Structure-based design of potent and selective 2-(quinazolin-2-yl) phenol inhibitors of checkpoint kinase 2

…, VE Anderson, L Antoni, K Boxall, F Urban…

文献索引：Caldwell, John J.; Welsh, Emma J.; Matijssen, Cornelis; Anderson, Victoria E.; Antoni, Laurent; Boxall, Kathy; Urban, Frederique; Hayes, Angela; Raynaud, Florence I.; Rigoreau, Laurent J. M.; Raynham, Tony; Aherne, G. Wynne; Pearl, Laurence H.; Oliver, Antony W.; Garrett, Michelle D.; Collins, Ian Journal of Medicinal Chemistry, 2011 , vol. 54, # 2 p. 580 - 590

全文：HTML全文

被引用次数: 30

摘要

Structure-based design was applied to the optimization of a series of 2-(quinazolin-2-yl) phenols to generate potent and selective ATP-competitive inhibitors of the DNA damage response signaling enzyme checkpoint kinase 2 (CHK2). Structure− activity relationships for multiple substituent positions were optimized separately and in combination leading to the 2- (quinazolin-2-yl) phenol 46 (IC50 3 nM) with good selectivity for CHK2 against CHK1 and ...