Indole derivatives

Patent metadata

Field	Value
Publication number	US-2018093989-A1
Application number	US-201615563259-A
Country	US
Kind code	A1
Filing date	Apr 14, 2016
Priority date	Apr 15, 2015
Publication date	Apr 5, 2018
Grant date	—

Abstract

The present invention relates to compounds of the general form (I). The present invention relates to new substituted diazepino-indole derivatives of the general formula (I), and to pharmaceutically acceptable salts thereof as well as to pharmaceutical compositions comprising such compounds, to new intermediate thereof as well as to the use of such compounds in treatment or prevention of disorders associated with melanin-concentrating hormone receptor 1 activity.

First claim

1 . Compounds of the general formula (I)

wherein
the meaning of A is CH or nitrogen atom;
the meaning of R is hydrogen or halogen atom or C 1 -C 6 straight or branched chain alkyl group;
the meaning of R 1 is hydrogen or halogen atom or
C 1 -C 6 straight or branched chain alkyl group, or
C 1 -C 6 straight or branched chain alkoxy group, or
mono- or polyhalogenated C 1 -C 6 straight or branched chain haloalkyl group;

the meaning of R 2 is hydrogen or halogen atom or
C 1 -C 6 straight or branched chain alkyl group, or
C 1 -C 6 straight or branched chain alkoxy group or
mono- or polyhalogenated C 1 -C 4 straight or branched chain haloalkyl group;

the meaning of R 3 is hydrogen or
C 1 -C 6 straight or branched chain alkyl group, optionally substituted with C 3 -C 6 cycloalkyl group, or
mono- or polyhalogenated C 1 -C 6 straight or branched chain haloalkyl group; or
C 3 -C 6 cycloalkyl group, or
C 1 -C 6 straight or branched chain alkanoyl group

and/or salts, and/or geometric isomers, and/or stereoisomers, and/or diastereomers, and/or hydrates, and/or solvates, and/or polymorph modifications thereof.

2 . Compounds of the general formula (I) according to claim 1 characterized by that the meaning of R 3 is:
hydrogen atom, or
C 1 -C 4 straight or branched chain alkyl group, optionally substituted with C 3 -C 6 cycloalkyl group, or
C 3 -C 6 cycloalkyl group, or
C 1 -C 4 straight or branched chain alkanoyl group, or
acetyl group.

3 . Compounds of the general formula (I) according to claim 1 or 2 characterized by that the meaning of R 3 is:
hydrogen atom,
C 1 -C 4 straight or branched chain alkyl group, optionally substituted with C 3 -C 4 cycloalkyl group or fluorine atom, or
C 3 -C 4 cycloalkyl group.

4 . Compounds of the general formula (I) according to any of claims 1 - 3 characterized by that the meaning of R 3 is methyl, ethyl, isopropyl, cyclopropylmethyl, cyclobutyl or fluoroethyl group.

5 . Compounds of the general formula (I) according to any of claims 1 - 4 characterized by that the meaning of R 3 is isopropyl or cyclopropylmethyl.

6 . Compounds of the general formula (I) according to any of claims 1 - 5 characterized by that the meaning of R 2 is hydrogen or halogen atom, trifluoromethyl or C 1 -C 3 alkyl group.

7 . Compounds of the general formula (I) according to any of claims 1 - 6 characterized by that the meaning of R 2 is hydrogen, fluorine or chlorine atom, or methyl group.

8 . Compounds of the general formula (I) according to any of claims 1 - 7 characterized by that the meaning of R 2 is hydrogen atom.

9 . Compounds of the general formula (I) according to any of claims 1 - 8 characterized by that the meaning of R 1 is
hydrogen or halogen atom, or
C 1 -C 4 straight or branched chain alkyl group, optionally mono- or polyhalogenated; or
C 1 -C 3 alkoxy group.

10 . Compounds of the general formula (I) according to any of claims 1 - 9 characterized by that the meaning of R 1 is hydrogen, fluorine or chlorine atom, or methoxy or trifluoromethyl group.

11 . Compounds of the general formula (I) according to any of claims 1 - 10 characterized by that the meaning of R 1 is hydrogen, fluorine or chlorine atom.

12 . Compounds of the general formula (I) according to any of claims 1 - 11 characterized by that the meaning of R is hydrogen atom.

13 . Compounds of the general formula (I) according to any of claims 1 - 12 characterized by that the meaning of R is hydrogen atom and the meaning of R 1 is chlorine atom

14 . Compounds of the general formula (I) according to any of claims 1 - 13 characterized by that the meaning of A is nitrogen atom

15 . Compounds of the general formula (I) according to any of claims 1 - 14 characterized by that the meaning of A is CH.

