Toll like receptor modulator compounds

Patent metadata

Field	Value
Publication number	US-11124487-B2
Application number	US-201916441339-A
Country	US
Kind code	B2
Filing date	Jun 14, 2019
Priority date	Sep 2, 2016
Publication date	Sep 21, 2021
Grant date	Sep 21, 2021

Abstract

This application relates generally to toll like receptor modulator compounds and pharmaceutical compositions which, among other things, modulate toll-like receptors (e.g. TLR8), and methods of making and using them.

First claim

What is claimed is:

1. A compound of Formula I

or a pharmaceutically acceptable salt thereof, wherein:
R 1 is —H, C 1-4 alkyl, or C 1-4 haloalkyl;
R 2 is C 1-6 alkyl or C 1-6 haloalkyl;
Q is CR 4 ;
R 3 and R 4 are taken together to form 5 to 6 membered heterocyclyl having 1 to 3 heteroatoms selected from oxygen, nitrogen, and sulfur, wherein:
the 5 to 6 membered heterocyclyl is optionally substituted with 1 to 3 R 7 ;

R 7 is halogen, —OH, C 1-4 alkyl, C 1-4 alkoxy, or —C(O)R 8 ;
each R 8 is independently C 1-4 alkyl optionally substituted with —CN or —NH 2 ; C 1-4 haloalkyl;
C 5-6 cycloalkyl; 5 to 6 membered heterocyclyl having 1 to 3 heteroatoms selected from oxygen, nitrogen, and sulfur optionally substituted with 1 to 3 R Z ; or 5 to 10 membered heteroaryl having 1 to 3 heteroatoms selected from oxygen, nitrogen, and sulfur optionally substituted with 1 to 3 R Z ; and
each R Z is independently —NH 2 , C 1-4 alkyl, halogen, —CN, —OC 1-4 alkyl, C 1-4 haloalkyl, or —C(O)NH 2 .

2. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 1 is —H or C 1-4 alkyl.

3. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 1 is methyl.

4. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 2 is C 3-6 alkyl.

5. The compound of claim 1 , wherein R 3 and R 4 are taken together to form tetrahydropyridinyl optionally substituted with —C(O)R 8 wherein R 8 is C 1-4 alkyl optionally substituted with —CN or —NH 2 ; C 1-3 haloalkyl; tetrahydropyranyl; thienyl optionally substituted with 1 to 3 C 1-3 alkyl; thiazolyl; imidazolyl optionally substituted with 1 to 3 C 1-2 alkyl;
oxazolyl; isoxazolyl optionally substituted with 1 to 3 C 1-2 alkyl; thiadiazolyl; pyrazinyl; or
quinolinyl.

6. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein
R 1 is —H or C 1-4 alkyl;
R 2 is C 3-6 alkyl; and
R 3 and R 4 are taken together to form 5 to 6 membered heterocyclyl having 1 to 3 heteroatoms selected from oxygen, nitrogen, and sulfur, wherein:
the 5 to 6 membered heterocyclyl is optionally substituted with 1 to 3—C(O)C 1-4 alkyl.

7. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein Formula I is represented by Formula II

8. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein Formula I is represented by Formula III

9. The compound of claim 6 , or a pharmaceutically acceptable salt thereof, wherein R 3 and R 4 are taken together to form tetrahydropyridinyl optionally substituted with 1 to 3 C(O)C 1-2 alkyl.

10. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 3 and R 4 are taken together to form:

11. The compound of claim 1 , selected from

or a pharmaceutically acceptable salt thereof.

12. A pharmaceutical composition comprises a compound of claim 1 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.

13. The pharmaceutical composition of claim 12 , further comprising one or more additional therapeutic agents.

14. A kit comprising a compound of claim 1 , or a pharmaceutically acceptable salt thereof.

Assignees

• Gilead Sciences Inc

Inventors

• Chin Gregory
• Mackman Richard L
• Mish Michael R
• Zablocki Jeff

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• C07D495/04

  Ortho-condensed systems · CPC title

• A61K31/517

  ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine · CPC title

• A61P31/18

  for HIV · CPC title

• C07D487/04

  Ortho-condensed systems · CPC title