Publication
In the framework of the design and development of TGR5 agonists, we reported that the introduction of a C(23)(S)-methyl group in the side chain of bile acids such as chenodeoxycholic acid (CDCA) and 6-ethylchenodeoxycholic acid (6-ECDCA, INT-747) affords selectivity for TGR5. Herein we report further lead optimization efforts that have led to the discovery of 6alpha-ethyl-23(S)-methylcholic acid (S-EMCA, INT-777) as a novel potent and selective TGR5 agonist with remarkable in vivo activity.
Kristina Schoonjans, Alessia Perino, Hadrien Charles Edouard Demagny, Laura Alejandra Velazquez Villegas
Kristina Schoonjans, Alessia Perino, Maroun Bou Sleiman, Giovanni Sorrentino, Ece Yildiz, Gaby El Alam