SAR, pharmacokinetics, safety, and efficacy of glucokinase activating 2-(4-sulfonylphenyl)-N-thiazol-2-ylacetamides: Discovery of PSN-GK1
Allosteric activators of the glucose-sensing enzyme glucokinase (GK) are currently attracting much interest as potential antidiabetic therapies because they can achieve powerful blood glucose lowering through actions in multiple organs. Here, the optimization of a weakly active high-throughput screening hit to (2R)-2-(4-cyclopropanesulfonylphenyl)-N-(5-fluorothiazol-2-yl)-3- (tetrahydropyran-4-yl)propionamide (PSN-GK1), a potent GK activator with an improved pharmacokinetic and safety profile, is described. Following oral administration, this compound elicited robust glucose lowering in rats.
Bertram, Lisa S.,Black, Daniel,Briner, Paul H.,Chatfield, Rosemary,Cooke, Andrew,Fyfe, Matthew C. T.,Murray, P. John,Naud, Frédéric,Nawano, Masao,Procter, Martin J.,Rakipovski, Günaj,Rasamison, Chrystelle M.,Reynet, Christine,Schofield, Karen L.,Shah, Vilas K.,Spindler, Felix,Taylor, Amanda,Turton, Roy,Williams, Geoffrey M.,Wong-Kai-In, Philippe,Yasuda, Kosuke
experimental part
p. 4340 - 4345
(2009/05/27)
FLUORINATION PROCESS OF PROTECTED AMINOTHIAZOLE
A process for the production of fluorinated compound formula (I) comprising fluorination of a protected aminothiazole. Compounds formula (I) are useful in the preparation of activators of glucokinase.
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Page/Page column 17
(2010/10/20)
ENANTIOSELECTIVE PROCESS
A process for the production of compounds comprising the enantioselective hydrogenation of 2-substituted acrylic acid derivatives.
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Page/Page column 14
(2008/06/13)
TRI(CYCLO) SUBSTITUTED AMIDE COMPOUNDS
Compounds of Formula (I): or pharmaceutically acceptable salts thereof, are useful in the prophylactic and therapeutic treatment of hyperglycemia and diabetes.
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Page 62
(2008/06/13)
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