Identification and optimization of novel Hsp90 inhibitors with tetrahydropyrido [4, 3-d] pyrimidines core through shape-based screening

…, F Liu, XK Guo, B Cherfaoui, HZ Huang, Y Pan…

Index: Sun, Hao-Peng; Jia, Jian-Min; Jiang, Fen; Xu, Xiao-Li; Liu, Fang; Guo, Xiao-Ke; Cherfaoui, Bahidja; Huang, Hao-Ze; Pan, Yang; You, Qi-Dong European Journal of Medicinal Chemistry, 2014 , vol. 79, p. 399 - 412

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Citation Number: 13

Abstract

Abstract Rapid Overlay of Chemical Structures (ROCS), which can rapidly identify potentially active compounds by shape comparison, is recognized as a powerful virtual screening tool. By ROCS, a class of novel Hsp90 inhibitors was identified. The calculated binding mode of the most potent hit 36 guided us to design and synthesize a series of analogs (57a–57h). Over 100-fold improvement was achieved in the target-based assay. The most potent ...