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7-methylation of chenodeoxycholic acid derivatives yields a substantial increase in TGR5 receptor potency

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)6824-6830
Number of pages7
JournalJournal of medicinal chemistry
Volume62
Issue number14
DOIs
StatePublished - Jul 25 2019

Bibliographical note

Publisher Copyright:
© 2019 American Chemical Society.

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

  1. SDG 3 - Good Health and Well-being
    SDG 3 Good Health and Well-being

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