QSAR modeling with the electrotopological state: TIBO derivatives

Quantitative structure-activity relationships (QSAR), based on the atom lev el E-state indices and calculated molecular properties (log P, MR), have be en developed for the affinity of a large set of TIBO derivatives against HI V-1 reverse transcriptase (HIV-1 RT) utilizing multiple linear regression t echniques. A model with five descriptors, including four atom level E-state indices (carbon atoms 2, 4, 8, and 9) and calculated log P, showed good st atistics both in the regression (r(2) = 0.85 and s = 0.52) and leave-one-ou t cross-validation (q(2) = 0.80 and s(PRESS) = 0.56) for the training set o f 41 compounds. The statistics for the prediction of anti-HIV activity in t he test set of 24 TIBO derivatives were r(2) = 0.80 and s = 0.64, respectiv ely. The model descriptors indicate the importance of Lipophilic and electr onic contributions toward HIV-1 RT inhibition of TIBO derivatives used in t his study.