7-Methylation of Chenodeoxycholic Acid Derivatives Yields a Substantial Increase in TGR5 Receptor Potency.

J Med Chem

Institute for Therapeutics Discovery and Development, Department of Medicinal Chemistry , University of Minnesota, 717 Delaware Street SE , Minneapolis , Minnesota 55414 , United States.

Published: July 2019

TGR5 agonists are potential therapeutics for a variety of conditions including type 2 diabetes, obesity, and inflammatory bowel disease. After screening a library of chenodeoxycholic acid (CDCA) derivatives, it was determined that a range of modifications could be made to the acid moiety of CDCA which significantly increased TGR5 agonist potency. Surprisingly, methylation of the 7-hydroxyl of CDCA led to a further dramatic increase in potency, allowing the identification of 5.6 nM TGR5 agonist .

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Source
http://dx.doi.org/10.1021/acs.jmedchem.9b00770DOI Listing

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