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. 2007 May 1;7(3):287–296. doi: 10.1111/j.1582-4934.2003.tb00229.x

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

Speranta Avram 1,✉, I Svab 2, C Bologa 3, Maria‐Luiza Flonta 1
PMCID: PMC6741422  PMID: 14594553

Abstract

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 1/Ki predict = 9.77) and the 1,2,3 triazole derivative (log 1/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.

Keywords: 3D‐QSAR‐CoMFA, the predicted biological activity, cyclic urea derivatives, HIV‐1 protease inhibitors

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