6-aminoisoquinoline compounds
View Patent ↗6-Amino isoquinoline compounds are provided that influence, inhibit or reduce the action of a kinase. Pharmaceutical compositions including therapeutically effective amounts of the 6-aminoisoquinoline compounds and pharmaceutically acceptable carriers are also provided. Various methods using the compounds and/or compositions to affect disease states or conditions such as cancer, obesity and glaucoma are also provided.
1. A compound according to Formula III:
wherein X 1 is selected from CH 2 , O, S, S(O), S(O)(O), and
wherein X 2 and X 3 are independently selected from CH 2 , O, S, S(O), S(O)(O),
and bond;
wherein at least one of X 2 and X 3 is a bond;
wherein R 1 and R 2 are, independently, hydrogen, hydroxyl, halogen, C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, amino, nitro, cyano, C 1 -C 4 carbonyl, C 1 -C 4 carbonylamino, C 1 -C 4 alkoxy, C 1 -C 4 sulfonyl, C 1 -C 4 sulfonylamino, C 1 -C 4 thioalkyl and C 1 -C 4 carboxyl;
wherein R 5 is aryl; and
wherein R 10 is halogen, alkenyl, alkynyl, alkoxy, amino, cyano, cycloalkyl, heterocycloalkyl, aryl, C 1 -C 4 alkyl aryl, heteroaryl, C 1 -C 4 alkyl heteroaryl, carbonyl, carbonylamino, thioalkyl, sulfonyl, sulfonylamino, acyl, or carboxyl.
2. The compound of claim 1 , wherein R 1 and R 2 are, independently, hydrogen, hydroxyl, halogen, methyl, ethyl, amino, nitro, cyano, C 1 -C 2 alkoxy, C 1 -C 2 thioalkyl and C 1 -C 2 carboxyl.
3. A compound according claim 1 , wherein R 1 and R 2 are each independently hydrogen, halogen, cyano, amino, or methyl.
4. A compound according to claim 1 , wherein X 1 is selected from CH 2 and O, X 2 is selected from CH 2 and NH, and X 3 is a bond.
5. A compound according to claim 1 , wherein X 1 is —O—, and at least one of X 2 and X 3 is —CH 2 —.
6. The compound of claim 1 , wherein the compound is selected from one of the following:
7. The compound of claim 1 , wherein X 1 and X 2 are both CH 2 .
8. The compound of claim 1 , wherein X 3 is O.
9. The compound of claim 1 , wherein R 1 and R 2 are both hydrogen.
10. The compound of claim 1 , wherein R 5 is pyridine.
11. The compound of claim 1 , wherein X 1 is CH 2 .
12. The compound of claim 1 , wherein X 2 is O.
13. The compound of claim 1 , wherein X 3 is a bond.
14. The compound of claim 1 , wherein X 1 is CH 2 , X 2 is O, X 3 is a bond, R 1 and R 2 are both hydrogen, and R 5 is substituted aryl.
15. A pharmaceutical composition comprising:
a) a 6-aminoisoquinoline derivative according to Formula III of claim 1 ; and
b) a carrier.
16. The composition of claim 15 , wherein the carrier is selected from the group consisting of systemic and topical carriers.
17. The composition of claim 15 , wherein the composition comprises about 0.001% to 10% of the 6-aminoisoquinoline derivative and 90 to 99.999% of the systemic carrier.
18. A method of treating a condition comprising administering to a subject in need of treatment a safe and effective amount of a 6-aminoisoquinoline derivative,
wherein the derivative is according to Formula III of claim 1 ; and
wherein the condition is eye disease.
19. The method of claim 18 , wherein the condition comprises glaucoma or a neurodegenerative eye disease.