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.
Ho
Koc-Kan
KK
Ligand Pharmaceuticals, Inc., 3000 Eastpark Boulevard, Cranbury, NJ 08512, USA. kho@ligand.com
Beasley
James R
JR
Belanger
Laura
L
Black
Darcey
D
Chan
Jui-Hsiang
JH
Dunn
David
D
Hu
Bing
B
Klon
Anthony
A
Kultgen
Steven G
SG
Ohlmeyer
Michael
M
Parlato
Susan M
SM
Ray
Peter C
PC
Pham
Quynhchi
Q
Rong
Yajing
Y
Roughton
Andrew L
AL
Walker
Tiffany L
TL
Wright
Jane
J
Xu
Kai
K
Xu
Yan
Y
Zhang
Limei
L
Webb
Maria
M
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