Identification of potent, nonabsorbable agonists of the calcium-sensing receptor for GI-specific administration.

Basic Information

ID: ALA4043225

Journal: Bioorg Med Chem Lett

Title: Identification of potent, nonabsorbable agonists of the calcium-sensing receptor for GI-specific administration.

Authors: Sparks SM, Spearing PK, Diaz CJ, Cowan DJ, Jayawickreme C, Chen G, Rimele TJ, Generaux C, Harston LT, Roller SG.

Abstract: Modulation of gastrointestinal nutrient sensing pathways provides a promising a new approach for the treatment of metabolic diseases including diabetes and obesity. The calcium-sensing receptor has been identified as a key receptor involved in mineral and amino acid nutrient sensing and thus is an attractive target for modulation in the intestine. Herein we describe the optimization of gastrointestinally restricted calcium-sensing receptor agonists starting from a 3-aminopyrrolidine-containing template leading to the identification of GI-restricted agonist 19 (GSK3004774).

CiteXplore: 28916340

DOI: 10.1016/j.bmcl.2017.09.008

Patent ID: