Pyridylthiazole-based ureas as inhibitors of Rho associated protein kinase (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 a chemical structure shown in Formula II
wherein
n is 1, 2, or 3;
R and R 1 are, independently of one another, H, alkyl, or acetyl;
R 8 and R 9 are, independently of one another, H, —OH, acetyl, —C(O)NH 2 , alkyl or aryl, wherein the alkyl or aryl 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 and R 9 together form a carbonyl;
R 10 is cycloalkyl or aryl, wherein the cycloalkyl or aryl is optionally substituted with one or more of —OH, —CO 2 CH 3 , —C(O)NH 2 , —C(O)CH 3 , —NO 2 , —NH 2 , —NR 6 R 7 , carbonyl, alkyl, alkoxy, alkylalkoxy, alkoxylalkoxy, cycloalkyl, aryl, —OCX 3 , —OCHX 2 , —OCH 2 X, —OSO 2 CH 3 , -tosyl, or halogen;
R 6 and R 7 are, independently of one another, H, alkyl, —SO 2 CH 3 , —C(O)CH 3 , or —C(O)NH 2 ;
X is independently H or halogen;
or a pharmaceutically acceptable salt thereof.
2. The compound of claim 1 , wherein n is 1.
3. The compound of claim 1 , wherein n is 2 or 3.
4. The compound of claim 1 , R 8 and R 9 are, independently, H, alkyl, or alkyl substituted with —OH, —NH 2 , alkoxy, or halogen.
5. The compound of claim 1 , wherein n is 1, and CR 8 R 9 is the R isomer of CHalkyl.
6. The compound of claim 1 , wherein n is 1, and CR 8 R 9 is the S isomer of CHalkyl, wherein the alkyl group is substituted with —OH, NH 2 , alkoxy, or halogen.
7. The compound of claim 1 , wherein R 10 is an aryl that is not substituted in the para position.
8. The compound of claim 1 , wherein R 10 is an aryl which is optionally substituted in the meta-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 , tosyl, or halogen.
9. The compound of claim 1 , wherein n is 1 and (CR 8 R 9 )R 10 has the structure:
10. The compound of claim 1 , wherein the compound has the formula:
or is a pharmaceutically acceptable salt thereof.
11. The compound of claim 1 , wherein the compound has the formula:
or is a pharmaceutically acceptable salt thereof.
12. The compound of claim 1 , wherein the compound has the formula:
or is a pharmaceutically acceptable salt thereof.