Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10594089 | Bioorganic & Medicinal Chemistry Letters | 2011 | 6 Pages |
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.
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Authors
Martin Lang, Markus H.-J. Seifert, Kristina K. Wolf, Andrea Aschenbrenner, Roland Baumgartner, Tanja Wieber, Viola Trentinaglia, Marcus Blisse, Nobumitsu Tajima, Tokuyuki Yamashita, Daniel Vitt, Hitoshi Noda,