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含噻唑啉部分的喹唑啉-3,4-(4H)-二胺的设计与合成作为二肽基肽酶-4(DPP-4)和二苯基苦味酰基自由基(DPPH)抑制剂的新类别

Design and synthesis of quinazoline-3,4-(4H)-diamine endowed with thiazoline moiety as new class for DPP-4 and DPPH inhibitor.

作者信息

Ali Zulphikar, Akhtar Md Jawaid, Haider Md Rafi, Khan Ahsan Ahmed, Siddiqui Anees Ahmad, Yar M Shahar

机构信息

Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Jamia Hamdard (Hamdard University), Hamdard Nagar, New Delhi 110062, India.

Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Jamia Hamdard (Hamdard University), Hamdard Nagar, New Delhi 110062, India.

出版信息

Bioorg Chem. 2017 Apr;71:181-191. doi: 10.1016/j.bioorg.2017.02.004. Epub 2017 Feb 10.

Abstract

New N3-benzylidene (substituted)-2-phenyl-N4-(thiazol-2-yl)-quinazoline-3,4-(4H)-diamine derivatives were design and synthesized by a sequence of reactions starting from appropriate 6-methyl anthranilic acid. The title compounds were screened for in vitro dipeptidyl peptidase IV (DPP-4) inhibitory activity and diphenyl-2-picryl-hydrazyl (DPPH) assay and results showed significant to good activity in compared to Linagliptin for antidiabetic activity and Ascorbic acid for antioxidant activity. Compound 7g (IC=0.76nM) exhibited most promising DPP-4 inhibitory activity and also showed good antioxid and result. Docking study was also performed to provide an insight about the binding mode into binding sites of DPP-4 enzyme. Hopefully in future, compound 7g could be used as a lead compound for developing new antidiabetic agent with good antioxidant property.

摘要

以适当的6-甲基邻氨基苯甲酸为原料,通过一系列反应设计并合成了新型N3-亚苄基(取代)-2-苯基-N4-(噻唑-2-基)喹唑啉-3,4-(4H)-二胺衍生物。对标题化合物进行了体外二肽基肽酶IV(DPP-4)抑制活性和二苯基-2-苦基肼(DPPH)测定,结果表明,与利那格列汀相比,其抗糖尿病活性显著,与抗坏血酸相比,其抗氧化活性良好。化合物7g(IC = 0.76 nM)表现出最有前景的DPP-4抑制活性,并且还显示出良好的抗氧化性能。还进行了对接研究,以深入了解其与DPP-4酶结合位点的结合模式。有望在未来,化合物7g可作为先导化合物用于开发具有良好抗氧化性能的新型抗糖尿病药物。

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