| Literature DB >> 19902954 |
Karen A Evans1, Brian W Budzik, Sean A Ross, David D Wisnoski, Jian Jin, Ralph A Rivero, Mythily Vimal, George R Szewczyk, Channa Jayawickreme, David L Moncol, Thomas J Rimele, Susan L Armour, Susan P Weaver, Robert J Griffin, Sarva M Tadepalli, Michael R Jeune, Todd W Shearer, Zibin B Chen, Lihong Chen, Donald L Anderson, J David Becherer, Maite De Los Frailes, Francisco Javier Colilla.
Abstract
A series of 3-aryl-4-isoxazolecarboxamides identified from a high-throughput screening campaign as novel, potent small molecule agonists of the human TGR5 G-protein coupled receptor is described. Subsequent optimization resulted in the rapid identification of potent exemplars 6 and 7 which demonstrated improved GLP-1 secretion in vivo via an intracolonic dose coadministered with glucose challenge in a canine model. These novel TGR5 receptor agonists are potentially useful therapeutics for metabolic disorders such as type II diabetes and its associated complications.Entities:
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Year: 2009 PMID： 19902954 DOI： 10.1021/jm901434t
Source DB: PubMed Journal: J Med Chem ISSN： 0022-2623 Impact factor: 7.446