Pyrazolo-pyrimidine inhibitors of bruton's tyrosine kinase
View Patent ↗Described herein are kinase inhibitor compounds, methods for synthesizing such inhibitors, and methods for using such inhibitors in the treatment of diseases. Further described herein are methods, assays and systems for determining an appropriate inhibitor of a protein, including a kinase.
1. A compound having the structure of Formula (I):
wherein:
R a , R b , R c , R d and R e are each independently selected from H, F, Cl, Br, I, —CN, —SR 2 , —OR 3 , —CO 2 R 3 ; or
R a or R b together with one of R c , R d and R e and the carbon atoms to which they are attached form an epoxide; wherein R a , R b , R c , R d , and R e cannot all be H;
R 2 is selected from H, C 1 -C 4 alkyl, a cysteinyl, or a glutathionyl;
R 3 is selected from H, C 1 -C 4 alkyl, phenyl, or benzyl; or a pharmaceutically acceptable salt thereof.
2. The compound of claim 1 wherein R a is H.
3. The compound of claim 2 wherein R b is —OR 3 .
4. The compound of claim 3 wherein R 3 is H.
5. The compound of claim 1 wherein at least two of R c , R d , and R e are H.
6. The compound of claim 5 wherein R c and R d are both H.
7. The compound of claim 6 wherein R e is —OR 3 .
8. The compound of claim 7 wherein R 3 is H.
9. The compound of claim 8 wherein R a is H and R b is —OR 3 .
10. The compound of claim 9 wherein R 3 is H.
11. The compound of claim 5 wherein R c , R d , and R e are each independently H.
12. The compound of claim 11 wherein R a is H and R b is —OR 3 .
13. The compound of claim 12 wherein R 3 is H.
14. The compound of claim 1 wherein R a or R b together with one of R c , R d and R e and the carbon atoms to which they are attached form an epoxide.
15. A compound having the structure
pharmaceutically acceptable salt thereof.
16. A pharmaceutical composition comprising a compound having the structure of Formula (I):
wherein:
R a , R b , R c , R d and R e are each independently selected from H, F, Cl, Br, I, —CN, —SR 2 , —OR 3 , —CO 2 R 3 ; or
R a or R b together with one of R c , R d and R e and the carbon atoms to which they are attached form an epoxide; wherein R a , R b , R c , R d , and R e cannot all be H;
R 2 is selected, from H, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, tert-butyl, a cysteinyl, or a glutathionyl;
R 3 is selected from H, C 1 -C 4 alkyl, phenyl, or benzyl; or a pharmaceutically acceptable salt thereof; and a pharmaceutically acceptable excipient, binder or carrier.