2,3-Diaminopyrazines as Rho kinase inhibitors.
Inhibition of rho kinase (ROCK) has been recognized as an important target for a number of diseases, including glaucoma. Herein we report SAR development around two hits from a kinase library that led to the discovery of the ROCK inhibitor compound 38. In vitro and in vivo analysis of this compound, including its effects in a monkey model of glaucoma will be discussed.
Henderson
Alan J
AJ
AMRI, 26 Corporate Circle, PO Box 15098, Albany, NY 12212-5098, USA. Alan.Henderson@amriglobal.com
Hadden
Mark
M
Guo
Cheng
C
Douglas
Neema
N
Decornez
Helene
H
Hellberg
Mark R
MR
Rusinko
Andrew
A
McLaughlin
Marsha
M
Sharif
Naj
N
Drace
Colene
C
Patil
Raj
R
D000818:Animals; D005901:Glaucoma / Q000188:drug therapy / Q000201:enzymology; D000882:Haplorhini; D006801:Humans; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D047428:Protein Kinase Inhibitors / Q000737:chemistry* / Q000378:metabolism / Q000627:therapeutic use; D011719:Pyrazines / Q000737:chemistry* / Q000378:metabolism / Q000627:therapeutic use; D011817:Rabbits; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism
D047428:Protein Kinase Inhibitors; D011719:Pyrazines; C515851:ROCK1 protein, human; C515852:ROCK2 protein, human; D054460:rho-Associated Kinases