IP Library › Granted Patent US 11,713,311

Granted Patent B2

US 11,713,311 · App. 17/550,173 · Granted Aug 1, 2023

Heterocyclic compound

Inventors: Eiji Kimura (Kanagawa, JP); Masaki Ogino (Kanagawa, JP); Yasuhisa Kohara (Kanagawa, JP); Tomoko Ohashi (Kanagawa, JP); Tomohiro Kaku (Kanagawa, JP); Yuya Oguro (Kanagawa, JP); Shigemitsu Matsumoto (Kanagawa, JP); Takeshi Wakabayashi (Kanagawa, JP); Norihito Tokunaga (Kanagawa, JP); Taku Kamei (Kanagawa, JP); Mitsuhiro Ito (Kanagawa, JP)

Assignee: Takeda Pharmaceutical Company Limited

C07D409/12 A61K9/2013 A61K9/2018 A61K9/2054 A61K9/2059 A61K9/2095 A61K9/4825 A61K9/4858 A61K9/4866 A61P25/06 A61P25/24 A61P25/28 C07D231/56 C07D235/06 C07D249/18 C07D401/12

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Quick Facts

Patent No.: US 11,713,311
App. No.: 17/550,173
Granted: Aug 1, 2023
Kind: B2

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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.

Claims (578)

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-4-yl)methyl)-5-fluoro-6-methoxynicotinamide;

N-((5-cyclopropyl-1H-indazol-4-yl)methyl)-3,5-difluoro-4-methylbenzamide;

N-((5-cyclopropyl-1H-indazol-4-yl)methyl)-4-(difluoromethyl)benzamide;

N-((5-cyclopropyl-1H-indazol-4-yl)methyl)-4-methylbenzamide;

N-((5-cyclopropyl-1H-indazol-4-yl)methyl)-4-(difluoromethoxy)benzamide;

N-((5-cyclopropyl-1H-indazol-4-yl)methyl)-4-methoxybenzamide;

4-chloro-N-((5-cyclopropyl-1H-indazol-4-yl)methyl)benzamide;

5-chloro-N-((5-cyclopropyl-1H-indazol-4-yl)methyl)-6-methoxynicotinamide;

5-chloro-N-((5-cyclopropyl-1H-indazol-4-yl)methyl)-6-ethoxynicotinamide;

N-((5-cyclopropyl-1H-indazol-4-yl)methyl)-6-(difluoromethoxy)-5-fluoronicotinamide;

N-((5-cyclopropyl-1H-indazol-4-yl)methyl)-6-(trifluoromethoxy)-nicotinamide;

3-chloro-N-((5-cyclopropyl-1H-indazol-4-yl)methyl)-4-(difluoromethoxy)-benzamide;

N-((5-cyclopropyl-1H-indazol-4-yl)methyl)-4-(difluoromethyl)-3,5-difluorobenzamide;

4-(difluoromethoxy)-N-((1,6-dimethyl-1H-benzimidazol-7-yl)methyl)-3-fluorobenzamide;

5-(difluoromethyl)-N-((6-methoxy-1-methyl-1H-benzimidazol-7-yl)methyl)thiophene-3-carboxamide;

3-chloro-5-fluoro-4-methoxy-N-((6-methoxy-1-methyl-1H-benzimidazol-7-yl)methyl)benzamide;

3-chloro-4-(difluoromethyl)-N-((6-methoxy-1-methyl-1H-benzimidazol-7-yl)methyl)benzamide;

5-chloro-N-((6-methoxy-1-methyl-1H-benzimidazol-7-yl)methyl)-6-(trifluoromethyl)-nicotinamide;

N-((6-methoxy-1-methyl-1H-benzimidazol-7-yl)methyl)-4-methylbenzamide;

5-cyclopropyl-N-((6-methoxy-1-methyl-1H-benzimidazol-7-yl)methyl)thiophene-3-carboxamide;

4-chloro-N-((6-methoxy-1-methyl-1H-benzimidazol-7-yl)methyl)benzamide;

