Selective inhibitors of Tec and Src protein kinase families
View Patent ↗The present invention relates to a novel family of inhibitors of protein kinases. In particular, the present invention relates to inhibitors of the members of the Tec and Src protein kinase families. In one embodiment, the inhibitors of the invention are encompassed by Formula 1:
1. A compound of Formula 1:
wherein,
R 1 is selected from the group consisting of hydrogen, heteroalkyl, carbocyclyl, heterocyclyl, C(O)R 4 and substituted and unsubstituted alkyl;
wherein the heteroalkyl, carbocyclyl and heterocyclyl may be further substituted by the groups consisting of hydroxy, alkoxy, alkyl, —OC(O)R 4 , —OC(O)NR 5 R 6 , —C(O)R 4 , —C(O)NR 5 R 6 , —NR 5 R 6 , —NR 2 C(O)R 4 , —NR 2 S(O) n R 4 and —NR 2 C(O)NR 5 R 6 ;
Y is
Z is
Y—Z—W is
X 1 and X 2 are independently selected from the group consisting of hydrogen, halogen and cyano;
n is an integer from 0 to 2;
m is an integer from 0 to 2;
m′ is an integer from 0 to 2;
W is —OR 3 ;
R 2 is hydrogen or alkyl;
R 3 is selected from the group consisting of substituted aralkyl, unsubstituted aralkyl, substituted heteroaralkyl, and unsubstituted heteroaralkyl;
R 4 is selected from the group consisting of substituted alkyl, unsubstituted alkyl, substituted alkenyl, unsubstituted alkenyl, substituted alkynyl, unsubstituted alkynyl, substituted heteroalkyl, unsubstituted heteroalkyl, substituted carbocyclyl, unsubstituted carbocyclyl, heterocyclyl, substituted aryl, unsubstituted aryl, substituted heteroaryl, unsubstituted heteroaryl, substituted aralkyl, unsubstituted aralkyl, substituted heteroaralkyl, and unsubstituted heteroaralkyl; and
R 5 and R 6 are independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, heteroalkyl, carbocyclyl, heterocyclyl, aryl, and heteroaryl; or alternatively R 5 and R 6 are fused to form a 3 to 8 membered heterocyclyl ring system; or
a pharmaceutically acceptable salt, solvate, or solvate of a salt thereof.
2. The compound of claim 1 , wherein W is selected from the group consisting of:
3. The compound according to claim 1 , wherein W is selected from the group consisting of:
4. The compound according to claim 1 , wherein R 1 is selected from the group consisting of:
5. The compound according to claim 1 , wherein R 1 is selected from the group consisting of:
6. The compound according to claim 1 , wherein Y is selected from the group consisting of:
7. The compound according to claim 1 , wherein Z is selected from the group consisting of:
8. The compound according to claim 1 , wherein Z is:
9. The compound according to claim 1 , wherein Y—Z—W is selected from the group consisting of:
10. A compound selected from the group consisting of:
11. A pharmaceutical composition comprising a compound of claim 1 and at least one pharmaceutically acceptable excipient.
12. A compound of Formula 1:
wherein,
R 1 is selected from the group consisting of:
Y is
Z is
Y—Z—W is
X 1 and X 2 are independently selected from the group consisting of hydrogen, halogen and cyano;
n is an integer from 0 to 2;
m is an integer from 0 to 2;
m′ is an integer from 0 to 2;
W is —OR 3 ;
R 2 is hydrogen or alkyl;
R 3 is selected from the group consisting of substituted aralkyl, unsubstituted aralkyl, substituted heteroaralkyl, and unsubstituted heteroaralkyl;
R 4 is selected from the group consisting of substituted alkyl, unsubstituted alkyl, substituted alkenyl, unsubstituted alkenyl, substituted alkynyl, unsubstituted alkynyl, substituted heteroalkyl, unsubstituted heteroalkyl, substituted carbocyclyl, unsubstituted carbocyclyl, heterocyclyl, substituted aryl, unsubstituted aryl, substituted heteroaryl, unsubstituted heteroaryl, substituted aralkyl, unsubstituted aralkyl, substituted heteroaralkyl, and unsubstituted heteroaralkyl; and
R 5 and R 6 are independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, heteroalkyl, carbocyclyl, heterocyclyl, aryl, and heteroaryl; or alternatively R 5 and R 6 are fused to form a 3 to 8 membered heterocyclyl ring system; or
a pharmaceutically acceptable salt, solvate, or solvate of a salt thereof.
13. The compound of claim 12 , wherein W is selected from the group consisting of:
14. The compound according to claim 12 , wherein W is selected from the group consisting of:
15. The compound according to claim 12 , wherein R 1 is selected from the group consisting of:
16. The compound according to claim 12 , wherein Y is selected from the group consisting of:
17. The compound according to claim 12 , wherein Z is selected from the group consisting of:
18. The compound according to claim 12 , wherein Z is:
19. The compound according to claim 12 , wherein Y—Z—W is selected from the group consisting of:
20. A pharmaceutical composition comprising a compound of claim 12 and at least one pharmaceutically acceptable excipient.