US 2016/0237084 A1 · DIHYDRO-PYRROLOPYRIDINONE INHIBITORS

Abstract

The present invention provides for compounds of formula (I) wherein R1, R2, R3, R4, and R5 have any of the values defined in the specification, and pharmaceutically acceptable salts thereof, that are useful as agents in the treatment of diseases and conditions, including inflammatory diseases, cancer, and AIDS. Also provided are pharmaceutical compositions comprising one or more compounds of formula (I).

A compound of formula (I) or a pharmaceutically acceptable salt thereof,

wherein
R1 is H, C1-C3 alkyl, or C1-C3 haloalkyl;
R2 is H, C1-C3 alkyl, or C1-C3 haloalkyl;
R3 is H, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, halogen, —OR3a, —NR3bR3c, —N(R3b)C(O)R3d, —N(R3b)C(O)NR3bR3c, —N(R3b)S(O)2NR3bR3c, —C(O)R3a, —C(O)OR3a, —C(O)NR3bR3c, —S(O)R3d, —S(O)2R3a, —S(O)2NR3bR3c, or G1;
wherein the C1-C6 alkyl, C2-C6 alkenyl, and C2-C6 alkynyl are each independently unsubstituted or substituted with 1 or 2 substituents independently selected from the group consisting of halogen, G1, —OR3a, and —NR3bR3c;
R3a, R3b, and R3c, at each occurrence, are each independently H, C1-C6 alkyl, C1-C6 haloalkyl, G1, —(C1-C6 alkylenyl)-G1, —(C1-C6 alkylenyl)-CN, —(C1-C6 alkylenyl)-ORz1, or —(C1-C6 alkylenyl)-NRz3Rz4;
R3d, at each occurrence, is independently C1-C6 alkyl, C1-C6 haloalkyl, G1, or —(C1-C6 alkylenyl)-G1;
G1, at each occurrence, is independently aryl, heteroaryl, heterocycle, cycloalkyl, or cycloalkenyl;
and each G1 is optionally substituted with 1, 2, 3, 4, or 5 R1g groups;
R4 is H, C1-C6 alkyl, halogen, or C1-C6 haloalkyl;
R5 is a monocyclic or bicyclic ring selected from the group consisting of aryl and heteroaryl;
each of which is substituted with 1, 2, or 3 substituents independently selected from the group consisting of C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, halogen, C1-C6 haloalkyl, —CN, NO2, G2, —ORa, —OC(O)Rb, —OC(O)NRcRd, —SRa, —S(O)2Ra, —S(O)2NRcRd, —C(O)Ra, —C(O)ORa, —C(O)NRcRd, —NRcRd, —N(Re)C(O)Rb, —N(Re)S(O)2Rb, —N(Re)C(O)O(Rb), —N(Re)C(O)NRcRd, —N(Re)S(O)2NRcRd, —(C1-C6 alkylenyl)-G2, —(C1-C6 alkylenyl)-ORa, —(C1-C6 alkylenyl)-OC(O)Rb, —(C1-C6 alkylenyl)-OC(O)NRcRd, —(C1-C6 alkylenyl)-S(O)2Ra, —(C1-C6 alkylenyl)-S(O)2NRcRd, —(C1-C6 alkylenyl)-C(O)Ra, —(C1-C6 alkylenyl)-C(O)ORa, —(C1-C6 alkylenyl)-C(O)NRcRd, —(C1-C6 alkylenyl)-NRcRd, —(C1-C6 alkylenyl)-N(Re)C(O)Rb, —(C1-C6 alkylenyl)-N(Re)S(O)2Rb, —(C1-C6 alkylenyl)-N(Re)C(O)O(Rb), —(C1-C6 alkylenyl)-N(Re)C(O)NRcRd, —(C1-C6 alkylenyl)-N(Re)S(O)2NRcRd, and —(C1-C6 alkylenyl)-CN;
Ra, R, Rd, and Re, at each occurrence, are each independently H, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, G2, or C1-C6 alkyl wherein the C1-C6 alkyl is optionally substituted with one substituent selected from the group consisting of —ORy1, —NRy3Ry4, —C(O)ORy1, —C(O)NRy3Ry4, —S(O)2Ry1, —S(O)2NRy3Ry4, and G2;
Rb, at each occurrence, is independently C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, G2, or C1-C6 alkyl wherein the C1-C6 alkyl is optionally substituted with one substituent selected from the group consisting of —ORy1, —NRy3Ry4, —C(O)ORy1, —C(O)NRy3Ry4, —S(O)2Ry1, —S(O)2NRy3Ry4, and G2;
G2, at each occurrence, are each independently aryl, heteroaryl, heterocycle, cycloalkyl, or cycloalkenyl;
and each G2 group is optionally substituted with 1, 2, 3, 4, or 5 R2g groups;
R1g, at each occurrence, is independently C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, halogen, C1-C6 haloalkyl, —CN, NO2, —ORz1, —OC(O)Rz2, —OC(O)NRz3Rz4, —SRz1, —S(O)2Rz1, —S(O)2NRz3Rz4, —C(O)Rz1, —C(O)(C3-C6 cycloalkyl), —C(O)ORz1, —C(O)NRz3Rz4, —NRz3Rz4, —N(Rz3)C(O)Rz2, —N(Rz3)S(O)2Rz2, —N(Rz3)C(O)O(Rz2), —N(Rz3)C(O)NRz3Rz4, —N(Rz3)S(O)2NRz3Rz4, —(C1-C6 alkylenyl)-ORz1, —(C1-C6 alkylenyl)-OC(O)Rz2, —(C1-C6 alkylenyl)-OC(O)NRz3Rz4, —(C1-C6 alkylenyl)-S(O)2Rz1, —(C1-C6 alkylenyl)-S(O)2NRz3Rz4, —(C1-C6 alkylenyl)-C(O)Rz1, —(C1-C6 alkylenyl)-C(O)ORz1, —(C1-C6 alkylenyl)-C(O)NRz3Rz4, —(C1-C6 alkylenyl)-NRz3Rz4, —(C1-C6 alkylenyl)-N(Rz3)C(O)Rz2, —(C1-C6 alkylenyl)-N(Rz3)S(O)2Rz2, —(C1-C6 alkylenyl)-N(Rz3)C(O)O(Rz2), —(C1-C6 alkylenyl)-N(Rz3)C(O)NRz3Rz4, —(C1-C6 alkylenyl)-N(Rz3)S(O)2NRz3Rz4, —(C1-C6 alkylenyl)-CN, or —O(phenyl);
wherein the phenyl moiety and the C3-C6 cycloalkyl moiety are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from the group consisting of C1-C6 alkyl, halogen, C1-C6 haloalkyl, —OH, —O(alkyl), —O(haloalkyl), CN, and NO2;
R2g, at each occurrence, is independently C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, halogen, C1-C6 haloalkyl, oxo, —CN, NO2, —ORy1, —OC(O)Ry2, —OC(O)NRy3Ry4, —SRy1, —S(O)2Ry1, —S(O)2NRy3Ry4, —C(O)Ry1, —C(O)ORy1, —C(O)NRy3Ry4, —NRy3Ry4, —N(Ry3)C(O)Ry2, —N(Ry3)S(O)2Ry2, —N(Ry3)C(O)O(Ry2), —N(Ry3)C(O)NRy3Ry4, —N(Ry3)S(O)2NRy3Ry4, G2b, —(C1-C6 alkylenyl)-OR, —(C1-C6 alkylenyl)-OC(O)Ry2, —(C1-C6 alkylenyl)-OC(O)NRy3Ry4, —(C1-C6 alkylenyl)-S(O)2Ry1, —(C1-C6 alkylenyl)-S(O)2NRy3Ry4, —(C1-C6 alkylenyl)-C(O)Ry1, —(C1-C6 alkylenyl)-C(O)ORy1, —(C1-C6 alkylenyl)-C(O)NRy3Ry4, —(C1-C6 alkylenyl)-NRy3Ry4, —(C1-C6 alkylenyl)-N(Ry3)C(O)Ry2, —(C1-C6 alkylenyl)-N(Ry3)S(O)2Ry2, —(C1-C6 alkylenyl)-N(Ry3)C(O)O(Ry2), —(C1-C6 alkylenyl)-N(Ry3)C(O)NRy3Ry4, —(C1-C6 alkylenyl)-N(Ry3)S(O)2NRy3Ry4, —(C1-C6 alkylenyl)-CN, or —(C1-C6 alkylenyl)-G2b;
Ry1, Ry3, and Ry4, at each occurrence, are each independently H, C1-C6 alkyl, C1-C6 haloalkyl, G2b, or —(C1-C6 alkylenyl)-G2b;
Ry2, at each occurrence, is independently C1-C6 alkyl, C1-C6 haloalkyl, G2b, or —(C1-C6 alkylenyl)-G2b;
G2b, at each occurrence, is independently aryl, heteroaryl, cycloalkyl, cycloalkenyl, or heterocycle;
and each G2b group is optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from the group consisting of C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, halogen, C1-C6 haloalkyl, —CN, NO2, —ORz1, —OC(O)Rz2, —OC(O)NRz3Rz4, —SRz1, —S(O)2Rz1, —S(O)2NRz3Rz4, —C(O)Rz1, —C(O)ORz1, —C(O)NRz3Rz4, —NRz3Rz4, —N(Rz3)C(O)Rz2, —N(Rz3)S(O)2Rz2, —N(Rz3)C(O)O(Rz2), —N(Rz3)C(O)NRz3Rz4, —N(Rz3)S(O)2NRz3Rz4, —(C1-C6 alkylenyl)-ORz1, —(C1-C6 alkylenyl)-OC(O)Rz2, —(C1-C6 alkylenyl)-OC(O)NRz3Rz4, —(C1-C6 alkylenyl)-S(O)2Rz1, —(C1-C6 alkylenyl)-S(O)2NRz3Rz4, —(C1-C6 alkylenyl)-C(O)Rz1, —(C1-C6 alkylenyl)-C(O)ORz1, —(C1-C6 alkylenyl)-C(O)NRz3Rz4, —(C1-C6 alkylenyl)-NRz3Rz4, —(C1-C6 alkylenyl)-N(Rz3)C(O)Rz2, —(C1-C6 alkylenyl)-N(Rz3)S(O)2Rz2, —(C1-C6 alkylenyl)-N(Rz3)C(O)O(Rz2), —(C1-C6 alkylenyl)-N(Rz3)C(O)NRz3Rz4, —(C1-C6 alkylenyl)-N(Rz3)S(O)2NRz3Rz4, and —(C1-C6 alkylenyl)-CN;
Rz1, Rz3, and Rz4, at each occurrence, are each independently H, C1-C6 alkyl, or C1-C6 haloalkyl;
and
Rz2, at each occurrence, is independently C1-C6 alkyl or C1-C6 haloalkyl.

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Abstract

Claims35