Discovery of 5-Chloro-4-((1-(5-chloropyrimidin-2-yl)piperidin-4-yl)oxy)-1-(2-fluoro-4-(methylsulfonyl)phenyl)pyridin-2(1H)-one (BMS-903452), an Antidiabetic Clinical Candidate Targeting GPR119 was written by Wacker, Dean A.;Wang, Ying;Broekema, Matthias;Rossi, Karen;O’Connor, Steven;Hong, Zhenqiu;Wu, Ginger;Malmstrom, Sarah E.;Hung, Chen-Pin;LaMarre, Linda;Chimalakonda, Anjaneya;Zhang, Lisa;Xin, Li;Cai, Hong;Chu, Cuixia;Boehm, Stephanie;Zalaznick, Jacob;Ponticiello, Randolph;Sereda, Larisa;Han, Song-Ping;Zebo, Rachel;Zinker, Bradley;Luk, Chiuwa Emily;Wong, Richard;Everlof, Gerry;Li, Yi-Xin;Wu, Chunyu K.;Lee, Michelle;Griffen, Steven;Miller, Keith J.;Krupinski, John;Robl, Jeffrey A.. And the article was included in Journal of Medicinal Chemistry in 2014.Reference of 142253-56-3 This article mentions the following:
G-protein-coupled receptor 119 (GPR119) is expressed predominantly in pancreatic β-cells and in enteroendocrine cells in the gastrointestinal tract. GPR119 agonists have been shown to stimulate glucose-dependent insulin release by direct action in the pancreas and to promote secretion of the incretin GLP-1 by action in the gastrointestinal tract. This dual mechanism of action has generated significant interest in the discovery of small mol. GPR119 agonists as a potential new treatment for type 2 diabetes. Herein, the authors describe the discovery and optimization of a new class of pyridone containing GPR119 agonists. The potent and selective BMS-903452 I was efficacious in both acute and chronic in vivo rodent models of diabetes. Dosing of I in a single ascending dose study in normal healthy humans showed a dose dependent increase in exposure and a trend toward increased total GLP-1 plasma levels. In the experiment, the researchers used many compounds, for example, 1-Boc-Azetidine-3-yl-methanol (cas: 142253-56-3Reference of 142253-56-3).
1-Boc-Azetidine-3-yl-methanol (cas: 142253-56-3) belongs to alcohols. Alcohols are weak acids. The most acidic simple alcohols (methanol and ethanol) are about as acidic as water, and most other alcohols are somewhat less acidic. Converting an alcohol to an alkene requires removal of the hydroxyl group and a hydrogen atom on the neighbouring carbon atom. Dehydrations are most commonly carried out by warming the alcohol in the presence of a strong dehydrating acid, such as concentrated sulfuric acid.Reference of 142253-56-3
Referemce:
Alcohol – Wikipedia,
Alcohols – Chemistry LibreTexts