Heterocyclic compound

Patent metadata

Field	Value
Publication number	US-11713311-B2
Application number	US-202117550173-A
Country	US
Kind code	B2
Filing date	Dec 14, 2021
Priority date	Jul 28, 2017
Publication date	Aug 1, 2023
Grant date	Aug 1, 2023

Abstract

Provided is a heterocyclic compound that can have an antagonistic action on an NMDA receptor containing the NR2B subunit, and is expected to be useful as a prophylactic or therapeutic agent for major depression, bipolar disorder, migraine, pain, peripheral symptoms of dementia and the like. A compound represented by the formula (I):

wherein each symbol is as described in the DESCRIPTION, or a salt thereof.

First claim

The invention claimed is:

1. A method for antagonizing an NMDA receptor containing an NR2B subunit in a mammal, comprising administering to the mammal an effective amount of a compound chosen from:
N-((2,5-dimethyl-2H-indazol-4-yl)methyl)-4-(trifluoromethoxy)benzamide;
N-((5-methyl-1H-indazol-4-yl)methyl)-4-(trifluoromethoxy)benzamide;
N-((5-methyl-1H-benzimidazol-4-yl)methyl)-4-(trifluoromethoxy)benzamide;
N-((5-iodo-1H-indazol-4-yl)methyl)-4-(trifluoromethoxy)benzamide;
4-(trifluoromethoxy)-N-((5-(trifluoromethyl)-1H-indazol-4-yl)methyl)benzamide;
N-((5-methoxy-1H-indazol-4-yl)methyl)-4-(trifluoromethoxy)benzamide;
N-(1H-indazol-4-ylmethyl)-4-(trifluoromethoxy)benzamide;
3,5-difluoro-4-methoxy-N-((6-methoxy-1-methyl-1H-benzimidazol-7-yl)methyl)benzamide;
3,5-difluoro-N-((6-methoxy-1-methyl-1H-benzimidazol-7-yl)methyl)-4-methylbenzamide;
5-fluoro-6-methoxy-N-((6-methoxy-1-methyl-1H-benzimidazol-7-yl)methyl)nicotinamide;
3-fluoro-4-methoxy-N-((6-methoxy-1-methyl-1H-benzimidazol-7-yl)methyl)benzamide;
N-((6-methoxy-1-methyl-1H-benzimidazol-7-yl)methyl)-4-(trifluoromethoxy)benzamide;
3-fluoro-N-((6-methoxy-1-methyl-1H-benzimidazol-7-yl)methyl)-4-(trifluoromethyl)benzamide;
3-fluoro-N-((6-methoxy-1-methyl-1H-benzimidazol-7-yl)methyl)-4-methylbenzamide;
4-chloro-3,5-difluoro-N-((6-methoxy-1-methyl-1H-benzimidazol-7-yl)methyl)benzamide;
N-((5-ethyl-1H-indazol-4-yl)methyl)-3,5-difluoro-4-methoxybenzamide;
N-((5-cyclopropyl-1H-indazol-4-yl)methyl)-3,5-difluoro-4-methoxybenzamide;
3-chloro-4,5-difluoro-N-((6-methoxy-1-methyl-1H-benzimidazol-7-yl)methyl)benzamide;
N-((1,6-dimethyl-1H-benzimidazol-7-yl)methyl)-5-fluoro-6-methoxynicotinamide;
N-((6-cyclopropyl-1-methyl-1H-benzimidazol-7-yl)methyl)-5-fluoro-6-methoxynicotinamide;
N-((6-cyclopropyl-1-methyl-1H-benzimidazol-7-yl)methyl)-3,5-difluoro-4-methoxybenzamide;
N-((6-ethyl-1-methyl-1H-benzimidazol-7-yl)methyl)-5-fluoro-6-methoxynicotinamide;
N-((6-ethyl-1-methyl-1H-benzimidazol-7-yl)methyl)-3,5-difluoro-4-methoxybenzamide;
3,5-difluoro-N-((6-methoxy-1-methyl-1H-benzimidazol-7-yl)methyl)-4-(trifluoromethyl)benzamide;
N-((1,6-dimethyl-1H-benzimidazol-7-yl)methyl)-3,5-difluoro-4-methoxybenzamide;
N-((1,6-dimethyl-1H-benzimidazol-7-yl)methyl)-3,5-difluoro-4-(trifluoromethyl)benzamide;
N-((6-methoxy-1-methyl-1H-benzimidazol-7-yl)methyl)-5-methylthiophene-3-carboxamide;
