14 research outputs found
Stimuli-Responsive Polymers. 5. Azobenzene Modified Polyaramides Containing Atropisomeric Binaphthyl Linkages:Â Tuning Chiroptical Behavior with Light and Heat
An amide-based sulfenamide prodrug of gamma secretase inhibitor BMS–708163 delivers parent drug from an oral conventional solid dosage form in male beagle dog
Synthesis and chiroptical properties of liquid crystalline copolymers containing azobenzene chromophores
Stimuli-responsive polymers. 11. Highly adaptive poly(urea-amide)s that display solvent, light and heat modulated chiroptical behavior
Photoinduced Racemization of an Optically Active Helical Polymer Formed by the Asymmetric Polymerization of 2,7-Bis(4- tert
Photoinduced Racemization of an Optically Active Helical Polymer Formed by the Asymmetric Polymerization of 2,7-Bis(4- tert
Synthesis and characterization of soluble aromatic azopolyamides containing sulfone and ether units
The Fabrication of a Photoresponsive Molecularly Imprinted Polymer for the Photoregulated Uptake and Release of Caffeine
Discovery of 5‑Chloro-4-((1-(5-chloropyrimidin-2-yl)piperidin-4-yl)oxy)-1-(2-fluoro-4-(methylsulfonyl)phenyl)pyridin-2(1<i>H</i>)‑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 (<b>42</b>) was efficacious in both acute and chronic in vivo rodent models
of diabetes. Dosing of <b>42</b> 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