N-((6-methoxy-1-methyl-1H-benzimidazol-7-yl)methyl)-4-(trifluoromethyl)benzamide;

N-((5-cyclopropyl-1H-indazol-4-yl)methyl)-4-(difluoromethyl)-3-fluorobenzamide;

N-((5-cyclopropyl-1H-indazol-4-yl)methyl)-6-ethoxy-5-fluoronicotinamide;

N-((5-cyclopropyl-1H-indazol-4-yl)methyl)-4-(difluoromethoxy)-3-fluorobenzamide;

5-chloro-N-((5-cyclopropyl-1H-indazol-4-yl)methyl)-6-(difluoromethoxy)-nicotinamide;

5-ethyl-N-((6-methoxy-1-methyl-1H-benzimidazol-7-yl)methyl)thiophene-2-carboxamide;

4-(difluoromethyl)-N-((6-methoxy-1-methyl-1H-benzimidazol-7-yl)methyl)benzamide;

4-(difluoromethyl)-3-fluoro-N-((6-methoxy-1-methyl-1H-benzimidazol-7-yl)methyl)benzamide;

5-(difluoromethyl)-N-((6-ethoxy-1-methyl-1H-benzimidazol-7-yl)methyl)thiophene-3-carboxamide;

5-(difluoromethyl)-N-((6-ethoxy-1-methyl-1H-benzimidazol-7-yl)methyl)thiophene-2-carboxamide;

N-((6-ethoxy-1-methyl-1H-benzimidazol-7-yl)methyl)-3,5-difluoro-4-methoxybenzamide;

N-((6-ethoxy-1-methyl-1H-benzimidazol-7-yl)methyl)-4-(trifluoromethyl)-benzamide;

N-((1,6-dimethyl-1H-benzimidazol-7-yl)methyl)-3-fluoro-4-methoxybenzamide;

N-((6-ethyl-1-methyl-1H-benzimidazol-7-yl)methyl)-3-fluoro-4-methoxybenzamide;

4-(difluoromethoxy)-N-((6-ethyl-1-methyl-1H-benzimidazol-7-yl)methyl)-3,5-difluorobenzamide;

5-(difluoromethyl)-N-((6-ethyl-1-methyl-1H-benzimidazol-7-yl)methyl)thiophene-3-carboxamide;

4-(difluoromethyl)-N-((6-ethyl-1-methyl-1H-benzimidazol-7-yl)methyl)benzamide;

6-(difluoromethoxy)-N-((1,6-dimethyl-1H-benzimidazol-7-yl)methyl)-5-fluoronicotinamide;

4-(difluoromethoxy)-N-((1,6-dimethyl-1H-benzimidazol-7-yl)methyl)benzamide;

4-(difluoromethyl)-N-((1,6-dimethyl-1H-benzimidazol-7-yl)methyl)-3-fluorobenzamide;

5-(difluoromethyl)-N-((1,6-dimethyl-1H-benzimidazol-7-yl)methyl)thiophene-2-carboxamide;

N-((1,6-dimethyl-1H-benzimidazol-7-yl)methyl)-6-(trifluoromethoxy)-nicotinamide;

N-((6-methoxy-1-methyl-1H-benzimidazol-7-yl)methyl)-5-(trifluoromethyl)-thiophene-3-carboxamide;

4-(difluoromethyl)-N-((6-ethoxy-1-methyl-1H-benzimidazol-7-yl)methyl)benzamide;

4-(difluoromethyl)-N-((6-ethoxy-1-methyl-1H-benzimidazol-7-yl)methyl)-3-fluorobenzamide;

5-(difluoromethyl)-N-((1,6-dimethyl-1H-benzimidazol-7-yl)methyl)thiophene-3-carboxamide;

6-(difluoromethoxy)-N-((6-ethyl-1-methyl-1H-benzimidazol-7-yl)methyl)-5-fluoronicotinamide;

