Pyrazolopyrimidine compounds for the treatment of cancer
Compound of Formula (I): are described, along with pharmaceutically acceptable salts thereof, compositions containing the same, and methods of use thereof in the treatment of cancer.
1. A compound of Formula I:
wherein:
R 1 is aryl, wherein the aryl is unsubstituted or substituted from 1 to 3 times with halo, alkyl, haloalkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heterocyclo, heterocycloalkyl, hydroxyl, alkoxy, alkenyloxy, alkynyloxy, haloalkoxy, cycloalkoxy, cycloalkylalkyloxy, aryloxy, arylalkyloxy, heterocyclooxy, heterocyclolalkyloxy, mercapto, alkyl-S(O) m , haloalkyl-S(O) m , alkenyl-S(O) m , alkynyl-S(O) m , cycloalkyl-S(O) m , cycloalkylalkyl-S(O) m , aryl-S(O) m , arylalkyl-S(O) m , heterocyclo-S(O) m , heterocycloalkyl-S(O) m , amino, carboxy, alkylamino, alkenylamino, alkynylamino, haloalkylamino, cycloalkylamino, cycloalkylalkylamino, arylamino, arylalkylamino, heterocycloamino, heterocycloalkylamino, disubstituted-amino, acylamino, acyloxy, ester, amide, sulfonamide, urea, alkoxyacylamino, aminoacyloxy, nitro or cyano where m=0, 1, 2 or 3;
or R 1 is heteroaryl, wherein the heteroaryl is unsubstituted or substituted from 1 to 3 times with halo, alkyl, haloalkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heterocyclo, heterocycloalkyl, hydroxyl, alkoxy, alkenyloxy, alkynyloxy, haloalkoxy, cycloalkoxy, cycloalkylalkyloxy, aryloxy, arylalkyloxy, heterocyclooxy, heterocyclolalkyloxy, mercapto, alkyl-S(O) m , haloalkyl-S(O) m , alkenyl-S(O) m , alkynyl-S(O) m , cycloalkyl-S(O) m , cycloalkylalkyl-S(O) m , aryl-S(O) m , arylalkyl-S(O) m , heterocyclo-S(O) m , heterocycloalkyl-S(O) m , amino, alkylamino, alkenylamino, alkynylamino, haloalkylamino, cycloalkylamino, cycloalkylalkylamino, arylamino, arylalkylamino, heterocycloamino, heterocycloalkylamino, disubstituted-amino, acylamino, acyloxy, ester, amide, sulfonamide, urea, alkoxyacylamino, aminoacyloxy, nitro or cyano where m=0, 1, 2 or 3;
R 2 is —R 5 R 6 , where R 5 is a covalent bond or C1 to C3 alkyl and R 6 is cycloalkyl, wherein R 6 is optionally substituted from one to two times with independently selected polar groups;
R 3 is —NR 7 R 8 , where R 7 and R 8 are each independently selected from H, alkyl, arylalkyl, and alkoxyalkyl; wherein the alkyl, arylalkyl, or alkoxyalkyl is unsubstituted or substituted from 1 to 3 times with alkyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, aryl, or heteroaryl; and
R 4 is H, loweralkyl, halo, or loweralkoxy;
or a pharmaceutically acceptable salt thereof.
2. The compound of claim 1 , wherein R 5 is C1 to C3 alkyl.
3. The compound of claim 2 , wherein R 5 is —CH 2 —.
4. The compound of claim 1 , wherein R 1 is phenyl, or pyridyl, which phenyl or pyridyl is unsubstituted or substituted from 1 to 3 times with halo, amino, nitro, alkyl, alkoxyl, haloalkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl.
5. The compound of claim 1 , wherein R 8 is C1-C8 alkyl or C1-C8 arylalkyl; wherein the alkyl or arylalkyl is unsubstituted or substituted from 1 to 3 times with alkyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, aryl, or heteroaryl.
