US 11,052,087 B2
Anti-HIV compounds
Elbert Chin, San Mateo, CA (US); Darryl Kato, San Francisco, CA (US); John O. Link, San Francisco, CA (US); Nathan Shapiro, Belmont, CA (US); and Zheng-Yu Yang, Palo Alto, CA (US)
Assigned to Gilead Sciences, Inc., Foster City, CA (US)
Filed by Gilead Sciences, Inc., Foster City, CA (US)
Filed on Jul. 29, 2019, as Appl. No. 16/525,203.
Claims priority of provisional application 62/711,768, filed on Jul. 30, 2018.
Prior Publication US 2020/0030327 A1, Jan. 30, 2020
Int. Cl. A61K 31/506 (2006.01); A61K 31/4995 (2006.01); C07D 487/08 (2006.01); A61P 31/18 (2006.01)
CPC A61K 31/506 (2013.01) [A61K 31/4995 (2013.01); A61P 31/18 (2018.01); C07D 487/08 (2013.01)] 86 Claims
 
1. A compound of Formula (I):

OG Complex Work Unit Chemistry
or a pharmaceutically acceptable salt thereof, wherein:
R1 is a 5 to 10-membered heterocycle having 1 to 5 heteroatoms selected from N, O, and S, or a 5 to 10-membered heteroaryl having 1 to 5 heteroatoms selected from N, O, and S, wherein the 5 to 10-membered heterocycle or 5 to 10-membered heteroaryl is optionally substituted with 1 to 5 Ra groups;
R2 and R3 are each independently C1-4 alkyl, C3-6 cycloalkyl, O—R2A, C1-2 alkyl-O—R2A, N—(R3A)2, or C1-2 alkyl-N—(R3A)2,
wherein each R2A is independently C1-4 alkyl, C3-6 cycloalkyl, or a 4 to 10-membered heterocyclyl having 1 to 5 heteroatoms selected from N, O, and S, wherein each R3A is independently hydrogen, C1-4 alkyl, C3-6 cycloalkyl, or COO(Re), wherein each Re is independently hydrogen or C1-4 alkyl,
and wherein each C3-6 cycloalkyl or 4 to 10-membered heterocyclyl is optionally substituted by 1 to 3 Rf groups, wherein each Rf is independently C1-2 alkyl or halogen;
R4 is hydrogen, halo, C1-4 alkyl, C1-4haloalkyl, C3-6 cycloalkyl, C1-4 alkoxy, or C1-4haloalkoxy;
R7 is hydrogen, halo, C1-4 alkyl, C1-4haloalkyl, C3-6 cycloalkyl, C1-4 alkoxy, or C1-4haloalkoxy;
R5, R6, R8, and R9 are each independently hydrogen, halo, C1-2 alkyl, C1-2 haloalkyl, or C3-6 cycloalkyl;
and wherein two or more of R4, R5 and R6 or two or more of R7, R8, and R9 optionally join together to form one or more C3-6 cycloalkyl groups that are optionally substituted with 1 to 4 groups selected from halogen, C1-2 alkyl, and C1-2 haloalkyl;
each R10 is independently halogen, cyano, C1-4 alkoxy, C1-6 alkyl, or C3-6 cycloalkyl;
n is 0 to 4;
each Ra is independently halogen, C1-4 alkyl, C1-4 alkyl with 1 to 2 groups selected from hydroxyl and C1-4 alkoxy, C1-4 haloalkyl, C1-4 alkoxy, C3-6 cycloalkyl, 4 to 10-membered heterocyclyl having 1 to 5 heteroatoms selected from N, O, and S which is optionally substituted with Ra1, or O—R3B,
wherein R3B is C3-6 cycloalkyl optionally substituted with Ra or a 4 to 10-membered heterocyclyl having 1 to 5 heteroatoms selected from N, O, and S optionally substituted with Ra1,
wherein each Ra1 is independently C1-4 alkyl, C3-6 cycloalkyl, C1-4 haloalkyl, or 4 to 8-membered heterocyclyl having 1 to 3 heteroatoms selected from N, O, and S;
A is ethynyl or a bond;
X1 is a 6 to 10-membered aryl or a 5 to 10-membered heteroaryl having 1 to 3 heteroatoms selected from N, O, and S, wherein each 6 to 10-membered aryl or 5 to 10-membered heteroaryl is optionally substituted with 1 to 4 Rb groups;
X2 is hydrogen or a 4 to 10-membered heterocyclyl having 1 to 5 heteroatoms selected from N, O, and S, wherein the 4 to 10-membered heterocyclyl is optionally substituted with one R11 and optionally substituted with 1 to 5 Rb groups;
R11 is —C═O(Rc), CH2(Rd), S(O)1-2(C1-4 alkyl), S(O)1-2—(C3-6 cycloalkyl), a 4 to 10-membered heterocyclyl having 1 to 5 heteroatoms selected from N, O, and S, or a 5 to 9-membered heteroaryl having 1 to 5 heteroatoms selected from N, O, and S, wherein each 4 to 10-membered heterocyclyl or 5 to 9-membered heteroaryl is optionally substituted with 1 to 5 Rb groups;
each Rb is independently halogen, oxo, C1-4 alkyl, C1-4 alkyl with 1 to 2 groups selected from hydroxyl and C1-4 alkoxy, C1-4 haloalkyl, C1-4 alkoxy, or COO(Re);
Rc is C1-4alkyl, C1-4haloalkyl, C1-4 alkoxy, N(Re)2, C3-6 cycloalkyl, or a 4 to 6-membered heterocyclyl having 1 to 3 heteroatoms selected from N, O, and S, wherein the C3-6 cycloalkyl and the 4 to 6-membered heterocyclyl are optionally substituted by 1 to 5 Rb groups;
Rd is COO(Re), N(Re)2, C3-6 cycloalkyl, or a 4 to 6-membered heterocyclyl having 1 to 3 heteroatoms selected from N, O, and S, wherein the C3-6 cycloalkyl and the 4 to 6-membered heterocyclyl is optionally substituted by 1 to 5 Rb groups;
each R12 is C1-2 alkyl, halo, —OC1-2 alkyl, or cyano;
each p is 0 to 4;
R13 is —C(═O)Rg1, —C(═O)ORg2, or —P(═O)(ORh)2;
Rg1 is H, C1-6 alkyl, C3-6 cycloalkyl, or 5- to 6-membered heteroaryl having 1 to 3 heteroatoms selected from N, O, and S;
wherein the C1-6 alkyl of Rg1 is optionally substituted with 1, 2, 3, or 4 substituents independently selected from halogen, C1-4 alkoxy, —N(Ri)2, —C1-4 alkyl-N(Ri)2, —N(Ri)3+, and 4- to 6-membered heterocyclyl having 1 to 3 heteroatoms selected from N, O, and S, wherein the 4- to 6-membered heterocyclyl is optionally substituted with 1, 2, 3, or 4 substituents independently selected from halogen, C1-4 alkyl, C1-4 alkoxy,
N(Ri)2, and —C1-4 alkyl-N(Ri)2;
wherein the 5- to 6-membered heteroaryl and C3-6 cycloalkyl of Rg1 are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from halogen, C1-6 alkyl, C1-4 alkoxy, —N(Ri)2, and —C1-4 alkyl-N(Ri)2;
Rg2 is C1-6 alkyl optionally substituted with 1, 2, 3, or 4 substituents independently selected from halogen, C1-6 alkyl, C1-4 alkoxy, —N(Ri)2, —C1-4 alkyl-N(Ri)2, and —O—P(═O)(ORh)2; and
Rh and Ri are each independently selected from H and C1-3 alkyl.