Triazine and pyrimidine based ROCK inhibitors with efficacy in spontaneous hypertensive rat model

…, D Dunn, B Hu, A Klon, SG Kultgen, M Ohlmeyer…

Index: Ho, Koc-Kan; Beasley, James R.; Belanger, Laura; Black, Darcey; Chan, Jui-Hsiang; Dunn, David; Hu, Bing; Klon, Anthony; Kultgen, Steven G.; Ohlmeyer, Michael; Parlato, Susan M.; Ray, Peter C.; Pham, Quynhchi; Rong, Yajing; Roughton, Andrew L.; Walker, Tiffany L.; Wright, Jane; Xu, Kai; Xu, Yan; Zhang, Limei; Webb, Maria Bioorganic and Medicinal Chemistry Letters, 2009 , vol. 19, # 21 p. 6027 - 6031

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Citation Number: 15

Abstract

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.