Synthesis, Biological Evaluation and Structure-Activity Relationships of Diflapolin Analogues as Dual sEH/FLAP Inhibitors.

ID: ALA4382289

Journal: ACS Med Chem Lett

Title: Synthesis, Biological Evaluation and Structure-Activity Relationships of Diflapolin Analogues as Dual sEH/FLAP Inhibitors.

Authors: Vieider L, Romp E, Temml V, Fischer J, Kretzer C, Schoenthaler M, Taha A, Hernández-Olmos V, Sturm S, Schuster D, Werz O, Garscha U, Matuszczak B.

Abstract: A series of derivatives of the potent dual soluble epoxide hydrolase (sEH)/5-lipoxygenase-activating protein (FLAP) inhibitor diflapolin was designed, synthesized, and characterized by ¹H NMR, ¹³C NMR, and elemental analysis. These novel compounds were biologically evaluated for their inhibitory activity against sEH and FLAP. Molecular modeling tools were applied to analyze structure-activity relationships (SAR) on both targets. Results show that even small modifications on the lead compound diflapolin markedly influence the inhibitory potential, especially on FLAP, suggesting very narrow SAR.

CiteXplore: 30655948

DOI: 10.1021/acsmedchemlett.8b00415

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