Toll like receptor modulator compounds

Patent metadata

Field	Value
Publication number	US-11827609-B2
Application number	US-202117399984-A
Country	US
Kind code	B2
Filing date	Aug 11, 2021
Priority date	Sep 2, 2016
Publication date	Nov 28, 2023
Grant date	Nov 28, 2023

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 a 6-membered cycloalkyl, wherein:
the 6-membered cycloalkyl is 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 , 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 , 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 a 6-membered cycloalkyl.

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

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

8. The compound of claim 1 , having the structure

or a pharmaceutically acceptable salt thereof.

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

10. The pharmaceutical composition of claim 9 , further comprising one or more additional therapeutic agents.

11. 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

• C07D239/95 Primary

  with hetero atoms directly attached in positions 2 and 4 · CPC title

• A61K31/517

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

• A61K31/519

  ortho- or peri-condensed with heterocyclic rings · CPC title

• A61K45/06

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

• A61P31/18

  for HIV · CPC title