Antiviral indolinyl compounds and uses thereof

Patent metadata

Field	Value
Publication number	US-12522582-B2
Application number	US-202318319846-A
Country	US
Kind code	B2
Filing date	May 18, 2023
Priority date	May 20, 2022
Publication date	Jan 13, 2026
Grant date	Jan 13, 2026

Abstract

The present disclosure relates to indolinyl compounds. The present disclosure further relates to compounds that inhibit viral helicase-primase. The present disclosure further relates to the use of the compounds for the preparation a medicament for the treatment of diseases and/or condition through inhibiting viral helicase-primase. The present disclosure also relates to use of those compounds in the treatment of viral infections. The present disclosure further relates to intermediates for its preparation and to pharmaceutical compositions containing those compounds.

First claim

The invention claimed is:

1 . A compound of Formula (I):

or a pharmaceutically acceptable salt thereof, wherein
R 1 is

R 2a , R 2b , and R 2c are each independently H, halogen, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, —CN, C 1-6 haloalkoxy, or —SCF 3 ;
R 3a and R 3b are each independently H, halogen, C 1-6 alkyl, or C 1-6 haloalkyl;
or R 3a and R 3b together with the carbon to which they are attached form C 3-6 cycloalkyl; wherein the cycloalkyl formed from R 3a and R 3b may be optionally substituted with one to three Z 3 , which may be the same or different;
X a and X b are each independently O or CR 7a R 7b ;
R 7a and R 7b are each independently H, C 1-6 alkyl, or C 1-6 haloalkyl;
or R 7a and R 7b together with the carbon to which they are attached form C 3-6 cycloalkyl; wherein the C 3-6 cycloalkyl formed from R 7a and R 7b may be optionally substituted with one to three Z 7 , which may be the same or different;
R 4a , R 4b , and R 4c are each independently H, halogen, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, —CN, —SCF 3 , or C 3-6 cycloalkyl optionally substituted with Z 4 ;
R 5 is C 6-10 aryl or heteroaryl; wherein the aryl or heteroaryl of R 5 may be optionally substituted with one to three Z 5 , which may be the same or different; the heteroaryl of R 5 is 5 to 10 membered heteroaryl having one to three heteroatoms each independently N, O, or S;
R 6 is H, C 1-6 alkyl, C 1-6 haloalkyl, C 2-8 alkoxyalkyl, or C 3-6 cycloalkyl, wherein the cycloalkyl of R 6 is optionally substituted with one to three Z 6 ; and
each Z 3 , Z 4 , Z 5 , Z 6 , and Z 7 is independently halogen, —CN, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, or C 1-6 haloalkoxy.

2 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein the compound of Formula (I) is represented by Formula (IIa) or (IIc):

3 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein the compound of Formula (I) is represented by Formula (IIe)

wherein R 7a1 and R 7b1 are each independently H, C 1-6 alkyl, or C 1-6 haloalkyl; or R 7a1 and R 7b1 together with the carbon to which they are attached form C 3-6 cycloalkyl; wherein the C 3-6 cycloalkyl formed from R 7a1 and R 7b1 may be optionally substituted with one to three Z 7 , which may be the same or different.

4 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein:
R 2a is H, halogen, or C 1-6 alkyl; R 2b is H or halogen; and R 2c is H, halogen, or C 1-6 alkyl.

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

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

7 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 4a is H or halogen.

8 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 4b is H or halogen.

9 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 4c is H or halogen.

10 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 5 is heteroaryl; wherein the heteroaryl of R 5 may be optionally substituted with one to three Z 5 , which may be the same or different.

11 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 5 is pyridyl optionally substituted with halogen, C 1-3 alkyl, —CN, or —OCH 3 .

12 . The compound of claim 3 , or a pharmaceutically acceptable salt thereof, wherein R 7a and R 7b are each independently H or C 1-6 alky: and R 7a1 and R 7b1 are each independently H or C 1-6 alkyl.

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

14 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 6 is —CH 3 .

15 . A pharmaceutical composition comprising a compound of claim 1 , or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable carrier.

16 . A method of treating a herpesvirus infection, comprising administering to a patient in need thereof, a therapeutically effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt thereof.

17 . The method of claim 16 , wherein the herpesvirus is HSV-1 or HSV-2.

18 . A method of treating a disorder induced, exacerbated, or accelerated by herpesviruses, comprising administering to a patient in need thereof, a therapeutically effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt thereof.

19 . The method of claim 18 , wherein the disorder is genital herpes, herpes labialis, HSV keratitis, HSV encephalitis, or disseminated HSV.

20 . A compound

or a pharmaceutically acceptable salt thereof.

21 . A pharmaceutical composition comprising a compound of claim 20 , or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable carrier.

22 . A method of treating a herpesvirus infection, comprising administering to a patient in need thereof, a therapeutically effective amount of a compound of claim 20 , or a pharmaceutically acceptable salt thereof.

23 . A compound

or a pharmaceutically acceptable salt thereof.

24 . A pharmaceutical composition comprising a compound of claim 23 , or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable carrier.

25 . A method of treating a herpesvirus infection, comprising administering to a patient in need thereof, a therapeutically effective amount of a compound of claim 23 , or a pharmaceutically acceptable salt thereof.

26 . A compound

or a pharmaceutically acceptable salt thereof.

27 . A pharmaceutical composition comprising a compound of claim 26 , or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable carrier.

28 . A method of treating a herpesvirus infection, comprising administering to a patient in need thereof, a therapeutically effective amount of a compound of claim 26 , or a pharmaceutically acceptable salt thereof.

29 . A compound

or a pharmaceutically acceptable salt thereof.

30 . A pharmaceutical composition comprising a compound of claim 29 , or a pha

Assignees

• Gilead Sciences Inc

Inventors

• Cho Aesop
• De La Fuente Katherine
• Stratton Thomas P
• Wang Peiyuan
• Watkins William J
• Xu Jie
• Yang Kin S

Classifications

• C07D417/10

  linked by a carbon chain containing aromatic rings · CPC title

• C07D413/10

  linked by a carbon chain containing aromatic rings · CPC title

• C07D405/14

  containing three or more hetero rings · CPC title

• C07D405/06

  linked by a carbon chain containing only aliphatic carbon atoms · CPC title

• C07D403/10

  linked by a carbon chain containing aromatic rings · CPC title