5-cyclopropyl-N-((1,6-dimethyl-1H-benzimidazol-7-yl)methyl)thiophene-3-carboxamide;

N-((6-ethyl-1-methyl-1H-benzimidazol-7-yl)methyl)-4-methoxybenzamide;

4-(difluoromethyl)-N-((6-ethyl-1-methyl-1H-benzimidazol-7-yl)methyl)-3-fluorobenzamide;

5-chloro-N-((6-ethyl-1-methyl-1H-benzimidazol-7-yl)methyl)thiophene-3-carboxamide;

4-(difluoromethoxy)-N-((6-ethyl-1-methyl-1H-benzimidazol-7-yl)methyl)benzamide;

N-((6-ethyl-1-methyl-1H-benzimidazol-7-yl)methyl)-6-(trifluoromethoxy)-nicotinamide;

N-((1-ethyl-6-methoxy-1H-benzimidazol-7-yl)methyl)-5-fluoro-6-methoxynicotinamide;

N-((1-ethyl-6-methoxy-1H-benzimidazol-7-yl)methyl)-3,5-difluoro-4-methoxybenzamide;

N-((1,6-dimethyl-1H-benzimidazol-7-yl)methyl)-4-(trifluoromethoxy)-benzamide;

N-((5-cyclopropyl-1H-indazol-4-yl)methyl)-4-(difluoromethoxy)-3,5-difluorobenzamide;

N-((5-cyclopropyl-1H-indazol-4-yl)methyl)-5-(difluoromethyl)-thiophene-3-carboxamide;

N-((5-cyclopropyl-1H-indazol-4-yl)methyl)-5-(difluoromethyl)-thiophene-2-carboxamide;

5-chloro-N-((1,6-dimethyl-1H-benzimidazol-7-yl)methyl)thiophene-3-carboxamide;

4-(difluoromethyl)-N-((1,6-dimethyl-1H-benzimidazol-7-yl)methyl)benzamide;

4-(difluoromethoxy)-N-((1,6-dimethyl-1H-benzimidazol-7-yl)methyl)-3,5-difluorobenzamide;

6-(difluoromethoxy)-N-((1,6-dimethyl-1H-benzimidazol-7-yl)methyl)nicotinamide;

3,5-difluoro-4-methoxy-N-((1-methyl-1H-benzimidazol-7-yl)methyl)benzamide;

4-(difluoromethoxy)-3,5-difluoro-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 hydrochloride;

N-((1,6-dimethyl-1H-benzimidazol-7-yl)methyl)-5-(trifluoromethyl)-thiophene-3-carboxamide;

6-(difluoromethoxy)-N-((6-ethyl-1-methyl-1H-benzimidazol-7-yl)methyl)nicotinamide;

N-((5-cyclopropyl-1H-benzotriazol-4-yl)methyl)-5-fluoro-6-methoxynicotinamide;

5-chloro-N-(1H-indazol-4-ylmethyl)thiophene-3-carboxamide;

N-(1H-indazol-4-ylmethyl)-5-(trifluoromethyl)-thiophene-2-carboxamide;

4,5-dichloro-N-(1H-indazol-4-ylmethyl)thiophene-2-carboxamide;

5-chloro-N-(1H-indazol-4-ylmethyl)-6-methoxynicotinamide;

N-(1H-indazol-4-ylmethyl)-6-(trifluoromethoxy)-nicotinamide;

6-ethoxy-5-fluoro-N-(1H-indazol-4-ylmethyl)nicotinamide;

5-fluoro-N-(1H-indazol-4-ylmethyl)-6-methoxynicotinamide;

3,5-difluoro-N-(1H-indazol-4-ylmethyl)-4-(trifluoromethyl)-benzamide;

3-fluoro-N-(1H-indazol-4-ylmethyl)-4-(trifluoromethyl)-benzamide;

N-(1H-indazol-4-ylmethyl)-4-(trifluoromethyl)-benzamide;

3-fluoro-N-(1H-indazol-4-ylmethyl)-4-methylbenzamide;

