title: 2,3-Diaminopyrazines as Rho kinase inhibitors.
abstract: 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.
authors.affiliation: AMRI, 26 Corporate Circle, PO Box 15098, Albany, NY 12212-5098, USA. Alan.Henderson@amriglobal.com
authors.forename: Alan J
authors.initials: AJ
authors.lastname: Henderson
authors.forename: Mark
authors.initials: M
authors.lastname: Hadden
authors.forename: Cheng
authors.initials: C
authors.lastname: Guo
authors.forename: Neema
authors.initials: N
authors.lastname: Douglas
authors.forename: Helene
authors.initials: H
authors.lastname: Decornez
authors.forename: Mark R
authors.initials: MR
authors.lastname: Hellberg
authors.forename: Andrew
authors.initials: A
authors.lastname: Rusinko
authors.forename: Marsha
authors.initials: M
authors.lastname: McLaughlin
authors.forename: Naj
authors.initials: N
authors.lastname: Sharif
authors.forename: Colene
authors.initials: C
authors.lastname: Drace
authors.forename: Raj
authors.initials: R
authors.lastname: Patil
mesh_terms: 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
chemical_list: D047428:Protein Kinase Inhibitors; D011719:Pyrazines; C515851:ROCK1 protein, human; C515852:ROCK2 protein, human; D054460:rho-Associated Kinases