TY - JOUR
T1 - 7-methylation of chenodeoxycholic acid derivatives yields a substantial increase in TGR5 receptor potency
AU - Nakhi, Ali
AU - Mcdermott, Connor M.
AU - Stoltz, Kristen L.
AU - John, Kristen
AU - Hawkinson, Jon E.
AU - Ambrose, Elizabeth A.
AU - Khoruts, Alexander
AU - Sadowsky, Michael J.
AU - Dosa, Peter I.
N1 - Publisher Copyright:
© 2019 American Chemical Society.
PY - 2019/7/25
Y1 - 2019/7/25
N2 - 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.
AB - 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.
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U2 - 10.1021/acs.jmedchem.9b00770
DO - 10.1021/acs.jmedchem.9b00770
M3 - Article
C2 - 31268316
AN - SCOPUS:85070542873
SN - 0022-2623
VL - 62
SP - 6824
EP - 6830
JO - Journal of medicinal chemistry
JF - Journal of medicinal chemistry
IS - 14
ER -
