基于骨架跃迁和药物拼接所确立的新型二肽基肽酶Ⅳ抑制剂

被引：4

作者：

王善春 ^{[1
]}

曾丽丽 ^{[2
]}

丁宇洋 ^{[3
]}

曾少高 ^{[2
]}

宋宏锐 ^{[3
]}

胡文辉 ^{[2
]}

谢慧 ^{[4
]}

机构：

[1] 江苏正大天晴药业股份有限公司

[2] 中国科学院广州生物医药与健康研究院

[3] 沈阳药科大学制药工程学院

[4] 广州医科大学附属第一医院

来源：

药学学报 | 2014年 / 01期

关键词：

2型糖尿病; DPP-Ⅳ抑制剂; 骨架跃迁; 药物拼接;

D O I：

10.16438/j.0513-4870.2014.01.017

中图分类号：

R978.7 [抗病毒药物];

学科分类号：

1007 ;

摘要：

截至目前,已有7个二肽基肽酶Ⅳ(DPP-Ⅳ)抑制剂成为抗糖尿病新药,它们的结构差异和内在关联性为进一步的结构修饰提供了新的思路。本研究针对阿格列汀和利那列汀的结构特征,采用骨架跃迁及药物拼接的原理,快速得到了新型的DPP-Ⅳ抑制剂8g(IC50=4.9 nmol·L-1),其活性和选择性均接近于上市新药。因此,运用经典的药物化学策略,对基于同一靶标的上市药物实施分子操作,可以有效地产生新型的活性分子。

引用

页码：61 / 67

页数：7

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