| Literature DB >> 23214471 |
Subba R Katamreddy1, Andrew J Carpenter, Carina E Ammala, Eric E Boros, Ron L Brashear, Celia P Briscoe, Sarah R Bullard, Richard D Caldwell, Christopher R Conlee, Dallas K Croom, Shane M Hart, Dennis O Heyer, Paul R Johnson, Jennifer A Kashatus, Doug J Minick, Gregory E Peckham, Sean A Ross, Shane G Roller, Vicente A Samano, Howard R Sauls, Sarva M Tadepalli, James B Thompson, Yun Xu, James M Way.
Abstract
GPR119 is a 7-transmembrane receptor that is expressed in the enteroendocrine cells in the intestine and in the islets of Langerhans in the pancreas. Indolines and 6,7-dihydro-5H-pyrrolo[2,3-a]pyrimidines were discovered as G protein-coupled receptor 119 (GPR119) agonists, and lead optimization efforts led to the identification of 1-methylethyl 4-({7-[2-fluoro-4-(methylsulfonyl)phenyl]-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-4-yl}oxy)-1-piperidinecarboxylate (GSK1104252A) (3), a potent and selective GPR119 agonist. Compound 3 showed excellent pharmacokinetic properties and sufficient selectivity with in vivo studies supporting a role for GPR119 in glucose homeostasis in the rodent. Thus, 3 appeared to modulate the enteroinsular axis, improve glycemic control, and strengthen previous suggestions that GPR119 agonists may have utility in the treatment of type 2 diabetes.Entities:
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Year: 2012 PMID： 23214471 DOI： 10.1021/jm301404a
Source DB: PubMed Journal: J Med Chem ISSN： 0022-2623 Impact factor: 7.446