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

被引：9

作者：

Vieider, Lisa ^{[1
]}

Romp, Erik ^{[2
]}

Temml, Veronika ^{[3
]}

Fischer, Jana ^{[2
]}

Kretzer, Christian ^{[2
]}

Schoenthaler, Martin ^{[1
]}

Taha, Abdulla ^{[2
]}

Hernandez-Olmos, Victor ^{[5
]}

Sturm, Sonja ^{[3
]}

Schuster, Daniela ^{[1
,4
]}

Werz, Oliver ^{[2
]}

Garscha, Ulrike ^{[2
]}

Matuszczak, Barbara ^{[1
]}

机构：

[1] Univ Innsbruck, Dept Pharmaceut Chem, Ctr Chem & Biomed, Inst Pharm, Innrain 80-82, A-6020 Innsbruck, Austria

[2] Friedrich Schiller Univ Jena, Chair Pharmaceut Med Chem, Philosophenweg 14, D-07743 Jena, Germany

[3] Univ Innsbruck, Inst Pharm, Dept Pharmacognosy, Ctr Chem & Biomed, Innrain 80-82, A-6020 Innsbruck, Austria

[4] Paracelsus Med Univ Salzburg, Inst Pharm, Dept Pharmaceut & Med Chem, Strubergasse 21, A-5020 Salzburg, Austria

[5] Fraunhofer Inst Mol Biol & Appl Ecol IME, Branch Translat Med & Pharmacol TMP, Theodor Stern Kai 7, D-60596 Frankfurt, Germany

来源：

ACS MEDICINAL CHEMISTRY LETTERS | 2019年 / 10卷 / 01期

基金：

奥地利科学基金会;

关键词：

Soluble epoxide hydrolase (sEH); 5-Lipoxygenase activating protein (FLAP); Arachidonic acid cascade; Diflapolin; Inflammation; SOLUBLE EPOXIDE HYDROLASE; MULTIPLE LIGANDS; DISCOVERY; BIOSYNTHESIS; LICOFELONE;

D O I：

10.1021/acsmedchemlett.8b00415

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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-1 NMR, C-13 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.

引用

页码：62 / 66

页数：9

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