1309458-28-3Relevant academic research and scientific papers
Discovery of Orally Efficacious Tetrahydrobenzimidazoles as TGR5 Agonists for Type 2 Diabetes
Zhang, Xuqing,Wall, Mark,Sui, Zhihua,Kauffman, Jack,Hou, Cuifen,Chen, Cailin,Du, Fuyong,Kirchner, Thomas,Liang, Yin,Johnson, Dana L.,Murray, William V.,Demarest, Keith
, p. 560 - 565 (2017)
We have discovered a novel series of tetrahydrobenzimidazoles 3 as TGR5 agonists. Initial structure-activity relationship studies with an assay that measured cAMP levels in murine enteroendocrine cells (STC-1 cells) led to the discovery of potent agonists with submicromolar EC50 values for mTGR5. Subsequent optimization through methylation of the 7-position of the core tetrahydrobenzimidazole ring resulted in the identification of potent agonists for both mTGR5 and hTGR5 (human enteroendocrine NCI-H716 cells). While the lead compounds displayed low to moderate exposure after oral dosing, they significantly reduced blood glucose levels in C57 BL/6 mice at 30 mg/kg and induced a 13-22% reduction in the area under the blood glucose curve (AUC)0-120 min in oral glucose tolerance tests (OGTT).
A boron-based synthesis of the natural product (+)-trans- dihydrolycoricidine
Poe, Sarah L.,Morken, James P.
, p. 4189 - 4192 (2011/06/20)
Diastereoselective diboration results in the highly selective 1,4-dihydroxylation of chiral cyclohexadienes (see scheme). Together with the catalytic enantioselective conjugate allylboration, the diene diboration facilitates the asymmetric synthesis of the cytotoxic agent (+)-trans- dihydrolycoricidine (1). pin=pinacol. Copyright
