Pyrazole compounds and method for making and using the compounds
Disclosed embodiments concern novel interleukin receptor associated kinases (IRAK) inhibitors and compositions comprising such inhibitors. Also disclosed are methods of making and using the compounds and compositions. The disclosed compounds and/or compositions may be used to treat or prevent an IRAK-associated disease or condition.
1. A compound having a formula
or a pharmaceutically acceptable salt thereof, wherein:
R 2 is aliphatic, cycloaliphatic, heteroaliphatic, or heterocycloaliphatic;
each of R 4 , R 5 , R 6 , and R 7 independently is H, aliphatic, alkoxy, halogen, —O-heterocyclyl or heterocyclic;
R 8 and R 9 are each independently H or aliphatic;
R 10 is H, aliphatic, carboxyl ester, acyl, alkyl phosphate, alkyl phosphonate or aralkyl; and
R 11 and R 12 are each independently H or aliphatic.
2. The compound of claim 1 , wherein each of R 4 , R 6 , and R 7 independently is H, halogen, alkyl, or haloalkyl.
3. The compound of claim 1 , wherein each of R 4 , R 6 , and R 7 independently is H, F or CF 3 .
4. The compound of claim 1 , wherein R 5 is H, halogen, alkyl, haloalkyl, alkoxy, heterocyclyl, or —O-heterocyclyl.
5. The compound of claim 1 , wherein R 5 is H, F, CF 3 , methoxy, morpholin-4-yl, 1-methylpiperidin-4-yl, —O—CH 2 C(CH 3 ) 2 OH, or —O-(oxetan-3-yl).
6. The compound of claim 1 , wherein R 8 and R 9 are each independently H, haloalkyl, or alkyl.
7. The compound of claim 1 , wherein R 10 is H, alkyl, carboxyl ester, acyl, alkyl phosphate, alkyl phosphonate or aralkyl.
8. The compound of claim 1 , wherein R 2 is alkyl, haloalkyl, or cycloalkyl.
9. The compound of claim 1 , wherein each of R 4 , R 5 , R 6 , and R 7 independently is H, or F.
10. The compound of claim 9 , wherein:
R 2 is alkyl, haloalkyl, or cycloalkyl;
R 8 and R 9 are each independently H, haloalkyl, or alkyl; and
R 10 is H, alkyl, alkyl phosphate, or alkyl phosphonate.
11. The compound of claim 1 , wherein the compound is
or a pharmaceutically acceptable salt thereof.
12. The compound of claim 1 , wherein the compound is
or a pharmaceutically acceptable salt thereof.
13. The compound of claim 1 , wherein the compound is
or a pharmaceutically acceptable salt thereof.
14. A composition, comprising a compound of claim 1 , and a pharmaceutically acceptable excipient.
15. The composition of claim 14 , wherein the compound is
or a pharmaceutically acceptable salt thereof.
16. The composition of claim 14 , wherein the compound is
or a pharmaceutically acceptable salt thereof.
17. The composition of claim 14 , wherein the compound is
or a pharmaceutically acceptable salt thereof.