QM-96639

Human immunodeficiency virus type 1 (HIV-1) is the pathogenic retrovirus and causative agent of acquired immunodeficiency syndrome (AIDS).HIV-1 reverse transcriptase (RT) is one of the key enzymes in the duplication of HIV-1.Inhibitors of HIV-1 RT are classified as nonnucleoside reverse-transcriptase inhibitors (NNRTIs) and nucleoside reverse-transcriptase inhibitors (NRTIs).NNRTIs bind in a region not associated with the active site of the enzyme.Within the NNRTIs category, there is a set of inhibitors commonly referred to as 1,1,3-trioxo-thiadiazine (TTD) derivativesBased on the structures and biodata of previous TDS analogs, three-dimensional (3D) quant. structure-activity relationship (QSAR) studies have been performed which resulted in two reliable computational models, comparative mol. field anal. (CoMFA) and comparative mol. similarity indexes anal. (CoMSIA) with R² values of 0.883 and 0.852 and Q² values of 0.639 and 0.608, resp.The predictive ability of the developed CoMFA and CoMSIA models was also confirmed by using a test (external validation) set comprised of eight mols., with predicted R² value of 0.832 and 0.760, resp.It is shown that the steric and electrostatic properties predicted by CoMFA contours and hydrophobic properties predicted by CoMSIA contours can be related to anti-HIV activity.These models are a significant guide to trace the features that really matter, especially with respect to design of novel compounds