Computational design of novel cyclic urea as HIV-1 protease inhibitor

摘要

A series of novel cyclic urea molecules 5,6-dihydroxy-1,3-diazepane-2,4,7-trione as HIV-1 protease inhibitors were designed using computational techniques.The designed molecules were compared with the known cyclic urea molecules by performing docking studies,calculating their ADME (Absorption,Distribution,Metabolism,and Excretion)properties and protein ligand interaction energy. These novel molecules were designed by substituting the P1/P1' positions(4~(th) and 7~(th) position of 1, 3-diazepan-2-one)with double bonded oxygens.This reduces the molecular weight and increases the bioavailability,indicating better ADME properties.The docking studies showed good binding affnity towards HIV-1 protease.The biological activity of these inhibitors were predicted by a model equation generated by the regression analysis between biological activity(log 1/K_i)of known inhibitors and their protein ligand interaction energy.The synthetic studies are in progress.