QSAR studies on a number of pyrrolidin-2-one antiarrhythmic arylpiperazinyls

Abstract

The activity of a number of 1-[3-(4-arylpiperazin-1-yl)propyl]pyrrolidin-2-one antiarrhythmic (AA) agents was described using the quantitative structure–activity relationship model by applying it to 33 compounds. The molecular descriptors of the AA activity were obtained by quantum chemical calculations combined with molecular modeling calculations. The resulting model explains up to 91% of the variance and it was successfully validated by four tests (LOO, LMO, external test, and Y-scrambling test). Statistical analysis shows that the AA activity of the studied compounds depends mainly on the PCR and JGI4 descriptors.Electronic supplementary materialThe online version of this article (doi:10.1007/s00044-010-9540-x) contains supplementary material, which is available to authorized users.

Quantitative structure–retention relationships models for prediction of high performance liquid chromatography retention time of small molecules: Endogenous metabolites and banned compounds

“…Therefore, two basic principles, internal validation and validation through an external test set, were used for the validation of the predictive capability of the QSRR model. The detailed procedures of these kinds of validations were described in an earlier work [25] and applied procedure was according to OECD principles [18,19]. Evaluation of the best correlation models was carried out by validation of each model using leave-one-out (LOO) and leave-many-out (LMO) cross validation (CV), as internal validation methods, and have been used in this study as internal validation methods.…”

“…The Dragon software (Talete srl, DRAGON for Windows Version 5.5 -2007 package [24]) was employed to calculate a set of physicochemical parameters for the investigated compounds. As Dragon software can calculate up to 3224 descriptors categorized in 22 different logical blocks, to reduce the total number of descriptors, several criteria were used [25], including automatic screening procedures, multiple linear regression, correlation analysis and data mining methods available in Statistica (version 10.0) software [26]. The three-dimensional structures of the neutral compounds were obtained through full optimization using the DFT method and applying the B3LYP hybrid functional and the 6-31G basis set.…”

Curated Database and Preliminary AutoML QSAR Model for 5-HT1A Receptor

“…In other words, JGI4 value is lower for unsubstituted compounds than for compounds substituted with groups of high electrostatic charge (–OH, –O–CH 3 , and –Cl). Therefore, in order to increase pKi value, it suggests the need for a unique charge distribution of the chemical compound [ 52 ]. This finding additionally supports the structure of the 5-HT1A receptor suggested by Zlatović et al, in which an acidic amino acid (Asp 116) is located at the ligand–protein binding site [ 51 ].…”