Granted Patent B2

US 12,473,314 · App. 18/332,587 · Granted Nov 18, 2025

Inventors: Scott E. Lazerwith (San Francisco, CA); Jonathan William Medley (San Bruno, CA); Philip A. Morganelli (Oakland, CA); Devan Naduthambi (San Bruno, CA); Thomas P. Stratton (San Francisco, CA); Peiyuan Wang (San Mateo, CA)

Assignee: Gilead Sciences, Inc.

C07F9/6561A61P31/12

Abstract

Claims (55)

1 . A compound of Formula I:

or a pharmaceutically acceptable salt thereof, wherein:

Z 1 is —CH 2 — or —CH 2 —CH 2 —;

Z 2 is —CH 2 — or —CH 2 —CH 2 —;

X is a bond, —O—, —(CR 12A R 12B ) q —, —O(CR 12A R 12B ) q —, or —OCR 12A R 12B —(CR 13 ═CR 14 )—; wherein

each R 12A is independently H or C 1 -C 6 alkyl;

each R 12B is independently H or C 1 -C 6 alkyl; or

R 12A and R 12B on the same carbon are joined together to form a C 3 -C 6 cycloalkylene;

R 13 is H, C 1 -C 6 alkyl, or phenyl;

R 14 is H, C 1 -C 6 alkyl, or phenyl; and

q is 1 or 2;

R 1 is C 3 -C 10 cycloalkyl, 4 to 6 membered heterocyclyl containing one, two or three heteroatoms selected from N, O, and S, or 5-10 membered heteroaryl containing one, two or three heteroatoms selected from N, S, and O; wherein the R 1 group is substituted with one or two R 1A groups;

wherein each R 1A is independently a C 1 -C 3 alkyl, phenyl, halo, C 1 -C 3 alkoxy, cyano, or C 1 -C 3 haloalkyl; or wherein two R 1A on same or adjacent carbons are joined together to form a 3 to 6 membered cycloalkyl or 4 to 6 membered heterocyclyl ring containing one, two or three heteroatoms selected from N, S, and O;

R 2 is H or C 1 -C 3 alkyl;

Y is absent;

R 3 is H, C 1 -C 3 alkyl, halo, C 1 -C 3 haloalkyl, or C 3 -C 6 cycloalkyl;

each R 4 is independently H, C 1 -C 3 alkyl, halo, C 1 -C 3 haloalkyl, or C 3 -C 6 cycloalkyl; or R 4 group together with the R 4 group of one adjacent carbon atom forms a double bond;

each R 5 is independently H, C 1 -C 3 alkyl, halo, C 1 -C 3 haloalkyl, or C 3 -C 6 cycloalkyl;

R 6 is H;

R 7 is H; and

m is an integer from 10 to 21.

2 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein X is a bond, —O—, —(CR 12A R 12B ) q —, or —O(CR 12A R 12B ) q —.

3 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein X is a bond, —O—, —OCH 2 , —OCH 2 -(CH—CH)- or —CH 2 CH 2 .

4 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein X is a bond.

5 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein X is —O—.

6 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein X is —OCH 2 —.

7 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein Z 1 is —CH 2 — and Z 2 is —CH 2 —.

8 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein at least one of Z 1 and Z 2 is —CH 2 —CH 2 —.

9 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein the compound is of Formula IV:

wherein n is an integer from 8 to 19.

10 . The compound of claim 9 , or a pharmaceutically acceptable salt thereof, wherein R 2 is H.

11 . The compound of claim 9 , or a pharmaceutically acceptable salt thereof, wherein R 2 is C 1 -C 3 alkyl.

12 . The compound of claim 10 , or a pharmaceutically acceptable salt thereof, wherein the compound is of Formula V, Formula Va or Formula Vb:

13 . The compound of claim 9 , or a pharmaceutically acceptable salt thereof, wherein each R 5 is independently H, or C 1 -C 3 alkyl.

14 . The compound of claim 13 , or a pharmaceutically acceptable salt thereof, wherein each R 5 is H.

15 . The compound of claim 13 , or a pharmaceutically acceptable salt thereof, wherein R 3 is H, C 1 -C 3 alkyl or C 3 -C 6 cycloalkyl.

16 . The compound of claim 15 , or a pharmaceutically acceptable salt thereof, wherein R 3 is H, methyl, ethyl, isopropyl or cyclopropyl.

17 . The compound of claim 13 , or a pharmaceutically acceptable salt thereof, each R 4 is independently H, C 1 -C 3 alkyl, halo, C 1 -C 3 haloalkyl, or C 3 -C 6 cycloalkyl.

18 . The compound of claim 17 , or a pharmaceutically acceptable salt thereof, wherein each R 4 is independently H, methyl or ethyl.

19 . The compound of claim 17 , or a pharmaceutically acceptable salt thereof, wherein n is an integer from 11-18.

20 . The compound of claim 19 , or a pharmaceutically acceptable salt thereof, wherein R 1 is C 3 -C 10 cycloalkyl or 5-6 membered heterocyclyl containing one, two or three heteroatoms selected from N, S, and O; wherein the R 1 group is optionally substituted with one or two R 1A groups.

21 . The compound of claim 19 , or a pharmaceutically acceptable salt thereof, wherein R 1 is C 3 -C 10 or 5-10 membered heteroaryl containing one, two or three heteroatoms selected from N, S, and O; wherein the R 1 group is optionally substituted with one or two R 1A groups.

22 . The compound of claim 19 , or a pharmaceutically acceptable salt thereof, wherein R 1 is C 3 -C 10 cycloalkyl; wherein the R 1 group is optionally substituted with one or two R 1A groups.

23 . The compound of claim 19 , or a pharmaceutically acceptable salt thereof, wherein R 1 is thiophenyl or cyclohexyl, wherein R 1 group is optionally substituted with one or two R 1A groups.

24 . The compound of claim 19 , or a pharmaceutically acceptable salt thereof, wherein each R 1A is independently C 1 -C 3 alkyl, phenyl, halo, C 1 -C 3 alkoxy, cyano, or C 1 -C 3 haloalkyl.

25 . The compound of claim 19 , or a pharmaceutically acceptable salt thereof, wherein each R 1A is independently chloro, fluoro, or cyano.

26 . The compound of claim 19 , or a pharmaceutically acceptable salt thereof, wherein two R 1A on same or adjacent carbons are joined together to form a 3 to 6 membered cycloalkyl.

27 . A compound selected from the group consisting of:

or a pharmaceutically acceptable salt thereof.

28 . A pharmaceutical formulation comprising a pharmaceutically effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier or excipient.

29 . The pharmaceutical formulation of claim 28 , wherein the pharmaceutical formulation is for oral administration.

30 . A method of treating a viral infection in a human in need thereof, wherein the method comprises administering to the human the compound of claim 1 , or a pharmaceutically acceptable salt thereof.

31 . The method of claim 30 , wherein the method comprises administering to the human at least one additional therapeutic or prophylactic agent.

32 . The method of claim 30 , wherein the viral infection is a coronavirus infection.

33 . The method of claim 30 , wherein the viral infection is SARS-COV-2 infection (COVID-19).

Assignments (1)

Continuity (5)

References Cited (212)