4-(difluoromethyl)-N-(1H-indazol-4-ylmethyl)benzamide;

4-(difluoromethyl)-3-fluoro-N-(1H-indazol-4-ylmethyl)benzamide;

3-fluoro-N-(1H-indazol-4-ylmethyl)-4-(trifluoromethoxy)-benzamide;

3,5-difluoro-N-(1H-indazol-4-ylmethyl)-4-methoxybenzamide;

3-fluoro-N-(1H-indazol-4-ylmethyl)-4-methoxybenzamide;

3-chloro-4-(difluoromethoxy)-N-(1H-indazol-4-ylmethyl)benzamide;

4-(difluoromethoxy)-N-(1H-indazol-4-ylmethyl)benzamide;

4-(difluoromethoxy)-3,5-difluoro-N-(1H-indazol-4-ylmethyl)benzamide;

3-chloro-N-(1H-indazol-4-ylmethyl)-4-methylbenzamide;

3-chloro-4-fluoro-N-(1H-indazol-4-ylmethyl)benzamide;

4-chloro-3-fluoro-N-(1H-indazol-4-ylmethyl)benzamide;

3-chloro-4,5-difluoro-N-(1H-indazol-4-ylmethyl)benzamide;

4-chloro-3,5-difluoro-N-(1H-indazol-4-ylmethyl)benzamide;

3-chloro-4-(difluoromethyl)-N-(1H-indazol-4-ylmethyl)benzamide;

6-(difluoromethoxy)-5-fluoro-N-(1H-indazol-4-ylmethyl)nicotinamide;

4-(difluoromethoxy)-3-fluoro-N-(1H-indazol-4-ylmethyl)benzamide;

5-fluoro-6-methoxy-N-((5-methyl-1H-benzotriazol-4-yl)methyl)nicotinamide;

N-((5-methyl-1H-benzotriazol-4-yl)methyl)-4-(trifluoromethoxy)-benzamide;

3,5-difluoro-N-((5-methyl-1H-benzotriazol-4-yl)methyl)-4-(trifluoromethyl)-benzamide;

3,5-difluoro-4-methyl-N-((5-methyl-1H-benzotriazol-4-yl)methyl)benzamide;

3,5-difluoro-4-methoxy-N-((5-methyl-1H-benzotriazol-4-yl)methyl)benzamide;

4-chloro-3,5-difluoro-N-((5-methyl-1H-benzotriazol-4-yl)methyl)benzamide;

3-fluoro-N-((5-methyl-1H-benzotriazol-4-yl)methyl)-4-(trifluoromethyl)-benzamide;

3-fluoro-4-methyl-N-((5-methyl-1H-benzotriazol-4-yl)methyl)benzamide;

3-fluoro-4-methoxy-N-((5-methyl-1H-benzotriazol-4-yl)methyl)benzamide;

3-chloro-4,5-difluoro-N-((5-methyl-1H-benzotriazol-4-yl)methyl)benzamide;

N-((5-cyclopropyl-1H-benzotriazol-4-yl)methyl)-4-(trifluoromethoxy)-benzamide;

N-((5-cyclopropyl-1H-benzotriazol-4-yl)methyl)-3,5-difluoro-4-methoxybenzamide;

N-((5-ethyl-1H-benzotriazol-4-yl)methyl)-3,5-difluoro-4-(trifluoromethyl)-benzamide;

N-((5-ethyl-1H-benzotriazol-4-yl)methyl)-3,5-difluoro-4-methoxybenzamide;

3,5-difluoro-4-methoxy-N-((5-methoxy-1H-benzotriazol-4-yl)methyl)benzamide;

N-((5-ethyl-1H-benzotriazol-4-yl)methyl)-5-fluoro-6-methoxynicotinamide;

N-((5-ethyl-1H-benzotriazol-4-yl)methyl)-4-(trifluoromethoxy)-benzamide;

3,5-difluoro-N-((6-fluoro-1-methyl-1H-benzimidazol-7-yl)methyl)-4-methoxybenzamide;