5-chloro-N-((6-methoxy-1-methyl-1H-benzimidazol-7-yl)methyl)thiophene-3-carboxamide;
5-ethyl-N-((6-methoxy-1-methyl-1H-benzimidazol-7-yl)methyl)thiophene-3-carboxamide;
N-((1,6-dimethyl-1H-benzimidazol-7-yl)methyl)-3-fluoro-4-(trifluoromethoxy)benzamide;
3-chloro-4-(difluoromethoxy)-N-((1,6-dimethyl-1H-benzimidazol-7-yl)methyl)benzamide;
N-((6-methoxy-1-methyl-1H-benzimidazol-7-yl)methyl)-5-methylthiophene-2-carboxamide;
N-((6-methoxy-1-methyl-1H-benzimidazol-7-yl)methyl)-2-(2-thienyl)acetamide;
3-chloro-4-methoxy-N-((6-methoxy-1-methyl-1H-benzimidazol-7-yl)methyl)benzamide;
4-methoxy-N-((6-methoxy-1-methyl-1H-benzimidazol-7-yl)methyl)-3,5-dimethylbenzamide;
5-chloro-N-((6-methoxy-1-methyl-1H-benzimidazol-7-yl)methyl)thiophene-2-carboxamide;
3-chloro-4-fluoro-N-((6-methoxy-1-methyl-1H-benzimidazol-7-yl)methyl)benzamide;
3-chloro-N-((6-methoxy-1-methyl-1H-benzimidazol-7-yl)methyl)-4-methylbenzamide;
4-chloro-N-((6-methoxy-1-methyl-1H-benzimidazol-7-yl)methyl)-3-methylbenzamide;
4-fluoro-N-((6-methoxy-1-methyl-1H-benzimidazol-7-yl)methyl)-3-(trifluoromethyl)benzamide;
3,4,5-trifluoro-N-((6-methoxy-1-methyl-1H-benzimidazol-7-yl)methyl)benzamide;
4-chloro-N-((6-methoxy-1-methyl-1H-benzimidazol-7-yl)methyl)thiophene-2-carboxamide;
N-((6-methoxy-1-methyl-1H-benzimidazol-7-yl)methyl)-4-methylthiophene-2-carboxamide;
4-chloro-3-fluoro-N-((6-methoxy-1-methyl-1H-benzimidazol-7-yl)methyl)benzamide;
4-chloro-3-methoxy-N-((6-methoxy-1-methyl-1H-benzimidazol-7-yl)methyl)benzamide;
4-fluoro-3-methoxy-N-((6-methoxy-1-methyl-1H-benzimidazol-7-yl)methyl)benzamide;
N-((6-methoxy-1-methyl-1H-benzimidazol-7-yl)methyl)-4-methyl-3-(trifluoromethyl)benzamide;
5-methoxy-N-((6-methoxy-1-methyl-1H-benzimidazol-7-yl)methyl)thiophene-2-carboxamide;
3,5-dichloro-4-fluoro-N-((6-methoxy-1-methyl-1H-benzimidazol-7-yl)methyl)benzamide;
N-((6-methoxy-1-methyl-1H-benzimidazol-7-yl)methyl)-5-(trifluoromethyl)thiophene-2-carboxamide;
3-chloro-N-((6-methoxy-1-methyl-1H-benzimidazol-7-yl)methyl)-4-(trifluoromethyl)benzamide;
3-fluoro-N-((6-methoxy-1-methyl-1H-benzimidazol-7-yl)methyl)-4-(trifluoromethoxy)benzamide;
4,5-dichloro-N-((6-methoxy-1-methyl-1H-benzimidazol-7-yl)methyl)thiophene-2-carboxamide;
3,4-difluoro-N-((6-methoxy-1-methyl-1H-benzimidazol-7-yl)methyl)-5-methylbenzamide;
3,4-dichloro-5-fluoro-N-((6-methoxy-1-methyl-1H-benzimidazol-7-yl)methyl)benzamide;
N-((6-methoxy-1-methyl-1H-benzimidazol-7-yl)methyl)-6-(trifluoromethoxy)-nicotinamide;
5-chloro-6-methoxy-N-((6-methoxy-1-methyl-1H-benzimidazol-7-yl)methyl)nicotinamide;
5-chloro-6-ethoxy-N-((6-methoxy-1-methyl-1H-benzimidazol-7-yl)methyl)nicotinamide;
6-(difluoromethoxy)-5-fluoro-N-((6-methoxy-1-methyl-1H-benzimidazol-7-yl)methyl)nicotinamide;
3-chloro-N-((1,6-dimethyl-1H-benzimidazol-7-yl)methyl)-4-(trifluoromethoxy)-benzamide;
N-((5-cyclopropyl-1H-indazol-4-yl)methyl)-4-(trifluoromethyl)benzamide;
N-((5-cyclopropyl-1H-indazol-4-yl)methyl)-4-(trifluoromethoxy)benzamide;
N-((5-cyclopropyl-1H-indazol-4-yl)methyl)-4-methylthiophene-2-carboxamide;
N-((5-cyclopropyl-1H-indazol-4-yl)methyl)-5-methylthiophene-2-carboxamide;
N-((5-cyclopropyl-1H-indazol-4-yl)methyl)-2-(2-thienyl)acetamide;
N-((5-cyclopropyl-1H-indazol-4-yl)methyl)-5-methylthiophene-3-carboxamide;
N-((5-cyclopropyl-1H-indazol-4-yl)methyl)-5-methoxythiophene-2-carboxamide;
N-((5-cyclopropyl-1H-indazol-4-yl)methyl)-4-methoxythiophene-2-carboxamide;
5-chloro-N-((5-cyclopropyl-1H-indazol-4-yl)methyl)thiophene-3-carboxamide;
4-chloro-N-((5-cyclopropyl-1H-indazol-4-yl)methyl)thiophene-2-carboxamide;
5-chloro-N-((5-cyclopropyl-1H-indazol-4-yl)methyl)thiophene-2-carboxamide;
N-((5-cyclopropyl-1H-indazol-4-yl)methyl)-4-fluoro-3-methoxybenzamide;
4-chloro-N-((5-cyclopropyl-1H-indazol-4-yl)methyl)-3-methylbenzamide;
3-chloro-N-((5-cyclopropyl-1H-indazol-4-yl)methyl)-4-methylbenzamide;
N-((5-cyclopropyl-1H-indazol-4-yl)methyl)-4-fluoro-3-methylbenzamide;
N-((5-cyclopropyl-1H-indazol-4-yl)methyl)-3,4-difluoro-5-methylbenzamide;
3-chloro-N-((5-cyclopropyl-1H-indazol-4-yl)methyl)-4-fluorobenzamide;
4-chloro-N-((5-cyclopropyl-1H-indazol-4-yl)methyl)-3-fluorobenzamide;
N-((5-cyclopropyl-1H-indazol-4-yl)methyl)-3,4,5-trifluorobenzamide;
3-chloro-N-((5-cyclopropyl-1H-indazol-4-yl)methyl)-4-methoxybenzamide;
4-chloro-N-((5-cyclopropyl-1H-indazol-4-yl)methyl)-3-methoxybenzamide;
N-((5-cyclopropyl-1H-indazol-4-yl)methyl)-5-(trifluoromethyl)thiophene-2-carboxamide;
4,5-dichloro-N-((5-cyclopropyl-1H-indazol-4-yl)methyl)thiophene-2-carboxamide;
N-((5-cyclopropyl-1H-indazol-4-yl)methyl)-4-methyl-3-(trifluoromethyl)benzamide;
N-((5-cyclopropyl-1H-indazol-4-yl)methyl)-4-fluoro-3-(trifluoromethyl)benzamide;
3,5-dichloro-N-((5-cyclopropyl-1H-indazol-4-yl)methyl)-4-fluorobenzamide;
3,4-dichloro-N-((5-cyclopropyl-1H-indazol-4-yl)methyl)-5-fluorobenzamide;
N-((5-cyclopropyl-1H-indazol-4-yl)methyl)-3-fluoro-4-(trifluoromethoxy)benzamide;
3-chloro-N-((5-cyclopropyl-1H-indazol-4-yl)methyl)-4-(trifluoromethyl)benzamide;
4-chloro-N-((5-cyclopropyl-1H-indazol-4-yl)methyl)-3,5-difluorobenzamide;
N-((5-cyclopropyl-1H-indazol-4-yl)methyl)-3,5-difluoro-4-(trifluoromethyl)benzamide;
N-((5-cyclopropyl-1H-indazol-4-yl)methyl)-3-fluoro-4-(trifluoromethyl)benzamide;
N-((5-cyclopropyl-1H-indazol-4-yl)methyl)-3-fluoro-4-methylbenzamide;
N-((5-cyclopropyl-1H-indazol-4-yl)methyl)-3-fluoro-4-methoxybenzamide;
3-chloro-N-((5-cyclopropyl-1H-indazol-4-yl)methyl)-4,5-difluorobenzamide;
N-((5-cyclopropyl-1H-indazol-

Assignees

• Takeda Pharmaceuticals Co

Inventors

• Kimura Eiji
• Ogino Masaki
• Kohara Yasuhisa
• Ohashi Tomoko
• Kaku Tomohiro
• Oguro Yuya
• Matsumoto Shigemitsu
• Wakabayashi Takeshi
• Tokunaga Norihito
• Kamei Taku
• Ito Mitsuhiro

Classifications

• C07D409/12 Primary

  linked by a chain containing hetero atoms as chain links · CPC title

• A61K9/2013

  Organic compounds, e.g. phospholipids, fats · CPC title

• A61K9/2018

  Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates · CPC title

• A61K9/2054

  Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose · CPC title

• A61K9/2059

  Starch, including chemically or physically modified derivatives; Amylose; Amylopectin; Dextrin · CPC title