BENZIMIDAZOLE AND IMADAZOPYRIDINE CARBOXIMIDAMIDE COMPOUNDS

摘要

The present disclosure provides indoleamine 2,3-dioxygenase 1 (IDOL) inhibitors of Formula I:;;or pharmaceutically acceptable salts thereof, in which X, L, n, m, R1, R2a, R2b, Rn, Rm, and Rt are as defined herein, as well as pharmaceutical compositions that include a compound of Formula I, or pharmaceutically acceptable salts thereof, and methods of using the same to treat conditions mediated by IDO1.

主权项

1. A compound of Formula I:wherein
R1 is mono or bicyclic aryl or heteroaryl, wherein each mono or bicyclic aryl or heteroaryl is optionally substituted with one, two, or three substituents independently selected from hydroxyl, halo, —CN, C1-6 haloalkyl, C1-6 haloalkoxy, C1-6 alkoxy, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, and C3-6 cycloalkyl, wherein two of the optional substituents can join to form an additional partially saturated heterocyclic ring; and
wherein each C1-6 alkoxy, C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, and C3-6 cycloalkyl is optionally substituted with one, two, or three substituents independently selected from hydroxyl, halo, —CN, —N(R20)(R22) and C3-6 cycloalkyl; X is N or CR2c; R2a, R2b, and R2c are independently hydrogen, hydroxyl, halo, CN, C1-6 haloalkyl, C1-6 haloalkoxy, C1-6 alkoxy, or C1-6 alkyl; R2d and R2e are independently hydrogen, C1-6 haloalkyl, C1-6 haloalkoxy, or C1-6 alkyl; n and m are independently 0, 1, 2, or 3; each Rn and Rm are independently hydrogen, hydroxyl, halo, C1-6 alkoxy, C1-6 alkyl, C3-6 cycloalkyl, aryl, heterocyclyl, or heteroaryl; or two Rn or Rm join to form a C3-6 cycloalkyl; and
wherein each C1-6 alkoxy, C1-6 alkyl, C3-6 cycloalkyl aryl, heterocyclyl, or heteroaryl is optionally substituted with one, two, or three substituents independently selected from hydroxyl, halo, —CN, —N(R20)(R22), C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C1-6 haloalkoxy, C1-6 alkoxy, C1-6 alkyl, and C3-6 cycloalkyl; L is a bond, —NR3—, —C(O)—NR3—, —NR3—C(O)—, —NR3SO2—, —NR3SO2—NR3—, —SO2NR3—, —O—, —S—, or —S(O)—, where t is 0, 1 or 2; each R3 is independently hydrogen, C1-6 alkyl, C3-6 cycloalkyl, aryl, heterocyclyl, or heteroaryl; and Rt is hydrogen, C1-6 alkyl, C1-6 alkoxy, —C(O)R20, —C(O)OR20, —NC(O)OR20, —N(R20)(R22), —C(O)N(R20)(R22), —SO2R20, —N(R20)SO2(R21), —N(R20)SO2—N(R21)(R22), —SO2N(R20)(R22), C3-15 cycloalkyl, aryl, heteroaryl, or heterocyclyl, provided that when Rt is C1-6 alkoxy, —NC(O)OR20, —N(R20)(R22), —N(R20)SO2(R21), —N(R20)SO2—N(R21)(R22), or —SO2N(R20)(R22), and m is 0, then L is a bond;
wherein said C1-6 alkyl, C1-6 alkoxy, C3-15 cycloalkyl, aryl, heterocyclyl, or heteroaryl is optionally substituted with one, two, or three substituents independently selected from hydroxyl, halo, —NO2, C1-6 haloalkyl, C1-6 haloalkoxy, —C(O)R20, —N(R20)(R22), —SO2R20, —N(R20)SO2(R21), —N(R20)SO2—N(R21)(R22), —SO2N(R2)(R22), C3-6 cycloalkyl, —CN, C1-6 alkoxy, C1-6 alkyl, and heterocyclyl; and wherein said heterocyclyl is optionally substituted with one or two oxo;
wherein said C3-6 cycloalkyl, C1-6 alkyl or C1-6 alkoxy is optionally substituted with one, two, or three substituents independently selected from hydroxyl, halo, —NO2, C1-6 haloalkyl, C1-6 haloalkoxy, C1-6 alkoxy, —N(R20)(R22), —SO2R20, —N(R20)SO2(R22), —N(R20)SO2—N(R21)(R22)—, and —SO2N(R20)(R22); and said C1-6 alkyl is optionally substituted with aryl; R20, R21, and R22 are independently selected from hydrogen, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, aryl, heterocyclyl, and heteroaryl;
wherein said aryl, heterocyclyl, or heteroaryl is optionally substituted with one, two, or three halogen;or a pharmaceutically acceptable salt, isomer, or mixture thereof.