-(2-1H-indol-3-yl-acetylamino)-propionamide
1:9 N-(3-Guanidino-propyl)-3-(1H-indol-3-yl)-2-(2-naphthalen-2-yl-acetylamino)-propionamide
1:10 N-(3-Amino-propyl)-3-(1H-indol-3-yl)-2-(3-1H-indol-3-yl-propionylamino)-propionamide
1:11 N-[1-(3-Amino-propylcarbamoyl)-2-(1H-indol-3-yl)-ethyl]4-(1H-indol-3-yl)-butyramide
1:12 N-(3-Guanidino-propyl)-3-(1H-indol-3-yl)-2-(2-1H-indol-3-yl-acetylamino)-propionamide
1:13 N-Cyclohexyl-2-[[2-(1H-indol-3-yl)-ethyl]-(3-phenyl-propionyl)-amino]4-phenyl-butyramide
1:14 N-Benzyl-N-(4-guanidino-butyl)-3-(1H-indol-3-yl)-2-(2-1H-indol-3-yl-acetylamino)-propionamide
1:15 N-[1-[Benzyl-(4-guanidino-butyl)-carbamoyl]-2-(1H-indol-3-yl)-ethyl]-4-phenyl-butyramide
1:16 3-Benzo[1,3]dioxol-5-yl-N-[1-[benzyl-(4-guanidino-butyl)-carbamoyl]-2-(1H-indol-3-yl)-ethyl]-propionamide
1:17 N-Benzyl-N-(4-guanidino-butyl)-3-(1H-indol-3-yl)-2-(2-naphthalen-2-yl-acetylamino)-propionamide
1:18 N-[(4-Cyano-phenyl)-cyclohexylcarbamoyl-methyl]-N-(2-dimethylamino-ethyl)-3-(1H-indol-3-yl)-propionamide
1:19 N-Benzhydryl-2-(2-methyl-1H-indol-3-yl)-acetamide
1:20 N-(1,2-Diphenyl-ethyl)-4-(1H-indol-3-yl)-butyramide
1:21 N-(1,2-Diphenyl-ethyl)-2,6-dimethoxy-nicotinamide
1:22 N-Benzhydryl-2,6-dimethoxy-nicotinamide
1:23 2-(2-Bromo-phenyl)-N-cyclohexyl-2-[(2-dimethylamino-ethyl)-(2-1H-indol-3 -yl-acetyl)-amino]-acetamide
1:24 2-[[2-(5-Bromo-1H-indol-3-yl)-acetyl]-(2-dimethylamino-ethyl)-amino]-2-(2-bromo-phenyl)-N-cyclohexyl-acetamide
1:25 N-Benzhydryl-2-chloro-6-methyl-nicotinamide
2:2 4-Guanidino-N-[2-(1H-indol-3-yl)-1-phenethylcarbamoyl-ethyl]-butyramide
2:3 4-Guanidino-N-[2-(1H-indol-3-yl)-1-(3-phenyl-propylcarbamoyl)-ethyl]-butyramide
2:4 4-Guanidino-N-{2-(1H-indol-3-yl)-1-[2-(1H-indol-3-yl)-ethylcarbamoyl]-ethyl}-butyramide
2:5 4-Guanidino-N-{2-(1H-indol-3-yl)-1-[2-(1H-indol-3-yl)-ethylcarbamoyl]-ethyl}-butyramide
2:6 N-[1-(9-Ethyl-9H-carbazol-3-ylcarbamoyl)-2-(1H-indol-3-yl)-ethyl]4-guanidino-butyramide
2:7 4-Amino-N-[1-(9-ethyl-9H-carbazol-3-ylcarbamoyl)-2-(1H-indol-3-yl)-ethyl]-butyramide
2:8 4-Amino-N-[2-(1H-indol-3-yl)-1-(naphthalen-2-ylcarbamoyl)-ethyl]-butyramide
2:9 N-[2-(1H-Indol-3-yl)-1-(naphthalen-2-ylcarbamoyl)-ethyl]4-(3-methyl-thioureido)-butyramide
2:10 2-(3-Guanidino-propionylamino)-3-(1H-indol-3-yl)-N-[2-(1H-indol-3-yl)-ethyl]-propionamide
2:11 4-Amino-N-[1-(9-ethyl-9H-carbazol-3-ylcarbamoyl)-2-(5-hydroxy-1H-indol-3-yl)-ethyl]-butyramide
2:12 4-Amino-N-[2-(1H-indol-3-yl)-1-(4-phenyl-butylcarbamoyl)-ethyl]-butyramide
2:13 4-Amino-N-[2-(5-hydroxy-1H-indol-3-yl)-1-(4-phenyl-butylcarbamoyl)-ethyl]-butyramide
2:14 2-(3-Amino-propionylamino)-N-(9-ethyl-9H-carbazol-3-yl)-3-(1H-indol-3-yl)-propionamide
2:15 4-Amino-N-[2-(5-hydroxy-1H-indol-3-yl)-1-phenethylcarbamoyl-ethyl]-butyramide
2:16 4-Amino-N-[1-[2-(3,4-dimethoxy-phenyl)-ethylcarbamoyl]-2-(5-hydroxy-1H-indol-3-yl)-ethyl]-butyramide