16 . The following compounds according to claim 1 and pharmaceutically acceptable salts thereof:
4-[(5-chloro-pyridin-2-yl)methoxy]-1-{1H,2H,3H,4H,5H-[1,4]diazepino[1,7-a]indol-9-yl}-1,2-dihydropyridin-2-one
4-[(5-chloro-pyridin-2-yl)methoxy]-1-{3-methyl-1H,2H,3H,4H,5H-[1,4]diazepino[1,7-a]indol-9-yl}-1,2-dihydropyridin-2-one
4-[(5-chloro-pyridin-2-yl)methoxy]-1-{3-ethyl-1H,2H,3H,4H,5H-[1,4]diazepino[1,7-a]indol-9-yl}-1,2-dihydropyridin-2-one
4-[(5-fluoro-pyridin-2-yl)methoxy]-1-[3-(propan-2-yl)-1H,2H,3H,4H,5H-[1,4]diazepino[1,7-a]indol-9-yl]-1,2-dihydropyridin-2-one
4-(benzyloxy)-1-[3-(propan-2-yl)-1H,2H,3H,4H, 5H-[1,4]diazepino[1,7-a]indol-9-yl]-1,2-dihydropyridin-2-one
4-[(5-chloro-pyridin-2-yl)methoxy]-1-[3-(propan-2-yl)-1H,2H,3H,4H,5H-[1,4]diazepino[1,7-a]indol-9-yl]-1,2-dihydropyridin-2-one
4-[(4-fluoro-phenyl)methoxy]-1-[3-(propan-2-yl)-1H,2H,3H,4H,5H-[1,4]diazepino[1,7-a]indol-9-yl]-1,2-dihydropyridin-2-one
4-[(4-chloro-phenyl)methoxy]-1-[3-(propan-2-yl)-1H,2H,3H,4H,5H-[1,4]diazepino[1,7-a]indol-9-yl]-1,2-dihydropyridin-2-one
4-[(2-fluoro-phenyl)methoxy]-1-[3-(propan-2-yl)-1H,2H,3H,4H,5H-[1,4]diazepino[1,7-a]indol-9-yl]-1,2-dihydropyridin-2-one
1-[11-chloro-3-(propan-2-yl)-1H,2H,3H,4H,5H-[1,4]diazepino[1,7-a]indol-9-yl]-4-[(5-chloro-pyridin-2-yl)methoxy]-1,2-dihydropyridin-2-one
4-(benzyloxy)-1-[11-chloro-3-(propan-2-yl)-1H,2H,3H,4H,5H-[1,4]diazepino[1,7-a]indol-9-yl]-1,2-dihydropyridin-2-one
4-[(5-chloro-pyridin-2-yl)methoxy]-1-[3-(cyclopropylmethyl)-1H,2H,3H,4H,5H-[1,4]diazepino[1,7-a]indol-9-yl]-1,2-dihydropyridin-2-one
4-[(5-chloro-pyridin-2-yl)methoxy]-1-{3-cyclopropyl-1H,2H,3H,4H, 5H-[1,4]diazepino[1,7-a]indol-9-yl}-1,2-dihydropyridin-2-one
4-[(5-chloro-pyridin-2-yl)methoxy]-1-{3-cyclobutyl-1H,2H,3H,4H,5H-[1,4]diazepino[1,7-a]indol-9-yl}-1,2-dihydropyridin-2-one
4-[(5-chloro-pyridin-2-yl)methoxy]-1-[1-methyl-3-(propan-2-yl)-1H,2H,3H,4H,5H-[1,4]diazepino[1,7-a]indol-9-yl]-1,2-dihydropyridin-2-one

17 . Use of a compound according to any of claims 1 - 16 for treatment and/or prevention of a disorder or condition associated with melanin concentrating hormone receptor 1 activity.

18 . Use of a compound according to any of claims 1 - 16 for treatment and/or prevention of obesity, obesity related comorbid conditions and complications, diabetes, metabolic disorders, psychiatric diseases accompanied by weight gain, inflammatory bowel diseases, affective dysfunctions, anxiety disorders, sleep-wake cycle disorders, substance abuse and addictive disorders.

19 . Use of a compound according to any of claims 1 - 16 for manufacturing a pharmaceutical composition.

20 . A pharmaceutical composition comprising a compound according to any of claims 1 - 16 together with excipients and carrier materials generally used for manufacturing pharmaceutical compositions.

21 . Use of a pharmaceutical composition according to claim 20 for treatment and/or prevention of a disorder or condition associated with melanin concentrating hormone receptor 1 activity.

22 . Use of a pharmaceutical composition according to claim 21 for treatment and/or prevention of obesity, obesity related comorbid conditions and complications, diabetes, metabolic disorders, psychiatric diseases accompanied by weight gain, inflammatory bowel diseases, affective dysfunctions, anxiety disorders, sleep-wake cycle disorders, substance abuse and addictive disorders.

23 . Method of treating and/or preventing a disease or condition associated wi

Assignees

• Richter Gedeon Nyrt

Inventors

• Beke Gyula
• Éles János
• Boros András
• Farkas Sándor
• Keserü György Miklós

Classifications

• A61P3/10

  for hyperglycaemia, e.g. antidiabetics · CPC title

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P25/22

  Anxiolytics · CPC title

• A61P3/00

  Drugs for disorders of the metabolism (of the blood or the extracellular fluid A61P7/00) · CPC title

• A61P25/20

  Hypnotics; Sedatives · CPC title