Nitrogen-containing aromatic heterocyclic compound

Patent metadata

Field	Value
Publication number	US-10717731-B2
Application number	US-201615769844-A
Country	US
Kind code	B2
Filing date	Oct 21, 2016
Priority date	Oct 23, 2015
Publication date	Jul 21, 2020
Grant date	Jul 21, 2020

Abstract

A compound represented by general formula [I] wherein X represents N or the like, Y represents CH or the like; RA represents a cycloalkyl group which may be substituted or the like, R1 represents an alkyl group or the like, R2 represents an alkyl group which may be substituted or the like, R3 represents a hydrogen atom or an alkyl group, or a pharmaceutically acceptable salt thereof has an inhibitory activity on aldosterone synthetase, and is useful as a prophylactic and/or therapeutic agent for various diseases or symptoms associated with aldosterone.

First claim

The invention claimed is:

1. A compound of the following formula [I]:

wherein
X and Y represent any of the following (1) to (3):
(1) X is N, and Y is CH or C—R Y ,
(2) X is CH, and Y is N, or
(3) X is CH, and Y is CH;
R Y represents an alkyl group;
R A represents a cycloalkyl group which may be substituted, a cycloalkenyl group which may be substituted, an aryl group which may be substituted, or a 6- to 10-membered monocyclic or bicyclic heteroaryl group which may be partially hydrogenated and may be substituted;
R 1 represents a hydrogen atom, or an alkyl group;
R 2 represents an alkyl group which may be substituted, a cycloalkyl group which may be substituted, an aliphatic heterocyclic group which may be substituted, or a heteroaryl group which may be partially hydrogenated and may be substituted; and
R 3 represents a hydrogen atom, or an alkyl group,
wherein
substituents of the cycloalkyl group which may be substituted, the cycloalkenyl group which may be substituted, the aryl group which may be substituted, and the 6- to 10-membered monocyclic or bicyclic heteroaryl group which may be partially hydrogenated and may be substituted, represented by R A , are 1-3 groups each independently selected from the group consisting of a halogen atom, a cyano group, an alkyl group, a haloalkyl group, an alkoxyalkyl group, and an alkoxy group,
in the aryl group which may be substituted, represented by R A , the aryl moiety is phenyl or naphthyl,
in the 6- to 10-membered heteroaryl group which may be partially hydrogenated and may be substituted, represented by R A , the heteroaryl moiety is pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, thiazinyl, triazinyvl, indolyl, isoindolyl, indazolyl, benzimidazolyvl, benzothiazolyl, benzofuranyvl, quinolyl, isoquinolyl, imidazopyridyl, or benzopyranyl;
a substituent of (i) the alkyl group which may be substituted, represented by R 2 , is 1-3 groups independently selected from the group consisting of a halogen atom; a hydroxyl group; an oxo group; a carbamoyl group which may be substituted with 1-2 alkyl groups; an alkylsulfonyl group; an alkoxy group which may be substituted with a carbamoyl group which may be substituted with 1-2 alkyl groups; an aliphatic heterocyclic group which may be substituted with 1-3 groups independently selected from the group consisting of a hydroxyl group, an oxo group, an alkyl group, an alkylsulfonyl group, and an alkoxycarbonyl group; an alkoxycarbonyl group; an amino group which may be substituted with 1-2 groups independently selected from the group consisting of an alkyl group and an alkanoyl group; and a heteroaryl group,
substituents of (ii) the cycloalkyl group which may be substituted, (iii) the aliphatic heterocyclic group which may be substituted, and (iv) the heteroaryl group which may be partially hydrogenated and may be substituted, represented by R 2 , are 1-3 groups each independently selected from the group consisting of a halogen atom; a hydroxyl group; an oxo group; an alkyl group which may be substituted with 1-3 groups independently selected from the group consisting of a hydroxyl group, a carbamoyl group which may be substituted with 1-2 alkyl groups, and an alkylsulfonyl group; an alkoxy group which may be substituted with a carbamoyl group which may be substituted with 1-2 alkyl groups; an aliphatic heterocyclic group which may be substituted with 1-3 groups independently selected from the group consisting of a hydroxyl group, an oxo group, an alkyl group, an alkylsulfonyl group, and alkoxycarbonyl group; an alkoxycarbonyl group; an amino group which may be substituted with 1-2 groups independently selected from the group consisting of an alkyl group and an alkanoyl group; and a heteroaryl group,
in the respective substituents of the above (i) to (iv), the aliphatic heterocyclic group is a group independently selected from the group consisting of azetidinyl, oxetanyl, pyrrolidinyl, tetrahydrothienyl, tetrahydrofuranyl, thiazolidinyl, piperidinyl, piperazinyl, morpholinyl, thiomorpholinyl, homomorpholinyl, tetrahydrothiopyranyl, tetrahydropyranyl, 1-azabicyclo[2.2.2]octyl(quinuclidinyl), 8-azabicyclo[3.2.1]octyl, 3-oxabicyclo[3.3.1]nonyl, and 3-oxo-9-azabicyclo[3.3.1]nonyl,
in the respective substituents of the above (i) to (iv), the heteroaryl group is a group independently selected from the group consisting of pyrrolyl, furanyl, thienyl, imidazolyl, pyrazolyl, oxazolyl, thiazolyl, triazolyl, tetrazolyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, thiazinyl, triazinyl, indolyl, isoindolyl, indazolyl, benzimidazolyl, benzothiazolyl, benzofuranyl, quinolyl, isoquinolyl, imidazopyridyl, and benzopyranyl,
in the aliphatic heterocyclic group which may be substituted, represented by R 2 , the aliphatic heterocyclic moiety is azetidinyl, oxetanyl, pyrrolidinyl, tetrahydrothienyl, tetrahydrofuranyl, thiazolidinyl, piperidinyl, piperazinyl, morpholinyl, thiomorpholinyl, homomorpholinyl, tetrahydrothiopyranyl, tetrahydropyranyl, 1-azabicyclo[2.2.2]octyl(quinuclidinyl), 8-azabicyclo[3.2.1]octyl, 3-oxabicyclo[3.3.1]nonyl, or 3-oxo-9-azabicyclo[3.3.1]nonyl, and
in the heteroaryl group which may be partially hydrogenated and may be substituted, represented by R 2 , the heteroaryl moiety is pyrrolyl, furanyl, thienyl, imidazolyl, pyrazolyl, oxazolyl, thiazolyl, triazolyl, tetrazolyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, thiazinyl, triazinyl, indolyl, isoindolyl, indazolyl, benzimidazolyl, benzothiazolyl, benzofuranyl, quinolyl, isoquinolyl, imidazopyridyl, or benzopyranyl,
or a pharmaceutically acceptable salt thereof.

