US 12,404,262 B2
Therapeutic compounds for HIV virus infection
Gediminas J. Brizgys, San Carlos, CA (US); Chienhung Chou, Dublin, CA (US); Hang Chu, San Mateo, CA (US); Julie Farand, San Mateo, CA (US); Michael Graupe, Pacifica, CA (US); Tezcan Guney, Foster City, CA (US); Darryl Kato, San Francisco, CA (US); Jiayao Li, Foster City, CA (US); John O. Link, San Francisco, CA (US); James B. C. Mack, San Mateo, CA (US); Dong Min Mun, Newark, CA (US); Scott D. Schroeder, Union City, CA (US); William J. Watkins, Saratoga, CA (US); Qiaoyin Wu, Foster City, CA (US); and Jennifer R. Zhang, Union City, CA (US)
Assigned to Gilead Sciences, Inc., Foster City, CA (US)
Filed by Gilead Sciences, Inc., Foster City, CA (US)
Filed on Dec. 2, 2022, as Appl. No. 18/061,150.
Claims priority of provisional application 63/285,745, filed on Dec. 3, 2021.
Prior Publication US 2023/0212148 A1, Jul. 6, 2023
Int. Cl. C07D 401/14 (2006.01); A61K 45/06 (2006.01); C07F 9/6558 (2006.01)
CPC C07D 401/14 (2013.01) [A61K 45/06 (2013.01); C07F 9/65583 (2013.01)] 22 Claims
 
1. A compound of Formula I,

OG Complex Work Unit Chemistry
or a pharmaceutically acceptable salt thereof,
wherein
X is —C(O)C(O)NR1R1, —C(O)C(O)OR2, —(C1-6 alkyl)OR3, —C(O)NR4R5, —C(O)OR6, or —C(O)C1-10 alkyl,
wherein the C1-10 alkyl is optionally substituted with one 4-7 membered monocyclic heterocyclyl,
wherein the 4-7 membered monocyclic heterocyclyl is optionally substituted with 1-3 groups independently selected from —CN, halogen, Ra, Rb, and Rc;
each R1 independently is H or C1-6 alkyl, wherein the C1-6 alkyl is optionally substituted with 1-3 groups independently selected from —CN, halogen, Ra, Rb, and Rc;
R2 is H or C1-6 alkyl, wherein the C1-6 alkyl is optionally substituted with 1-3 groups independently selected from —CN, halogen, Ra, Rb, and Rc;
R3 is —P(O)(OH)2, —C(O)R3a, —C(O)OR3a, —C(O)NR3bR3b, —C(O)C(O)OR3a, —S(O)2R3a, —S(O)2NR3bR3b, or —S(O)2OR3a;
R3a is H or C1-6 alkyl, wherein the C1-6 alkyl is substituted with 1-3 groups independently selected from —CN, Ra, Rd, —OC(O)R9, —OC(O)C(O)OR9, —NR10C(O)R9, —NR10C(O)NR10R10, —NR10C(O)OR9, —NR10C(O)C(O)OR9, —NR10C(═NR10a)NR10R10, and —NR10S(O)2R9;
each R3b independently is Rd or C1-6 alkyl, wherein the C1-6 alkyl is substituted with 1-3 groups independently selected from —CN, Ra, Rd, —OC(O)R9, —OC(O)C(O)OR9, —NR10C(O)R9, —NR10C(O)NR10R10, —NR10C(O)OR9, —NR10C(O)C(O)OR9, —NR10C(═NR10a)NR10R10, and —NR10S(O)2R9;
R4 is H, or C1-6 alkyl, wherein the C1-6 alkyl is optionally substituted with 1-3 groups independently selected from —B(OH)2, —CN, halogen, Ra, Rb, and Rc;
R5 is H, C1-6 alkyl, or 8-10 membered fused bicyclic heteroaryl,
wherein the C1-6 alkyl is optionally substituted with 1-3 groups independently selected from —B(OH)2, —CN, halogen, Ra, Rb, Rc, and R5a,
wherein the 8-10 membered fused bicyclic heteroaryl is optionally substituted with 1-3 groups independently selected from —CN, halogen, Ra, Rb, Rc and R5b;
each R5a independently is 4-7 membered monocyclic heterocyclyl, phenyl, naphthalenyl, 5-6 membered monocyclic heteroaryl, or 8-10 membered fused bicyclic heteroaryl,
wherein the 4-7 membered monocyclic heterocyclyl, phenyl, naphthalenyl, 5-6 membered monocyclic heteroaryl, and 8-10 membered fused bicyclic heteroaryl are each independently optionally substituted with 1-3 groups independently selected from —CN, halogen, Ra, Rb, and Rc;
