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Bioorg Med Chem Lett. 2011 Feb 15;21(4):1134-40. doi: 10.1016/j.bmcl.2010.12.123. Epub 2010 Dec 31.

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

Author information

1
F. Hoffmann-La Roche Ltd, Pharmaceutical Research, Grenzacherstrasse, CH-4070 Basel, Switzerland. hans.richter@roche.com

Abstract

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 oral administration to LDL receptor deficient mice.

PMID:
21269824
DOI:
10.1016/j.bmcl.2010.12.123
[Indexed for MEDLINE]

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