IP Library › Granted Patent US 12,509,466
Granted Patent B2
US 12,509,466 · App. 17/854,818 · Granted Dec 30, 2025

Methods and compounds for treating paramyxoviridae virus infections

Inventors: Richard L. Mackman (Millbrae, CA); Jay P. Parrish (Redwood City, CA); Adrian S. Ray (Redwood City, CA); Dorothy Agnes Theodore (Castro Valley, CA)
Assignee: Gilead Sciences, Inc.
C07D487/04A61K9/0078A61K31/706A61K45/06C07F9/6561C07H7/06C07H19/04
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Quick Facts
Patent No.
US 12,509,466
App. No.
17/854,818
Granted
Dec 30, 2025
Kind
B2
Abstract

Provided are methods for treating Paramyxoviridae virus infections by administering ribosides, riboside phosphates and prodrugs thereof, of Formula I: wherein the 1′ position of the nucleoside sugar is substituted. The compounds, compositions, and methods provided are particularly useful for the treatment of Human parainfluenza and Human respiratory syncytial virus infections.

Claims (56)

1 . A method of treating a Paramyxoviridae infection in a human in need thereof, the method comprising administering to the human a compound of Formula III or a pharmaceutically acceptable salt thereof:

wherein

R 2 and R 3 are each OR a ;

R 6 is CN;

R 7 is —(C═O)R 11 or

R 8 is NH 2 ;

R 9 is H;

each occurrence of R a is independently H or —(C═O)R 11 ; and

each occurrence of R 11 is independently H or (C 1 -C 8 )alkyl which is optionally substituted by NH 2 ; and

each occurrence of R is independently H or (C 1 -C 8 )alkyl.

2 . The method of claim 1 , wherein R 2 and R 3 are each OH.

3 . The method of claim 2 , wherein R 7 is —(C═O)—(C 1 -C 8 )alkyl; wherein the (C 1 -C 8 )alkyl of R 7 is selected from the group consisting of methyl, ethyl, n-propyl, i-propyl, 1-butyl, 2-methyl-1-propyl, 2-butyl, 2-methyl-2-propyl, 2-pentyl, 3-pentyl, 2-methyl-2-butyl, 3-methyl-2-butyl, 3-methyl-1-butyl, and 2-methyl-1-butyl, each of which is optionally substituted by NH 2 .

4 . The method of claim 3 , wherein R 7 is —(C═O)—CH(CH 3 ) 2 .

5 . The method of claim 3 , wherein R 7 is —(C═O)—CH(NH 2 )CH(CH 3 ) 2 .

6 . The method of claim 3 , wherein R 7 is —(C═O)—(C 1 -C 8 )alkyl.

7 . The method of claim 6 wherein the (C 1 -C 8 )alkyl of R 7 is selected from the group consisting of methyl, ethyl, n-propyl, i-propyl, 1-butyl, 2-methyl-1-propyl, 2-butyl, 2-methyl-2-propyl, 2-pentyl, 3-pentyl, 2-methyl-2-butyl, 3-methyl-2-butyl, 3-methyl-1-butyl, and 2-methyl-1-butyl.

8 . The method of claim 2 , wherein R 7 is

9 . The method of claim 1 , wherein R 2 and R 3 are each —O(C═O)(C 1 -C 8 )alkyl, wherein the (C 1 -C 8 )alkyl groups of R 2 and R 3 are each optionally substituted with NH 2 .

10 . The method of claim 9 , wherein the (C 1 -C 8 )alkyl groups of R 2 and R 3 are each selected from the group consisting of methyl, ethyl, n-propyl, i-propyl, 1-butyl, 2-methyl-1-propyl, 2-butyl, 2-methyl-2-propyl, 2-pentyl, 3-pentyl, 2-methyl-2-butyl, 3-methyl-2-butyl, 3-methyl-1-butyl, and 2-methyl-1-butyl, each of which is optionally substituted with NH 2 .

11 . The method of claim 10 , wherein each of R 2 and R 3 is selected from the group consisting of —O(C═O)—CH(CH 3 ) 2 and —O(C═O)—CH(NH 2 )CH(CH 3 ) 2 .

