Bioorganic & Medicinal Chemistry Letters 2010-02-15

Synthesis and structure-activity relationships of a series of 3-aryl-4-isoxazolecarboxamides as a new class of TGR5 agonists.

Brian W Budzik, Karen A Evans, David D Wisnoski, Jian Jin, Ralph A Rivero, George R Szewczyk, Channa Jayawickreme, David L Moncol, Hongshi Yu

Index: Bioorg. Med. Chem. Lett. 20(4) , 1363-7, (2010)

Full Text: HTML

Abstract

A series of 3-aryl-4-isoxazolecarboxamides identified from a high-throughput screening campaign as novel, potent agonists of the human TGR5 G-protein-coupled receptor is described. Many analogues were readily accessible via solution-phase synthesis which resulted in the rapid identification of key structure-activity relationships (SAR), and the discovery of potent exemplars (up to pEC50=9). Details of the SAR and optimization of this series are presented herein.Copyright 2010 Elsevier Ltd. All rights reserved.