Heterocyclic compound and use thereof

Patent metadata

Field	Value
Publication number	US-11952344-B2
Application number	US-202017754118-A
Country	US
Kind code	B2
Filing date	Sep 25, 2020
Priority date	Sep 25, 2019
Publication date	Apr 9, 2024
Grant date	Apr 9, 2024

Abstract

Provided is a heterocyclic compound that can have an antagonistic action on an NMD A receptor containing the NR2B subunit and that is expected to be useful as a prophylactic or therapeutic agent for depression, bipolar disorder, migraine, pain, peripheral symptoms of dementia and the like. A compound represented by the formula (I), wherein each symbol is as defined in the DESCRIPTION, or a salt thereof.

First claim

The invention claimed is:

1. A compound represented by the formula (I):

wherein
R 1 is

wherein
X is CH or a nitrogen atom;
R a is

(1) a C 1-3 alkyl group optionally substituted by fluorine atom(s),
(2) a C 3-6 cycloalkyl group optionally substituted by fluorine atom(s),
(3) a C 1-6 alkoxy group optionally substituted by fluorine atom(s), or
(4) a C 3-6 cycloalkyloxy group optionally substituted by fluorine atom(s);
R b is

(1) a hydrogen atom,
(2) a C 1-6 alkyl group optionally substituted by fluorine atom(s),
(3) a C 1-6 alkoxy group optionally substituted by fluorine atom(s), or
(4) a halogen atom; and
R c is

(1) a C 2-6 alkyl group optionally substituted by fluorine atom(s),
(2) a C 1-6 alkoxy group optionally substituted by fluorine atom(s), or
(3) a halogen atom; and
R 2 is

(1)

wherein
R d is

(a) a C 3-6 cycloalkyl group optionally substituted by fluorine atom(s),
(b) a C 1-6 alkoxy group optionally substituted by fluorine atom(s),
(c) a C 3-6 cycloalkyloxy group optionally substituted by fluorine atom(s),
(d) a difluoromethyl group, or
(e) a trifluoromethyl group; and
R f1 and R f2 are each independently a hydrogen atom, a fluorine atom, a chlorine atom, or a methyl group,

(2)

wherein
R e is

(a) a C 3-6 cycloalkyl group optionally substituted by fluorine atom(s),
(b) a C 1-6 alkoxy group optionally substituted by fluorine atom(s),
(c) a C 3-6 cycloalkyloxy group optionally substituted by fluorine atom(s), or
(d) a C 1-2 alkyl group substituted by fluorine atom(s); and
ring B is optionally further substituted by 1 to 3 substituents selected from a fluorine atom, a chlorine atom, and a methyl group, or

(3)

wherein
ring C is further substituted by 1 or 2 substituents selected from

(a) a C 3-6 cycloalkyl group optionally substituted by fluorine atom(s),
(b) a C 1-6 alkoxy group optionally substituted by fluorine atom(s),
(c) a C 3-6 cycloalkyloxy group optionally substituted by fluorine atom(s), and
(d) a C 1-2 alkyl group substituted by fluorine atom(s),
or a pharmacologically acceptable salt thereof.

2. The compound according to claim 1 , wherein R 1 is

wherein
X is CH or a nitrogen atom;
R a is

(1) a C 1-3 alkyl group optionally substituted by 1 to 3 fluorine atoms,
(2) a C 3-6 cycloalkyl group optionally substituted by 1 to 3 fluorine atoms,
(3) a C 1-6 alkoxy group optionally substituted by 1 to 3 fluorine atoms, or
(4) a C 3-6 cycloalkyloxy group optionally substituted by 1 to 3 fluorine atoms;
R b is

(1) a hydrogen atom, or
(2) a halogen atom; and
R c is

(1) a C 1-6 alkoxy group optionally substituted by 1 to 3 fluorine atoms, or
(2) a halogen atom; and
R 2 is

(1)

wherein
R d is

(a) a C 1-6 alkoxy group optionally substituted by 1 to 3 fluorine atoms,
(b) a difluoromethyl group, or
(c) a trifluoromethyl group; and
R f1 and R f2 are each independently a hydrogen atom, fluorine atom, or chlorine atom,

(2)

wherein
R e is

(a) a C 3-6 cycloalkyl group optionally substituted by 1 to 3 fluorine atoms,
(b) a C 1-6 alkoxy group optionally substituted by 1 to 3 fluorine atoms, or
(c) a C 1-2 alkyl group substituted by 1-5 fluorine atoms; and
ring B is optionally further substituted by 1 to 3 substituents selected from a fluorine atom, and a chlorine atom, or

(3)

wherein
ring C is further substituted by 1 or 2 substituents selected from

(a) a C 3-6 cycloalkyl group optionally substituted by 1 to 3 fluorine atoms, and
(b) a C 1-2 alkyl group substituted by 1 to 3 fluorine atoms,
or a pharmacologically acceptable salt thereof.

3. A medicament comprising the compound according to claim 1 or a pharmacologically acceptable salt thereof and a pharmacologically acceptable carrier.

4. A method for treating depression, bipolar disorder, migraine, pain, or peripheral symptoms of dementia in a mammal, comprising administering an effective amount of the compound according to claim 1 or a pharmacologically acceptable salt thereof to the mammal.

5. A method according to claim 4 , wherein the mammal is a human.

Assignees

• Takeda Pharmaceuticals Co

Inventors

• Oguro Yuya
• Kamata Makoto
• Ikeda Shuhei
• Wakabayashi Takeshi
• Tokunaga Norihito
• Kamei Taku
• Ito Mitsuhiro
• Matsumoto Shigemitsu
• KAMITANI Hirotaka
• Hirayama Takaharu
• Tanaka Toshio
• Banno Hiroshi
• Takakura Nobuyuki
• Yonemori Jinichi
• Fujimoto Takuya

Classifications

• C07D211/04 Primary

  with only hydrogen or carbon atoms directly attached to the ring nitrogen atom · CPC title

• C07D237/08

  with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms · CPC title

• C07D239/26

  with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms · CPC title

• C07D405/02

  containing two hetero rings · CPC title

• C07D213/65 Primary

  attached in position 3 or 5 · CPC title