12 . The method of claim 10 , wherein R 2 and R 3 are —O(C═O)—CH(NH 2 )CH(CH 3 ) 2 and —O(C═O)—CH(CH 3 ) 2 , respectively; —O(C═O)—CH(CH 3 ) 2 and —O(C═O)—CH(NH 2 )CH(CH 3 ) 2 , respectively; or —O(C═O)—CH(NH 2 )CH(CH 3 ) 2 and —O(C═O)—CH(NH 2 )CH(CH 3 ) 2 , respectively.

13 . The method of claim 9 , wherein R 2 and R 3 are each —O(C═O)(C 1 -C 8 )alkyl.

14 . The method of claim 13 , wherein the (C 1 -C 8 )alkyl groups of R 2 and R 3 are each selected from the group consisting of methyl, ethyl, n-propyl, i-propyl, 1-butyl, 2-methyl-1-propyl, 2-butyl, 2-methyl-2-propyl, 2-pentyl, 3-pentyl, 2-methyl-2-butyl, 3-methyl-2-butyl, 3-methyl-1-butyl, and 2-methyl-1-butyl.

15 . The method of claim 13 , wherein R 2 and R 3 are each —O(C═O)—CH(CH 3 ) 2 .

16 . The method of claim 9 , wherein R 7 is —(C═O)—(C 1 -C 8 )alkyl, wherein the (C 1 -C 8 )alkyl of R 7 is optionally substituted by NH 2 .

17 . The method of claim 16 , wherein the (C 1 -C 8 )alkyl of R 7 is selected from the group consisting of methyl, ethyl, n-propyl, i-propyl, 1-butyl, 2-methyl-1-propyl, 2-butyl, 2-methyl-2-propyl, 2-pentyl, 3-pentyl, 2-methyl-2-butyl, 3-methyl-2-butyl, 3-methyl-1-butyl, and 2-methyl-1-butyl, each of which is optionally substituted by NH 2 .

18 . The method of claim 17 , wherein R 7 is —(C═O)—CH(CH 3 ) 2 .

19 . The method of claim 17 , wherein R 7 is —(C═O)—CH(NH 2 )CH(CH 3 ) 2 .

20 . The method of claim 13 , wherein R 7 is —(C═O)—(C 1 -C 8 )alkyl.

21 . The method of claim 20 , wherein the (C 1 -C 8 )alkyl of R 7 is selected from the group consisting of methyl, ethyl, n-propyl, i-propyl, 1-butyl, 2-methyl-1-propyl, 2-butyl, 2-methyl-2-propyl, 2-pentyl, 3-pentyl, 2-methyl-2-butyl, 3-methyl-2-butyl, 3-methyl-1-butyl, and 2-methyl-1-butyl.

22 . The method of claim 9 , wherein R 7 is

23 . The method of claim 9 , wherein R 2 is —O(C═O)—CH(CH 3 ) 2 , R 3 is —O(C═O)—CH(CH 3 ) 2 , and R 7 is —(C═O)—CH(CH 3 ) 2 .

24 . The method of claim 1 , wherein R 2 is OH and R 3 is —O(C═O)(C 1 -C 8 )alkyl, wherein the (C 1 -C 8 )alkyl of R 3 is optionally substituted by NH 2 .

25 . The method of claim 24 , wherein the (C 1 -C 8 )alkyl of R 3 is selected from the group consisting of methyl, ethyl, n-propyl, i-propyl, 1-butyl, 2-methyl-1-propyl, 2-butyl, 2-methyl-2-propyl, 2-pentyl, 3-pentyl, 2-methyl-2-butyl, 3-methyl-2-butyl, 3-methyl-1-butyl, and 2-methyl-1-butyl, each of which is optionally substituted by NH 2 .

26 . The method of claim 25 , wherein R 3 is —O(C═O)—CH(CH 3 ) 2 .

27 . The method of claim 25 , wherein R 3 is —O(C═O)—CH(NH 2 )CH(CH 3 ) 2 .

28 . The method of claim 24 , wherein R 7 is —(C═O)—(C 1 -C 8 )alkyl; wherein the (C 1 -C 8 )alkyl of R 7 is selected from the group consisting of methyl, ethyl, n-propyl, i-propyl, 1-butyl, 2-methyl-1-propyl, 2-butyl, 2-methyl-2-propyl, 2-pentyl, 3-pentyl, 2-methyl-2-butyl, 3-methyl-2-butyl, 3-methyl-1-butyl, and 2-methyl-1-butyl, each of which is optionally substituted by NH 2 .

29 . The method of claim 28 , wherein R 7 is —(C═O)—CH(CH 3 ) 2 .

30 . The method of claim 28 , wherein R 7 is —(C═O)—CH(NH 2 )CH(CH 3 ) 2 .

31 . The method of claim 28 , wherein R 7 is —(C═O)—(C 1 -C 8 )alkyl.

32 . The method of claim 31 , wherein the (C 1 -C 8 )alkyl of R 7 is selected from the group consisting of methyl, ethyl, n-propyl, i-propyl, 1-butyl, 2-methyl-1-propyl, 2-butyl, 2-methyl-2-propyl, 2-pentyl, 3-pentyl, 2-methyl-2-butyl, 3-methyl-2-butyl, 3-methyl-1-butyl, and 2-methyl-1-butyl.

33 . The method of claim 24 , wherein R 7 is

34 . The method of claim 1 , wherein R 3 is OH and R 2 is —O(C═O)(C 1 -C 8 )alkyl, wherein the (C 1 -C 8 )alkyl of R 2 is optionally substituted by NH 2 .

35 . The method of claim 34 , wherein the (C 1 -C 8 )alkyl of R 2 is selected from the group consisting of methyl, ethyl, n-propyl, i-propyl, or 1-butyl, 2-methyl-1-propyl, 2-butyl, 2-methyl-2-propyl, 2-pentyl, 3-pentyl, 2-methyl-2-butyl, 3-methyl-2-butyl, 3-methyl-1-butyl, and 2-methyl-1-butyl, each of which is optionally substituted by NH 2 .

36 . The method of claim 35 , wherein R 2 is —O(C═O)—CH(CH 3 ) 2 .

37 . The method of claim 35 , wherein R 2 is —O(C═O)—CH(NH 2 )CH(CH 3 ) 2 .

38 . The method of claim 34 , wherein R 7 is —(C═O)—(C 1 -C 8 )alkyl; wherein the (C 1 -C 8 )alkyl of R 7 is selected from the group consisting of methyl, ethyl, n-propyl, i-propyl, 1-butyl, 2-methyl-1-propyl, 2-butyl, 2-methyl-2-propyl, 2-pentyl, 3-pentyl, 2-methyl-2-butyl, 3-methyl-2-butyl, 3-methyl-1-butyl, and 2-methyl-1-butyl, each of which is optionally substituted by NH 2 .

39 . The method of claim 38 , wherein R 7 is —(C═O)—CH(CH 3 ) 2 .

40 . The method of claim 38 , wherein R 7 is —(C═O)—CH(NH 2 )CH(CH 3 ) 2 .

41 . The method of claim 38 , wherein R 7 is —(C═O)—(C 1 -C 8 )alkyl.

42 . The method of claim 41 , wherein the (C 1 -C 8 )alkyl of R 7 is selected from the group consisting of methyl, ethyl, n-propyl, i-propyl, 1-butyl, 2-methyl-1-propyl, 2-butyl, 2-methyl-2-propyl, 2-pentyl, 3-pentyl, 2-methyl-2-butyl, 3-methyl-2-butyl, 3-methyl-1-butyl, and 2-methyl-1-butyl.

43 . The method of claim 34 , wherein R 7 is

44 . The method of claim 1 , wherein the Paramyxoviridae infection is a respiratory syncytial virus infection.

45 . The method of claim 4 , wherein the Paramyxoviridae infection is a respiratory syncytial virus infection.

46 . The method of claim 8 , wherein the Paramyxoviridae infection is a respiratory syncytial virus infection.

47 . The method of claim 23 , wherein the Paramyxoviridae infection is a respiratory syncytial virus infection.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Dec 22, 2022
From: MACKMAN, RICHARD L.; PARRISH, JAY P.; RAY, ADRIAN S.; THEODORE, DOROTHY AGNES
To: GILEAD SCIENCES, INC.
Reel/Frame 062191/0031 →
Continuity (6)
Division 16879491 · May 20, 2020
Continuation 16042085 · Jul 23, 2018
Division 14613719 · Feb 4, 2015
Continuation 13189373 · Jul 22, 2011
Provisional Application 61366609 · Jul 22, 2010
Related Publication 20230125751A1 · Apr 27, 2023
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