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脲类:在药物设计中的应用。

Ureas: Applications in Drug Design.

作者信息

Jagtap Ajit Dhananjay, Kondekar Nagendra Bharatrao, Sadani Amit A, Chern Ji-Wang

机构信息

School of Pharmacy, and Center for Innovative Therapeutics Discovery, National Taiwan University, No. 33, Lin Sen South Road, Taipei 10050. Taiwan.

出版信息

Curr Med Chem. 2017;24(6):622-651. doi: 10.2174/0929867323666161129124915.

Abstract

The unique hydrogen binding capabilities of ureas make them an important functional group to make drug-target interactions and thus incorporated in small molecules displaying broad range of bioactivities. The related research and numerous excellent achievements of ureas applicability in drug design for the modulation of selectivity, stability, toxicity and pharmacokinetic profile of lead molecules have become active topic. This review aims to provide insights in to the significance of urea in drug design by summarizing successful studies of various urea derivatives as modulators biological targets (viz. kinases, NAMPT, soluble epoxide hydrolases, mTOR, proteases, gyrB/parE, and epigenetic enzymes (such as HDAC, PRMT or DOT1L etc.). The findings of this review confirm the importance of urea moiety in medicinal chemistry and stimulate its use as a structural motif with rational decision making approach.

摘要

脲独特的氢键结合能力使其成为药物与靶点相互作用的重要官能团,因而被引入具有广泛生物活性的小分子中。脲在药物设计中用于调节先导分子的选择性、稳定性、毒性和药代动力学特征方面的相关研究及众多卓越成果已成为热门话题。本综述旨在通过总结各种脲衍生物作为生物靶点(即激酶、烟酰胺磷酸核糖转移酶、可溶性环氧化物水解酶、哺乳动物雷帕霉素靶蛋白、蛋白酶、gyrB/parE以及表观遗传酶(如组蛋白去乙酰化酶、蛋白质精氨酸甲基转移酶或DOT1L等)调节剂的成功研究,深入探讨脲在药物设计中的重要性。本综述的研究结果证实了脲部分在药物化学中的重要性,并促使其作为一种结构基序以合理的决策方法加以应用。

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