US 11,932,601 B2 · Immunoregulatory agents

Abstract

Compounds that modulate the oxidoreductase enzyme indoleamine 2,3-dioxygenase, and compositions containing the compounds, are described herein. The use of such compounds and compositions for the treatment and/or prevention of a diverse array of diseases, disorders and conditions, including cancer- and immune-related disorders, that are mediated by indoleamine 2,3-dioxygenase is also provided.

A compound that is:

cis-N-(5-Chloropyridin-2-yl)-2-((1,4)-4-phenylcyclohexyl) acetamide;
trans-N-(5-Chloropyridin-2-yl)-241,4)-4-phenylcyclohexyl)acetamide;
cis-N-(4-(2-Hydroxypropan-2-yl)phenyl)-2-((1,4)-4-phenylcyclohexyl)acetamide;
trans-N-(4-(2-Hydroxypropan-2-yl)phenyl)-2-((1,4)-4-phenylcyclohexyl)acetamide;
cis-N-(4-(Hydroxymethyl)phenyl)-2-((1,4)-4-phenylcyclohexyl)acetamide;
trans-N-(4-(Hydroxymethyl)phenyl)-2-((1,4)-4-phenylcyclohexyl)acetamide;
cis-N-(4-Chlorophenyl)-2-(4-phenylcyclohexyl)acetamide;
trans-N-(4-Chlorophenyl)-2-(4-phenylcyclohexyl)acetamide;
cis-N-Phenyl-2-(4-phenylcyclohexyl)acetamide;
cis-N-(4-Methoxyphenyl)-2-(4-phenylcyclohexyl)acetamide;
cis-N-(4-Methoxy-3-fluorophenyl)-2-(4-phenylcyclohexyl)acetamide;
cis-N-(4-Fluorophenyl)-2-(4-phenylcyclohexyl)acetamide;
cis-N-(4-Methylphenyl)-2-(4-phenylcyclohexyl)acetamide;
N-(4-Cyanophenyl)-2-(4-phenylcyclohexyl)acetamide;
N-(4-Trifluoromethoxyphenyl)-2-(4-phenylcyclohexyl)acetamide,
N-(4-Bromophenyl)-2-(4-phenylcyclohexyl)acetamide,
cis-N-(4-Tertbutylphenyl)-2-(4-phenylcyclohexyl)acetamide,
cis-N-(3-Fluoro-4-chlorophenyl)-2-(4-(4-methoxyphenyl)cyclohexyl)acetamide,
trans-N-(3-Fluoro-4-chlorophenyl)-2-(4-(4-methoxyphenyl)cyclohexyl)acetamide,
cis-N-([1, 1-Biphenyl]-4-yl)-2-(4-phenylcyclohexyl)acetamide,
trans-N-([1, 1’-Biphenyl]-4-yl)-2-(4-phenylcyclohexyl)acetamide,
cis-N-(4-Chloro-2-fluorophenyl)-2-(4-phenylcyclohexyl)acetamide,
trans-N-(4-Chloro-2-fluorophenyl)-2-(4-phenyl cyclohexyl)acetamide,
2-(-4-(4-Methoxyphenyl)cyclohexyl)-N-(4-(methylthio)phenyl)acetamide,
trans-2-(4-(4-Methoxyphenyl)cyclohexyl)-N-(4-(methylthio)phenyl)acetamide,
cis-2-(4-(4-Methoxyphenyl)cyclohexyl)-N-(4-(methyl sulfonyl)phenyl)acetamide,
cis-N-(3-Cyanophenyl)-2-(4-(4-methoxyphenyl)cyclohexyl)acetamide,
trans-N-(3-Cyanophenyl)-2-(4-(4-methoxyphenyl)cyclohexyl)acetamide,
cis-N-(4-Cyclopropylphenyl)-2-41,4)-4-(4-methoxyphenyl)cyclohexyl)acetamide,
trans-N-(4-Cyclopropylphenyl)-2-41,4)-4-(4-methoxyphenyl)cyclohexyl)acetamide,
cis-N-(3-Fluoro-4-chlorophenyl)-2-(4-(4-methoxyphenyl)cyclohexyl)acetamide,
cis-N-(4-Tertbutylphenyl)-2-(4-(4-methoxyphenyl)cyclohexyl)acetamide,
cis-N-(3,4-Difluorophenyl)-2-(4-(4-methoxyphenyl)cyclohexyl)acetamide,
trans-N-(3,4-Difluorophenyl)-2-(4-(4-methoxyphenyl)cyclohexyl)acetamide,
cis-N-(4-Fluorophenyl)-2-(4-(4-methoxyphenyl)cyclohexyl)acetamide,
trans-N-(4-Fluorophenyl)-2-(4-(4-methoxyphenyl)cyclohexyl)acetamide,
cis-N-(4-Cyanophenyl)-2-(4-(4-methoxyphenyl)cyclohexyl)acetamide,
cis-N-(4-Chlorophenyl)-241,4)-4-(4-methoxyphenyl)cyclohexyl)acetamide,
cis-N-(4-Chlorophenyl)-241,4)-4-(4-methoxyphenyl)cyclohexyl)acetamide,
cis-N-([1, 1′-Biphenyl]-4-yl)-2-(4-(4-methoxyphenyl)cyclohexyl)acetamide,
cis-N-(4-Chloro-2-fluorophenyl)-2-(4-(4-methoxyphenyl)cyclohexyl)acetamide,
trans-N-(4-Chloro-2-fluorophenyl)-2-(4-(4-methoxyphenyl)cyclohexyl)acetamide,
cis-N-(4-Chlorophenyl)-2-(4-(4-cyanophenyl)cyclohexyl)acetamide,
cis-N-(4-Fluorophenyl)-2-(4-(4-cyanophenyl)cyclohexyl)acetamide,
cis-N-(4-Chlorophenyl)-2-(4-(4-fluorophenyl)cyclohexyl)acetamide;
trans-N-(4-Chlorophenyl)-2-(4-(4-fluorophenyl)cyclohexyl)acetamide;
cis-N-(4-Fluorophenyl)-2-(4-(4-fluorophenyl)cyclohexyl)acetamide;
trans-N-(4-Fluorophenyl)-2-(4-(4-fluorophenyl)cyclohexyl)acetamide;
cis-N-(4-Chlorophenyl)-2-(4-(4-methylphenyl)cyclohexyl)acetamide;
cis-N-(4-Chlorophenyl)-2-(4-(4-methylphenyl)cyclohexyl)acetamide;
cis-N-(4-Fluorophenyl)-2-(4-(4-methylphenyl)cyclohexyl)acetamide;
N-(4-Chlorophenyl)-2-(4-(4-morpholinophenyl)cyclohexyl)acetamide;
N-(4-Chlorophenyl)-2-(4-(4-morpholinophenyl)cyclohexyl)acetamide;
N-(4-Fluorophenyl)-2-(4-(4-morpholinophenyl)cyclohexyl)acetamide;
2-(4-(4-(Dimethylamino)phenyl)cyclohexyl)-N-(4-chlorophenyl)acetamide;
2-(4-(4-(Dimethylamino)phenyl)cyclohexyl)-N-(4-fluorophenyl)acetamide;
cis-N-(4-Chlorophenyl)-2-(4-(4-isopropoxyphenyl)cyclohexyl)acetamide;
trans-N-(4-Chlorophenyl)-2-(4-(4-isopropoxyphenyl)cyclohexyl)acetamide;
cis-N-(4-Chlorophenyl)-2-(4-(4-isopropoxyphenyl)cyclohexyl)acetamide;
trans-N-(4-Chlorophenyl)-2-(4-(4-isopropoxyphenyl)cyclohexyl)acetamide;
cis-N-(4-Fluorophenyl)-2-(4-(4-isopropoxyphenyl)cyclohexyl)acetamide;
trans-N-(4-Fluorophenyl)-2-(4-(4-isopropoxyphenyl)cyclohexyl)acetamide;
cis-N-(4-Fluorophenyl)-2-(4-(4-isopropoxyphenyl)cyclohexyl)acetamide;
trans-N-(4-Fluorophenyl)-2-(4-(4-isopropoxyphenyl)cyclohexyl)acetamide;
cis-N-(4-Fluorophenyl)-2-(4-(4-ethoxyphenyl)cyclohexyl)acetamide;
trans-N-(4-Fluorophenyl)-2-(4-(4-ethoxyphenyl)cyclohexyl)acetamide;
cis-N-(4-Chlorophenyl)-2-(4-(4-(methylsulfonyl)phenyl)cyclohexyl)acetamide;
trans-N-(4-Chlorophenyl)-2-(4-(4-(methylsulfonyl)phenyl)cyclohexyl)acetamide;
cis-N-(4-Fluorophenyl)-2-(4-(4-(methylsulfonyl)phenyl)cyclohexyl)acetamide;
trans-N-(4-Fluorophenyl)-2-(4-(4-(methylsulfonyl)phenyl)cyclohexyl)acetamide;
cis-4-(-4-(2-((4-Chlorophenyl)amino)-2-oxoethyl)cyclohexyl)benzoic acid;
trans-4-(4-(2-((4-Chlorophenyl)amino)-2-oxoethyl)cyclohexyl)benzoic acid;
cis-4-(4-(2-((4-Chlorophenyl)amino)-2-oxoethyl)cyclohexyl)benzamide;
trans-4-(4-(2-(4-Chlorophenyl)amino)-2-oxoethyl)cyclohexyl)benzamide;
cis-4-(4-(2-((4-Chlorophenyl)amino)-2-oxoethyl)cyclohexyl)benzamide,
trans-4-(4-(2-(4-Chlorophenyl)amino)-2-oxoethyl)cyclohexyl)benzamide,
cis-4-(4-(2-((4-Fluorophenyl)amino)-2-oxoethyl)cyclohexyl)benzamide,
trans-4-(4-(2-((4-Fluorophenyl)amino)-2-oxoethyl)cyclohexyl)benzamide,
cis-4-(4-(2-((4-Fluorophenyl)amino)-2-oxoethyl)cyclohexyl)benzamide,
trans-4-(4-(2-((4-Fluorophenyl)amino)-2-oxoethyl)cyclohexyl)benzamide,
cis-N-(4-Cyanophenyl)-2-41,4)-4-(4-(trifluoromethoxy)phenyl)cyclohexyl)-acetamide,
trans-N-(4-Cyanophenyl)-2-((1,4)-4-(4-(trifluoromethoxy)phenyl)cyclohexyl)-acetamide,
cis-N-(4-Fluorophenyl)-2-41,4)-4-(4-(trifluoromethoxy)phenyl)cyclohexyl)-acetamide,
trans-N-(4-Fluorophenyl)-2-41,4)-4-(4-(trifluoromethoxy)phenyl)cyclohexyl)-acetamide,
cis-N-(4-Chlorophenyl)-2-41,4)-4-(4-(trifluoromethoxy)phenyl)cyclohexyl)-acetamide,
trans-N-(4-Chlorophenyl)-2-41,4)-4-(4-(trifluoromethoxy)phenyl)cyclohexyl)-acetamide,
cis-N-(4-Chlorophenyl)-2-(4-(4-ethoxyphenyl)cyclohexyl)acetamide,
trans-N-(4-Chlorophenyl)-2-(4-(4-ethoxyphenyl)cyclohexyl)acetamide,
cis-N-(4-Chlorophenyl)-2-(4-(3-cyanophenyl)cyclohexyl)acetamide,
trans-N-(4-Chlorophenyl)-2-(4-(3-cyanophenyl)cyclohexyl)acetamide;
cis-N-(4-Fluorophenyl)-2-(4-(3-cyanophenyl)cyclohexyl)acetamide,
trans-N-(4-Fluorophenyl)-2-(4-(3-cyanophenyl)cyclohexyl)acetamide,
cis-N-(4-Cyanophenyl)-2-(4-(3-cyanophenyl)cyclohexyl)acetamide,
trans-N-(4-Cyanophenyl)-2-(4-(3-cyanophenyl)cyclohexyl)acetamide;
cis-N-(4-Chlorophenyl)-2-(4-(3-((2-oxopyrrolidin-1-yl)methyl)phenyl)cyclohexyl) acetamide,
trans-N-(4-Chlorophenyl)-2-(4-(3-((2-oxopyrrolidin-1-yl)methyl)phenyl)cyclohexyl) acetamide,
cis-N-(4-Fluorophenyl)-2-(4-(3-((2-oxopyrrolidin-1-yl)methyl)phenyl)cyclohexyl) acetamide,
trans-N-(4-Fluorophenyl)-2-(4-(3-((2-oxopyrrolidin-1-yl)methyl)phenyl)cyclohexyl) acetamide,
cis-N-(4-Cyanophenyl)-2-(4-(3-((2-oxopyrrolidin-1-yl)methyl)phenyl)cyclohexyl) acetamide;
trans-N-(4-Cyanophenyl)-2-(4-(3-((2-oxopyrrolidin-1-yl)methyl)phenyl)cyclohexyl) acetamide;
cis-N-(4-Chlorophenyl)-2-(4-(3-fluorophenyl)cyclohexyl)acetamide;
cis-N-(4-Chlorophenyl)-2-(4-(3-fluorophenyl)cyclohexyl)acetamide;
cis-N-(4-Fluorophenyl)-2-(4-(3-fluorophenyl)cyclohexyl)acetamide;
trans-N-(4-Fluorophenyl)-2-(4-(3-fluorophenyl)cyclohexyl)acetamide;
cis-N-(4-Cyanophenyl)-2-(4-(3-carboxyphenyl)cyclohexyl)acetamide;
trans-N-(4-Cyanophenyl)-2-(4-(3-carboxyphenyl)cyclohexyl)acetamide;
cis-N-(4-Chlorophenyl)-2-(4-(3-carboxyphenyl)cyclohexyl)acetamide;
trans-N-(4-Chlorophenyl)-2-(4-(3-carboxyphenyl)cyclohexyl)acetamide;
cis-N-(4-Fluorophenyl)-2-(4-(3-carboxyphenyl)cyclohexyl)acetamide;
trans-N-(4-Fluorophenyl)-2-(4-(3-carboxyphenyl)cyclohexyl)acetamide;
cis-N-(4-Cyanophenyl)-2-(4-(3-carboxamidophenyl)cyclohexyl)acetamide;
trans-N-(4-Cyanophenyl)-2-(4-(3-carboxamidophenyl)cyclohexyl)acetamide;
cis-N-(4-Chlorophenyl)-2-(4-(3-carboxamidophenyl)cyclohexyl)acetamide;
trans-N-(4-Chlorophenyl)-2-(4-(3-carboxamidophenyl)cyclohexyl)acetamide;
cis-N-(4-Fluorophenyl)-2-(4-(3-carboxamidophenyl)cyclohexyl)acetamide;
trans-N-(4-Fluorophenyl)-2-(4-(3-carboxamidophenyl)cyclohexyl)acetamide;
cis-N-(4-Chlorophenyl)-2-(4-(2-fluorophenyl)cyclohexyl)acetamide;
cis-N-(4-Fluorophenyl)-2-(4-(2-fluorophenyl)cyclohexyl)acetamide;
cis-N-(4-Fluorophenyl)-2-(4-(2-fluorophenyl)cyclohexyl)acetamide;
trans-N-(4-Chlorophenyl)-2-(4-(3-methoxyphenyl)cyclohexyl)acetamide;
cis-N-(4-Chloro-3-fluorophenyl)-2-(4-(3-methoxyphenyl)cyclohexyl)acetamide;
trans-N-(4-Chloro-3-fluorophenyl)-2-(4-(3-methoxyphenyl)cyclohexyl)acetamide;
cis-N-(4-Cyanophenyl)-2-(4-(3-methoxyphenyl)cyclohexyl)acetamide;
cis-N-(4-Fluorophenyl)-2-(4-(3-methoxyphenyl)cyclohexyl)acetamide;
trans-N-(4-Fluorophenyl)-2-(4-(3-methoxyphenyl)cyclohexyl)acetamide;
cis-N-(4-Chlorophenyl)-2-(4-(2-methoxyphenyl)cyclohexyl)acetamide;
trans-N-(4-Chlorophenyl)-2-(4-(2-methoxyphenyl)cyclohexyl)acetamide,
cis-N-(4-Cyanophenyl)-2-(4-(2-methoxyphenyl)cyclohexyl)acetamide,
cis-N-(4-Cyanophenyl)-2-(4-(2-methoxyphenyl)cyclohexyl)acetamide,
cis-N-(4-Fluorophenyl)-2-(4-(2-methoxyphenyl)cyclohexyl)acetamide,
trans-N-(4-Fluorophenyl)-2-(4-(2-methoxyphenyl)cyclohexyl)acetamide,
cis-2-(4-(2-Chloro-4-methoxyphenyl)cyclohexyl)-N-(4-chlorophenyl)acetamide,
cis-2-(4-(2-Chloro-4-methoxyphenyl)cyclohexyl)-N-(4-fluorophenyl)acetamide,
cis-2-(4-(4-Chloro-2-fluorophenyl)cyclohexyl)-N-(4-chlorophenyl)acetamide,
trans-2-(4-(4-Chloro-2-fluorophenyl)cyclohexyl)-N-(4-chlorophenyl)acetamide;
cis-2-(4-(4-Chloro-2-fluorophenyl)cyclohexyl)-N-(4-fluorophenyl)acetamide,
trans-2-(4-(4-Chloro-2-fluorophenyl)cyclohexyl)-N-(4-fluorophenyl)acetamide,
cis-2-(4-(4-Chloro-3-fluorophenyl)cyclohexyl)-N-(4-chlorophenyl)acetamide,
trans-2-(4-(4-Chloro-3-fluorophenyl)cyclohexyl)-N-(4-chlorophenyl)acetamide;
cis-2-(4-(4-Chloro-3-fluorophenyl)cyclohexyl)-N-(4-fluorophenyl)acetamide,
trans-2-(4-(4-Chloro-3-fluorophenyl)cyclohexyl)-N-(4-fluorophenyl)acetamide,
N-(4-Cyanophenyl)-2-(4-(2-fluoro-4-methoxyphenyl)cyclohexyl)acetamide,
N-(4-Fluorophenyl)-2-(4-(2-fluoro-4-methoxyphenyl)cyclohexyl)acetamide,
N-(4-Chlorophenyl)-2-(4-(2-fluoro-4-methoxyphenyl)cyclohexyl)acetamide,
cis-N-(4-Chlorophenyl)-2-(4-(3-chloro-4-methoxyphenyl)cyclohexyl)acetamide,
trans-N-(4-Chlorophenyl)-2-(4-(3-chloro-4-methoxyphenyl)cyclohexyl)acetamide,
cis-N-(4-Cyanophenyl)-2-(4-(3-chloro-4-methoxyphenyl)cyclohexyl)acetamide,
trans-N-(4-Cyanophenyl)-2-(4-(3-chloro-4-methoxyphenyl)cyclohexyl)acetamide,
cis-N-(4-Fluorophenyl)-2-(4-(3-chloro-4-methoxyphenyl)cyclohexyl)acetamide,
trans-N-(4-Fluorophenyl)-2-(4-(3-chloro-4-methoxyphenyl)cyclohexyl)acetamide,
cis-N-(4-Cyanophenyl)-2,2-di fluoro-2-(1-hydroxy-4-phenylcyclohexyl)acetamide,
cis-N-(4-Chlorophenyl)-2,2-difluoro-2-(1-hydroxy-4-phenylcyclohexyl)acetamide,
cis-N-(4-Fluorophenyl)-2,2-difluoro-2-(1-hydroxy-4-phenylcyclohexyl)acetamide,
trans-N-(4-Cyanophenyl)-2,2-difluoro-2-(1-hydroxy-4-phenylcyclohexyl)acetamide,
cis-N-(4-Chlorophenyl)-2,2-difluoro-2-(1-hydroxy-4-phenylcyclohexyl)acetamide,
trans-N-(4-Fluorophenyl)-2,2-difluoro-2-(1-hydroxy-4-phenylcyclohexyl)acetamide,
trans-N-(4-Fluorophenyl)-2-(1-hydroxy-4-phenylcyclohexyl)acetamide;
trans-N-(4-Chlorophenyl)-2-(1-hydroxy-4-phenylcyclohexyl)acetamide;
trans-N-(4-Cyanophenyl)-2-(1-hydroxy-4-phenylcyclohexyl)acetamide;
cis-N-(4-Fluorophenyl)-2-(1-hydroxy-4-phenylcyclohexyl)acetamide;
cis-N-(4-Chlorophenyl)-2-(1-hydroxy-4-phenylcyclohexyl)acetamide;
cis-N-(4-Cyanophenyl)-2-(1-hydroxy-4-phenylcyclohexyl)acetamide;
cis-N-(4-Chlorophenyl)-2-(1-hydroxy-4-phenylcyclohexyl)propenamide;
cis-N-(4-Fluorophenyl)-2-(1-hydroxy-4-phenylcyclohexyl)propenamide;
cis-N-(4-Cyanophenyl)-2-(1-hydroxy-4-phenylcyclohexyl)propenamide;
cis-N-(4-Cyanophenyl)-2-41,4)-4-(4-methoxyphenyl)cyclohexyl)propenamide;
trans-N-(4-Cyanophenyl)-2-41,4)-4-(4-methoxyphenyl)cyclohexyl)propenamide;
cis-N-(4-Fluorophenyl)-2-41,4)-4-(4-methoxyphenyl)cyclohexyl)propenamide;
cis-N-(4-Chlorophenyl)-2-41,4)-4-(4-methoxyphenyl)cyclohexyl)propenamide;
trans-N-(4-Chlorophenyl)-2-41,4)-4-(4-methoxyphenyl)cyclohexyl)propenamide;
cis-N-(4-Cyanophenyl)-2-((1,4)-4-phenylcyclohexyl)propenamide;
trans-N-(4-Cyanophenyl)-2-((1,4)-4-phenylcyclohexyl)propenamide;
cis-N-(4-Fluorophenyl)-2-((1,4)-4-phenylcyclohexyl)propenamide;
trans-N-(4-Fluorophenyl)-2-((1,4)-4-phenylcyclohexyl)propenamide;
cis-N-(4-Chlorophenyl)-241,4)-4-phenylcyclohexyl)propenamide;
trans-N-(4-Chlorophenyl)-241,4)-4-phenylcyclohexyl)propenamide;
N-(4-Chlorophenyl)-2-(4-fluoro-4-phenylcyclohexyl)acetamide;
(cis)-N-(4-Chlorophenyl)-2-(4-(2,4-dimethoxyphenyl)cyclohexyl)acetamide;
(trans)-N-(4-Chlorophenyl)-2-(4-(2,4-dimethoxyphenyl)cyclohexyl)-acetamide;
(cis)-N-(4-Cyanophenyl)-2-(4-(2,4-dimethoxyphenyl)cyclohexyl)acetamide;
(cis)-N-(4-Fluorophenyl)-2-(4-(2,4-dimethoxyphenyl)cyclohexyl)acetamide;
2-(4-(4-Acetamidophenyl)cyclohexyl)-N-(4-chlorophenyl)-acetamide;
2-(4-(4-A cetamidophenyl)cyclohexyl)-N-(4-fluorophenyl)-acetamide;
cis-2-(4-(4-Methoxyphenyl)cyclohexyl)-N-(4-(tetrahydro-2H-pyran-4-yl)phenyl) acetamide;
N-(4-Chlorophenyl)-2-(4-(4-hydroxyphenyl)cyclohexyl)acetamide;
(S)—N-(4-Cyanophenyl)-2-((1s,4r-4-phenylcyclohexyl)propenamide,
(R)—N-(4-Cyanophenyl)-2-((1s,4r)-4-phenylcyclohexyl)propenamide,
(R)—N-(4-Cyanophenyl)-2-((1s,4s)-4-(4-methoxyphenyl)cyclohexyl)propenamide,
2-(4-([1,1′-biphenyl]-3-yl)cyclohexyl)-N-(4-chlorophenyl) propenamide,
or a pharmaceutically acceptable salt, hydrate or solvate thereof.

187 more elements

Immunoregulatory agents

Life of this patent

Immunoregulatory agents

Life of this patent

Abstract

Claims17