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 (I):
wherein A is —NH—*CH 2 — wherein *C indicates the carbon is directly attached to the carbonyl portion of Formula (I),
—SCH 2 —, —CH 2 S(O)—, —CH 2 S(O)(O)—, —S(O)CH 2 —, —S(O)(O)CH 2 —, —CH 2 CH 2 —, —CH(R 10 )CH 2 —, —CH 2 CH(R 10 )—, —CH═CH—,
wherein R 10 is hydrogen, unsubstituted C 1 -C 4 alkyl, C 1 -C 4 alkenyl, C 1 -C 4 alkynyl, or amino;
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 or C 1 -C 4 carboxyl; and
wherein R 3 is hydrogen, halogen, alkyl, 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. A compound according to Formula (I):
wherein A is
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 or C 1 -C 4 carboxyl; and
wherein R 3 is hydrogen, halogen, alkyl, 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.
3. A compound according to claim 2 , wherein the compound is a single enantiomer.
4. A compound according to claim 2 , wherein R 1 and R 2 are hydrogen.
5. A compound according to claim 2 , wherein R 10 is hydrogen.
6. A compound according to Formula (II):
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 or C 1 -C 4 carboxyl;
wherein R 4 is hydrogen, halogen, alkyl, 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; and
wherein B is a chain containing 0 member atoms, X represents n carbon member atoms and n is an integer from 0 to 1.
7. A compound according to claim 6 , wherein R 1 , and R 2 are, independently, hydrogen, hydroxyl, halogen, methyl, ethyl, amino, nitro or cyano.
8. A compound according to claim 7 , wherein R 4 is alkyl, alkenyl, alkynyl, alkoxy, amino, cycloalkyl, heterocycloalkyl, aryl, C 1 -C 4 alkyl aryl, heteroaryl, C 1 -C 4 alkyl heteroaryl, acyl, or carboxyl.
9. The compound of claim 6 , wherein n is 1.
10. A compound according to claim 6 , wherein R 4 is cycloalkyl, heterocycloalkyl, aryl, C 1 -C 4 alkyl aryl, heteroaryl, or C 1 -C 4 alkyl heteroaryl.
11. A compound according to claim 10 , wherein R 4 is aryl and X is —CR′R′—; and wherein each R′ is, independently, hydrogen, halogen, C 1 -C 4 alkyl, amino or cyano.
12. A compound according to claim 6 , wherein the compound is selected from the following:
13. The compound of claim 1 , wherein the compound is selected from one of the following:
14. The compound of claim 1 , wherein the compound is selected from the following:
15. The compound of claim 1 , wherein the compound is selected from one of the following:
16. A pharmaceutical composition comprising:
a) a 6-aminoisoquinoline derivative having the structure
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 or C 1 -C 4 carboxyl; and
wherein R 4 is hydrogen, halogen, alkyl, 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; and
b) a carrier.
17. The composition of claim 16 , wherein the carrier is selected from the group consisting of systemic and topical carriers.
18. The composition of claim 16 , wherein the composition comprises about 0.001% to 10% of the 6-aminoisoquinoline derivative and 90 to 99.999% of the systemic carrier.
19. 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 (I) of claim 1 , and wherein the condition comprises eye disease.
20. The method of claim 19 , wherein the condition comprises glaucoma or a neurodegenerative eye disease.
21. The method of claim 19 , wherein 6-aminoisoquinoline derivative has the structure:
wherein Ar is hydrogen, halogen, C 1 -C 4 alkyl, alkoxy, phenoxy, amino, cyano, aryl, C 1 -C 4 alkylaryl, heteroaryl, C 1 -C 4 alkyl heteroaryl, carbonylamino, thioalkyl, sulfonyl, sulfonylamino, acyl, or carboxyl.