Quantitative structure-activity relationship studies on cyclic cyanoguanidines acting as HIV-1 protease inhibitors.
Quantitative structure-activity relationship studies on cyclic cyanoguanidines acting as HIV-1 protease inhibitors.
复制标题
环状氰基胍作为 HIV-1 蛋白酶抑制剂的定量构效关系研究。
DOI：
10.1016/s0968-0896(99)00175-3
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发表时间：
1999
影响因子：
3.5
通讯作者：
M. S. Babu
中科院分区：
文献类型：
--
作者：
S. Gupta;M. S. Babu
对具有抗HIV-1蛋白酶（HIV-1-PR）活性的环氰胍类化合物进行了定量构效关系研究，并与环脲类化合物的构效关系进行了比较。环氰胍和环脲衍生物的酶抑制活性和抗病毒活性主要受氮原子上取代基的疏水性（P2/P2′）控制，而取代基中的OH或NH 2基团（如果有的话）可进一步增强其活性。然而，芳香族取代基被发现是不利的环氰胍的活动，但不是任何环脲衍生物的活动。环脲衍生物被表明比环氰基胍更有效。提出了一个环氰胍与受体相互作用的模型。
A quantitative structure–activity relationship study has been performed on some cyclic cyanoguanidines that inhibit the enzyme HIV-1 protease (HIV-1-PR) and exhibit antiviral potency, and the results have been compared with those of cyclic urea derivatives. Both the enzyme inhibition activity and antiviral potency in cyclic cyanoguanidines as well as in cyclic urea derivatives are found to be primarily governed by hydrophobic property of substituents attached to nitrogen (P2/P2′) and further enhanced by OH or NH2group, if any, present in the substituents. However, aromatic substituents are found to be unfavourable to both the activities of cyclic cyanoguanidines but not to any activity of cyclic urea derivatives. Cyclic urea derivatives are indicated to be more potent than cyclic cyanoguanidines. A model for the interaction of cyclic cyanoguanidines with the receptor is proposed.