2. Academic Validation
  3. SAR, pharmacokinetics, safety, and efficacy of glucokinase activating 2-(4-sulfonylphenyl)-N-thiazol-2-ylacetamides: discovery of PSN-GK1

SAR, pharmacokinetics, safety, and efficacy of glucokinase activating 2-(4-sulfonylphenyl)-N-thiazol-2-ylacetamides: discovery of PSN-GK1

  • J Med Chem. 2008 Jul 24;51(14):4340-5. doi: 10.1021/jm8003202.
Lisa S Bertram 1,  Daniel Black,  Paul H Briner,  Rosemary Chatfield,  Andrew Cooke,  Matthew C T Fyfe,  P John Murray,  Frédéric Naud,  Masao Nawano,  Martin J Procter,  Günaj Rakipovski,  Chrystelle M Rasamison,  Christine Reynet,  Karen L Schofield,  Vilas K Shah,  Felix Spindler,  Amanda Taylor,  Roy Turton,  Geoffrey M Williams,  Philippe Wong-Kai-In,  Kosuke Yasuda
Affiliations

Affiliation

  • 1 OSI) Prosidion, Windrush Court, Watlington Road, Oxford OX4 6LT, United Kingdom.
PMID: 18588279 DOI: 10.1021/jm8003202
Abstract

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 (2 R)-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.

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