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US 9,539,252 B2Granted
Piperazine-substituted benzothiophene derivatives as antipsychotic agents
AssigneeOtsuka Pharmaceutical Co., Ltd.
InventorsHiroshi Yamashita, Yohji Sakurai, Motoyuki Miyamoto, Yuichi Nakamura, Hideaki Kuroda, Takuya Minowa
Life of this patent
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Abstract
Provided is a superior, novel heterocyclic compound with improved solubility in oil such as sesame oil and benzyl benzoate, which has a broader treatment spectrum, causes less side effects, and is superior in tolerability and safety, and use thereof. A heterocyclic compound represented by the formula (I) wherein each symbol is as defined in the specification, or a salt thereof.
Claims8
A pharmaceutical composition comprising a heterocyclic compound represented by the formula (I) or a pharmaceutically acceptable salt thereof as an active ingredient and a pharmaceutically acceptable carrier:
- wherein
- A is a lower alkylene group;
- in the monocyclic heterocycle containing Q is
- wherein
- R2′ is the following group
- wherein
- Y1′ is a lower alkylene group,
- R3 ′is
- (1) an alkyl group,
- (2) a cycloalkyl group optionally substituted by a lower alkyl group,
- (3) a phenyl group,
- (4) a phenyl lower alkyl group
- (5) a lower alkoxy group,
- (6) a cycloalkyloxy group,
- (7) an amino group optionally having 1 or 2 substituents selected from the group consisting of an alkyl group and a phenyl lower alkyl group, or
- (8) a piperidyl group optionally having a piperidyl group;
- at the 3-position and the 4-position of the bicyclic heterocycle skeleton containing Z and W is —CH═CH— or
- wherein R6 and R7 are the same or different and each is a hydrogen or a lower alkyl group;
- wherein
- R2 is a hydrogen or
- the following group
- wherein
- Y1is a lower alkylene group optionally substituted by
- (1) a lower alkoxycarbonyl group or
- (2) a lower alkyl group,
- Y2 is a lower alkylene group,
- Y3 is a single bond or a lower alkylene group optionally substituted by a lower alkyl group,
- R3 is
- (1) an alkyl group,
- (2) a halogen-substituted lower alkyl group,
- (3) an alkenyl group,
- (4) an amino lower alkyl group,
- (5) a cycloalkyl group,
- (6) a phenyl group,
- (7) a phenyl lower alkyl group,
- (8) a piperidyl group optionally having 1 or 2 substituents selected from the group consisting of a lower alkyl group and a piperidyl group,
- (9) a halogen-substituted piperidyl group,
- (10) a morpholinyl group,
- (11) a pyrrolidinyl group,
- (12) a tetrahydropyranyl group,
- (13) a fury) group,
- (14) a thienyl group,
- (15) a pyridyl group,
- (16) a pyrimidinyl group,
- (17) a pyridazinyl group,
- (18) a benzofuryl group,
- (19) a quinolyl group,
- (20) a lower alkoxycarbonyl lower alkyl group,
- (21) a lower alkoxy lower alkoxy lower alkyl group,
- (22) a lower alkoxy lower alkoxy lower alkoxy lower alkyl group,
- (23) an amino group optionally having 1 or 2 substituents selected from the group consisting of an alkyl group, a cycloalkyl group, a cycloalkyl lower alkyl group, a lower alkenyl group, a halogen-substituted lower alkyl group, a lower alkoxy group, a lower alkoxy lower alkyl group, a lower alkoxycarbonyl lower alkyl group, a phenyl lower alkyl group, a phenyl lower alkoxy group, a furyl lower alkyl group, a pyridyl lower alkyl group, a hydroxy-substituted lower alkyl group,
- (24) an amino lower alkyl group optionally having a lower alkylcarbonyl group,
- (25) a piperazinyl group optionally having a lower alkyl group, or
- (26) the following group
- wherein Ac is an alkylene group, and other symbols are as defined above,
- R4 is
- (1) an alkyl group,
- (2) a phenyl group,
- (3) a phenyl lower alkyl group,
- (4) a halogen-substituted lower alkyl group, or
- (5) a cycloalkyl group,
- R5 is
- (1) a hydrogen,
- (2) a lower alkyl group,
- (3) a halogen-substituted lower alkyl group,
- (4) a phenyl lower alkyl group,
- (5) a phenyl lower alkoxy lower alkyl group,
- (6) a tri-lower alkylsilyl group,
- (7) a tetrahydropyranyl group, or
- (8) a phosphono group,
- R10 is
- (1) an alkenyl group,
- (2) a phenyl lower alkyl group,
- (3) a hydroxy-substituted lower alkyl group,
- (4) a cycloalkyl group,
- (5) an amino lower alkyl group optionally having 1 or 2 substituents selected from the group consisting of an amino lower alkylcarbonyl group and a lower alkylcarbonyl group,
- (6) a pyrrolidinyl group optionally having an amino lower alkylcarbonyl group,
- (7) an alkoxy group,
- (8) a lower alkoxy lower alkoxy lower alkyl group,
- (9) a lower alkoxy lower alkoxy lower alkoxy lower alkyl group,
- (10) a phenyl lower alkoxy group,
- (11) an amino group optionally having 1 or 2 substituents selected from the group consisting of an alkyl group, a hydroxy-substituted lower alkyl group and a phenyl lower alkyl group,
- (12) a morpholino group,
- (13) a piperazinyl group optionally having a lower alkyl group,
- (14) a piperidyl group optionally having a piperidyl group, or
- (15) a cycloalkyloxy group;
- provided when
- then
- R2 is not a hydrogen.
