Beta- and gamma-amino-isoquinoline amide compounds and substituted benzamide compounds
View Patent ↗Disclosed are beta and gamma-amino isoquinoline amide compounds and substituted benzamide compounds. In particular, the invention provides compounds that affect the function of kinases in a cell and that are useful as therapeutic agents or with therapeutic agents. The compounds of the invention are useful in the treatment of a variety of diseases and conditions including eye diseases such as glaucoma, cardiovascular diseases, and diseases characterized by abnormal growth, such as cancers. The invention further provides compositions containing the beta or gamma-amino isoquinoline amide compounds or substituted benzamide compounds.
1. A compound selected from:
a dihydrochloride salt of 3-amino-N-(isoquinolin-6-yl)-3-(thiophen-3-yl)propanamide;
a dihydrochloride salt of 3-(dimethylamino)-N-(isoquinolin-6-yl)-2-(thiophen-3-yl)propanamide;
a dihydrochloride salt of 3-amino-N-(isoquinolin-6-yl)-2-(thiophen-3-yl)propanamide; or
a dihydrochloride salt of 4-amino-N-(isoquinolin-6-yl)-4-(thiophen-3-yl)butanamide.
2. A composition comprising the compound of claim 1 and a pharmaceutically acceptable carrier.
3. The composition of claim 2 , wherein the carrier is saline buffered to a pH of about 5.5 to about 6.5.
4. A method of treating an eye disease in a subject in need thereof, the method comprising administering to the subject an effective amount of the compound of claim 1 .
5. The method of claim 4 , wherein the eye disease comprises glaucoma.
6. The method of claim 4 , wherein the eye disease comprises a neurodegenerative eye disease.
7. A compound selected from:
or the formula:
R1
R2
R3
R4
H
H
CH 3
H
H
H
H
H
F
H
H
H
Cl
H
H
H
H
H
—OMe
H
Cl
Cl
H
H
—Me
H
H
H
H
H
F
H
CH 3
CH 3
H
H
CH 3
H
H
H
H
H
H
OMe
H
H
H
OH
H
H
H
NH 2 ;
or the formula:
R1
R2
R3
R4
R5
R6
H
H
3-thienyl
Cl
Cl
H
H
H
3-thienyl
H
H
H
H
H
3-thienyl
F
F
H
H
H
C 6 H 6
H
H
H
CH 3
CH 3
C 6 H 6
H
H
H
CH 3
CH 3
C 6 H 6
F
Cl
H
CH 3
CH 3
cyclohexyl
H
H
H
CH 3
CH 3
—CH(CH 3 ) 2
H
H
H
CH 3
CH 3
3-thienyl
CF 3
H
H
CH 3
CH 3
3-thienyl
OCF 3
H
H
CH 3
CH 3
3-thienyl
CN
H
H
CH 3
CH 3
2-pyridyl
H
H
H
CH 3
CH 3
3-pyridyl
H
H
H
CH 3
CH 3
4-pyridyl
H
H
H
CH 3
CH 3
2-thienyl
H
H
H
H
CH 3
3-thienyl
H
H
H
CH 3
CH 3
3-thienyl
NO 2
H
H;
or the formula:
R1
R2
R3
R4
R5
R6
R7
H
H
3-thienyl
H
H
H
H
CH 3
CH 3
3-thienyl
H
H
H
H
H
H
H
3-thienyl
H
H
H
CH 3
CH 3
H
3-thienyl
H
H
H
CH 3
CH 3
3-thienyl
H
F
H
H
CH 3
CH 3
3-thienyl
H
H
F
H
CH 3
CH 3
3-thienyl
H
H
H
F
CH 3
CH 3
H
3-thienyl
CH 3
H
H
CH 3
CH 3
H
3-thienyl
H
CH 3
H
CH 3
CH 3
H
3-thienyl
H
H
CH 3
CH 3
CH 3
C 6 H 5
H
H
H
H
H
H
cyclohexyl
H
H
H
H
CH 3
H
—CH(CH 3 ) 2
H
H
H
H
CH 3
CH 3
H
C 6 H 6
H
H
H
CH 3
H
H
cyclohexyl
H
H
H
H
H
H
—CH(CH 3 ) 2
H
H
H
CH 3
CH 3
—C≡C—C 6 H 5
H
H
H
H
CH 3
CH 3
3-thienyl
H
Cl
Cl
H;
or the formula:
R1
R2
R3
R4
R5
R6
R7
H
H
3-thienyl
H
H
H
H
CH 3
CH 3
3-thienyl
H
H
H
H
H
H
H
3-thienyl
H
H
H
CH 3
CH 3
H
3-thienyl
H
H
H
CH 3
CH 3
H
H
3-thienyl
H
H
CH 3
CH 3
H
H
3-thienyl
F
H
H
H
cyclohexyl
H
H
H
F
H
H
H
—CH(CH 3 ) 2
H
H
H
H
H
H
H
C 6 H 5
CH 3
H
CH 3
CH 3
H
cyclopropyl
H
H
CH 3
CH 3
CH 3
C 6 H 5
H
H
H
H
H
H
H
4-pyridyl
H
H
H;
or a pharmaceutically acceptable salt thereof.
8. A composition comprising the compound of claim 7 and a pharmaceutically acceptable carrier.
9. The composition of claim 8 , wherein the carrier is saline buffered to a pH of about 5.5 to about 6.5.
10. A method of treating an eye disease in a subject in need thereof, the method comprising administering to the subject an effective amount of the compound of claim 7 .
11. The method of claim 10 , wherein the eye disease comprises glaucoma.
12. The method of claim 10 , wherein the eye disease comprises a neurodegenerative eye disease.
13. A method of modulating kinase activity in a cell, comprising contacting the cell with the compound of claim 7 in an amount effective to modulate kinase activity.
14. The method of claim 13 , wherein the cell is in a subject.
15. A method of reducing intraocular pressure in a subject in need thereof, comprising administering an effective amount of the compound of claim 7 to an eye of the subject.
16. The method of claim 15 , wherein the subject suffers from glaucoma.
17. The method of claim 15 , wherein the subject suffers from a neurodegenerative eye disease.
18. A method of modulating kinase activity in a cell, comprising contacting the cell with the compound of claim 1 in an amount effective to modulate kinase activity.
19. The method of claim 18 , wherein the cell is in a subject.
20. A method of reducing intraocular pressure in a subject in need thereof, comprising administering an effective amount of the compound of claim 1 to an eye of the subject.
21. The method of claim 20 , wherein the subject suffers from glaucoma.
22. The method of claim 20 , wherein the subject suffers from a neurodegenerative eye disease.