each R5b independently is C1-6 alkyl, wherein the C1-6 alkyl is optionally substituted with 1-3 groups independently selected from —CN, halogen, Ra, Rb, and Rc;
R6 is C1-10 alkyl or C3-7 monocyclic cycloalkyl,
wherein the C1-10 alkyl is optionally substituted with 1-3 groups independently selected from —CN, halogen, Ra, Rb, Rc, and —OC(O)(C2-6 alkenylene)C(O)OR9, 4-7 membered monocyclic heterocyclyl, phenyl, naphthalenyl, 5-6 membered monocyclic heteroaryl, and 8-10 membered fused bicyclic heteroaryl,
wherein the C3-7 monocyclic cycloalkyl is optionally substituted with 1-3 groups independently selected from —CN, halogen, Ra, Rb, and Rc;
each Ra independently is —P(O)(OH)2 or —OP(O)(OH)2;
each Rb independently is —C(O)R7, —C(O)OR7, —C(O)NR8R8, —C(O)C(O)OR7, —C(═NR8a)(NR8R8), —S(O)2R7, —S(O)2NR8R8, or —S(O)2OR7;
each Rc independently is —OR7, —OC(O)R7, —OC(O)C(O)OR7, —(O(C1-4 alkyl))nOR7a, —NR8R8, —N+R8R8R8a, —NR8C(O)R7, —NR8C(O)NR8R8, —NR8C(O)OR7, —NR8C(O)C(O)OR7, —NR8C(═NR8a)NR8R8, or —NR8S(O)2R7;
each R7 independently is H or C1-6 alkyl, wherein the C1-6 alkyl is optionally substituted with 1-3 groups independently selected from —CN, halogen, Ra, Rd, and Re;
each R7a independently is H, —P(O)(OH)2, or C1-6 alkyl, wherein the C1-6 alkyl is optionally substituted with 1-3 groups independently selected from —CN, halogen, Ra, Rd, and Re;
each R8 independently is H, Rd, or C1-6 alkyl,
wherein the C1-6 alkyl is optionally substituted with 1-3 groups independently selected from —CN, halogen, Ra, Rd, and Re;
each R8a independently is H or C1-3 alkyl;
each Rd independently is —C(O)R9, —C(O)OR9, —C(O)NR10R10, —C(O)C(O)OR9, —C(═NR10a)(NR10R10), —S(O)2R9, —S(O)2NR10R10, or —S(O)2OR9;
each Re independently is —OR9, —OC(O)R9, —OC(O)C(O)OR9, —NR10R10, —N+R10R10R10a, —NR10C(O)R9, —NR10C(O)NR10R10, —NR10C(O)OR9, —NR10C(O)C(O)OR9, —NR10C(═NR10a)NR10R10, or —NR10S(O)2R9;
each R9 independently is H or C1-6 alkyl, wherein the C1-6 alkyl is optionally substituted with 1-3 groups independently selected from CN, halogen, Ra, Rf, and Rg;
each R10 independently is H, Rf or C1-6 alkyl, wherein the C1-6 alkyl is optionally substituted with 1-3 groups independently selected from —CN, halogen, Ra, Rf, and Rg;
each R10a independently is H or C1-3 alkyl;
each Rf independently is —C(O)R11, —C(O)OR11, —C(O)NR11R11, —C(O)C(O)OR11, —C(═NR11a)(NR11R11), —S(O)2R11, —S(O)2NR11R11, or —S(O)2OR11;
each Rg independently is —OR11, —OC(O)R11, —OC(O)C(O)OR11, —NR11R11, —N+R11R11R11a, —NR11C(O)R11, —NR11C(O)NR11R11, —NR11C(O)OR11, —NR11C(O)C(O)OR11, —NR11C(═NR11a)NR11R11, or —NR11S(O)2R11;
each R11 independently is H or C1-6 alkyl, wherein the C1-6 alkyl is optionally substituted with 1-3 groups independently selected from —OH, CN, halogen, —COOH, and Ra;
each R11a independently is H or C1-3 alkyl;
n is 1, 2, 3, 4, or 5;
wherein each 4 membered monocyclic heterocyclyl has 1 ring heteroatom selected from N, O, and S;
wherein each 5-7 membered monocyclic heterocyclyl has 1-2 ring heteroatoms independently selected from N, O, and S; and
wherein each 5-6 membered monocyclic heteroaryl and 8-10 membered fused bicyclic heteroaryl independently have 1-4 ring heteroatoms independently selected from N, O, and S.