US 12,637,435 B2Granted

Nitrogen-containing heterocyclic compound or salt thereof, use thereof, and intermediate thereof

AssigneeFUJIFILM Corporation

InventorsTakayuki Yamakawa, Yasuhiro Tsutsui

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Abstract

An object of the present invention is to provide a compound useful as an anti-tumor agent or the like; an intermediate thereof; and a pharmaceutical composition, an anti-tumor agent, and a dihydroorotate dehydrogenase inhibitor, each of which contains the compound. According to the present invention, there is provided a compound represented by General Formula (1) or a salt thereof: in the formula, Z1, Z2, and Z3 are the same as or different from each other and represent a nitrogen atom or CH; Z4 represents a nitrogen atom or a general formula of CR6; Z5 represents a nitrogen atom or a general formula of CR7 provided that at least one of Z1, Z2, Z3, Z4, or Z5 represents a nitrogen atom; R1 represents a general formula of CONHR8 or the like; R2 represents a C3-8 cycloalkyl group which may be substituted or the like; R3, R5, R6, and R7 are the same as or different from each other and represent a hydrogen atom, a halogen atom, or the like; R4 represents an aryl group which may be substituted or a heterocyclic group which may be substituted; R8 represents a general formula of SO2R9 or the like; and R9 represents an amino group which may be protected or the like.

Claims14

Dependent claims

A compound represented by General Formula (1) or a salt thereof:

in the formula,
Z1 is a nitrogen atom;
Z2 is C;
Z3 represents a nitrogen atom or CH;
Z4 represents a general formula of CR6;
Z5 represents a general formula of CR7;
R1 represents a general formula of CONHR8, a general formula of CH2NHR8, CH2OH, CH(OH)CH3, C(O)CH3, CHO, Formula (1-1), Formula (1-2), or Formula (1-3);
R2 represents a C1-6 alkyl group which may be substituted or a C3-8 cycloalkyl group which may be substituted;
R3, R5, R6, and R7 are the same as or different from each other and represent a hydrogen atom, a halogen atom, a hydroxyl group which may be protected, an amino group which may be protected, a C1-6 alkyl group which may be substituted, a C2-6 alkenyl group which may be substituted, a C2-6 alkynyl group which may be substituted, a C3-8 cycloalkyl group which may be substituted, a C1-6 alkoxy group which may be substituted, a C3-8 cycloalkoxy group which may be substituted, a C1-6 alkylamino group which may be substituted, a di(C1-6 alkyl)amino group which may be substituted, or a C1-6 alkoxy C1-6 alkyl group which may be substituted;
R4 represents an aryl group which may be substituted or a heterocyclic group which may be substituted;
R8 represents a hydrogen atom, a hydroxyl group which may be protected, an amino group which may be protected, a C1-6 alkyl group which may be substituted, a C3-8 cycloalkyl group which may be substituted, a C1-6 alkoxy group which may be substituted, a C3-8 cycloalkoxy group which may be substituted, a C1-6 alkylamino group which may be substituted, a di(C1-6 alkyl)amino group which may be substituted, or a general formula of SO2R9;
and
R9 represents a hydroxyl group which may be protected, an amino group which may be protected, a C1-6 alkyl group which may be substituted, a C3-8 cycloalkyl group which may be substituted, a C1-6 alkoxy group which may be substituted, a C3-8 cycloalkoxy group which may be substituted, a C1-6 alkylamino group which may be substituted, or a di(C1-6 alkyl)amino group which may be substituted.

10 more elements

A compound selected from Compound Group X or a salt thereof:

Compound Group X:
6-cyclopropyl-3-((3-(2,6-dimethylpyridin-3-yl)-2-(2,2,2-trifluoroethoxy)phenyl)amino)pyrazine-2-carboxylic acid, 3-((4′-cyano-2′-methyl-2-(2,2,2-trifluoroethoxy)-[1,1′-biphenyl]-3-yl)amino)-6-cyclopropylpyrazine-2-carboxylic acid, (S)-5-cyclopropyl-2-((2-(3,6-dihydro-2H-pyran-4-yl)-3-((1,1,1-trifluoropropan-2-yl)oxy)pyridin-4-yl)amino)benzoic acid, 5-cyclopropyl-2-((5-(3,6-dihydro-2H-pyran-4-yl)-4-(2,2,2-trifluoroethoxy)pyridin-3-yl)amino)benzoic acid, 5-cyclopropyl-2-((3-(tetrahydro-2H-pyran-4-yl)-2-(2,2,2-trifluoroethoxy)phenyl)amino)nicotinic acid, 5-cyclopropyl-2-((2-(difluoromethoxy)-5-fluoro-3-(tetrahydro-2H-pyran-4-yl)phenyl)amino)nicotinic acid, 3-((4′-cyano-2-(2,2,2-trifluoroethoxy)-[1,1′-biphenyl]-3-yl)amino)-6-cyclopropylpyrazine-2-carboxylic acid, 5-cyclopropyl-2-((3-(3,6-dihydro-2H-pyran-4-yl)-2-(2,2,2-trifluoroethoxy)phenyl)amino)nicotinic acid, (S)-5-cyclopropyl-2-((5-(3,6-dihydro-2H-pyran-4-yl)-4-((1,1,1-trifluoropropan-2-yl)oxy)pyridin-3-yl)amino)benzoic acid, 2-((4′-cyano-2-(2,2,2-trifluoroethoxy)-[1,1′-biphenyl]-3-yl)amino)-5-cyclopropylnicotinic acid, 5-cyclopropyl-2-((5-fluoro-3-(tetrahydro-2H-pyran-4-yl)-2-(2,2,2-trifluoroethoxy)phenyl)amino)nicotinic acid, 3-((3′-cyano-2-(2,2,2-trifluoroethoxy)-[1,1′-biphenyl]-3-yl)amino)-6-cyclopropylpyrazine-2-carboxylic acid, 5-cyclopropyl-2-((2-ethyl-3-(tetrahydro-2H-pyran-4-yl)phenyl)amino)nicotinic acid, 3-((4′-cyano-2-(difluoromethoxy)-[1,1′-biphenyl]-3-yl)amino)-6-cyclopropylpyrazine-2-carboxylic acid, 3-((4′-cyano-2-(difluoromethoxy)-5-fluoro-[1,1′-biphenyl]-3-yl)amino)-6-cyclopropylpyrazine-2-carboxylic acid, 6-cyclopropyl-3-((4′-fluoro-2-(2,2,2-trifluoroethoxy)-[1,1′-biphenyl]-3-yl)amino)pyrazine-2-carboxylic acid, 5-cyclopropyl-2-((3-(3,6-dihydro-2H-pyran-4-yl)-2-ethoxy-6-fluorophenyl)amino)nicotinic acid, 5-cyclopropyl-2-((3-(3,6-dihydro-2H-pyran-4-yl)-2-ethoxy-4-fluorophenyl)amino)nicotinic acid, 2-cyclopropyl-5-((3-(3,6-dihydro-2H-pyran-4-yl)-2-(2,2,2-trifluoroethoxy)phenyl)amino)isonicotinic acid, and (S)-6-cyclopropyl-3-((3-(tetrahydro-2H-pyran-4-yl)-2-((1,1,1-trifluoropropan-2-yl)oxy)phenyl)amino)pyrazine-4-carboxylic acid.

Dependencies are inferred from the claim text.

Facts

Application: 18/160,690Filed 27 Jan 2023 · continuation
Priority: JP 2020-12883230 Jul 2020
Published: US 2023/0167074 A11 Jun 2023
Granted: 26 May 2026
Term ends: Not estimatedThe source records don’t support an estimate.

Classification15 codes

A61P 35/00
Antineoplastic agents
C07D 241/28
With nitrogen atoms directly attached to ring carbon atoms: in which said hetero-bound carbon atoms have double bonds to oxygen, sulfur or…
A61P 35/02
Antineoplastic agents: specific for leukemia
A61P 43/00
Drugs for specific purposes, not provided for in groups a61p1/00-a61p41/00