2:17 4-Amino-N-[2-(5-methyl-1H-indol-3-yl)-1-phenethylcarbamoyl-ethyl]-butyramide
2:18 2-(3-Amino-propionylamino)-3-(1H-indol-3-yl)-N-phenethyl-propionamide
2:19 2-(3-Amino-propionylamino)-3-(1H-indol-3-yl)-N-[2-(1H-indol-3-yl)-ethyl]-propionamide
2:20 4-Amino-N-[1-benzylcarbamoyl-2-(1H-indol-3-yl)-ethyl]-butyramide
2:21 Piperidine4-carboxylic_acid—[1-(9-ethyl-9H-carbazol-3-ylcarbamoyl)-2-(1H-indol-3-yl)-ethyl]-amide
2:22 Piperidine4-carboxylic_acid—{2-(1H-indol-3-yl)-1-[2-(1H-indol-3-yl)-ethylcarbamoyl]-ethyl}-amide
2:23 2-(3-Amino-propionylamino)-N-[2-(3,4-dimethoxy-phenyl)-ethyl]-3-(1H-indol-3-yl)-propionamide
2:24 Piperidine-4-carboxylic_acid—[2-(1H-indol-3-yl)-1-phenethylcarbamoyl-ethyl]-amide
2:25 2-(3-Amino-propionylamino)-3-(1H-indol-3-yl)-N-(3-phenyl-propyl)-propionamide
2:26 4-Amino-N-[1-[(benzo[1,3]dioxol-5-ylmethyl)-carbamoyl]-2-(1H-indol-3-yl)-ethyl]-butyramide
2:27 2-(3-Amino-propionylamino)-3-(1H-indol-3-yl)-N-(4-phenyl-butyl)-propionamide
2:28 4-Amino-N-[2-(1H-indol-3-yl)-1-(quinolin-4-ylcarbamoyl)-ethyl]-butyramide
2:29 4-Amino-N-[2-(1H-indol-3-yl)-1-(pyridin-2-ylcarbamoyl)-ethyl]-butyramide
2:30 4-Amino-N-[1-(indan-2-ylcarbamoyl)-2-(1H-indol-3-yl)-ethyl]-butyramide
2:31 4-Amino-N-[2-(1H-indol-3-yl)-1-(3,4,5-trimethoxy-benzylcarbamoyl)-ethyl]-butyramide
2:32 4-Amino-N-{2-(1H-indol-3-yl)-1-[(naphthalen-2-ylmethyl)-carbamoyl]-ethyl}-butyramide
2:33 4-Amino-N-[1-(1,2-diphenyl-ethylcarbamoyl)-2-(1H-indol-3-yl)-ethyl]-butyramide
2:34 4-Amino-N-[2-(1H-indol-3-yl)-1-(pyridin-3-ylcarbamoyl)-ethyl]-butyramide
2:35 4-Amino-N-[2-(1H-indol-3-yl)-1-(quinolin-6-ylcarbamoyl)-ethyl]-butyramide
2:36 4-Amino-N-[2-(1H-indol-2-yl)-1-(4-trifluoromethyl-phenylcarbamoyl)-ethyl]-butyramide
2:37 4-Amino-N-[1-(9-ethyl-9H-carbazol-3-ylcarbamoyl)-2-phenyl-ethyl]-butyramide
2:38 4-Amino-N-{2-(1H-indol-3-yl)-1-[(naphthalen-1-ylmethyl)-carbamoyl]-ethyl}-butyramide
2:39 4-Amino-N-[1-(benzyl-phenyl-carbamoyl)-2-(1H-indol-3-yl)-ethyl]-butyramide
2:40 4-Amino-N-[2-(1H-indol-3-yl)-1-(4-trifluoromethyl-phenylcarbamoyl)-ethyl]-butyramide
2:41 N-(1,2-Diphenyl-ethyl)-2-(2-methyl-1H-indol-3-yl)-acetamide
2:42 1H-Indole-3-carboxylic acid (1,2-diphenyl-ethyl)-amide
2:43 N-Benzhydryl4-(1H-indol-3-yl)-butyramide
2:44 1H-Indole-3-carboxylic acid benzhydryl-amide
2:45 N-Benzhydryl-2-(5-methoxy-2-methyl-1H-indol-3-yl)-acetamide
2:46 N-(1,2-Diphenyl-ethyl)-2-(5-methoxy-2-methyl-1H-indol-3-yl)-acetamide
2:47 N-Benzhydryl-nicotinamide
2:48 N-(1,2-Diphenyl-ethyl)-nicotinamide
2:49 2-Chloro-N-(1,2-diphenyl-ethyl)-6-methyl-nicotinamide
2:50 4-Amino-N-[1-(benzhydryl-carbamoyl)-2-(1H-indol-3-yl)-ethyl]-butyramide
2:51 4-Amino-N-[1-(1,2-diphenyl-ethylcarbamoyl)-2-(1H-indol-3-yl)-ethyl]-butyramide
or a pharmaceutically acceptable salt thereof.

72 more elements

Dependencies are inferred from the claim text.

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Abstract