Toll like receptor modulator compounds
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.
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.