Beta- and gamma-amino-isoquinoline amide compounds and substituted benzamide compounds
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:
X
R 3
R 2
R 1
H
(S)-C 6 H 5
Me
H;
H
(±)-p-fluoro-C 6 H 4
Me
H;
H
(R)-3-thienyl
Me
Me;
OH
(R)-3-thienyl
Me
Me;
OH
(S)-3-thienyl
Me
H;
H
(R)-2-thienyl
Me
Me;
H
3-furyl
H
H;
OH
2-furyl
Me
Me;
OH
3,5-difluoroC 6 H 3
Me
H;
H
2-pyridyl
H
H;
OH
4-pyridyl
Me
Me;
H
Benzyl
H
H;
H
Cyclohexyl
Me
Me;
H
Cyclopropyl
H
H;
OH
Methyl cyclohexyl
Me
H;
H
4-fluorobenzyl
H
H;
H
2-thiazole
Me
Me;
OH
2-oxazole
H
Me;
H
3-piperdyl
Me
Me;
X
R 4
R 2
R 1
OH
(±)-3-thienyl
H
H;
OH
C 6 H 5
Me
Me;
H
(±)-2-thienyl
H
H;
OH
(±)-2-thienyl
Me
Me;
H
(R)-C 6 H 5
H
H;
H
(S)-C 6 H 5
H
H;
OH
p-fluoro-C 6 H 4
Me
Me;
H
p-fluoro-C 6 H 4
benzyl
H;
H
Benzyl
Me
H;
H
p-fluoro benzyl
Me
H;
OH
3-pyridyl
H
H;
H
4-pyridyl
Me
Me;
OH
3-furyl
H
H;
H
cyclopropyl
Me
Me;
H
cyclopentyl
Me
Me;
OH
cyclohexyl
H
H;
H
3-benzo[b]thiophene
Me
Me;
H
H
H;
OH
2-oxazole
H
H;
X
R 5
R 4
R 3
R 2
R 1
H
C 6 H 5
H
H
H
H;
OH
C 6 H 5
H
H
H
H;
H
(S)-C 6 H 5
H
H
H
H;
OH
(R)-C 6 H 5
H
H
H
H;
OH
(S)-C 6 H 5
H
H
H
H;
H
(S)-C 6 H 5
H
H
CH 3
CH 3 ;
H
p-fluoro-
H
H
H
H;
C 6 H 4
H
p-fluoro-
H
H
CH 3
H;
C 6 H 4
OH
cyclopropyl
H
H
CH 3
H;
H
3-thienyl
H
H
H
H;
H
(S)-3-
H
H
H
H;
thienyl
OH
cyclohexyl
H
H
CH 3
CH 3 ,
H
C 6 H 5
H
H
CH 2 C 6 H 5
H;
H
H
p-fluoro-
H
H
H;
C 6 H 4
OH
H
CH 2 C 6 H 5
H
CH 3
H;
H
H
3-thienyl
H
CH 3
H;
OH
H
2-thienyl
H
CH 3
CH 3 ,
H
H
p-chloro
H
H
H;
benzyl
or a pharmaceutically acceptable salt thereof.
2. A composition comprising a 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 a 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.