Melanocortin-4 receptor agonist

Patent metadata

Field	Value
Publication number	US-2024190856-A1
Application number	US-202218547800-A
Country	US
Kind code	A1
Filing date	Feb 25, 2022
Priority date	Feb 26, 2021
Publication date	Jun 13, 2024
Grant date	—

Abstract

The present invention relates to a compound showing an excellent agonistic activity for a melanocortin receptor and, more specifically, to the compound of chemical formula 1, a pharmaceutical composition containing same as an active ingredient, and a use thereof. In detail, the compound of the present invention exhibits an excellent agonistic activity for melanocortin-4 receptor and thus, can be advantageously used especially for preventing or treating obesity, diabetes, inflammation, and impotence.

First claim

1 . A compound of the following Formula 1, or a pharmaceutically acceptable salt or isomer thereof:

wherein
R1 is C 2 -C 5 alkyl;
R2 is halo;
R3 is hydrogen or halo;
R4 is C 1 -C 3 alkyl; and
n is an integer of 1 or 2;
provided that n is 2, when R2 is chloride and R3 is hydrogen.

2 . The compound, or a pharmaceutically acceptable salt or isomer thereof according to claim 1 , wherein R1 is C 2 -C 4 alkyl.

3 . The compound, or a pharmaceutically acceptable salt or isomer thereof according to claim 2 , wherein the compound of Formula 1 is selected from the following group:
N-((3S,5S)-14(3S,4R)-1-(tert-butyl)-4-(2,4-difluorophenyl)pyrrolidine-3-carbonyl)-5-(morpholine-4-carbonyl)pyrrolidin-3-yl)-N-((1s,4R)-4-methylcyclohexyl)pivalamide; N-((3S,5S)-1-((3S,4R)-1-(tert-butyl)-4-(2,4-difluorophenyl)pyrrolidine-3-carbonyl)-5-(morpholine-4-carbonyl)pyrrolidin-3-yl)-N-((1s,4R)-4-methylcyclohexyl)isobutyramide; N4(3S,5S)-1-((3S,4R)-1-(tert-butyl)-4-(4-chloro-2-fluorophenyl)pyrrolidine-3-carbonyl)-5-(morpholine-4-carbonyl)pyrrolidin-3-yl)-N-((1s,4R)-4-methylcyclohexyl)isobutyramide; N4(3S,5S)-1-((3S,4R)-1-(tert-butyl)-4-(4-chloro-2-fluorophenyl)pyrrolidine-3-carbonyl)-5-(morpholine-4-carbonyl)pyrrolidin-3-yl)-N-((1s,4R)-4-methylcyclohexyl)pivalamide; N-((3S,5S)-1-((3S,4R)-1-(tert-butyl)-4-(4-chlorophenyl)pyrrolidine-3-carbonyl)-5-(morpholine-4-carbonyl)pyrrolidin-3-yl)-N-(4,4-dimethylcyclohexyl)isobutyramide; and N-((3S,5S)-1-((3S,4R)-1-(tert-butyl)-4-(4-chlorophenyl)pyrrolidine-3-carbonyl)-5-(morpholine-4-carbonyl)pyrrolidin-3-yl)-N-(4,4-dimethylcyclohexyl)pivalamide.

4 . The compound, or a pharmaceutically acceptable salt or isomer thereof according to claim 1 , wherein the pharmaceutically acceptable salt is selected from the group consisting of hydrochloric acid, sulfuric acid, nitric acid, phosphoric acid, hydrobromic acid and hydroiodic acid.

5 . The compound, or a pharmaceutically acceptable salt or isomer thereof according to claim 4 , wherein the pharmaceutically acceptable salt is hydrochloride.

6 . A melanocortin-4 receptor agonistic pharmaceutical composition comprising the compound of Formula 1, or a pharmaceutically acceptable salt or isomer thereof as defined in claim 1 , together with a pharmaceutically acceptable carrier.

7 . The melanocortin receptor agonistic pharmaceutical composition according to claim 6 , which is for the prevention or treatment of obesity.

8 . The melanocortin receptor agonistic pharmaceutical composition according to claim 6 , which is for the prevention or treatment of diabetes.

9 . The melanocortin receptor agonistic pharmaceutical composition according to claim 6 , which is for the prevention or treatment of inflammation.

10 . The melanocortin receptor agonistic pharmaceutical composition according to claim 6 , which is for the prevention or treatment of erectile dysfunction.

11 . A method for preventing or treating obesity, comprising administering to a subject in need thereof the compound of Formula 1, or a pharmaceutically acceptable salt or isomer thereof according to claim 1 .

12 . A method for preventing or treating diabetes, comprising administering to a subject in need thereof the compound of Formula 1, or a pharmaceutically acceptable salt or isomer thereof according to claim 1 .

13 . A method for preventing or treating inflammation, comprising administering to a subject in need thereof the compound of Formula 1, or a pharmaceutically acceptable salt or isomer thereof according to claim 1 .

14 . A method for preventing or treating erectile dysfunction, comprising administering to a subject in need thereof the compound of Formula 1, or a pharmaceutically acceptable salt or isomer thereof according to claim 1 .

Assignees

• Lg Chemical Ltd

Inventors

• Choi Eun Sil
• Park Hee Dong
• Kang Seung Wan
• Ahn Hye Won
• Park Deok Seong

Classifications

• C07D207/14 Primary

  Nitrogen atoms not forming part of a nitro radical · CPC title

• A61K31/5377

  not condensed and containing further heterocyclic rings, e.g. timolol · CPC title

• C07D413/14 Primary

  containing three or more hetero rings · CPC title

• A61P15/10

  for impotence · CPC title

• A61P29/00

  Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] · CPC title