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

  • Bioorg Med Chem Lett. 2017 Oct 15;27(20):4673-4677. doi: 10.1016/j.bmcl.2017.09.008.
Steven M Sparks  1 ,  Paul K Spearing  2 ,  Caroline J Diaz  2 ,  David J Cowan  2 ,  Channa Jayawickreme  2 ,  Grace Chen  2 ,  Thomas J Rimele  2 ,  Claudia Generaux  2 ,  Lindsey T Harston  2 ,  Shane G Roller  2
Affiliations
  • 1. Enteroendocrine Discovery Performance Unit and Platform Technologies and Science, GlaxoSmithKline, 5 Moore Drive, Research Triangle Park, NC 27709, United States. Electronic address: [email protected].
  • 2. Enteroendocrine Discovery Performance Unit and Platform Technologies and Science, GlaxoSmithKline, 5 Moore Drive, Research Triangle Park, NC 27709, United States.
PMID: 28916340 DOI: 10.1016/j.bmcl.2017.09.008
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).

Keywords
Calcium sensing receptor; GI-restricted; Nutrient sensing.
Products