Inhibitors of APOL1 and methods of using same

A compound represented by the formula:

• a tautomer thereof, a deuterated derivative of that compound or tautomer, or a pharmaceutically acceptable salt of any of the foregoing, wherein:
• Ring A is chosen from C6 aryl and 5- and 6-membered heteroaryl groups;
• R1, for each occurrence, is independently chosen from halogen, —OH, ═O, cyano, phenyl, C1-C6 alkyl, C1-C6 alkoxy, C3-C6 carbocyclyl, 4- to 6-membered heterocyclyl, —C(═O)N(Rc)2, and —SO2(Rc) groups, wherein:
• Rc, for each occurrence, is independently chosen from hydrogen and C1-C4 alkyl groups;
• the 4- to 6-membered heterocyclyl of R1 comprises one heteroatom chosen from nitrogen and oxygen;
• the C1-C6 alkyl of R1 is optionally substituted with 1 to 3 groups independently chosen from halogen, cyano, —OH, —NH2, —NH(C1-C4 alkyl), —N(C1-C4 alkyl)2, and C1-C4 alkoxy groups;
• the C1-C6 alkoxy of R1 is optionally substituted with 1 to 3 groups independently chosen from —OH, cyano, and halogen groups;
• the C3-C6 carbocyclyl of R1 is optionally substituted with 1 to 3 groups independently chosen from halogen, cyano, —OH, —NH2, —NH(C1-C4 alkyl), —N(C1-C4 alkyl)2, C1-C4 alkyl, C1-C4 alkoxy, —C(═O)NH2, —C(═O)NH(C1-C4 alkyl), and —C(═O)N(C1-C4 alkyl)2 groups;
• and
• the phenyl of R1 is optionally substituted with 1 to 3 groups independently chosen from halogen, cyano, —OH, —NH2, —NH(C1-C4 alkyl), —N(C1-C4 alkyl)2, C1-C4 alkyl, C1-C4 alkoxy, —C(═O)NH2, —C(═O)NH(C1-C4 alkyl), and —C(═O)N(C1-C4 alkyl)2 groups;
• or
• wherein two R1 groups taken together with the Ring A atoms connecting them form a 5- to 6-membered cycloalkyl, 5- to 8-membered heterocyclyl, 5- to 6-membered aryl, or 5- to 6-membered heteroaryl ring,
• wherein the 5- to 6-membered cycloalkyl, 5- to 8-membered heterocyclyl, 5- to 6-membered aryl, 5- to 6-membered heteroaryl are each optionally substituted with 1 to 4 groups chosen from halogen, —OH, and C1-C4 alkyl;
• R2 is chosen from C1-C6 alkyl, —C(═O)O(C1-C4 alkyl), C2-C6 alkynyl, and
• wherein:
• the C1-C6 alkyl of R2 is substituted with 1 to 3 groups independently chosen from halogen, cyano, —OH, —NH2, —NH(C1-C4 alkyl), —N(C1-C4 alkyl)2, C1-C4 alkoxy, —C(═O)NH2, —C(═O)NH(C1-C4 alkyl), —C(═O)N(C1-C4 alkyl)2, C3-C6 carbocyclyl, 5- to 10-membered heterocyclyl, C6 aryl, and 5- to 10-membered heteroaryl groups;
• Ring B is chosen from C3-C12 carbocyclyl, 3- to 12-membered heterocyclyl, C6 and C10 aryl, and 5- to 10-membered heteroaryl groups, wherein Ring B is optionally substituted with 1, 2, 3, 4, or 5 Ra groups;
• wherein:
• Ra, for each occurrence, is independently chosen from halogen, cyano, C1-C6 alkyl, C2-C6 alkenyl, C1-C6 alkoxy, C1-C6 haloalkyl, C1-C6 haloalkenyl, C1-C6 haloalkoxy, —C(═O)NRhRi, —NRhRi, —NRhC(═O)Rk, —NRhC(═O)ORk, —NRhC(═O)NRiRj, —NRhS(═O)pRk, —ORk, —OC(═O)Rk, —OC(═O)ORk, —OC(═O)NRhRi, —[O(CH2)q]rO(C1-C6 alkyl), —S(═O)pRk, —S(═O)pNRhRi, —C(═O)ORk, C3-C12 carbocyclyl, 3- to 12-membered heterocyclyl, C6 and C10 aryl, and 5- to 10-membered heteroaryl groups, wherein:
• the C1-C6 alkyl, C1-C6 alkoxy, and the C2-C6 alkenyl of Ra are each optionally substituted with 1 to 3 groups independently chosen from C6 to C10 aryl (optionally substituted with 1 to 3 Rm groups), 5- to 10-membered heterocyclyl (optionally substituted with 1 to 3 Rm groups), 5- to 10-membered heteroaryl (optionally substituted with 1 to 3 Rm groups), cyano, —C(═O)Rk, —C(═O)ORk, —C(═O)NRhRi, —NRhRi, —NRhC(═O)Rk, —NRhC(═O)ORk, —NRhC(═O)NRiRj, —NRhS(═O)pRk, —ORk, —OC(═O)Rk, —OC(═O)ORk, —OC(═O)NRhRi, —S(═O)pRk, —S(═O)pNRhRi, —O(C6 aryl) (optionally substituted with 1 to 3 Rm groups), and C3-C6 carbocyclyl groups (optionally substituted with 1 to 3 Rm groups);
• the C3-C12 carbocyclyl, the 3- to 12-membered heterocyclyl, the C6 and C10 aryl, and the 5- to 10-membered heteroaryl of Ra are each optionally substituted with 1 to 3 groups independently chosen from halogen, cyano, C1-C4 alkyl, —NRhRi, and —ORk groups, wherein:
• Rh, Ri, and Rj, for each occurrence, are each independently chosen from hydrogen, C1-C4 alkyl, C6-C10 aryl, and C3-C6 cycloalkyl groups, wherein:
• the C1-C4 alkyl of any one of Rh, Ri, and Rj is optionally substituted with 1 to 3 groups independently chosen from halogen, cyano, and —OH groups;
• Rk, for each occurrence, is independently chosen from hydrogen, C1-C4 alkyl, 5- to 10-membered heterocyclyl, and C3-C6 carbocyclyl groups, wherein:
• the C1-C4 alkyl of any one of Rk is optionally substituted with 1 to 3 groups independently chosen from halogen, cyano, and —OH groups;
• Rm, for each occurrence, is independently chosen from halogen, cyano, oxo, C1-C6 alkyl, C1-C6 alkoxy, —S(═O)pRk, and —ORk groups, wherein:
• the C1-C6 alkyl of Rm is optionally substituted with 1 to 3 groups independently chosen from halogen, cyano, —OH, and —O(C1-C4 alkyl) groups;
• R3 is chosen from C1-C6 alkyl, C3-C12 carbocyclyl, 3- to 12-membered heterocyclyl, and 5- to 10-membered heteroaryl groups, wherein:
• the C1-C6 alkyl of R3 is optionally substituted with 1 to 3 groups independently chosen from halogen, cyano, —OH, —NH2, —NH(C1-C4 alkyl), —N(C1-C4 alkyl)2, C1-C4 alkoxy, —C(═O)NH2, —C(═O)NH(C1-C4 alkyl), and —C(═O)N(C1-C4 alkyl)2 groups;
• the C3-C12 carbocyclyl, the 3- to 12-membered heterocyclyl, the C6 and C10 aryl, and the 5- to 10-membered heteroaryl of R3 are each optionally substituted with 1 to 3 groups independently chosen from halogen, cyano, —OH, —NH2, —NH(C1-C4 alkyl) (optionally substituted with —OH), —N(C1-C4 alkyl)2, C1-C5 alkyl (optionally substituted with —OH or —S(═O)2(C1-C4 alkyl)), C1-C4 alkoxy, —C(═O)NH2, —C(═O)NH(C1-C4 alkyl), —NHC(═O) (C1-C4 alkyl), —C(═O) (C1-C4 alkoxy), and —C(═O)N(C1-C4 alkyl)2 groups;
• R4 is chosen from halogen, C1-C6 alkyl, C1-C6 haloalkyl, —(CH2)nC(═O)NRnRo, —NRnRo, —NRoC(═O)Rp, —NRnS(═O)pRp, —(CH2)nORp, —S(═O)pRp, and —(CH2)nC(═O)ORp groups, wherein:
• Rn and Ro, for each occurrence, are each independently chosen from hydrogen and C1-C4 alkyl groups;
• and
• Rp, for each occurrence, is independently chosen from hydrogen, C1-C4 alkyl, and C1-C4 haloalkyl groups;
• m is an integer chosen from 0, 1, 2, 3, 4, and 5;
• n is an integer chosen from 0, 1, and 2;
• p, for each occurrence, is an integer independently chosen from 1 and 2;
• and
• q and r, for each occurrence, are each an integer independently chosen from 1, 2, 3, and 4.