Hept Class And Pyran Anti-hiv Compounds, Quantum Chemistry And Quantitative Structure-activity Relationship Studies

Human immunodeficiency virus(HIV) is the putative etiological agent of acquired immunodeficiency syndrome(AIDS). HIV encodes three enzymes: reverse transcriptase (RT),protease (PR),and integrase (IN). And anti-HIV drugs focus on the inhibitors of these three enzymes. As far, none of drugs can treat AIDS completely. Recently, the analogs of l-[(2-Hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT) and Pyranones were found to have low anti-HIV bio-activity, which the former is RT inhibitors and the latter PR inhibitors. The purpose of this thesis is to find a good structure-activity relationship on the level of microcosmic structure so as to provide some useful information for new compounds design latter.In this thesis, 44 HEPT analogs compounds and 30 Pyranones compounds have been calculated by use of molecular mechanics and quantum chemistry methods. The structure-activity relationship and the components of orbits have been discussed. Some significant results are obtained.(1) As for HEPT analogs, N-l, O-2, C-5, C-6 are the possible active sites where drugs interacts with receptors. The hydrophobicity is the main factor to affect the bioactivity, and the bioactivity is increased with hydrophobicity. The hydrophobicity is related to molecular volume and polarity. The bulky C-5 and highly hydrophobic N-l substituents would favor activity.(2) As for Pyranones compounds, the 4-hydroxyl group , the lactone moiety and the branches at C-3 and C-6 position are the active sites. The relationship between activity and hydrophobicity is formed a parabola, and the optimum ClogP value is 3.75 or so. The hydrophobicity is a good relation to molecular volume. The bulky C-6 and lower hydrophobic C-3 substituents would favor activity.