2. The compound according to claim 1 ,
wherein
substituents of the cycloalkyl group which may be substituted, the cycloalkenyl group which may be substituted, the aryl group which may be substituted, and the 6- to 10-membered monocyclic or bicyclic heteroaryl group which may be partially hydrogenated and may be substituted, represented by R A , are 1-3 groups each independently selected from the group consisting of a halogen atom, a cyano group, an alkyl group, a haloalkyl group, an alkoxyalkyl group, and an alkoxy group,
in the aryl group which may be substituted, represented by R A , the aryl moiety is phenyl or naphthyl,
in the 6- to 10-membered monocyclic or bicyclic heteroaryl group which may be partially hydrogenated and may be substituted, represented by R A , the heteroaryl moiety is pyridyl, indazolyl, or benzofuranyl;
a substituent of (i) the alkyl group which may be substituted, represented by R 2 , is 1-3 groups independently selected from the group consisting of a halogen atom; a hydroxyl group; an oxo group; a carbamoyl group which may be substituted with 1-2 alkyl groups; an alkylsulfonyl group; an alkoxy group which may be substituted with a carbamoyl group which may be substituted with 1-2 alkyl groups; an aliphatic heterocyclic group which may be substituted with 1-3 groups independently selected from the group consisting of a hydroxyl group, an oxo group, an alkyl group, an alkylsulfonyl group, and an alkoxycarbonyl group; an alkoxycarbonyl group; an amino group which may be substituted with 1-2 groups independently selected from the group consisting of an alkyl group and an alkanoyl group; and a heteroaryl group,
substituents of (ii) the cycloalkyl group which may be substituted, (iii) the aliphatic heterocyclic group which may be substituted, and (iv) the heteroaryl group which may be partially hydrogenated and may be substituted, represented by R 2 , are 1-3 groups each independently selected from the group consisting of a halogen atom; a hydroxyl group; an oxo group; an alkyl

Assignees

• Mitsubishi Tanabe Pharma Corp

Inventors

• Sakakibara Ryo
• Ushirogochi Hideki
• Sasaki Wataru
• Onda Yuichi
• Yamaguchi Minami
• Akahoshi Fumihiko

Classifications

• C07D451/04

  with hetero atoms directly attached in position 3 of the 8-azabicyclo [3.2.1] octane or in position 7 of the 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring system · CPC title

• C07D453/02

  containing not further condensed quinuclidine ring systems · CPC title

• C07D405/04

  directly linked by a ring-member-to-ring-member bond · CPC title

• C07D417/12

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

• C07D409/12

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