Inhibition of soluble epoxide hydrolase (sEH) is considered as a promising target to reduce blood pressure, improve insulin sensitivity, and decrease inflammation. In this study, a series of some novel quinazoline-4(3H)-one derivatives (3a-t) with varying steric and electronic properties was designed, synthesized and evaluated as sEH Inhibitors. Most of the synthesized compounds had similar inhibitory activity to the commercial reference inhibitor, 12-(3-adamantan-1-ylureido)dodecanoic acid, and amongst them, 4-chloro-N-(4-(4-oxo-3,4-dihydroquinazoline-2-yl)phenyl)benzamide (3g) was identified as the most active sEH inhibitor (IC50 = 0.5 nM), about 2-fold more potent compared to the reference inhibitor. The results of molecular modeling followed by biological studies indicate that a quinazolinone ring serves as a suitable scaffold to develop novel small molecule candidates to inhibit sEH and the nature of substituent on the amide moiety has a moderate effect on the activity.

中文翻译：

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喹唑啉-4（3H）-1衍生物作为可溶性环氧化物水解酶的新型有效抑制剂：设计，合成和生物学评估。

可溶性环氧化物水解酶（sEH）的抑制被认为是降低血压，改善胰岛素敏感性和减少炎症的有希望的目标。在这项研究中，设计，合成和评估了一系列具有不同空间和电子性质的新型喹唑啉-4（3H）-一衍生物（3a-t），并作为sEH抑制剂进行了评估。大多数合成的化合物具有与商业参考抑制剂12-（3-金刚烷-1-基脲基）十二烷酸相似的抑制活性，其中4-氯-N-（4-（4-氧代-3,4 -二氢喹唑啉-2-基）苯基）苯甲酰胺（3g）被确定为活性最高的sEH抑制剂（IC50 = 0.5 nM），比参考抑制剂的效价高约2倍。