Benzoylbenzimidazole-based selective inhibitors targeting Cryptosporidium parvum and Toxoplasma gondii calcium-dependent protein kinase-1
Calcium-dependent protein kinase-1 (CDPK1) from Cryptosporidium parvum (CpCDPK1) and Toxoplasma gondii (TgCDPK1) have become attractive targets for discovering selective inhibitors to combat infections caused by these protozoa. We used structure-based design to improve a series of benzoylbenzimidazole-based compounds in terms of solubility, selectivity, and potency against CpCDPK1 and TgCDPK1. The best inhibitors show inhibitory potencies below 50 nM and selectivity well above 200-fold over two human kinases with small gatekeeper residues.
Zhang, Zhongsheng,Ojo, Kayode K.,Johnson, Steven M.,Larson, Eric T.,He, Penqing,Geiger, Jennifer A.,Castellanos-Gonzalez, Alejandro,White Jr., A. Clinton,Parsons, Marilyn,Merritt, Ethan A.,Maly, Dustin J.,Verlinde, Christophe L.M.J.,Van Voorhis, Wesley C.,Fan, Erkang
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p. 5264 - 5267
(2012/09/07)
Synthesis of potential antifilarial agents. 1. 1-(5-Benzoylbenzimidazol-2-yl)-3-alkyl- and -arylureas
A series of 1-(5-benzoylbenzimidazol-2-yl)-3-substituted ureas has been synthesized by reacting an appropriate isocyanate with 2-amino-5-benzoylbenzimidazole or by reacting methyl (5-benzoylbenzimidazol-2-yl)carbamate with various amines. Several of the c