N-(1H-benzotriazol-4-yl methyl)-3,5-difluoro-4-methoxybenzamide;

N-((5-cyclopropyl-1H-benzotriazol-4-yl)methyl)-4-(difluoromethoxy)-3-fluorobenzamide;

N-((5-methoxy-1H-benzotriazol-4-yl)methyl)-4-(trifluoromethoxy)-benzamide;

3,5-difluoro-4-methoxy-N-((6-methoxy-1,2-dimethyl-1H-benzimidazol-7-yl)methyl)benzamide;

1-((6-methoxy-1-methyl-1H-benzimidazol-7-yl)methyl)-3-(3-methylphenyl)urea;

1-(3-fluorophenyl)-3-((6-methoxy-1-methyl-1H-benzimidazol-7-yl)methyl)urea;

1-(4-fluoro-3-methylphenyl)-3-((6-methoxy-1-methyl-1H-benzimidazol-7-yl)methyl)urea;

1-(3-fluoro-4-methylphenyl)-3-((6-methoxy-1-methyl-1H-benzimidazol-7-yl)methyl)urea;

1-(3-chlorophenyl)-3-((6-methoxy-1-methyl-1H-benzimidazol-7-yl)methyl)urea;

1-((6-methoxy-1-methyl-1H-benzimidazol-7-yl)methyl)-3-(3,4,5-trifluorophenyl)urea;

1-(4-(difluoromethoxy)-phenyl)-3-((6-methoxy-1-methyl-1H-benzimidazol-7-yl)methyl)urea;

1-((6-methoxy-1-methyl-1H-benzimidazol-7-yl)methyl)-3-(3-(trifluoromethyl)-phenyl)urea;

1-((6-methoxy-1-methyl-1H-benzimidazol-7-yl)methyl)-3-(4-(trifluoromethoxy)-phenyl)urea;

1-(4-fluorophenyl)-3-((6-methoxy-1-methyl-1H-benzimidazol-7-yl)methyl)urea;

1-(3-fluoro-4-methoxyphenyl)-3-((6-methoxy-1-methyl-1H-benzimidazol-7-yl)methyl)urea;

N-((5-cyclopropyl-1H-benzotriazol-4-yl)methyl)-6-(difluoromethoxy)-5-fluoronicotinamide;

3-fluoro-N-((5-methoxy-1H-benzotriazol-4-yl)methyl)-4-(trifluoromethoxy)-benzamide;

5-chloro-N-((6-methoxy-1,2-dimethyl-1H-benzimidazol-7-yl)methyl)thiophene-3-carboxamide;

5-chloro-N-((6-methoxy-1,2-dimethyl-1H-benzimidazol-7-yl)methyl)thiophene-2-carboxamide;

N-((6-methoxy-1,2-dimethyl-1H-benzimidazol-7-yl)methyl)-5-(trifluoromethyl)-thiophene-3-carboxamide;

N-((6-methoxy-1,2-dimethyl-1H-benzimidazol-7-yl)methyl)-5-(trifluoromethyl)-thiophene-2-carboxamide;

5-(difluoromethyl)-N-((6-methoxy-1,2-dimethyl-1H-benzimidazol-7-yl)methyl)thiophene-3-carboxamide;

N-((6-methoxy-1,2-dimethyl-1H-benzimidazol-7-yl)methyl)-6-(trifluoromethoxy)-nicotinamide;

6-ethoxy-5-fluoro-N-((6-methoxy-1,2-dimethyl-1H-benzimidazol-7-yl)methyl)nicotinamide;

5-fluoro-6-methoxy-N-((6-methoxy-1,2-dimethyl-1H-benzimidazol-7-yl)methyl)nicotinamide;

3-fluoro-N-((6-methoxy-1,2-dimethyl-1H-benzimidazol-7-yl)methyl)-4-(trifluoromethyl)-benzamide;

