Correlation between the predicted and the observed biological activity of the symmetric and nonsymmetric cyclic urea derivatives used as HIV-1 protease inhibitors. A 3D-QSAR-CoMFA method for new antiviral drug design

被引:14
作者
Avram, S
Svab, I
Bologa, C
Flonta, ML
机构
[1] Univ Bucharest, Fac Biol, Dept Physiol & Biophys, Bucharest 76201, Romania
[2] Inst Cellular Biol & Pathol, Lab Cellular Pharmacol, R-79691 Bucharest, Romania
[3] West Univ, Fac Chem Biol & Geog, Dept Chem, Timisoara, Romania
来源
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE | 2003年 / 7卷 / 03期
关键词
3D-QSAR-CoMFA; the predicted biological activity; cyclic urea derivatives; HIV-1 protease inhibitors;
D O I
10.1111/j.1582-4934.2003.tb00229.x
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
The predicted inhibition constant (Ki) and the predicted inhibitor concentration (IC90) of the HIV-1 protease (HIV-1 PR) inhibitors: symmetric and nonsymmetric - benzyl, ketone, oxime, pyrazole, imidazole, and triazole cyclic urea derivatives, were obtained by the 3D-CoMFA (Comparative Molecular Field Analysis) method. The CoMFA statistical parameters: cross-validate correlation coefficient (q2), higher than 0.5, and the fitted correlation coefficient (r2), higher than 0.90 validated the predicted biological activities. The best predictions were found for the trifluoromethyl ketoxime derivative (log 1/Ki predict = 8.42), the m-pyridineCH2 pyrazole derivative ( log I /Ki predict = 9.77) and the 1,2,3 triazole derivative ( log I /Ki predict = 7.03). We attempted to design a new potent HIV-1 protease inhibitor by addition of o-benzyl to the (p-HOPhCH2) pyrazole 12f derivative inhibitor. A favorable steric area surrounded the o-benzyl, suggesting a possible new potent HIV-1 protease inhibitor.
引用
收藏
页码:287 / 296
页数:10
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