Toll like receptor modulator compounds

Patent metadata

Field	Value
Publication number	US-10370342-B2
Application number	US-201715692093-A
Country	US
Kind code	B2
Filing date	Aug 31, 2017
Priority date	Sep 2, 2016
Publication date	Aug 6, 2019
Grant date	Aug 6, 2019

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 phenyl
optionally substituted with 1 to 3 R 5 ;
each R 5 is independently halogen, —OH, —NH 2 , —CN, C 1-4 alkyl optionally substituted with 1 to 3 R Z , C 1-4 haloalkyl, C 1-4 alkoxy, —C(O)OH, —C(O)C 1-4 alkyl, —C(O)OC 1-4 alkyl, —C(O)NH 2 , —C(O)NH(C 1-4 alkyl), —C(O)N(C 1-4 alkyl) 2 , —N(H)C(O)C 1-4 alkyl, —S(O) 2 C 1-4 alkyl, or 5 to 6 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 , wherein R 1 is —H or C 1-4 alkyl.

3. The compound of claim 1 , wherein R 1 is methyl.

4. The compound of claim 1 , 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 phenyl optionally substituted with 1 to 3 chloro, fluoro, bromo, —CN, C 1-2 alkyl optionally substituted with —OH, C 1-2 alkoxy, —C(O)C 1-2 alkyl, —C(O)OC 1-2 alkyl, pyrazolyl optionally substituted with 1 to 3 C 1-2 alkyl; or imidazolyl optionally substituted with 1 to 3 C 1-2 alkyl.

6. The compound of claim 1 , wherein:
R 1 is —H or C 1-4 alkyl;
R 2 is C 3-6 alkyl;
R 3 and R 4 are taken together to form phenyl optionally substituted with 1 to 3 halogen.

7. The compound of claim 1 , wherein Formula I is represented by Formula II

8. The compound of claim 1 , wherein Formula I is represented by Formula III

9. The compound of claim 6 , wherein R 3 and R 4 are taken together to form phenyl optionally substituted with 1 to 3 fluoro.

10. The compound of claim 1 , selected from

or a pharmaceutically acceptable salt thereof.

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

12. The pharmaceutical composition of claim 11 , further comprising one or more additional therapeutic agents.

13. 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

• A61K45/06

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title

• C07D495/04

  Ortho-condensed systems · CPC title

• C07D471/04

  Ortho-condensed systems · CPC title

• A61P31/18

  for HIV · CPC title

• C07D487/04

  Ortho-condensed systems · CPC title