Heterocyclic compound and use thereof
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.
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.