6. The compound of claim 1 , wherein R 6 is cyclohexyl.
7. The compound of claim 1 , wherein R 6 is substituted once with hydroxyl.
8. The compound of claim 1 , wherein R 7 is H.
9. The compound of claim 1 , wherein R 8 is loweralkyl.
10. The compound of claim 1 , wherein R 4 is H.
11. The compound of claim 1 , wherein said compound has the structure:
or a pharmaceutically acceptable salt thereof.
12. A composition comprising a compound of claim 1 in a pharmaceutically acceptable carrier.
13. A compound of Formula I:
wherein:
R 1 is phenyl, which phenyl is unsubstituted or substituted from 1 to 3 times with halo, amino, nitro, alkyl, alkoxyl, haloalkyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, aryl, or heteroaryl,
R 2 is —R 5 R 6 , where R 5 is a covalent bond or C1 to C3 alkyl and R 6 is cycloalkyl, wherein R 6 is optionally substituted from one to two times with independently selected polar groups;
R 3 is —NR 7 R 8 , where R 7 and R 8 are each independently selected from H, alkyl, arylalkyl, and alkoxyalkyl; wherein the alkyl, arylalkyl, or alkoxyalkyl is unsubstituted or substituted from 1 to 3 times with alkyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, aryl, or heteroaryl; and
R 4 is H, loweralkyl, halo, or loweralkoxy;
or a pharmaceutically acceptable salt thereof.
14. The compound of claim 13 , wherein R 6 is cyclohexyl substituted once with hydroxyl.
15. The compound of claim 13 , wherein R 7 is H.
16. The compound of claim 14 , wherein R 8 is loweralkyl.
17. The compound of claim 15 , wherein R 4 is H.
18. The compound of claim 1 , wherein the compound has the structure:
or a pharmaceutically acceptable salt thereof.
19. The compound of claim 1 , wherein the compound has the structure:
or a pharmaceutically acceptable salt thereof.
20. A compound of Formula I,
wherein:
R 1 is aryl or heteroaryl; wherein the aryl or heteroaryl is unsubstituted or substituted from 1 to 3 times with halo, alkyl, haloalkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heterocyclo, heterocycloalkyl, hydroxyl, alkoxy, alkenyloxy, alkynyloxy, haloalkoxy, cycloalkoxy, cycloalkylalkyloxy, aryloxy, arylalkyloxy, heterocyclooxy, heterocyclolalkyloxy, mercapto, alkyl-S(O) m , haloalkyl-S(O) m , alkenyl-S(O) m , alkynyl-S(O) m , cycloalkyl-S(O) m , cycloalkylalkyl-S(O) m , aryl-S(O) m , arylalkyl-S(O) m , heterocyclo-S(O) m , heterocycloalkyl-S(O) m , amino, carboxy, alkylamino, alkenylamino, alkynylamino, haloalkylamino, cycloalkylamino, cycloalkylalkylamino, arylamino, arylalkylamino, heterocycloamino, heterocycloalkylamino, disubstituted-amino, acylamino, acyloxy, ester, amide, sulfonamide, urea, alkoxyacylamino, aminoacyloxy, nitro or cyano where m=0, 1, 2 or 3;
R 2 is —R 5 R 6 , where R 5 is a covalent bond or C1 to C3 alkyl and R 6 is cycloalkyl, wherein R 6 is optionally substituted from one to two times with independently selected polar groups;
R 3 is —NR 7 R 8 , where R 7 is selected from H, alkyl, arylalkyl, and alkoxyalkyl; and R 8 is
C3-C8 cycloalkyl, wherein the cycloalkyl is unsubstituted or substituted from 1 to 3 times with alkyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, aryl, or heteroaryl; and
R 4 is H, loweralkyl, halo, or loweralkoxy;
or a pharmaceutically acceptable salt thereof.
21. A composition comprising a compound of claim 13 in a pharmaceutically acceptable carrier.
22. A composition comprising a compound of claim 20 in a pharmaceutically acceptable carrier.