A quantitative structure-activity relationship study on some sulfolanes and arylthiomethanes acting as HIV-1 protease inhibitors

A quantitative structure-activity relationship (QSAR) study on some sulfola nes and arylthiomethanes acting as human immunodeficiency virus-1 (HIV-1) p rotease inhibitors reveals that in the case of sulfolanes an octahydropyrin dene ring and a five-membered 3(S)-sulfolane ring with a hydrophobic 2-subs tituent (cis to 3-substituent) will be crucial for the inhibition activity. The binding of a sulfolane, which is a nonpeptidic molecule, with the enzy me is shown to partly mimic the binding of a peptidic inhibitor. The 2-subs tituent is found to have strong hydrophobic interaction with the receptor. Similarly, in the case of arylthiomethanes, one of the substituents of the methane is found to have strong hydrophobic interaction with the enzyme, wh ile the aryl substituent (4-hydroxy-6-phenyl-2-oxo-2H-pyran-3-yl) is assume d to be involved in the hydrogen bondings. (C) 1998 Elsevier Science Ltd. A ll rights reserved.