QSAR ANALYSIS OF COMPLEXATION OF ETHERS OF 7-BROM-3-HYDROXY-5-(2'-CHLORO) PHENYL-1,2-DIHYDRO-3H-1,4-BENZODIAZEPIN-2-ONES WITH CENTRAL BENZODIAZEPINE RECEPTORS CNS

• Main Authors: E. A. Lukianova, L. N. Ognichenko, T. A. Yurpalova, N. A. Burenkova, S. P. Smulsky, V. I. Pavlovsky, S. A. Andronati, V. E. Kuz`min
• Format: Article
• Language: English
• Published: Odessa I. I. Mechnikov National University 2018-02-01
• Series: Vìsnik Odesʹkogo Nacìonalʹnogo Unìversitetu: Hìmìâ
• Subjects: QSAR аналіз; бенздіазепінові рецептори; термодинаміка комплексоутворення; симплексне представлення молекулярної структури
• Online Access: http://heraldchem.onu.edu.ua/article/view/124547

QSAR analysis of the structural infl uence of 3-substituted 1,2-dihydro-3Н-1,4-benzodiazepine derivatives on the thermodynamic characteristics (ΔН0, ΔS0 and ΔG0) of their complexation with compounds was the main problem of QSAR analysis in this study. For small sets a new approach was developed for constructing statistical models and estimating their predictive ability. The developed special procedure for the generation of ensembles of QSAR models made it possible to construct adequate «structure – thermodynamic parameters» models for an «extremely small» set (6 compounds). 2D-PLS QSAR models were developed using the structural descriptors calculated by Dragon program and the descriptors calculated by the method based on the simplex representation of the molecular structure. The consensus models with quite good statistical characteristics (R2 > 0.95 for work set, R2 test > 0.78 for test set) were obtained for thermodynamic charact eristics complexation of investigated compounds. The prognosis of the thermodynamic parameters of binding of the related compounds with R = H, iso-C4H9, sec.-C4H9 to the CBDR was carried out using the simplex descriptors and Dragon descriptors. The increa se in the corresponding alkyl substituent from ethyl to isomeric butyl does not signifi cantly affect the interaction of ligands with the CBDR. It is assumed that the amount of Hydrogen atoms bounding to the Carbon atom adjacent to the carbonyl group has a certain infl uence on the thermodynamic characteristics of ligands interaction with CBDR; this may be due to the hyperconjugation effect. Exner’s method has revealed that the mechanism of interaction of the methyl-substituted compound with the CBDR differs from the mechanism of interaction with the CBDR of other investigated compounds.