抗糖尿病噻唑烷二酮的三维定量构效关系(3D-QSAR)。

Drug design and discovery Pub Date : 1999-08-01
Y Kurogi
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引用次数: 0

摘要

噻唑烷-2,4-二酮(TZDs)是一种新型的胰岛素抵抗释放化合物,可作为口服抗糖尿病药物。20多年来,许多tzd已被合成并通过体内筛选进行了评价。近年来,人们发现TZDs是过氧化物酶体增殖激活受体(PPAR-gamm)的选择性激动剂,被认为参与胰岛素抵抗的调节。本文报道了我们通过对TZDs的三维构效关系进行药效团建模研究,以深入了解TZDs的分子机制以及降糖与ppar - γ拮抗活性的关系。通过构象分析和Apex-3D QSAR方法进行建模研究,以确定一系列选定的7个tzd的共同分子特征。虽然研究中包含的化合物数量相当少,但活性的变化很好地阐明了3d位点特定的理化参数。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Three-dimensional quantitative structure-activity relationships (3D-QSAR) of antidiabetic thiazolidinediones.

Thiazolidine-2,4-diones (TZDs) are novel insulin resistance releasing compounds that serve as orally active antidiabetic agents. Many TZDs have been synthesized and evaluated by in vivo screening for over 20 years. Recently, TZDs have been found to be selective agonists of peroxisome proliferator-activated receptor-y (PPAR-gamm), which is believed to work in the regulation of insulin resistance. This paper reports our efforts for the pharmacophore modeling study through 3D (three-dimensional) structure-activity relationship of TZDs to gain an insight into their molecular mechanism as well as the relation between antihyperglycemic and PPAR-gamma agonistic activities. The modeling study was carried out by conformational analysis along with the Apex-3D QSAR method to identify molecular features common to a series of 7 selected TZDs. Although the number of compounds included in the study was rather low, the variations in the activities were nicely elucidated with 3D-site specific physiochemical parameters significantly.

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