Discovery of novel hedgehog antagonists from cell-based screening: Isosteric modification of p38 bisamides as potent inhibitors of SMO

…, R Godin, P Brassil, E Devereaux, JW Janetka

Index: Yang, Bin; Hird, Alexander W.; Russell, Daniel John; Fauber, Benjamin P.; Dakin, Les A.; Zheng, Xiaolan; Su, Qibin; Godin, Robert; Brassil, Patrick; Devereaux, Erik; Janetka, James W. Bioorganic and Medicinal Chemistry Letters, 2012 , vol. 22, # 14 p. 4907 - 4911

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Citation Number: 10

Abstract

Cell-based subset screening of compounds using a Gli transcription factor reporter cell assay and shh stimulated cell differentiation assay identified a series of bisamide compounds as hedgehog pathway inhibitors with good potency. Using a ligand-based optimization strategy, heteroaryl groups were utilized as conformationally restricted amide isosteres replacing one of the amides which significantly increased their potency against ...