Abstract: The study describes SAR and QSAR of inhibition of Reverse Transcriptase-1 by HEPT derivatives using both classical and non-conventional physicochemical parameters along with hydrophobic parameter and indicator parameters. The set of HEPT derivatives Studied contains 85 compounds with different substitution at various positions. Application of multiple linear regression analysis indicated that combination of classical physicochemical parameters with indicator parameters yielded statistically significant model for modeling inhibitory activity (log1/C) against Reverse Transcriptase-1. Final selection of the potential HEPT derivative for the inhibition of Reverse Transcriptase-1 is made with the help of molecular modeling parameters.