Optimization of a novel class of benzimidazole-based farnesoid X receptor (FXR) agonists to improve physicochemical and ADME properties

…, JM Plancher, MG Rudolph, F Schuler, S Taylor

文献索引：Richter, Hans G.F.; Benson; Bleicher; Blum; Chaput; Clemann; Feng; Gardes; Grether; Hartman; Kuhn; Martin; Plancher; Rudolph; Schuler; Taylor Bioorganic and Medicinal Chemistry Letters, 2011 , vol. 21, # 4 p. 1134 - 1140

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被引用次数: 29

摘要

Structure-guided lead optimization of recently described benzimidazolyl acetamides addressed the key liabilities of the previous lead compound 1. These efforts culminated in the discovery of 4-{(S)-2-[2-(4-chloro-phenyl)-5, 6-difluoro-benzoimidazol-1-yl]-2-cyclohexyl- acetylamino}-3-fluoro-benzoic acid 7g, a highly potent and selective FXR agonist with excellent physicochemical and ADME properties and potent lipid lowering activity after ...