Synthesis and biological evaluation of 4-quinazolinones as Rho kinase inhibitors

Xingang Fang; Yen Ting Chen; E Hampton Sessions; Sarwat Chowdhury; Tomas Vojkovsky; Yan Yin; Jennifer R Pocas; Wayne Grant; Thomas Schröter; Li Lin; Claudia Ruiz; Michael D Cameron; Philip LoGrasso; Thomas D Bannister; Yangbo Feng

doi:10.1016/j.bmcl.2011.01.039

Synthesis and biological evaluation of 4-quinazolinones as Rho kinase inhibitors

Bioorg Med Chem Lett. 2011 Mar 15;21(6):1844-8. doi: 10.1016/j.bmcl.2011.01.039. Epub 2011 Jan 14.

Authors

Xingang Fang¹, Yen Ting Chen, E Hampton Sessions, Sarwat Chowdhury, Tomas Vojkovsky, Yan Yin, Jennifer R Pocas, Wayne Grant, Thomas Schröter, Li Lin, Claudia Ruiz, Michael D Cameron, Philip LoGrasso, Thomas D Bannister, Yangbo Feng

Affiliation

¹ Translational Research Institute, The Scripps Research Institute, Scripps Florida, Jupiter, FL 33458, USA.

PMID: 21349713
DOI: 10.1016/j.bmcl.2011.01.039

Abstract

Rho kinase (ROCK) is an attractive therapeutic target for various diseases including glaucoma, hypertension, and spinal cord injury. Herein, we report the development of a series of ROCK-II inhibitors based on 4-quinazolinone and quinazoline scaffolds. SAR studies at three positions of the quinazoline core led to the identification of analogs with high potency against ROCK-II and good selectivity over protein kinase A (PKA).

MeSH terms

Protein Kinase Inhibitors / chemical synthesis*
Protein Kinase Inhibitors / chemistry
Protein Kinase Inhibitors / pharmacology*
Quinazolinones / chemical synthesis*
Quinazolinones / chemistry
Quinazolinones / pharmacology*
Structure-Activity Relationship
rho-Associated Kinases / antagonists & inhibitors*

Substances

Protein Kinase Inhibitors
Quinazolinones
rho-Associated Kinases