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

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.