Quantitative structure-activity relationship studies on cyclic urea-based HIV protease inhibitors

A quantitative structure-activity relationship (QSAR) study is described on some cyclic ureas that inhibit the enzyme HIV-I protease (HIV-1-PR) and exhibit antiviral potency. Both the enzyme inhibition activity and the antiviral potency were found to be primarily governed by the hydrophobic property of the substituents at the nitrogens (N2/N2') of the urea. Adjacent to the nitrogens, the C1/C1'-substituents are, however, found to affect the activity (inhibition) by their molecular size. The essential binding of the ureas with the receptor is, however, through multiple hydrogen bonding, where the substituents, too, can participate in such binding if they are capable of doing so. A schematic diagram of the overall interaction of the inhibitors with the receptor is presented.