2. Academic Validation
  3. Discovery of 6alpha-ethyl-23(S)-methylcholic acid (S-EMCA, INT-777) as a potent and selective agonist for the TGR5 receptor, a novel target for diabesity

Discovery of 6alpha-ethyl-23(S)-methylcholic acid (S-EMCA, INT-777) as a potent and selective agonist for the TGR5 receptor, a novel target for diabesity

  • J Med Chem. 2009 Dec 24;52(24):7958-61. doi: 10.1021/jm901390p.
Roberto Pellicciari 1,  Antimo Gioiello,  Antonio Macchiarulo,  Charles Thomas,  Emiliano Rosatelli,  Benedetto Natalini,  Roccaldo Sardella,  Mark Pruzanski,  Aldo Roda,  Elisabetta Pastorini,  Kristina Schoonjans,  Johan Auwerx
Affiliations

Affiliation

  • 1 Dipartimento di Chimica e Tecnologia del Farmaco, Universita di Perugia, 06123 Perugia, Italy. [email protected]
PMID: 20014870 DOI: 10.1021/jm901390p
Abstract

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.

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