7-Methylation of Chenodeoxycholic Acid Derivatives Yields a Substantial Increase in TGR5 Receptor Potency.
Basic Information
ID: ALA4364296
Journal: J Med Chem
Title: 7-Methylation of Chenodeoxycholic Acid Derivatives Yields a Substantial Increase in TGR5 Receptor Potency.
Authors: Nakhi A, McDermott CM, Stoltz KL, John K, Hawkinson JE, Ambrose EA, Khoruts A, Sadowsky MJ, Dosa PI.
Abstract: 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 17.
CiteXplore: 31268316
DOI: 10.1021/acs.jmedchem.9b00770
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