Inhibitors of rho associated protein kinases (ROCK) and methods of use
View Patent ↗Compounds and compositions having activity as inhibitors of Rho-associated proteinkinases (ROCKs), and methods of making and using the subject compounds are disclosed.
1. A compound having the chemical structure shown in Formula IV
wherein
R is H, alkyl, acetyl, or heteroalkyl;
R 1 is H, alkyl, acetyl, or heteroalkyl;
R 8 and R 9 are, independently of one another, H, —OH, acetyl, —C(O)NH 2 , alkyl, cycloalkyl, hereterocycloalkyl, aryl, or heteroaryl, wherein any one of the alkyl, cycloalkyl, hereterocycloalkyl, aryl, or heteroaryl groups is optionally substituted with one or more of —OH, —NO 2 , —NH 2 , —NR 6 R 7 , carbonyl, alkoxy, alkyl, —OCX 3 , —OCHX 2 , —OCH 2 X, or halogen, or both R 8 together form a carbonyl; and
R 10 is cycloalkyl, aryl, or heteroaryl, any of which is optionally substituted with one or more of —OH, —C(O)NH 2 , —C(O)CH 3 , —NO 2 , —NH 2 , —NR 6 R 7 , carbonyl, alkyl, alkoxy, alkylalkoxy, alkoxylalkoxy, halogenated alkoxyl, cycloalkyl, heterocycloalkyl, heteroarylcarbonyl, aryl, heteroaryl, —OCX 3 , —OCHX 2 , —OCH 2 X, —OSO 2 CH 3 , or -tosyl;
R 6 and R 7 are, independently, H, alkyl, —SO 2 CH 3 , —C(O)CH 3 , or —C(O)NH 2 ;
X is independently H or halogen; and
n is 2 or 3.
2. The compound of claim 1 , wherein n is 2.
3. The compound of claim 1 , wherein R 8 and R 9 are, independently, H, alkyl, or alkyl substituted with —OH, —NH 2 , alkoxy, or halogen.
4. The compound of claim 1 , wherein R 10 is an aryl or heteroaryl, any of which is optionally substituted in the ortho-, meta-, orpara-position with —OH, —CO 2 CH 3 , —C(O)NH 2 , —NO 2 , —NH 2 , —NR 6 R 7 , alkoxy, alkylalkoxy, alkyl, —OSO 2 CH 3 , or tosyl.
5. The compound of claim 1 having the formula