QSAR modeling with the electrotopological state: TIBO derivatives.
Quantitative structure-activity relationships (QSAR), based on the atom level E-state indices and calculated molecular properties (log P, MR), have been developed for the affinity of a large set of TIBO derivatives against HIV-1 reverse transcriptase (HIV-1 RT) utilizing multiple linear regression techniques. 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 statistics both in the regression (r2 = 0.85 and s = 0.52) and leave-one-out cross-validation (q2 = 0.80 and s(PRESS) = 0.56) for the training set of 41 compounds. The statistics for the prediction of anti-HIV activity in the test set of 24 TIBO derivatives were r2 = 0.80 and s = 0.64, respectively. The model descriptors indicate the importance of lipophilic and electronic contributions toward HIV-1 RT inhibition of TIBO derivatives used in this study.
Huuskonen
J
J
Division of Pharmaceutical Chemistry, Department of Pharmacy, POB 56, FIN-00014 University of Helsinki, Finland. jarmo.huuskonen@helsinki.fi
D001569:Benzodiazepines / Q000737:chemistry* / Q000494:pharmacology; D016208:Databases, Factual; D004563:Electrochemistry; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors; D006801:Humans; D007093:Imidazoles / Q000737:chemistry* / Q000494:pharmacology; D008956:Models, Chemical; D021281:Quantitative Structure-Activity Relationship; D012044:Regression Analysis; D018894:Reverse Transcriptase Inhibitors / Q000737:chemistry / Q000494:pharmacology
C097516:8-chlorotetrahydroimidazo(4,5,1-jk)(1,4)-benzodiazepin-2(1H)-thione; D007093:Imidazoles; D018894:Reverse Transcriptase Inhibitors; D001569:Benzodiazepines; C092133:R 79882; D054303:HIV Reverse Transcriptase