86 more elements
A method for treating disease selected from the group consisting of schizophrenia, treatment-resistant, refractory or chronic schizophrenia, cognitive impairment in schizophrenia and cognitive impairment caused by treatment-resistant, refractory or chronic schizophrenia comprising admininistering a heterocyclic compound represented by the formula (I) or a pharmaceutically acceptable salt thereof to a human or animal:
- wherein
- A is a lower alkylene group;
- in the monocyclic heterocycle containing Q is
- wherein
- R2′ is the following group
- wherein
- Y1′ is a lower alkylene group,
- R3′ is
- (1) an alkyl group,
- (2) a cycloalkyl group optionally substituted by a lower alkyl group,
- (3) a phenyl group,
- (4) a phenyl lower alkyl group
- (5) a lower alkoxy group,
- (6) a cycloalkyloxy group,
- (7) an amino group optionally having 1 or 2 substituents selected from the group consisting of an alkyl group and a phenyl lower alkyl group, or
- (8) a piperidyl group optionally having a piperidyl group;
- at the 3-position and the 4-position of the bicyclic heterocycle skeleton containing Z and W is —CH═CH— or
- wherein R6 and R7 are the same or different and each is a hydrogen or a lower alkyl group;
- wherein
- R2 is a hydrogen or
- the following group
- wherein
- Y1 is a lower alkylene group optionally substituted by
- (1) a lower alkoxycarbonyl group or
- (2) a lower alkyl group,
- Y2 is a lower alkylene group,
- Y3 is a single bond or a lower alkylene group optionally substituted by a lower alkyl group,
- R3 is
- (1) an alkyl group,
- (2) a halogen-substituted lower alkyl group,
- (3) an alkenyl group,
- (4) an amino lower alkyl group,
- (5) a cycloalkyl group,
- (6) a phenyl group,
- (7) a phenyl lower alkyl group,
- (8) a piperidyl group optionally having 1 or 2 substituents selected from the group consisting of a lower alkyl group and a piperidyl group,
- (9) a halogen-substituted piperidyl group,
- (10) a morpholinyl group,
- (11) a pyrrolidinyl group,
- (12) a tetrahydropyranyl group,
- (13) a furyl group,
- (14) a thienyl group,
- (15) a pyridyl group,
- (16) a pyrimidinyl group,
- (17) a pyridazinyl group,
- (18) a benzofuryl group,
- (19) a quinolyl group,
- (20) a lower alkoxycarbonyl lower alkyl group,
- (21) a lower alkoxy lower alkoxy lower alkyl group,
- (22) a lower alkoxy lower alkoxy lower alkoxy lower alkyl group,
- (23) an amino group optionally having 1 or 2 substituents selected from the group consisting of an alkyl group, a cycloalkyl group, a cycloalkyl lower alkyl group, a lower alkenyl group, a halogen-substituted lower alkyl group, a lower alkoxy group, a lower alkoxy lower alkyl group, a lower alkoxycarbonyl lower alkyl group, a phenyl lower alkyl group, a phenyl lower alkoxy group, a furyl lower alkyl group, a pyridyl lower alkyl group, a hydroxy-substituted lower alkyl group,
- (24) an amino lower alkyl group optionally having a lower alkylcarbonyl group,
- (25) a piperazinyl group optionally having a lower alkyl group, or
- (26) the following group
- wherein Ac is an alkylene group, and other symbols are as defined above,
- R4 is
- (1) an alkyl group,
- (2) a phenyl group,
- (3) a phenyl lower alkyl group,
- (4) a halogen-substituted lower alkyl group, or
- (5) a cycloalkyl group,
- R5 is
- (1) a hydrogen,
- (2) a lower alkyl group,
- (3) a halogen-substituted lower alkyl group,
- (4) a phenyl lower alkyl group,
- (5) a phenyl lower alkoxy lower alkyl group,
- (6) a tri-lower alkylsilyl group,
- (7) a tetrahydropyranyl group, or
- (8) a phosphono group,
- R10 is
- (1) an alkenyl group,
- (2) a phenyl lower alkyl group,
- (3) a hydroxy-substituted lower alkyl group,
- (4) a cycloalkyl group,
- (5) an amino lower alkyl group optionally having 1 or 2 substituents selected from the group consisting of an amino lower alkylcarbonyl group and a lower alkylcarbonyl group,
- (6) a pyrrolidinyl group optionally having an amino lower alkylcarbonyl group,
- (7) an alkoxy group,
- (8) a lower alkoxy lower alkoxy lower alkyl group,
- (9) a lower alkoxy lower alkoxy lower alkoxy lower alkyl group,
- (10) a phenyl lower alkoxy group,
- (11) an amino group optionally having 1 or 2 substituents selected from the group consisting of an alkyl group, a hydroxy-substituted lower alkyl group and a phenyl lower alkyl group,
- (12) a morpholino group,
- (13) a piperazinyl group optionally having a lower alkyl group,
- (14) a piperidyl group optionally having a piperidyl group, or
- (15) a cycloalkyloxy group;
- provided when
- then
- R2 is not a hydrogen.
86 more elements
Dependencies are inferred from the claim text.