Discovery of 6α-Ethyl-23(S)-methylcholic Acid (S-EMCA, INT-777) as a Potent and Selective Agonist for the TGR5 Receptor, a Novel Target for Diabesity
R Pellicciari, A Gioiello, A Macchiarulo… - Journal of medicinal …, 2009 - ACS Publications
Journal of medicinal chemistry, 2009•ACS Publications
In the framework of the design and development of TGR5 agonists, we reported that the
introduction of a C23 (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 6α-ethyl-23 (S)-methylcholic acid (S-EMCA, INT-777) as a novel potent and
selective TGR5 agonist with remarkable in vivo activity.
introduction of a C23 (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 6α-ethyl-23 (S)-methylcholic acid (S-EMCA, INT-777) as a novel potent and
selective TGR5 agonist with remarkable in vivo activity.
In the framework of the design and development of TGR5 agonists, we reported that the introduction of a C23(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 6α-ethyl-23(S)-methylcholic acid (S-EMCA, INT-777) as a novel potent and selective TGR5 agonist with remarkable in vivo activity.
ACS Publications