1339944-48-7

Upstream product

• 5382-16-1 4-HYDROXYPIPERIDINE 
• 1108164-37-9 1-(5-chloropyrimidin-2-yl)piperidin-4-ol 
• 1339944-39-6 5-chloro-4-((1-(5-chloropyrimidin-2-yl)piperidin-4-yl)oxy)pyridin-2(1H)-one 
• 236739-02-9 2,4-difluoro-1-(methylsulfonyl)benzene 
• 1339944-49-8 tert-butyl 4-(5-chloro-1-(3-fluoro-4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate 
• 1339944-36-3 tert-butyl 4-((5-chloro-2-oxo-1,2-dihydropyridin-4-yl)oxy)-piperidine-1-carboxylate 
• 874676-81-0 5-chloro-2-iodopyrimidine 
• 1339944-50-1 5-chloro-1-(3-fluoro-4-(methylsulfonyl)phenyl)-4-(piperidin-4-yloxy)pyridin-2(1H)-one hydrochloride salt 
• 109384-19-2 t-butyl 4-hydroxy piperidine-1-carboxylate 
• 103766-25-2 5-chloro-4-hydroxy-2(1H)-pyridinone 

Relevant academic research and scientific papers

Discovery of 5-chloro-4-((1-(5-chloropyrimidin-2-yl)piperidin-4-yl)oxy)-1-(2-fluoro-4-(methylsulfonyl)phenyl)pyridin-2(1 H)-one (BMS-903452), an antidiabetic clinical candidate targeting GPR119

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 molecule GPR119 agonists as a potential new treatment for type 2 diabetes. Herein, we describe the discovery and optimization of a new class of pyridone containing GPR119 agonists. The potent and selective BMS-903452 (42) was efficacious in both acute and chronic in vivo rodent models of diabetes. Dosing of 42 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.

PYRIMIDINYLPIPERIDINYLOXYPYRIDINONE ANALOGUES AS GPR119 MODULATORS

Novel compounds of structure Formula I: or an enantiomer, a diastereomer, or a pharmaceutically acceptable salt thereof, wherein n1, R1, R2, R3 and R4 are defined herein, are provided which are GPR119 G protein-coupled receptor modulators. GPR119 G protein-coupled receptor modulators are useful in treating, preventing, or slowing the progression of diseases requiring GPR119 G protein-coupled receptor modulator therapy. Thus, the disclosure also concerns compositions comprising these novel compounds and methods of treating diseases or conditions related to the activity of the GPR119 G protein-coupled receptor by using any of these novel compounds or a composition comprising any of such novel compounds.