US 11,767,337 B2
Antiviral compounds
Gregory F. Chin, San Francisco, CA (US); Byoung-Kwon Chun, Pleasanton, CA (US); Michael O. Clarke, Redwood City, CA (US); Bindu Goyal, Fremont, CA (US); Hon C. Hui, San Mateo, CA (US); Petr Jansa, Foster City, CA (US); Richard L. Mackman, Millbrae, CA (US); Dustin S. Siegel, Half Moon Bay, CA (US); and Hai Yang, San Mateo, CA (US)
Assigned to GILEAD SCIENCES, INC., Foster City, CA (US)
Filed by Gilead Sciences, Inc., Foster City, CA (US)
Filed on Feb. 18, 2021, as Appl. No. 17/178,463.
Claims priority of provisional application 62/977,881, filed on Feb. 18, 2020.
Prior Publication US 2021/0284670 A1, Sep. 16, 2021
Int. Cl. C07F 9/6561 (2006.01); A61P 31/14 (2006.01)
CPC C07F 9/6561 (2013.01) [A61P 31/14 (2018.01)] 43 Claims
 
1. A compound of Formula (II):

OG Complex Work Unit Chemistry
or a pharmaceutically acceptable salt thereof, wherein:
Base is

OG Complex Work Unit Chemistry
R1A and R2A are each independently:
(A) C1-12 alkyl optionally substituted with 1 to 3 R1B,
(B) 3 to 6 membered heterocyclyl having 1 to 3 heteroatoms independently selected from N, O and S, wherein the 3 to 6 membered heterocyclyl is optionally substituted with 1 to 3 R1C, or
(C) phenyl, wherein
each R1B is independently —OH, —NH2, C1-6 alkoxy, methoxyethoxy, or 3 to 6 membered heterocyclyl having 1 to 3 heteroatoms independently selected from N, O and S, and
each R1C is independently C1-3 alkyl;
R3 is —N(H)R3A or —N═C(R3B)(R3C);
R3A is H, —CH2OP(O)(OH)2, or —C(O)R3D, wherein
R3D is C1-6 alkyl optionally substituted with 1 methoxy, or 3 to 6 membered heterocyclyl having 1 to 3 heteroatoms independently selected from N, O and S, optionally substituted with C1-3 alkyl;
R3B is H or C1-3 alkyl;
R3C is —N(R3C1)(R3C2);
R3C1 and R3C2 are each independently H or C1-6 alkyl; or
R3C1 and R3C2 together with the atom to which they are attached form a 3 to 6 membered heterocyclyl having 1 to 3 heteroatoms independently selected from N, O and S, optionally substituted with C1-6 alkyl;
R4A is O or S; and
R4B and R4C are each independently
(A) —OH;
(B) —OR4B1, wherein
R4B1 is C1-6 alkyl optionally substituted with 1 to 3 R4B2 groups, or C6-12 aryl, wherein
each R4B2 group is independently C1-6 alkoxy, —S—R4B3, or —S(O)2—R4B3, and
each R4B3 group is independently C1-6 alkyl;
(C)

OG Complex Work Unit Chemistry
 wherein
m is 0, 1, 2, 3, 4, or 5; and
each R4D is independently C1-3 alkyl optionally substituted with 1 to 3 R4D1 groups, C1-3 alkoxy optionally substituted with 1 to 3 R4D2 groups, or —C(O)N(R4D3)2, wherein
each R4D1 group is independently —NH2 or —C(O)OR4D3,
each R4D2 is independently C1-3 alkoxy, and
each R4D3 is independently C1-3 alkyl;
(D)

OG Complex Work Unit Chemistry
 wherein
R4E1 and R4E2 are each independently H or C1-6 alkyl,
R4F1 and R4F2 are each independently H or C1-6 alkyl, or R4F1 and R4F2 together are oxo,
R4G is C1-12 alkyl optionally substituted with 1 to 3 R4G1, C3-7 cycloalkyl optionally substituted with 1 to 3 R4G2, 3 to 8 membered heterocyclyl having 1 to 3 heteroatoms selected from N, O and S, optionally substituted with 1 to 3 R4G3, or —C(O)R4G4,
each R4G1 is independently —OH, C1-6 alkyl, C1-3 alkoxy, —(CH2OCH2)1-5—CH3, —N(R4G8)2, —OP(O)(OH)2, C3-7 cycloalkyl optionally substituted with 1 to 3 R4G9, 3 to 6 membered heterocyclyl having 1 to 3 heteroatoms independently selected from N, O and S, optionally substituted with 1 to 3 R4G10, or phenyl,
each R4G2 is independently C1-6 alkyl, C1-3 haloalkyl, or —NH2,
each R4G3 is independently halogen or C1-3 alkyl;
each R4G4 is independently C1-12 alkyl,
each R4G8 is independently C1-6 alkyl,
each R4G9 is independently C1-3 haloalkyl, or —NH2, and
each R4G1° is independently C1-3 haloalkyl; or
(E) —(OP(O)(OH))1-2—OH; and
R5A and R5B are each C1-6 alkyl substituted with —OP(O)(OH)2.