Triazine and pyrimidine based ROCK inhibitors with efficacy in spontaneous hypertensive rat model.
The profile of a series of triazine and pyrimidine based ROCK inhibitors is described. An initial binding mode was established based on a homology model and the proposed interactions are consistent with the observed SAR. Compounds from the series are potent in a cell migration assay and possess a favorable kinase selectivity. In vivo activity was demonstrated for compound 1A in a spontaneous hypertensive rat model.
Ligand Pharmaceuticals, Inc., 3000 Eastpark Boulevard, Cranbury, NJ 08512, USA. kho@ligand.com
Koc-Kan
KK
Ho
James R
JR
Beasley
Laura
L
Belanger
Darcey
D
Black
Jui-Hsiang
JH
Chan
David
D
Dunn
Bing
B
Hu
Anthony
A
Klon
Steven G
SG
Kultgen
Michael
M
Ohlmeyer
Susan M
SM
Parlato
Peter C
PC
Ray
Quynhchi
Q
Pham
Yajing
Y
Rong
Andrew L
AL
Roughton
Tiffany L
TL
Walker
Jane
J
Wright
Kai
K
Xu
Yan
Y
Xu
Limei
L
Zhang
Maria
M
Webb
D000818:Animals; D000959:Antihypertensive Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D001665:Binding Sites; D003198:Computer Simulation; D004195:Disease Models, Animal; D006973:Hypertension / Q000188:drug therapy*; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D011743:Pyrimidines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D051381:Rats; D013329:Structure-Activity Relationship; D014227:Triazines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism
D000959:Antihypertensive Agents; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D014227:Triazines; D054460:rho-Associated Kinases