Vieider Lisa, Romp Erik, Temml Veronika, Fischer Jana, Kretzer Christian, Schoenthaler Martin, Taha Abdulla, Hernández-Olmos Victor, Sturm Sonja, Schuster Daniela, Werz Oliver, Garscha Ulrike, Matuszczak Barbara
Institute of Pharmacy, Department of Pharmaceutical Chemistry, Center for Chemistry and Biomedicine, University of Innsbruck, Innrain 80-82, A-6020 Innsbruck, Austria.
Chair of Pharmaceutical/Medicinal Chemistry, Friedrich-Schiller University Jena, Philosophenweg 14, D-07743 Jena, Germany.
ACS Med Chem Lett. 2018 Nov 29;10(1):62-66. doi: 10.1021/acsmedchemlett.8b00415. eCollection 2019 Jan 10.
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 H NMR, C 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.
设计、合成了一系列强效双功能可溶性环氧化物水解酶（sEH）/5-脂氧合酶激活蛋白（FLAP）抑制剂二氟拉林的衍生物，并通过氢核磁共振（¹H NMR）、碳核磁共振（¹³C NMR）和元素分析对其进行了表征。对这些新型化合物针对sEH和FLAP的抑制活性进行了生物学评估。应用分子建模工具分析了这两个靶点的构效关系（SAR）。结果表明，即使对先导化合物二氟拉林进行微小修饰也会显著影响抑制潜力，尤其是对FLAP的抑制潜力，这表明构效关系非常狭窄。
