Martin Lang - Discovery and hit-to-lead optimization of novel allosteric glucokinase activators

Document created by Martin Lang on Aug 22, 2014
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  Publication Details (including relevant citation   information):

  Bioorg. Med. Chem. Lett. 2011,   21, 5417-5422.

  Abstract:

  We report on a hit generation and hit-to-lead program of a novel   class of glucokinase activators (GKAs). Hit compounds, activators   at low glucose concentration only were identified by vHTS.   Scaffold modification reliably afforded activators also at high   substrate level. Potency was increased by introduction of a   hydrogen bond acceptor as proposed by molecular docking.   Replacement of the initial alkylene linkers with a rigid   1,2-phenylene motif followed by further studies eventually   furnished a series of potent lead compounds exhibiting steep SAR.

  Address (URL): http://dx.doi.org/10.1016/j.bmcl.2011.06.128

 

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