Substituted benzoxazoles as PI3 kinase inhibitors
The present invention provides substituted benzoxazole compounds of the Formula: wherein the variables R 1 , R 2 , W 1 , W 2 , W 3 , W 4 , W 5 , are W 6 are defined herein. The compounds are useful as phosphoinositide 3-kinase (PI3 kinase) inhibitors.
1. A compound of the Formula I:
or a pharmaceutically acceptable salt thereof, wherein:
W 1 is N or CR 3 ; W 2 is N or CR 4 ; W 3 is N or CR 5 ; W 4 is N; wherein no more than two N atoms are adjacent;
W 5 is N;
W 6 is N or CR 8 ;
R 1 and R 2 are independently hydrogen, alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, alkoxy, heterocycloalkyloxy, amido, amino, acyl, acyloxy, alkoxycarbonyl, sulfonamido, halo, cyano, hydroxy, nitro, phosphate, urea, or carbonate;
R 3 and R 4 are independently hydrogen, alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, alkoxy, heterocycloalkyloxy, amido, amino, acyl, acyloxy, alkoxycarbonyl, sulfonamido, halo, cyano, hydroxy, nitro, phosphate, urea, or carbonate wherein R 4 is optionally substituted with one or more substituents selected from alkyl, alkenyl, alkynyl, cycloalkyl, heteroalkyl, heterocycloalkyl, heterocycloalkyloxy, aryl, arylalkyl, heteroaryl, heteroarylalkyl, acyl, alkoxy, amido, amino, sulfonamido, acyloxy, alkoxycarbonyl, halo, cyano, hydroxy, nitro, phosphate, urea, or carbonate; wherein said substituents are optionally further substituted with one or more of alkyl, alkoxy, amido, amino, sulfonamido, acyloxy, alkoxycarbonyl, halo, cyano, hydroxy, nitro, oxo, phosphate, urea, or carbonate;
or R 3 and R 4 taken together form a cyclic moiety; and
R 5 and R 8 are independently hydrogen, alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, alkoxy, heterocycloalkyloxy, amido, amino, acyl, acyloxy, alkoxycarbonyl, sulfonamido, halo, cyano, hydroxy, nitro, phosphate, urea, or carbonate.
2. The compound or pharmaceutically acceptable salt of claim 1 , wherein W 2 is CR 4 .
3. The compound or pharmaceutically acceptable salt of claim 1 , wherein W 3 is CR 5 .
4. The compound or pharmaceutically acceptable salt of claim 1 , wherein W 2 and W 3 are CH.
5. The compound or pharmaceutically acceptable salt of claim 1 , wherein W 6 is CR 8 .
6. The compound or pharmaceutically acceptable salt of claim 1 , wherein W 1 is N.
7. The compound or pharmaceutically acceptable salt of claim 1 , wherein W 1 is CR 3 .
8. The compound or pharmaceutically acceptable salt of claim 1 , wherein R 2 is amino.
9. The compound or pharmaceutically acceptable salt of claim 1 , wherein R 1 is hydrogen.
10. The compound or pharmaceutically acceptable salt of claim 1 , wherein the compound has the Formula:
wherein R 1 is hydrogen; and R 2 is NH 2 .
11. The compound or pharmaceutically acceptable salt of claim 1 , wherein the compound has the Formula:
wherein R 1 is hydrogen; and R 2 is NH 2 .
12. The compound or pharmaceutically acceptable salt of claim 10 or 11 , wherein W 6 is CH.
13. The compound or pharmaceutically acceptable salt of claim 10 , wherein the compound has the Formula:
14. The compound or pharmaceutically acceptable salt of claim 11 , wherein the compound has the Formula:
15. The compound or pharmaceutically acceptable salt of any one of claims 1 , 10 , 11 , 13 or 14 , wherein W 2 is CR 4 and R 4 is alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, alkoxy, heterocycloalkyloxy, amido, amino, acyl, acyloxy, alkoxycarbonyl, sulfonamido, halo, cyano, hydroxy, nitro, phosphate, urea, or carbonate.
16. The compound or pharmaceutically acceptable salt of claim 15 , wherein R 4 is aryl, heteroaryl, or heterocycloalkyl, wherein R 4 is optionally substituted with one or more substituents selected from alkyl, alkenyl, alkynyl, cycloalkyl, heteroalkyl, heterocycloalkyl, heterocycloalkyloxy, aryl, arylalkyl, heteroaryl, heteroarylalkyl, acyl, alkoxy, amido, amino, sulfonamido, acyloxy, alkoxycarbonyl, halo, cyano, hydroxy, nitro, phosphate, urea, or carbonate; wherein said substituents are optionally further substituted with one or more of alkyl, alkoxy, amido, amino, sulfonamido, acyloxy, alkoxycarbonyl, halo, cyano, hydroxy, nitro, oxo, phosphate, urea, or carbonate.
17. The compound or pharmaceutically acceptable salt of claim 15 , wherein R 4 is cycloalkyl, heterocycloalkyl, aryl or heteroaryl.
18. The compound or pharmaceutically acceptable salt of claim 16 , wherein R 4 is 5-membered heteroaryl, or 6-membered heteroaryl.
19. The compound or pharmaceutically acceptable salt of claim 16 , wherein R 4 is 4-membered heterocycloalkyl, 5-membered heterocycloalkyl, 6-membered heterocycloalkyl, or 8-membered heterocycloalkyl.
20. The compound or pharmaceutically acceptable salt of claim 19 , wherein the heterocycloalkyl is morpholine, piperazine, azetidine, pyrrolidine, or piperidine.
21. The compound or pharmaceutically acceptable salt of claim 1 , wherein the compound is selected from the group consisting of:
22. A compound or a pharmaceutically acceptable salt thereof, wherein the compound has the following structure: