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Design, synthesis, and biological evaluation of some 1,2,3-triazole derivatives as novel amide-based inhibitors of soluble epoxide hydrolase
Medicinal Chemistry Research ( IF 2.6 ) Pub Date : 2021-08-02 , DOI: 10.1007/s00044-021-02752-3
Elham Rezaee 1 , Hamid Reza Shadzad 1 , Maryam Nazari 1 , Sayyed Abbas Tabatabai 1
Affiliation  

Epoxyeicosatrienoic acids (EETs) are produced by the effect of cytochrome P 450 (CYP) on arachidonic acid (AA), and have a beneficial performance to renal and cardiovascular systems. In recent decades, many new pharmacological agents have been developed to inhibit the soluble epoxide hydrolase (sEH) and consequently, maintain EETs serum level in high concentrations. In the present study, a series of novel amide derivatives were designed and investigated with a 1,2,3-triazole ring as a secondary pharmacophore against sEH enzyme. Based on docking studies, these novel structures were suitably located in the active site of the enzyme. All final compounds showed satisfactory inhibitory activity against sEH with proper IC50 values (0.9–55.5 nM). Compound 5l, as the most potent compound, could be a valuable structure for further investigation. According to in silico ADME calculations, these novel compounds could be formulated as orally active agents.



中文翻译:

一些 1,2,3-三唑衍生物作为可溶性环氧化物水解酶的新型酰胺基抑制剂的设计、合成和生物学评价

环氧二十碳三烯酸 (EET) 是由细胞色素 P 450 (CYP) 对花生四烯酸 (AA) 的作用产生的,对肾脏和心血管系统具有有益的作用。近几十年来,已经开发出许多新的药物来抑制可溶性环氧化物水解酶 (sEH),从而将 EET 的血清水平维持在高浓度。在本研究中,设计并研究了一系列新型酰胺衍生物,其中 1,2,3-三唑环作为抗 sEH 酶的二级药效团。基于对接研究,这些新结构适当地位于酶的活性位点。所有最终化合物均显示出令人满意的 sEH 抑制活性,具有适当的 IC 50值 (0.9–55.5 nM)。化合物5l,作为最有效的化合物,可能是进一步研究的有价值的结构。根据计算机 ADME 计算,这些新化合物可以配制成口服活性剂。

更新日期:2021-08-02
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