N-((6-methoxy-1,2-dimethyl-1H-benzimidazol-7-yl)methyl)-4-(trifluoromethyl)-benzamide;

3-fluoro-N-((6-methoxy-1,2-dimethyl-1H-benzimidazol-7-yl)methyl)-4-methylbenzamide;

3,5-difluoro-N-((6-methoxy-1,2-dimethyl-1H-benzimidazol-7-yl)methyl)-4-methylbenzamide;

4-(difluoromethyl)-3,5-difluoro-N-((6-methoxy-1,2-dimethyl-1H-benzimidazol-7-yl)methyl)benzamide;

4-(difluoromethyl)-N-((6-methoxy-1,2-dimethyl-1H-benzimidazol-7-yl)methyl)benzamide;

4-(difluoromethyl)-3-fluoro-N-((6-methoxy-1,2-dimethyl-1H-benzimidazol-7-yl)methyl)benzamide;

3-fluoro-4-methoxy-N-((6-methoxy-1,2-dimethyl-1H-benzimidazol-7-yl)methyl)benzamide;

3-chloro-4-(difluoromethoxy)-N-((6-methoxy-1,2-dimethyl-1H-benzimidazol-7-yl)methyl)benzamide;

4-(difluoromethoxy)-N-((6-methoxy-1,2-dimethyl-1H-benzimidazol-7-yl)methyl)benzamide;

4-(difluoromethoxy)-3,5-difluoro-N-((6-methoxy-1,2-dimethyl-1H-benzimidazol-7-yl)methyl)benzamide;

3-chloro-4-fluoro-N-((6-methoxy-1,2-dimethyl-1H-benzimidazol-7-yl)methyl)benzamide;

4-chloro-3-fluoro-N-((6-methoxy-1,2-dimethyl-1H-benzimidazol-7-yl)methyl)benzamide;

4-chloro-N-((6-methoxy-1,2-dimethyl-1H-benzimidazol-7-yl)methyl)benzamide;

3-chloro-4-(difluoromethyl)-N-((6-methoxy-1,2-dimethyl-1H-benzimidazol-7-yl)methyl)benzamide;

6-(difluoromethoxy)-5-fluoro-N-((6-methoxy-1,2-dimethyl-1H-benzimidazol-7-yl)methyl)nicotinamide;

N-((6-methoxy-1,2-dimethyl-1H-benzimidazol-7-yl)methyl)-4-(trifluoromethoxy)-benzamide;

4-(difluoromethoxy)-3-fluoro-N-((6-methoxy-1,2-dimethyl-1H-benzimidazol-7-yl)methyl)benzamide;

6-(difluoromethoxy)-N-((6-methoxy-1,2-dimethyl-1H-benzimidazol-7-yl)methyl)nicotinamide;

1-((6-methoxy-1-methyl-1H-benzimidazol-7-yl)methyl)-3-phenylurea;

1-((6-methoxy-1-methyl-1H-benzimidazol-7-yl)methyl)-3-(4-methylphenyl)urea;

1-(4-chlorophenyl)-3-((6-methoxy-1-methyl-1H-benzimidazol-7-yl)methyl)urea;

1-(3,4-difluorophenyl)-3-((6-methoxy-1-methyl-1H-benzimidazol-7-yl)methyl)urea;

1-(2,3-difluoro-4-methoxyphenyl)-3-((6-methoxy-1-methyl-1H-benzimidazol-7-yl)methyl)urea;

1-(2-fluoro-4-(trifluoromethyl)-phenyl)-3-((6-methoxy-1-methyl-1H-benzimidazol-7-yl)methyl)urea;

1-(3-fluoro-4-(trifluoromethyl)-phenyl)-3-((6-methoxy-1-methyl-1H-benzimidazol-7-yl)methyl)urea;

1-((6-methoxy-1-methyl-1H-benzimidazol-7-yl)methyl)-3-(4-(trifluoromethyl)-phenyl)urea;

4-(difluoromethoxy)-3-fluoro-N-((5-methyl-1H-benzotriazol-4-yl)methyl)benzamide;

4-methoxy-N-((5-methyl-1H-benzotriazol-4-yl)methyl)benzamide;

4-(difluoromethoxy)-N-((5-methyl-1H-benzotriazol-4-yl)methyl)benzamide;

1-((6-methoxy-1-methyl-1H-benzimidazol-7-yl)methyl)-3-(4-methoxyphenyl)urea;

1-(4-fluoro-3-(trifluoromethyl)-phenyl)-3-((6-methoxy-1-methyl-1H-benzimidazol-7-yl)methyl)urea;

6-(difluoromethoxy)-5-fluoro-N-((5-methyl-1H-benzotriazol-4-yl)methyl)nicotinamide;

3-fluoro-N-((3-methyl-1H-indazol-4-yl)methyl)-4-(trifluoromethoxy)-benzamide;

3,5-difluoro-4-methoxy-N-((3-methyl-1H-indazol-4-yl)methyl)benzamide;

6-(difluoromethoxy)-5-fluoro-N4(3-methyl-1H-indazol-4-yl)methyl)nicotinamide;

N-[(3-bromo-1H-indazol-4-yl)methyl]-3-fluoro-4-(trifluoromethoxy)-benzamide;

N-[(5-fluoro-1H-indazol-4-yl)methyl]-4-(trifluoromethoxy)-benzamide;

3-fluoro-N-[(1-methyl-1H-benzotriazol-7-yl)methyl]-4-(trifluoromethoxy)-benzamide;

6-(difluoromethoxy)-5-fluoro-N-[(1-methyl-1H-benzotriazol-7-yl)methyl]pyridine-3-carboxamide;

6-(difluoromethoxy)-N-[(6-methoxy-1-methyl-1H-benzimidazol-7-yl)methyl]pyridine-3-carboxamide;

4-(difluoromethoxy)-2-fluoro-N-[(6-methoxy-1-methyl-1H-benzimidazol-7-yl)methyl]benzamide;

N-[(6-methoxy-1-methyl-1H-benzimidazol-7-yl)methyl]-4-(2,2,2-trifluoroethyl)-benzamide;

3,5-difluoro-4-methoxy-N-{[6-(methoxymethyl)-1-methyl-1H-benzimidazol-7-yl]methyl}benzamide;

N-{[6-(methoxymethyl)-1-methyl-1H-benzimidazol-7-yl]methyl}-4-(trifluoromethyl)-benzamide;

6-(difluoromethoxy)-5-fluoro-N-{[6-(methoxymethyl)-1-methyl-1H-benzimidazol-7-yl]methyl}pyridine-3-carboxamide;

N-{[6-(methoxymethyl)-1-methyl-1H-benzimidazol-7-yl]methyl}-5-(trifluoromethyl)-thiophene-3-carboxamide;

3-chloro-4-(difluoromethoxy)-N-{[6-(methoxymethyl)-1-methyl-1H-benzimidazol-7-yl]methyl}benzamide;

3-fluoro-N-{[6-(methoxymethyl)-1-methyl-1H-benzimidazol-7-yl]methyl}-4-(trifluoromethoxy)-benzamide,

and salts thereof.

2. The method of claim 1 , wherein the compound is 3,5-difluoro-4-methoxy-N-((6-methoxy-1-methyl-1H-benzimidazol-7-yl)methyl)benzamide or a salt thereof.

3. The method of claim 1 , wherein the compound is 6-(difluoromethoxy)-N-((1,6-dimethyl-1H-benzimidazol-7-yl)methyl)-5-fluoronicotinamide or a salt thereof.

4. The method of claim 1 , wherein the compound is N-((1,6-dimethyl-1H-benzimidazol-7-yl)methyl)-4-(trifluoromethoxy)benzamide or a salt thereof.

5. A method for treating major depression, bipolar disorder, migraine, pain or peripheral symptoms of dementia in a mammal, comprising administering to the mammal an effective amount of a compound chosen from: