US 12,331,054 B2Granted

Perk inhibiting imidazolopyrazine compounds

AssigneeHiberCell, Inc.

InventorsMark J. Mulvihill, An-Hu Li, Matthew David Surman

Life of this patent

Estimating the term…

Abstract

Provided herein are compounds, compositions, and methods useful for inhibiting PERK and for treating related conditions, diseases, and disorders.

Claims36

Dependent claims

A compound of the formula (I):

Ar1 is aryl, heteroaryl, or cycloalkyl, optionally substituted by one or more independent R1 substituents;
Ar2 is aryl or heteroaryl, optionally substituted by one or more independent R2 substituents;
Y is CR3aR3b, C(O), CF2, or CNOR3bb;
R3a is H, alkyl, or cycloalkyl;
R3b is H, alkyl, OR3c, or NR3dR3e;
R3bb is H or alkyl;
R4 is H, alkyl, or OH;
X is CR7 or N;
R1 is one or more independent H, deuterium, halo, CN, NO2, alkyl, cycloalkyl, C0-6alkyl-O—C1-12alkyl, C0-6alkyl-OH, C0-6alkyl-O—C3-12cycloalkyl, or C0-6alkyl-O—C3-12heterocycloalkyl, optionally substituted by one or more independent G1 substituents;
R2 is one or more independent H, deuterium, halo, CN, NO2, alkyl, C0-6alkylcycloalkyl, C0-6alkyl-O—C1-12alkyl, C0-6alkyl-OH, or C0-6alkyl-O—C3-12cycloalkyl, optionally substituted by one or more independent G2 substituents;
R3c, R3d and R3e are each independently H, alkyl, or cycloalkyl, optionally substituted by one or more independent G3 substituents;
R5 is H, deuterium, halo, alkyl, cycloalkyl, or heterocycloalkyl, optionally substituted by one or more independent G4 substituents;
R6 is H, alkyl, CD3, or CF3;
R7 is H, deuterium, halo, CN, alkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl, optionally substituted by one or more independent H, deuterium or halo;
G1, G2, G3, or G4 are each independently H, deuterium, halo, CN, NO2, C1-12alkyl, C0-12alkylC3-12cycloalkyl, C0-12alkylC3-12heterocycloalkyl, OR8, NR8R9, C(O)R8, C(O)OR8, C(O)NR8R9, OC(O)R8, OC(O)OR8, OC(O)NR8R9, N(R10)C(O)R8, N(R10)C(O)OR8, N(R10)C(O)NR8R9, S(O)nR8, S(O)nOR8, S(O)nNR8R9, N(R10)S(O)nR8, N(R10)S(O)nOR8, or N(R10)S(O)nNR8R9, optionally substituted by one or more independent H, deuterium, halo, OH, CN, or NO2;
R8, R9, or R10 are each independently selected from H, deuterium, halo, CN, NO2, alkyl, cycloalkyl or heterocycloalkyl, optionally substituted by one or more independent H, deuterium, halo, OH, CN, or NO2;
n is 0, 1, or 2;
or a pharmaceutically acceptable salt thereof.

15 more elements

A compound selected from the group consisting of:

N-(4-(8-amino-3-methylimidazo[1,5-a]pyrazin-1-yl)-3-methylphenyl)-2-(3-fluorophenyl)-2-hydroxyacetamide;
(R)—N-(4-(8-amino-3-methylimidazo[1,5-a]pyrazin-1-yl)-3-methylphenyl)-2-(3-fluorophenyl)-2-hydroxyacetamide;
(S)—N-(4-(8-amino-3-methylimidazo[1,5-a]pyrazin-1-yl)-3-methylphenyl)-2-(3-fluorophenyl)-2-hydroxyacetamide;
N-(4-(8-amino-3,6-dimethylimidazo[1,5-a]pyrazin-1-yl)-3-methylphenyl)-2-(3-fluorophenyl)-2-hydroxyacetamide;
(R)—N-(4-(8-amino-3,6-dimethylimidazo[1,5-a]pyrazin-1-yl)-3-methylphenyl)-2-(3-fluorophenyl)-2-hydroxyacetamide;
(S)—N-(4-(8-amino-3,6-dimethylimidazo[1,5-a]pyrazin-1-yl)-3-methylphenyl)-2-(3-fluorophenyl)-2-hydroxyacetamide;
N-(4-(8-amino-6-methyl-3-(trideuteriomethyl)imidazo[1,5-a]pyrazin-1-yl)-3-methylphenyl)-2-(3-fluorophenyl)-2-hydroxyacetamide;
(R)—N-(4-(8-amino-6-methyl-3-(trideuteriomethyl)imidazo[1,5-a]pyrazin-1-yl)-3-methylphenyl)-2-(3-fluorophenyl)-2-hydroxyacetamide;
(S)—N-(4-(8-amino-6-methyl-3-(trideuteriomethyl)imidazo[1,5-a]pyrazin-1-yl)-3-methylphenyl)-2-(3-fluorophenyl)-2-hydroxyacetamide;
N-(4-(8-amino-3,5-dimethylimidazo[1,5-a]pyrazin-1-yl)-3-methylphenyl)-2-(3-fluorophenyl)-2-hydroxyacetamide;
(R)—N-(4-(8-amino-3,5-dimethylimidazo[1,5-a]pyrazin-1-yl)-3-methylphenyl)-2-(3-fluorophenyl)-2-hydroxyacetamide;
(S)—N-(4-(8-amino-3,5-dimethylimidazo[1,5-a]pyrazin-1-yl)-3-methylphenyl)-2-(3-fluorophenyl)-2-hydroxyacetamide;
N-(4-(8-amino-5-methyl-3-(trideuteriomethyl)imidazo[1,5-a]pyrazin-1-yl)-3-methylphenyl)-2-(3-fluorophenyl)-2-hydroxyacetamide;
(R)—N-(4-(8-amino-5-methyl-3-(trideuteriomethyl)imidazo[1,5-a]pyrazin-1-yl)-3-methylphenyl)-2-(3-fluorophenyl)-2-hydroxyacetamide;
(S)—N-(4-(8-amino-5-methyl-3-(trideuteriomethyl)imidazo[1,5-a]pyrazin-1-yl)-3-methylphenyl)-2-(3-fluorophenyl)-2-hydroxyacetamide;
N-(4-(8-amino-3,6-dimethylimidazo[1,5-a]pyrazin-1-yl)-3-methylphenyl)-2-(3-fluorophenyl)-2-hydroxyacetamide;
(R)—N-(4-(8-amino-3,6-dimethylimidazo[1,5-a]pyrazin-1-yl)-3-methylphenyl)-2-(3-fluorophenyl)-2-hydroxyacetamide;
(S)—N-(4-(8-amino-3,6-dimethylimidazo[1,5-a]pyrazin-1-yl)-3-methylphenyl)-2-(3-fluorophenyl)-2-hydroxyacetamide;
N-[4-[8-amino-6-methyl-3-(trideuteriomethyl)imidazo[1,5-a]pyrazin-1-yl]-3-methyl-phenyl]-2-hydroxy-2-[3-(trifluoromethyl)phenyl]acetamide;
(R)—N-[4-[8-amino-6-methyl-3-(trideuteriomethyl)imidazo[1,5-a]pyrazin-1-yl]-3-methyl-phenyl]-2-hydroxy-2-[3-(trifluoromethyl)phenyl]acetamide;
(S)—N-[4-[8-amino-6-methyl-3-(trideuteriomethyl)imidazo[1,5-a]pyrazin-1-yl]-3-methyl-phenyl]-2-hydroxy-2-[3-(trifluoromethyl)phenyl]acetamide;
N-[4-[8-amino-5-methyl-3-(trideuteriomethyl)imidazo[1,5-a]pyrazin-1-yl]-3-methyl-phenyl]-2-hydroxy-2-[3-(trifluoromethyl)phenyl]acetamide;
(R)—N-[4-[8-amino-5-methyl-3-(trideuteriomethyl)imidazo[1,5-a]pyrazin-1-yl]-3-methyl-phenyl]-2-hydroxy-2-[3-(trifluoromethyl)phenyl]acetamide;
(S)—N-[4-[8-amino-5-methyl-3-(trideuteriomethyl)imidazo[1,5-a]pyrazin-1-yl]-3-methyl-phenyl]-2-hydroxy-2-[3-(trifluoromethyl)phenyl]acetamide;
N-[4-[8-amino-5-chloro-3-(trideuteriomethyl)imidazo[1,5-a]pyrazin-1-yl]-3-methyl-phenyl]-2-hydroxy-2-[3-(trifluoromethyl)phenyl]acetamide;
(R)—N-[4-[8-amino-5-chloro-3-(trideuteriomethyl)imidazo[1,5-a]pyrazin-1-yl]-3-methyl-phenyl]-2-hydroxy-2-[3-(trifluoromethyl)phenyl]acetamide;
(S)—N-[4-[8-amino-5-chloro-3-(trideuteriomethyl)imidazo[1,5-a]pyrazin-1-yl]-3-methyl-phenyl]-2-hydroxy-2-[3-(trifluoromethyl)phenyl]acetamide;
N-[4-[8-amino-3-(trideuteriomethyl)-5-(trifluoromethyl)imidazo[1,5-a]pyrazin-1-yl]-3-methyl-phenyl]-2-hydroxy-2-[3-(trifluoromethyl)phenyl]acetamide;
(R)—N-[4-[8-amino-3-(trideuteriomethyl)-5-(trifluoromethyl)imidazo[1,5-a]pyrazin-1-yl]-3-methyl-phenyl]-2-hydroxy-2-[3-(trifluoromethyl)phenyl]acetamide;
(S)—N-[4-[8-amino-3-(trideuteriomethyl)-5-(trifluoromethyl)imidazo[1,5-a]pyrazin-1-yl]-3-methyl-phenyl]-2-hydroxy-2-[3-(trifluoromethyl)phenyl]acetamide;
N-(4-(8-amino-3,5,6-trimethylimidazo[1,5-a]pyrazin-1-yl)-3-methylphenyl)-2-(3-fluorophenyl)-2-hydroxyacetamide;
(R)—N-(4-(8-amino-3,5,6-trimethylimidazo[1,5-a]pyrazin-1-yl)-3-methylphenyl)-2-(3-fluorophenyl)-2-hydroxyacetamide;
(S)—N-(4-(8-amino-3,5,6-trimethylimidazo[1,5-a]pyrazin-1-yl)-3-methylphenyl)-2-(3-fluorophenyl)-2-hydroxyacetamide;
N-(4-(8-amino-3-(3-hydroxy-3-methylcyclobutyl)-6-methylimidazo[1,5-a]pyrazin-1-yl)-3-methylphenyl)-2-(3-fluorophenyl)-2-hydroxyacetamide;
(R)—N-(4-(8-amino-3-(3-hydroxy-3-methylcyclobutyl)-6-methylimidazo[1,5-a]pyrazin-1-yl)-3-methylphenyl)-2-(3-fluorophenyl)-2-hydroxyacetamide;
(S)—N-(4-(8-amino-3-(3-hydroxy-3-methylcyclobutyl)-6-methylimidazo[1,5-a]pyrazin-1-yl)-3-methylphenyl)-2-(3-fluorophenyl)-2-hydroxyacetamide;
N-(4-(8-amino-3-methyl-5-(trifluoromethyl)imidazo[1,5-a]pyrazin-1-yl)-3-methylphenyl)-2-(3-fluorophenyl)-2-hydroxyacetamide;
(R)—N-(4-(8-amino-3-methyl-5-(trifluoromethyl)imidazo[1,5-a]pyrazin-1-yl)-3-methylphenyl)-2-(3-fluorophenyl)-2-hydroxyacetamide;
(S)—N-(4-(8-amino-3-methyl-5-(trifluoromethyl)imidazo[1,5-a]pyrazin-1-yl)-3-methylphenyl)-2-(3-fluorophenyl)-2-hydroxyacetamide;
N-(4-(8-amino-5-chloro-3-methylimidazo[1,5-a]pyrazin-1-yl)-3-methylphenyl)-2-(3-fluorophenyl)-2-hydroxyacetamide;
(R)—N-(4-(8-amino-5-chloro-3-methylimidazo[1,5-a]pyrazin-1-yl)-3-methylphenyl)-2-(3-fluorophenyl)-2-hydroxyacetamide;
(S)—N-(4-(8-amino-5-chloro-3-methylimidazo[1,5-a]pyrazin-1-yl)-3-methylphenyl)-2-(3-fluorophenyl)-2-hydroxyacetamide;
N-[4-[8-amino-3-(trideuteriomethyl)-5-(trifluoromethyl)imidazo[1,5-a]pyrazin-1-yl]-3-methyl-phenyl]-2-(3-fluorophenyl)-2-hydroxy-acetamide;
(R)—N-[4-[8-amino-3-(trideuteriomethyl)-5-(trifluoromethyl)imidazo[1,5-a]pyrazin-1-yl]-3-methyl-phenyl]-2-(3-fluorophenyl)-2-hydroxy-acetamide;
(S)—N-[4-[8-amino-3-(trideuteriomethyl)-5-(trifluoromethyl)imidazo[1,5-a]pyrazin-1-yl]-3-methyl-phenyl]-2-(3-fluorophenyl)-2-hydroxy-acetamide;
N-[4-[8-amino-5-chloro-3-(trideuteriomethyl)imidazo[1,5-a]pyrazin-1-yl]-3-methyl-phenyl]-2-(3-fluorophenyl)-2-hydroxy-acetamide;
(R)—N-[4-[8-amino-5-chloro-3-(trideuteriomethyl)imidazo[1,5-a]pyrazin-1-yl]-3-methyl-phenyl]-2-(3-fluorophenyl)-2-hydroxy-acetamide;
(S)—N-[4-[8-amino-5-chloro-3-(trideuteriomethyl)imidazo[1,5-a]pyrazin-1-yl]-3-methyl-phenyl]-2-(3-fluorophenyl)-2-hydroxy-acetamide;
N-[4-[8-amino-6-methyl-3-(trideuteriomethyl)imidazo[1,5-a]pyrazin-1-yl]-3-methyl-phenyl]-2-(3-chlorophenyl)-2-hydroxy-acetamide;
(R)—N-[4-[8-amino-6-methyl-3-(trideuteriomethyl)imidazo[1,5-a]pyrazin-1-yl]-3-methyl-phenyl]-2-(3-chlorophenyl)-2-hydroxy-acetamide;
(S)—N-[4-[8-amino-6-methyl-3-(trideuteriomethyl)imidazo[1,5-a]pyrazin-1-yl]-3-methyl-phenyl]-2-(3-chlorophenyl)-2-hydroxy-acetamide;
N-[4-[8-amino-5-methyl-3-(trideuteriomethyl)imidazo[1,5-a]pyrazin-1-yl]-3-methyl-phenyl]-2-(3-chlorophenyl)-2-hydroxy-acetamide;
(R)—N-[4-[8-amino-5-methyl-3-(trideuteriomethyl)imidazo[1,5-a]pyrazin-1-yl]-3-methyl-phenyl]-2-(3-chlorophenyl)-2-hydroxy-acetamide;
(S)—N-[4-[8-amino-5-methyl-3-(trideuteriomethyl)imidazo[1,5-a]pyrazin-1-yl]-3-methyl-phenyl]-2-(3-chlorophenyl)-2-hydroxy-acetamide;
N-(4-(8-amino-3,5-dimethylimidazo[1,5-a]pyrazin-1-yl)-3-methylphenyl)-2-(3-chlorophenyl)-2-hydroxyacetamide;
(R)—N-(4-(8-amino-3,5-dimethylimidazo[1,5-a]pyrazin-1-yl)-3-methylphenyl)-2-(3-chlorophenyl)-2-hydroxyacetamide;
(S)—N-(4-(8-amino-3,5-dimethylimidazo[1,5-a]pyrazin-1-yl)-3-methylphenyl)-2-(3-chlorophenyl)-2-hydroxyacetamide;
N-[4-[8-amino-3-(trideuteriomethyl)-5-(trifluoromethyl)imidazo[1,5-a]pyrazin-1-yl]-3-methyl-phenyl]-2-(3-chlorophenyl)-2-hydroxy-acetamide;
(R)—N-[4-[8-amino-3-(trideuteriomethyl)-5-(trifluoromethyl)imidazo[1,5-a]pyrazin-1-yl]-3-methyl-phenyl]-2-(3-chlorophenyl)-2-hydroxy-acetamide;
(S)—N-[4-[8-amino-3-(trideuteriomethyl)-5-(trifluoromethyl)imidazo[1,5-a]pyrazin-1-yl]-3-methyl-phenyl]-2-(3-chlorophenyl)-2-hydroxy-acetamide;
N-[4-[8-amino-5-chloro-3-(trideuteriomethyl)imidazo[1,5-a]pyrazin-1-yl]-3-methyl-phenyl]-2-(3-chlorophenyl)-2-hydroxy-acetamide;
(R)—N-[4-[8-amino-5-chloro-3-(trideuteriomethyl)imidazo[1,5-a]pyrazin-1-yl]-3-methyl-phenyl]-2-(3-chlorophenyl)-2-hydroxy-acetamide;
(S)—N-[4-[8-amino-5-chloro-3-(trideuteriomethyl)imidazo[1,5-a]pyrazin-1-yl]-3-methyl-phenyl]-2-(3-chlorophenyl)-2-hydroxy-acetamide;
N-[4-[8-amino-6-methyl-3-(trideuteriomethyl)imidazo[1,5-a]pyrazin-1-yl]-3-methyl-phenyl]-2-(3,5-difluorophenyl)-2-hydroxy-acetamide;
(R)—N-[4-[8-amino-6-methyl-3-(trideuteriomethyl)imidazo[1,5-a]pyrazin-1-yl]-3-methyl-phenyl]-2-(3,5-difluorophenyl)-2-hydroxy-acetamide;
(S)—N-[4-[8-amino-6-methyl-3-(trideuteriomethyl)imidazo[1,5-a]pyrazin-1-yl]-3-methyl-phenyl]-2-(3,5-difluorophenyl)-2-hydroxy-acetamide;
N-[4-[8-amino-3-(trideuteriomethyl)-5-(trifluoromethyl)imidazo[1,5-a]pyrazin-1-yl]-3-methyl-phenyl]-2-(3,5-difluorophenyl)-2-hydroxy-acetamide;
(R)—N-[4-[8-amino-3-(trideuteriomethyl)-5-(trifluoromethyl)imidazo[1,5-a]pyrazin-1-yl]-3-methyl-phenyl]-2-(3,5-difluorophenyl)-2-hydroxy-acetamide;
(S)—N-[4-[8-amino-3-(trideuteriomethyl)-5-(trifluoromethyl)imidazo[1,5-a]pyrazin-1-yl]-3-methyl-phenyl]-2-(3,5-difluorophenyl)-2-hydroxy-acetamide;
N-[4-[8-amino-5-chloro-3-(trideuteriomethyl)imidazo[1,5-a]pyrazin-1-yl]-3-methyl-phenyl]-2-(3,5-difluorophenyl)-2-hydroxy-acetamide;
(R)—N-[4-[8-amino-5-chloro-3-(trideuteriomethyl)imidazo[1,5-a]pyrazin-1-yl]-3-methyl-phenyl]-2-(3,5-difluorophenyl)-2-hydroxy-acetamide;
(S)—N-[4-[8-amino-5-chloro-3-(trideuteriomethyl)imidazo[1,5-a]pyrazin-1-yl]-3-methyl-phenyl]-2-(3,5-difluorophenyl)-2-hydroxy-acetamide;
N-[4-[8-amino-5-methyl-3-(trideuteriomethyl)imidazo[1,5-a]pyrazin-1-yl]-3-methyl-phenyl]-2-(3,5-difluorophenyl)-2-hydroxy-acetamide;
(R)—N-[4-[8-amino-5-methyl-3-(trideuteriomethyl)imidazo[1,5-a]pyrazin-1-yl]-3-methyl-phenyl]-2-(3,5-difluorophenyl)-2-hydroxy-acetamide;
(S)—N-[4-[8-amino-5-methyl-3-(trideuteriomethyl)imidazo[1,5-a]pyrazin-1-yl]-3-methyl-phenyl]-2-(3,5-difluorophenyl)-2-hydroxy-acetamide;
N-[4-[8-amino-6-methyl-3-(trideuteriomethyl)imidazo[1,5-a]pyrazin-1-yl]-3-methyl-phenyl]-2-[3-fluoro-5-(trifluoromethyl)phenyl]-2-hydroxy-acetamide;
(R)—N-[4-[8-amino-6-methyl-3-(trideuteriomethyl)imidazo[1,5-a]pyrazin-1-yl]-3-methyl-phenyl]-2-[3-fluoro-5-(trifluoromethyl)phenyl]-2-hydroxy-acetamide;
(S)—N-[4-[8-amino-6-methyl-3-(trideuteriomethyl)imidazo[1,5-a]pyrazin-1-yl]-3-methyl-phenyl]-2-[3-fluoro-5-(trifluoromethyl)phenyl]-2-hydroxy-acetamide;
N-[4-[8-amino-5-methyl-3-(trideuteriomethyl)imidazo[1,5-a]pyrazin-1-yl]-3-methyl-phenyl]-2-[3-fluoro-5-(trifluoromethyl)phenyl]-2-hydroxy-acetamide;
(R)—N-[4-[8-amino-5-methyl-3-(trideuteriomethyl)imidazo[1,5-a]pyrazin-1-yl]-3-methyl-phenyl]-2-[3-fluoro-5-(trifluoromethyl)phenyl]-2-hydroxy-acetamide;
(S)—N-[4-[8-amino-5-methyl-3-(trideuteriomethyl)imidazo[1,5-a]pyrazin-1-yl]-3-methyl-phenyl]-2-[3-fluoro-5-(trifluoromethyl)phenyl]-2-hydroxy-acetamide;
N-[4-[8-amino-5-chloro-3-(trideuteriomethyl)imidazo[1,5-a]pyrazin-1-yl]-3-methyl-phenyl]-2-[3-fluoro-5-(trifluoromethyl)phenyl]-2-hydroxy-acetamide;
(R)—N-[4-[8-amino-5-chloro-3-(trideuteriomethyl)imidazo[1,5-a]pyrazin-1-yl]-3-methyl-phenyl]-2-[3-fluoro-5-(trifluoromethyl)phenyl]-2-hydroxy-acetamide;
(S)—N-[4-[8-amino-5-chloro-3-(trideuteriomethyl)imidazo[1,5-a]pyrazin-1-yl]-3-methyl-phenyl]-2-[3-fluoro-5-(trifluoromethyl)phenyl]-2-hydroxy-acetamide;
N-(4-(8-amino-3,5-dimethylimidazo[1,5-a]pyrazin-1-yl)-3-methylphenyl)-2-(3-fluoro-5-(trifluoromethyl)phenyl)-2-hydroxyacetamide;
(R)—N-(4-(8-amino-3,5-dimethylimidazo[1,5-a]pyrazin-1-yl)-3-methylphenyl)-2-(3-fluoro-5-(trifluoromethyl)phenyl)-2-hydroxyacetamide;
(S)—N-(4-(8-amino-3,5-dimethylimidazo[1,5-a]pyrazin-1-yl)-3-methylphenyl)-2-(3-fluoro-5-(trifluoromethyl)phenyl)-2-hydroxyacetamide;
N-[4-[8-amino-3-(trideuteriomethyl)-5-(trifluoromethyl)imidazo[1,5-a]pyrazin-1-yl]-3-methyl-phenyl]-2-[3-fluoro-5-(trifluoromethyl)phenyl]-2-hydroxy-acetamide;
(R)—N-[4-[8-amino-3-(trideuteriomethyl)-5-(trifluoromethyl)imidazo[1,5-a]pyrazin-1-yl]-3-methyl-phenyl]-2-[3-fluoro-5-(trifluoromethyl)phenyl]-2-hydroxy-acetamide;
(S)—N-[4-[8-amino-3-(trideuteriomethyl)-5-(trifluoromethyl)imidazo[1,5-a]pyrazin-1-yl]-3-methyl-phenyl]-2-[3-fluoro-5-(trifluoromethyl)phenyl]-2-hydroxy-acetamide;
N-(4-(8-amino-3,5-dimethylimidazo[1,5-a]pyrazin-1-yl)-3-methylphenyl)-2-(3-fluoro-5-methylphenyl)-2-hydroxyacetamide;
(R)—N-(4-(8-amino-3,5-dimethylimidazo[1,5-a]pyrazin-1-yl)-3-methylphenyl)-2-(3-fluoro-5-methylphenyl)-2-hydroxyacetamide;
(S)—N-(4-(8-amino-3,5-dimethylimidazo[1,5-a]pyrazin-1-yl)-3-methylphenyl)-2-(3-fluoro-5-methylphenyl)-2-hydroxyacetamide;
N-(4-(8-amino-3,5-dimethylimidazo[1,5-a]pyrazin-1-yl)-2-fluoro-5-methylphenyl)-2-(3-fluorophenyl)-2-hydroxyacetamide;
(R)—N-(4-(8-amino-3,5-dimethylimidazo[1,5-a]pyrazin-1-yl)-2-fluoro-5-methylphenyl)-2-(3-fluorophenyl)-2-hydroxyacetamide;
(S)—N-(4-(8-amino-3,5-dimethylimidazo[1,5-a]pyrazin-1-yl)-2-fluoro-5-methylphenyl)-2-(3-fluorophenyl)-2-hydroxyacetamide;
N-(4-(8-amino-3,5-dimethylimidazo[1,5-a]pyrazin-1-yl)-3-ethylphenyl)-2-(3-fluorophenyl)-2-hydroxyacetamide;
(R)—N-(4-(8-amino-3,5-dimethylimidazo[1,5-a]pyrazin-1-yl)-3-ethylphenyl)-2-(3-fluorophenyl)-2-hydroxyacetamide;
(S)—N-(4-(8-amino-3,5-dimethylimidazo[1,5-a]pyrazin-1-yl)-3-ethylphenyl)-2-(3-fluorophenyl)-2-hydroxyacetamide;
N-(4-(8-amino-3,5-dimethylimidazo[1,5-a]pyrazin-1-yl)phenyl)-2-(3-fluorophenyl)-2-hydroxyacetamide;
(R)—N-(4-(8-amino-3,5-dimethylimidazo[1,5-a]pyrazin-1-yl)phenyl)-2-(3-fluorophenyl)-2-hydroxyacetamide;
(S)—N-(4-(8-amino-3,5-dimethylimidazo[1,5-a]pyrazin-1-yl)phenyl)-2-(3-fluorophenyl)-2-hydroxyacetamide;
N-(4-(8-amino-3,5-dimethylimidazo[1,5-a]pyrazin-1-yl)-3-fluorophenyl)-2-(3-fluorophenyl)-2-hydroxyacetamide;
(R)—N-(4-(8-amino-3,5-dimethylimidazo[1,5-a]pyrazin-1-yl)-3-fluorophenyl)-2-(3-fluorophenyl)-2-hydroxyacetamide;
(S)—N-(4-(8-amino-3,5-dimethylimidazo[1,5-a]pyrazin-1-yl)-3-fluorophenyl)-2-(3-fluorophenyl)-2-hydroxyacetamide;
N-[4-[8-amino-5-methyl-3-(trideuteriomethyl)imidazo[1,5-a]pyrazin-1-yl]-3-fluoro-phenyl]-2-(3-fluorophenyl)-2-hydroxy-acetamide;
(R)—N-[4-[8-amino-5-methyl-3-(trideuteriomethyl)imidazo[1,5-a]pyrazin-1-yl]-3-fluoro-phenyl]-2-(3-fluorophenyl)-2-hydroxy-acetamide;
(S)—N-[4-[8-amino-5-methyl-3-(trideuteriomethyl)imidazo[1,5-a]pyrazin-1-yl]-3-fluoro-phenyl]-2-(3-fluorophenyl)-2-hydroxy-acetamide;
N-[4-[8-amino-5-chloro-3-(trideuteriomethyl)imidazo[1,5-a]pyrazin-1-yl]-3-fluoro-phenyl]-2-(3-fluorophenyl)-2-hydroxy-acetamide;
(R)—N-[4-[8-amino-5-chloro-3-(trideuteriomethyl)imidazo[1,5-a]pyrazin-1-yl]-3-fluoro-phenyl]-2-(3-fluorophenyl)-2-hydroxy-acetamide;
(S)—N-[4-[8-amino-5-chloro-3-(trideuteriomethyl)imidazo[1,5-a]pyrazin-1-yl]-3-fluoro-phenyl]-2-(3-fluorophenyl)-2-hydroxy-acetamide;
N-(4-(8-amino-3,5-dimethylimidazo[1,5-a]pyrazin-1-yl)-3-fluorophenyl)-2-(3-chlorophenyl)-2-hydroxyacetamide;
(R)—N-(4-(8-amino-3,5-dimethylimidazo[1,5-a]pyrazin-1-yl)-3-fluorophenyl)-2-(3-chlorophenyl)-2-hydroxyacetamide;
(S)—N-(4-(8-amino-3,5-dimethylimidazo[1,5-a]pyrazin-1-yl)-3-fluorophenyl)-2-(3-chlorophenyl)-2-hydroxyacetamide;
N-[4-[8-amino-6-methyl-3-(trideuteriomethyl)imidazo[1,5-a]pyrazin-1-yl]-3-fluoro-phenyl]-2-(3-chlorophenyl)-2-hydroxy-acetamide;
(R)—N-[4-[8-amino-6-methyl-3-(trideuteriomethyl)imidazo[1,5-a]pyrazin-1-yl]-3-fluoro-phenyl]-2-(3-chlorophenyl)-2-hydroxy-acetamide;
(S)—N-[4-[8-amino-6-methyl-3-(trideuteriomethyl)imidazo[1,5-a]pyrazin-1-yl]-3-fluoro-phenyl]-2-(3-chlorophenyl)-2-hydroxy-acetamide;
N-[4-[8-amino-3-(trideuteriomethyl)-5-(trifluoromethyl)imidazo[1,5-a]pyrazin-1-yl]-3-fluoro-phenyl]-2-(3-chlorophenyl)-2-hydroxy-acetamide;
(R)—N-[4-[8-amino-3-(trideuteriomethyl)-5-(trifluoromethyl)imidazo[1,5-a]pyrazin-1-yl]-3-fluoro-phenyl]-2-(3-chlorophenyl)-2-hydroxy-acetamide;
(S)—N-[4-[8-amino-3-(trideuteriomethyl)-5-(trifluoromethyl)imidazo[1,5-a]pyrazin-1-yl]-3-fluoro-phenyl]-2-(3-chlorophenyl)-2-hydroxy-acetamide;
N-[4-[8-amino-5-methyl-3-(trideuteriomethyl)imidazo[1,5-a]pyrazin-1-yl]-3-fluoro-phenyl]-2-(3-chlorophenyl)-2-hydroxy-acetamide;
(R)—N-[4-[8-amino-5-methyl-3-(trideuteriomethyl)imidazo[1,5-a]pyrazin-1-yl]-3-fluoro-phenyl]-2-(3-chlorophenyl)-2-hydroxy-acetamide;
(S)—N-[4-[8-amino-5-methyl-3-(trideuteriomethyl)imidazo[1,5-a]pyrazin-1-yl]-3-fluoro-phenyl]-2-(3-chlorophenyl)-2-hydroxy-acetamide;
N-[4-[8-amino-5-chloro-3-(trideuteriomethyl)imidazo[1,5-a]pyrazin-1-yl]-3-fluoro-phenyl]-2-(3-chlorophenyl)-2-hydroxy-acetamide;
(R)—N-[4-[8-amino-5-chloro-3-(trideuteriomethyl)imidazo[1,5-a]pyrazin-1-yl]-3-fluoro-phenyl]-2-(3-chlorophenyl)-2-hydroxy-acetamide;
(S)—N-[4-[8-amino-5-chloro-3-(trideuteriomethyl)imidazo[1,5-a]pyrazin-1-yl]-3-fluoro-phenyl]-2-(3-chlorophenyl)-2-hydroxy-acetamide;
N-(4-(8-amino-3,5-dimethylimidazo[1,5-a]pyrazin-1-yl)-3-fluorophenyl)-2-hydroxy-2-(m-tolyl) acetamide;
(R)—N-(4-(8-amino-3,5-dimethylimidazo[1,5-a]pyrazin-1-yl)-3-fluorophenyl)-2-hydroxy-2-(m-tolyl) acetamide;
(S)—N-(4-(8-amino-3,5-dimethylimidazo[1,5-a]pyrazin-1-yl)-3-fluorophenyl)-2-hydroxy-2-(m-tolyl) acetamide;
N-[4-[8-amino-5-methyl-3-(trideuteriomethyl)imidazo[1,5-a]pyrazin-1-yl]-3-fluoro-phenyl]-2-hydroxy-2-(m-tolyl) acetamide;
(R)—N-[4-[8-amino-5-methyl-3-(trideuteriomethyl)imidazo[1,5-a]pyrazin-1-yl]-3-fluoro-phenyl]-2-hydroxy-2-(m-tolyl) acetamide;
(S)—N-[4-[8-amino-5-methyl-3-(trideuteriomethyl)imidazo[1,5-a]pyrazin-1-yl]-3-fluoro-phenyl]-2-hydroxy-2-(m-tolyl) acetamide;
N-(4-(8-amino-3,5-dimethylimidazo[1,5-a]pyrazin-1-yl)-3-fluorophenyl)-2-hydroxy-2-(3-(trifluoromethyl)phenyl) acetamide;
(R)—N-(4-(8-amino-3,5-dimethylimidazo[1,5-a]pyrazin-1-yl)-3-fluorophenyl)-2-hydroxy-2-(3-(trifluoromethyl)phenyl) acetamide;
(S)—N-(4-(8-amino-3,5-dimethylimidazo[1,5-a]pyrazin-1-yl)-3-fluorophenyl)-2-hydroxy-2-(3-(trifluoromethyl)phenyl) acetamide;
N-[4-[8-amino-5-methyl-3-(trideuteriomethyl)imidazo[1,5-a]pyrazin-1-yl]-3-fluoro-phenyl]-2-hydroxy-2-[3-(trifluoromethyl)phenyl]acetamide;
(R)—N-[4-[8-amino-5-methyl-3-(trideuteriomethyl)imidazo[1,5-a]pyrazin-1-yl]-3-fluoro-phenyl]-2-hydroxy-2-[3-(trifluoromethyl)phenyl]acetamide;
(S)—N-[4-[8-amino-5-methyl-3-(trideuteriomethyl)imidazo[1,5-a]pyrazin-1-yl]-3-fluoro-phenyl]-2-hydroxy-2-[3-(trifluoromethyl)phenyl]acetamide;
N-[4-[8-amino-6-methyl-3-(trideuteriomethyl)imidazo[1,5-a]pyrazin-1-yl]-3-fluoro-phenyl]-2-hydroxy-2-[3-(trifluoromethyl)phenyl]acetamide;
(R)—N-[4-[8-amino-6-methyl-3-(trideuteriomethyl)imidazo[1,5-a]pyrazin-1-yl]-3-fluoro-phenyl]-2-hydroxy-2-[3-(trifluoromethyl)phenyl]acetamide;
(S)—N-[4-[8-amino-6-methyl-3-(trideuteriomethyl)imidazo[1,5-a]pyrazin-1-yl]-3-fluoro-phenyl]-2-hydroxy-2-[3-(trifluoromethyl)phenyl]acetamide;
N-[4-[8-amino-3-(trideuteriomethyl)-5-(trifluoromethyl)imidazo[1,5-a]pyrazin-1-yl]-3-fluoro-phenyl]-2-hydroxy-2-[3-(trifluoromethyl)phenyl]acetamide;
(R)—N-[4-[8-amino-3-(trideuteriomethyl)-5-(trifluoromethyl)imidazo[1,5-a]pyrazin-1-yl]-3-fluoro-phenyl]-2-hydroxy-2-[3-(trifluoromethyl)phenyl]acetamide;
(S)—N-[4-[8-amino-3-(trideuteriomethyl)-5-(trifluoromethyl)imidazo[1,5-a]pyrazin-1-yl]-3-fluoro-phenyl]-2-hydroxy-2-[3-(trifluoromethyl)phenyl]acetamide;
N-[4-[8-amino-5-chloro-3-(trideuteriomethyl)imidazo[1,5-a]pyrazin-1-yl]-3-fluoro-phenyl]-2-hydroxy-2-[3-(trifluoromethyl)phenyl]acetamide;
(R)—N-[4-[8-amino-5-chloro-3-(trideuteriomethyl)imidazo[1,5-a]pyrazin-1-yl]-3-fluoro-phenyl]-2-hydroxy-2-[3-(trifluoromethyl)phenyl]acetamide;
(S)—N-[4-[8-amino-5-chloro-3-(trideuteriomethyl)imidazo[1,5-a]pyrazin-1-yl]-3-fluoro-phenyl]-2-hydroxy-2-[3-(trifluoromethyl)phenyl]acetamide;
N-[4-[8-amino-6-methyl-3-(trideuteriomethyl)imidazo[1,5-a]pyrazin-1-yl]-3-fluoro-phenyl]-2-(3,5-difluorophenyl)-2-hydroxy-acetamide;
(R)—N-[4-[8-amino-6-methyl-3-(trideuteriomethyl)imidazo[1,5-a]pyrazin-1-yl]-3-fluoro-phenyl]-2-(3,5-difluorophenyl)-2-hydroxy-acetamide;
(S)—N-[4-[8-amino-6-methyl-3-(trideuteriomethyl)imidazo[1,5-a]pyrazin-1-yl]-3-fluoro-phenyl]-2-(3,5-difluorophenyl)-2-hydroxy-acetamide;
N-[4-[8-amino-5-methyl-3-(trideuteriomethyl)imidazo[1,5-a]pyrazin-1-yl]-3-fluoro-phenyl]-2-(3,5-difluorophenyl)-2-hydroxy-acetamide;
(R)—N-[4-[8-amino-5-methyl-3-(trideuteriomethyl)imidazo[1,5-a]pyrazin-1-yl]-3-fluoro-phenyl]-2-(3,5-difluorophenyl)-2-hydroxy-acetamide;
(S)—N-[4-[8-amino-5-methyl-3-(trideuteriomethyl)imidazo[1,5-a]pyrazin-1-yl]-3-fluoro-phenyl]-2-(3,5-difluorophenyl)-2-hydroxy-acetamide;
N-[4-[8-amino-3-(trideuteriomethyl)-5-(trifluoromethyl)imidazo[1,5-a]pyrazin-1-yl]-3-fluoro-phenyl]-2-(3,5-difluorophenyl)-2-hydroxy-acetamide;
(R)—N-[4-[8-amino-3-(trideuteriomethyl)-5-(trifluoromethyl)imidazo[1,5-a]pyrazin-1-yl]-3-fluoro-phenyl]-2-(3,5-difluorophenyl)-2-hydroxy-acetamide;
(S)—N-[4-[8-amino-3-(trideuteriomethyl)-5-(trifluoromethyl)imidazo[1,5-a]pyrazin-1-yl]-3-fluoro-phenyl]-2-(3,5-difluorophenyl)-2-hydroxy-acetamide;
N-[4-[8-amino-5-chloro-3-(trideuteriomethyl)imidazo[1,5-a]pyrazin-1-yl]-3-fluoro-phenyl]-2-(3,5-difluorophenyl)-2-hydroxy-acetamide;
(R)—N-[4-[8-amino-5-chloro-3-(trideuteriomethyl)imidazo[1,5-a]pyrazin-1-yl]-3-fluoro-phenyl]-2-(3,5-difluorophenyl)-2-hydroxy-acetamide;
(S)—N-[4-[8-amino-5-chloro-3-(trideuteriomethyl)imidazo[1,5-a]pyrazin-1-yl]-3-fluoro-phenyl]-2-(3,5-difluorophenyl)-2-hydroxy-acetamide;
N-[4-[8-amino-5-methyl-3-(trideuteriomethyl)imidazo[1,5-a]pyrazin-1-yl]-3-fluoro-phenyl]-2-[3-fluoro-5-(trifluoromethyl)phenyl]-2-hydroxy-acetamide;
(R)—N-[4-[8-amino-5-methyl-3-(trideuteriomethyl)imidazo[1,5-a]pyrazin-1-yl]-3-fluoro-phenyl]-2-[3-fluoro-5-(trifluoromethyl)phenyl]-2-hydroxy-acetamide;
(S)—N-[4-[8-amino-5-methyl-3-(trideuteriomethyl)imidazo[1,5-a]pyrazin-1-yl]-3-fluoro-phenyl]-2-[3-fluoro-5-(trifluoromethyl)phenyl]-2-hydroxy-acetamide;
N-[4-[8-amino-3-(trideuteriomethyl)-5-(trifluoromethyl)imidazo[1,5-a]pyrazin-1-yl]-3-fluoro-phenyl]-2-[3-fluoro-5-(trifluoromethyl)phenyl]-2-hydroxy-acetamide;
(R)—N-[4-[8-amino-3-(trideuteriomethyl)-5-(trifluoromethyl)imidazo[1,5-a]pyrazin-1-yl]-3-fluoro-phenyl]-2-[3-fluoro-5-(trifluoromethyl)phenyl]-2-hydroxy-acetamide;
(S)—N-[4-[8-amino-3-(trideuteriomethyl)-5-(trifluoromethyl)imidazo[1,5-a]pyrazin-1-yl]-3-fluoro-phenyl]-2-[3-fluoro-5-(trifluoromethyl)phenyl]-2-hydroxy-acetamide;
N-[4-[8-amino-5-chloro-3-(trideuteriomethyl)imidazo[1,5-a]pyrazin-1-yl]-3-fluoro-phenyl]-2-[3-fluoro-5-(trifluoromethyl)phenyl]-2-hydroxy-acetamide;
(R)—N-[4-[8-amino-5-chloro-3-(trideuteriomethyl)imidazo[1,5-a]pyrazin-1-yl]-3-fluoro-phenyl]-2-[3-fluoro-5-(trifluoromethyl)phenyl]-2-hydroxy-acetamide;
(S)—N-[4-[8-amino-5-chloro-3-(trideuteriomethyl)imidazo[1,5-a]pyrazin-1-yl]-3-fluoro-phenyl]-2-[3-fluoro-5-(trifluoromethyl)phenyl]-2-hydroxy-acetamide;
N-[4-[8-amino-6-methyl-3-(trideuteriomethyl)imidazo[1,5-a]pyrazin-1-yl]-3-fluoro-phenyl]-2-[3-fluoro-5-(trifluoromethyl)phenyl]-2-hydroxy-acetamide;
(R)—N-[4-[8-amino-6-methyl-3-(trideuteriomethyl)imidazo[1,5-a]pyrazin-1-yl]-3-fluoro-phenyl]-2-[3-fluoro-5-(trifluoromethyl)phenyl]-2-hydroxy-acetamide;
(S)—N-[4-[8-amino-6-methyl-3-(trideuteriomethyl)imidazo[1,5-a]pyrazin-1-yl]-3-fluoro-phenyl]-2-[3-fluoro-5-(trifluoromethyl)phenyl]-2-hydroxy-acetamide;
N-(4-(8-amino-3,6-dimethylimidazo[1,5-a]pyrazin-1-yl)-2-fluorophenyl)-2-(3-fluorophenyl)-2-hydroxyacetamide;
(R)—N-(4-(8-amino-3,6-dimethylimidazo[1,5-a]pyrazin-1-yl)-2-fluorophenyl)-2-(3-fluorophenyl)-2-hydroxyacetamide;
(S)—N-(4-(8-amino-3,6-dimethylimidazo[1,5-a]pyrazin-1-yl)-2-fluorophenyl)-2-(3-fluorophenyl)-2-hydroxyacetamide;
N-[4-[8-amino-6-methyl-3-(trideuteriomethyl)imidazo[1,5-a]pyrazin-1-yl]-2-fluorophenyl]-2-(3-fluorophenyl)-2-hydroxy-acetamide;
(R)—N-[4-[8-amino-6-methyl-3-(trideuteriomethyl)imidazo[1,5-a]pyrazin-1-yl]-2-fluorophenyl]-2-(3-fluorophenyl)-2-hydroxy-acetamide;
(S)—N-[4-[8-amino-6-methyl-3-(trideuteriomethyl)imidazo[1,5-a]pyrazin-1-yl]-2-fluorophenyl]-2-(3-fluorophenyl)-2-hydroxy-acetamide;
N-[4-[8-amino-5-methyl-3-(trideuteriomethyl)imidazo[1,5-a]pyrazin-1-yl]-2-fluoro-phenyl]-2-(3-fluorophenyl)-2-hydroxy-acetamide;
(R)—N-[4-[8-amino-5-methyl-3-(trideuteriomethyl)imidazo[1,5-a]pyrazin-1-yl]-2-fluoro-phenyl]-2-(3-fluorophenyl)-2-hydroxy-acetamide;
(S)—N-[4-[8-amino-5-methyl-3-(trideuteriomethyl)imidazo[1,5-a]pyrazin-1-yl]-2-fluoro-phenyl]-2-(3-fluorophenyl)-2-hydroxy-acetamide;
N-(4-(8-amino-3,5-dimethylimidazo[1,5-a]pyrazin-1-yl)-2-fluorophenyl)-2-(3-fluorophenyl)-2-hydroxyacetamide;
(R)—N-(4-(8-amino-3,5-dimethylimidazo[1,5-a]pyrazin-1-yl)-2-fluorophenyl)-2-(3-fluorophenyl)-2-hydroxyacetamide;
(S)—N-(4-(8-amino-3,5-dimethylimidazo[1,5-a]pyrazin-1-yl)-2-fluorophenyl)-2-(3-fluorophenyl)-2-hydroxyacetamide;
N-(4-(8-amino-3,5-dimethylimidazo[1,5-a]pyrazin-1-yl)-3-(trifluoromethoxy)phenyl)-2-(3-fluorophenyl)-2-hydroxyacetamide;
(R)—N-(4-(8-amino-3,5-dimethylimidazo[1,5-a]pyrazin-1-yl)-3-(trifluoromethoxy)phenyl)-2-(3-fluorophenyl)-2-hydroxyacetamide;
(S)—N-(4-(8-amino-3,5-dimethylimidazo[1,5-a]pyrazin-1-yl)-3-(trifluoromethoxy)phenyl)-2-(3-fluorophenyl)-2-hydroxyacetamide;
N-(4-(8-amino-3,6-dimethylimidazo[1,5-a]pyrazin-1-yl)-2,3-difluorophenyl)-2-(3-fluorophenyl)-2-hydroxyacetamide;
(R)—N-(4-(8-amino-3,6-dimethylimidazo[1,5-a]pyrazin-1-yl)-2,3-difluorophenyl)-2-(3-fluorophenyl)-2-hydroxyacetamide;
(S)—N-(4-(8-amino-3,6-dimethylimidazo[1,5-a]pyrazin-1-yl)-2,3-difluorophenyl)-2-(3-fluorophenyl)-2-hydroxyacetamide;
N-[4-[8-amino-6-methyl-3-(trideuteriomethyl)imidazo[1,5-a]pyrazin-1-yl]-2,3-difluoro-phenyl]-2-(3-fluorophenyl)-2-hydroxy-acetamide;
(R)—N-[4-[8-amino-6-methyl-3-(trideuteriomethyl)imidazo[1,5-a]pyrazin-1-yl]-2,3-difluoro-phenyl]-2-(3-fluorophenyl)-2-hydroxy-acetamide;
(S)—N-[4-[8-amino-6-methyl-3-(trideuteriomethyl)imidazo[1,5-a]pyrazin-1-yl]-2,3-difluoro-phenyl]-2-(3-fluorophenyl)-2-hydroxy-acetamide;
N-[4-[8-amino-5-methyl-3-(trideuteriomethyl)imidazo[1,5-a]pyrazin-1-yl]-2,3-difluoro-phenyl]-2-(3-fluorophenyl)-2-hydroxy-acetamide;
(R)—N-[4-[8-amino-5-methyl-3-(trideuteriomethyl)imidazo[1,5-a]pyrazin-1-yl]-2,3-difluoro-phenyl]-2-(3-fluorophenyl)-2-hydroxy-acetamide;
(S)—N-[4-[8-amino-5-methyl-3-(trideuteriomethyl)imidazo[1,5-a]pyrazin-1-yl]-2,3-difluoro-phenyl]-2-(3-fluorophenyl)-2-hydroxy-acetamide;
N-[4-[8-amino-3-(trideuteriomethyl)-5-(trifluoromethyl)imidazo[1,5-a]pyrazin-1-yl]-2,3-difluoro-phenyl]-2-(3-fluorophenyl)-2-hydroxy-acetamide;
(R)—N-[4-[8-amino-3-(trideuteriomethyl)-5-(trifluoromethyl)imidazo[1,5-a]pyrazin-1-yl]-2,3-difluoro-phenyl]-2-(3-fluorophenyl)-2-hydroxy-acetamide;
(S)—N-[4-[8-amino-3-(trideuteriomethyl)-5-(trifluoromethyl)imidazo[1,5-a]pyrazin-1-yl]-2,3-difluoro-phenyl]-2-(3-fluorophenyl)-2-hydroxy-acetamide;
N-[4-[8-amino-5-chloro-3-(trideuteriomethyl)imidazo[1,5-a]pyrazin-1-yl]-2,3-difluoro-phenyl]-2-(3-fluorophenyl)-2-hydroxy-acetamide;
(R)—N-[4-[8-amino-5-chloro-3-(trideuteriomethyl)imidazo[1,5-a]pyrazin-1-yl]-2,3-difluoro-phenyl]-2-(3-fluorophenyl)-2-hydroxy-acetamide;
(S)—N-[4-[8-amino-5-chloro-3-(trideuteriomethyl)imidazo[1,5-a]pyrazin-1-yl]-2,3-difluoro-phenyl]-2-(3-fluorophenyl)-2-hydroxy-acetamide;
N-[4-[8-amino-5-methyl-3-(trideuteriomethyl)imidazo[1,5-a]pyrazin-1-yl]-2,3-difluoro-phenyl]-2-(3-chlorophenyl)-2-hydroxy-acetamide;
(R)—N-[4-[8-amino-5-methyl-3-(trideuteriomethyl)imidazo[1,5-a]pyrazin-1-yl]-2,3-difluoro-phenyl]-2-(3-chlorophenyl)-2-hydroxy-acetamide;
(S)—N-[4-[8-amino-5-methyl-3-(trideuteriomethyl)imidazo[1,5-a]pyrazin-1-yl]-2,3-difluoro-phenyl]-2-(3-chlorophenyl)-2-hydroxy-acetamide;
N-[4-[8-amino-6-methyl-3-(trideuteriomethyl)imidazo[1,5-a]pyrazin-1-yl]-2,3-difluoro-phenyl]-2-(3-chlorophenyl)-2-hydroxy-acetamide;
(R)—N-[4-[8-amino-6-methyl-3-(trideuteriomethyl)imidazo[1,5-a]pyrazin-1-yl]-2,3-difluoro-phenyl]-2-(3-chlorophenyl)-2-hydroxy-acetamide;
(S)—N-[4-[8-amino-6-methyl-3-(trideuteriomethyl)imidazo[1,5-a]pyrazin-1-yl]-2,3-difluoro-phenyl]-2-(3-chlorophenyl)-2-hydroxy-acetamide;
N-[4-[8-amino-3-(trideuteriomethyl)-5-(trifluoromethyl)imidazo[1,5-a]pyrazin-1-yl]-2,3-difluoro-phenyl]-2-(3-chlorophenyl)-2-hydroxy-acetamide;
(R)—N-[4-[8-amino-3-(trideuteriomethyl)-5-(trifluoromethyl)imidazo[1,5-a]pyrazin-1-yl]-2,3-difluoro-phenyl]-2-(3-chlorophenyl)-2-hydroxy-acetamide;
(S)—N-[4-[8-amino-3-(trideuteriomethyl)-5-(trifluoromethyl)imidazo[1,5-a]pyrazin-1-yl]-2,3-difluoro-phenyl]-2-(3-chlorophenyl)-2-hydroxy-acetamide;
N-[4-[8-amino-5-chloro-3-(trideuteriomethyl)imidazo[1,5-a]pyrazin-1-yl]-2,3-difluoro-phenyl]-2-(3-chlorophenyl)-2-hydroxy-acetamide;
(R)—N-[4-[8-amino-5-chloro-3-(trideuteriomethyl)imidazo[1,5-a]pyrazin-1-yl]-2,3-difluoro-phenyl]-2-(3-chlorophenyl)-2-hydroxy-acetamide;
(S)—N-[4-[8-amino-5-chloro-3-(trideuteriomethyl)imidazo[1,5-a]pyrazin-1-yl]-2,3-difluoro-phenyl]-2-(3-chlorophenyl)-2-hydroxy-acetamide;
N-[4-[8-amino-5-methyl-3-(trideuteriomethyl)imidazo[1,5-a]pyrazin-1-yl]-2,3-difluoro-phenyl]-2-hydroxy-2-[3-(trifluoromethyl)phenyl]acetamide;
(R)—N-[4-[8-amino-5-methyl-3-(trideuteriomethyl)imidazo[1,5-a]pyrazin-1-yl]-2,3-difluoro-phenyl]-2-hydroxy-2-[3-(trifluoromethyl)phenyl]acetamide;
(S)—N-[4-[8-amino-5-methyl-3-(trideuteriomethyl)imidazo[1,5-a]pyrazin-1-yl]-2,3-difluoro-phenyl]-2-hydroxy-2-[3-(trifluoromethyl)phenyl]acetamide;
N-[4-[8-amino-3-(trideuteriomethyl)-5-(trifluoromethyl)imidazo[1,5-a]pyrazin-1-yl]-2,3-difluoro-phenyl]-2-hydroxy-2-[3-(trifluoromethyl)phenyl]acetamide;
(R)—N-[4-[8-amino-3-(trideuteriomethyl)-5-(trifluoromethyl)imidazo[1,5-a]pyrazin-1-yl]-2,3-difluoro-phenyl]-2-hydroxy-2-[3-(trifluoromethyl)phenyl]acetamide;
(S)—N-[4-[8-amino-3-(trideuteriomethyl)-5-(trifluoromethyl)imidazo[1,5-a]pyrazin-1-yl]-2,3-difluoro-phenyl]-2-hydroxy-2-[3-(trifluoromethyl)phenyl]acetamide;
N-[4-[8-amino-6-methyl-3-(trideuteriomethyl)imidazo[1,5-a]pyrazin-1-yl]-2,3-difluoro-phenyl]-2-hydroxy-2-[3-(trifluoromethyl)phenyl]acetamide;
(R)—N-[4-[8-amino-6-methyl-3-(trideuteriomethyl)imidazo[1,5-a]pyrazin-1-yl]-2,3-difluoro-phenyl]-2-hydroxy-2-[3-(trifluoromethyl)phenyl]acetamide;
(S)—N-[4-[8-amino-6-methyl-3-(trideuteriomethyl)imidazo[1,5-a]pyrazin-1-yl]-2,3-difluoro-phenyl]-2-hydroxy-2-[3-(trifluoromethyl)phenyl]acetamide;
N-[4-[8-amino-5-chloro-3-(trideuteriomethyl)imidazo[1,5-a]pyrazin-1-yl]-2,3-difluoro-phenyl]-2-hydroxy-2-[3-(trifluoromethyl)phenyl]acetamide;
(R)—N-[4-[8-amino-5-chloro-3-(trideuteriomethyl)imidazo[1,5-a]pyrazin-1-yl]-2,3-difluoro-phenyl]-2-hydroxy-2-[3-(trifluoromethyl)phenyl]acetamide;
(S)—N-[4-[8-amino-5-chloro-3-(trideuteriomethyl)imidazo[1,5-a]pyrazin-1-yl]-2,3-difluoro-phenyl]-2-hydroxy-2-[3-(trifluoromethyl)phenyl]acetamide;
N-[4-[8-amino-5-methyl-3-(trideuteriomethyl)imidazo[1,5-a]pyrazin-1-yl]-2,3-difluoro-phenyl]-2-(3,5-difluorophenyl)-2-hydroxy-acetamide;
(R)—N-[4-[8-amino-5-methyl-3-(trideuteriomethyl)imidazo[1,5-a]pyrazin-1-yl]-2,3-difluoro-phenyl]-2-(3,5-difluorophenyl)-2-hydroxy-acetamide;
(S)—N-[4-[8-amino-5-methyl-3-(trideuteriomethyl)imidazo[1,5-a]pyrazin-1-yl]-2,3-difluoro-phenyl]-2-(3,5-difluorophenyl)-2-hydroxy-acetamide;
N-[4-[8-amino-5-chloro-3-(trideuteriomethyl)imidazo[1,5-a]pyrazin-1-yl]-2,3-difluoro-phenyl]-2-(3,5-difluorophenyl)-2-hydroxy-acetamide;
(R)—N-[4-[8-amino-5-chloro-3-(trideuteriomethyl)imidazo[1,5-a]pyrazin-1-yl]-2,3-difluoro-phenyl]-2-(3,5-difluorophenyl)-2-hydroxy-acetamide;
(S)—N-[4-[8-amino-5-chloro-3-(trideuteriomethyl)imidazo[1,5-a]pyrazin-1-yl]-2,3-difluoro-phenyl]-2-(3,5-difluorophenyl)-2-hydroxy-acetamide;
N-[4-[8-amino-5-methyl-3-(trideuteriomethyl)imidazo[1,5-a]pyrazin-1-yl]-2,3-difluoro-phenyl]-2-[3-fluoro-5-(trifluoromethyl)phenyl]-2-hydroxy-acetamide;
(R)—N-[4-[8-amino-5-methyl-3-(trideuteriomethyl)imidazo[1,5-a]pyrazin-1-yl]-2,3-difluoro-phenyl]-2-[3-fluoro-5-(trifluoromethyl)phenyl]-2-hydroxy-acetamide;
(S)—N-[4-[8-amino-5-methyl-3-(trideuteriomethyl)imidazo[1,5-a]pyrazin-1-yl]-2,3-difluoro-phenyl]-2-[3-fluoro-5-(trifluoromethyl)phenyl]-2-hydroxy-acetamide;
N-[4-[8-amino-3-(trideuteriomethyl)-5-(trifluoromethyl)imidazo[1,5-a]pyrazin-1-yl]-2,3-difluoro-phenyl]-2-[3-fluoro-5-(trifluoromethyl)phenyl]-2-hydroxy-acetamide;
(R)—N-[4-[8-amino-3-(trideuteriomethyl)-5-(trifluoromethyl)imidazo[1,5-a]pyrazin-1-yl]-2,3-difluoro-phenyl]-2-[3-fluoro-5-(trifluoromethyl)phenyl]-2-hydroxy-acetamide;
(S)—N-[4-[8-amino-3-(trideuteriomethyl)-5-(trifluoromethyl)imidazo[1,5-a]pyrazin-1-yl]-2,3-difluoro-phenyl]-2-[3-fluoro-5-(trifluoromethyl)phenyl]-2-hydroxy-acetamide;
N-[4-[8-amino-5-chloro-3-(trideuteriomethyl)imidazo[1,5-a]pyrazin-1-yl]-2,3-difluoro-phenyl]-2-[3-fluoro-5-(trifluoromethyl)phenyl]-2-hydroxy-acetamide;
(R)—N-[4-[8-amino-5-chloro-3-(trideuteriomethyl)imidazo[1,5-a]pyrazin-1-yl]-2,3-difluoro-phenyl]-2-[3-fluoro-5-(trifluoromethyl)phenyl]-2-hydroxy-acetamide;
(S)—N-[4-[8-amino-5-chloro-3-(trideuteriomethyl)imidazo[1,5-a]pyrazin-1-yl]-2,3-difluoro-phenyl]-2-[3-fluoro-5-(trifluoromethyl)phenyl]-2-hydroxy-acetamide;
N-[4-[8-amino-6-methyl-3-(trideuteriomethyl)imidazo[1,5-a]pyrazin-1-yl]-2,3-difluoro-phenyl]-2-[3-fluoro-5-(trifluoromethyl)phenyl]-2-hydroxy-acetamide;
(R)—N-[4-[8-amino-6-methyl-3-(trideuteriomethyl)imidazo[1,5-a]pyrazin-1-yl]-2,3-difluoro-phenyl]-2-[3-fluoro-5-(trifluoromethyl)phenyl]-2-hydroxy-acetamide;
(S)—N-[4-[8-amino-6-methyl-3-(trideuteriomethyl)imidazo[1,5-a]pyrazin-1-yl]-2,3-difluoro-phenyl]-2-[3-fluoro-5-(trifluoromethyl)phenyl]-2-hydroxy-acetamide;
N-(4-(8-amino-3,5-dimethylimidazo[1,5-a]pyrazin-1-yl)-2-fluoro-3-methylphenyl)-2-(3-fluorophenyl)-2-hydroxyacetamide;
(R)—N-(4-(8-amino-3,5-dimethylimidazo[1,5-a]pyrazin-1-yl)-2-fluoro-3-methylphenyl)-2-(3-fluorophenyl)-2-hydroxyacetamide;
(S)—N-(4-(8-amino-3,5-dimethylimidazo[1,5-a]pyrazin-1-yl)-2-fluoro-3-methylphenyl)-2-(3-fluorophenyl)-2-hydroxyacetamide;
N-[5-[8-amino-6-methyl-3-(trideuteriomethyl)imidazo[1,5-a]pyrazin-1-yl]-6-methyl-2-pyridyl]-2-(3-fluorophenyl)-2-hydroxy-acetamide;
(R)—N-[5-[8-amino-6-methyl-3-(trideuteriomethyl)imidazo[1,5-a]pyrazin-1-yl]-6-methyl-2-pyridyl]-2-(3-fluorophenyl)-2-hydroxy-acetamide;
(S)—N-[5-[8-amino-6-methyl-3-(trideuteriomethyl)imidazo[1,5-a]pyrazin-1-yl]-6-methyl-2-pyridyl]-2-(3-fluorophenyl)-2-hydroxy-acetamide;
N-[5-[8-amino-5-methyl-3-(trideuteriomethyl)imidazo[1,5-a]pyrazin-1-yl]-6-methyl-2-pyridyl]-2-(3-fluorophenyl)-2-hydroxy-acetamide;
(R)—N-[5-[8-amino-5-methyl-3-(trideuteriomethyl)imidazo[1,5-a]pyrazin-1-yl]-6-methyl-2-pyridyl]-2-(3-fluorophenyl)-2-hydroxy-acetamide;
(S)—N-[5-[8-amino-5-methyl-3-(trideuteriomethyl)imidazo[1,5-a]pyrazin-1-yl]-6-methyl-2-pyridyl]-2-(3-fluorophenyl)-2-hydroxy-acetamide;
N-[5-[8-amino-5-methyl-3-(trideuteriomethyl)imidazo[1,5-a]pyrazin-1-yl]-6-methyl-2-pyridyl]-2-hydroxy-2-[3-(trifluoromethyl)phenyl]acetamide;
(R)—N-[5-[8-amino-5-methyl-3-(trideuteriomethyl)imidazo[1,5-a]pyrazin-1-yl]-6-methyl-2-pyridyl]-2-hydroxy-2-[3-(trifluoromethyl)phenyl]acetamide;
(S)—N-[5-[8-amino-5-methyl-3-(trideuteriomethyl)imidazo[1,5-a]pyrazin-1-yl]-6-methyl-2-pyridyl]-2-hydroxy-2-[3-(trifluoromethyl)phenyl]acetamide;
N-[5-[8-amino-6-methyl-3-(trideuteriomethyl)imidazo[1,5-a]pyrazin-1-yl]-4-methyl-2-pyridyl]-2-(3-fluorophenyl)-2-hydroxy-acetamide;
(R)—N-[5-[8-amino-6-methyl-3-(trideuteriomethyl)imidazo[1,5-a]pyrazin-1-yl]-4-methyl-2-pyridyl]-2-(3-fluorophenyl)-2-hydroxy-acetamide;
(S)—N-[5-[8-amino-6-methyl-3-(trideuteriomethyl)imidazo[1,5-a]pyrazin-1-yl]-4-methyl-2-pyridyl]-2-(3-fluorophenyl)-2-hydroxy-acetamide;
N-[5-[8-amino-5-methyl-3-(trideuteriomethyl)imidazo[1,5-a]pyrazin-1-yl]-4-methyl-2-pyridyl]-2-(3-fluorophenyl)-2-hydroxy-acetamide;
(R)—N-[5-[8-amino-5-methyl-3-(trideuteriomethyl)imidazo[1,5-a]pyrazin-1-yl]-4-methyl-2-pyridyl]-2-(3-fluorophenyl)-2-hydroxy-acetamide;
(S)—N-[5-[8-amino-5-methyl-3-(trideuteriomethyl)imidazo[1,5-a]pyrazin-1-yl]-4-methyl-2-pyridyl]-2-(3-fluorophenyl)-2-hydroxy-acetamide;
or a pharmaceutically acceptable salt thereof.

259 more elements

Dependencies are inferred from the claim text.

Facts

Application: 17/639,183Filed 28 Aug 2020 · us provisional application
Priority: 29 Aug 2019
Published: US 2022/0348583 A13 Nov 2022
Granted: 17 Jun 2025
Term ends: Not estimatedThe source records don’t support an estimate.

Classification6 codes

C07D 487/04
In which the condensed system contains two hetero rings: ortho-condensed systems
A61P 35/00
Antineoplastic agents
C07B 2200/05
Indexing scheme relating to specific properties of organic compounds: isotopically modified compounds, e.g. labelled
C07D
Heterocyclic compounds

Family

Application62/893,519Us provisional application · filed 29 Aug 2019
US 2022/0348583 A1Pre-grant publication · published 3 Nov 2022
US 12,331,054 B2This patent

From the US filing history. Foreign family members aren’t listed.

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Abstract

Provided herein are compounds, compositions, and methods useful for inhibiting PERK and for treating related conditions, diseases, and disorders.

A compound of the formula (I):

Ar1 is aryl, heteroaryl, or cycloalkyl, optionally substituted by one or more independent R1 substituents;
Ar2 is aryl or heteroaryl, optionally substituted by one or more independent R2 substituents;
Y is CR3aR3b, C(O), CF2, or CNOR3bb;
R3a is H, alkyl, or cycloalkyl;
R3b is H, alkyl, OR3c, or NR3dR3e;
R3bb is H or alkyl;
R4 is H, alkyl, or OH;
X is CR7 or N;
R1 is one or more independent H, deuterium, halo, CN, NO2, alkyl, cycloalkyl, C0-6alkyl-O—C1-12alkyl, C0-6alkyl-OH, C0-6alkyl-O—C3-12cycloalkyl, or C0-6alkyl-O—C3-12heterocycloalkyl, optionally substituted by one or more independent G1 substituents;
R2 is one or more independent H, deuterium, halo, CN, NO2, alkyl, C0-6alkylcycloalkyl, C0-6alkyl-O—C1-12alkyl, C0-6alkyl-OH, or C0-6alkyl-O—C3-12cycloalkyl, optionally substituted by one or more independent G2 substituents;
R3c, R3d and R3e are each independently H, alkyl, or cycloalkyl, optionally substituted by one or more independent G3 substituents;
R5 is H, deuterium, halo, alkyl, cycloalkyl, or heterocycloalkyl, optionally substituted by one or more independent G4 substituents;
R6 is H, alkyl, CD3, or CF3;
R7 is H, deuterium, halo, CN, alkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl, optionally substituted by one or more independent H, deuterium or halo;
G1, G2, G3, or G4 are each independently H, deuterium, halo, CN, NO2, C1-12alkyl, C0-12alkylC3-12cycloalkyl, C0-12alkylC3-12heterocycloalkyl, OR8, NR8R9, C(O)R8, C(O)OR8, C(O)NR8R9, OC(O)R8, OC(O)OR8, OC(O)NR8R9, N(R10)C(O)R8, N(R10)C(O)OR8, N(R10)C(O)NR8R9, S(O)nR8, S(O)nOR8, S(O)nNR8R9, N(R10)S(O)nR8, N(R10)S(O)nOR8, or N(R10)S(O)nNR8R9, optionally substituted by one or more independent H, deuterium, halo, OH, CN, or NO2;
R8, R9, or R10 are each independently selected from H, deuterium, halo, CN, NO2, alkyl, cycloalkyl or heterocycloalkyl, optionally substituted by one or more independent H, deuterium, halo, OH, CN, or NO2;
n is 0, 1, or 2;
or a pharmaceutically acceptable salt thereof.

15 more elements

Facts

Application

17/639,183Filed 28 Aug 2020 · us provisional application

Priority

29 Aug 2019

Published

US 2022/0348583 A13 Nov 2022

Granted

17 Jun 2025

Term ends

Not estimatedThe source records don’t support an estimate.

Classification6 codes

C07D 487/04
In which the condensed system contains two hetero rings: ortho-condensed systems
A61P 35/00
Antineoplastic agents
C07B 2200/05
Indexing scheme relating to specific properties of organic compounds: isotopically modified compounds, e.g. labelled
C07D
Heterocyclic compounds