Synthesis and structure-activity relationships for some novel diflapolin derivatives with benzimidazole subunit

一些新型苯并咪唑亚基二甲胺衍生物的合成及构效关系

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作者:Lisa Vieider, Eva Zoeller, Erik Romp, Martin Schoenthaler, Victor Hernández-Olmos, Veronika Temml, Thomas Hasenoehrl, Daniela Schuster, Oliver Werz, Ulrike Garscha, Barbara Matuszczak

Abstract

A series of derivatives of the potent dual soluble epoxide hydrolase (sEH)/5-lipoxygenase-activating protein (FLAP) inhibitor diflapolin was designed, synthesised, and characterised. These novel compounds, which contain a benzimidazole subunit were evaluated for their inhibitory activity against sEH and FLAP. Molecular modelling tools were applied to analyse structure-activity relationships (SAR) on both targets and to predict solubility and gastrointestinal (GI) absorption. The most promising dual inhibitors of these series are 5a, 6b, and 6c.

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