No abstract

The strategy of rational approaches to the search for selective COX-2 inhibitors as potential antiinflammatory agents has been proposed and elaborated. It is based on the use of PASS-prediction and molecular docking. The choice of the basic structure of 4-amino-3-thio-1,2,4-triazole as a promising object of chemical modification has been substantiated. Using a modification of the primary molecule, a virtual library of S-derivatives of 5-substituted 4-amino(pyrrol)3-thio-4H-1,2,4-triazoles in the amount of 100 compounds (ten groups) has been obtained by introducing various pharmacophore fragments. Based on the analysis of the results of the PASS-prediction and molecular docking, six of the ten planned groups of compounds have been selected for the synthesis as promising selective COX-2 inhibitors. The reliability of the prediction results has already been confirmed for one of the promising group 4-amino-5-(pyridine-4-yl)-1,2,4-triazole (4?)-3-yl-thioacetamides.

Диклофенак натрію-нестероїдний протизапальний засіб, який широко використовується в медичній практиці. Вивчено квантово-хімічні властивості молекули диклофенаку. Оптимізацію геометрії молекули проведено методом РМ3 із використанням алгоритму Полака-Райбера. Визначено заряди атомів, загальний дипольний момент молекули, характеристики молекулярних орбіталей. Негативний електростатичний потен ціал диклофенаку міститься на атомах оксигену та нітрогену. За енергетичними характеристиками ВЗМО і НВМО диклофенак є м'яким реагентом. Встановлені квантовохімічні властивості диклофенаку можуть бути основою молекулярних механізмів його фармакологічної дії.

PURPOSE: Analben has been created by the researchers of the National University of Pharmacy and recommended in the solid dosage form as a promising non-narcotic analgesic and anti-inflammatory drug. The aim of the work is to develop physico-chemical and chemical methods of identification and quantitative determination of the active pharmaceutical ingredient in Analben tablets. MATERIALS AND METHODS: As the object of research a pilot batch of tablets "Analben, 1 mg" produced by the pharmaceutical firm "Neopharm" together with the company "Zdorovie" was selected. Analytical studies were performed by the methods of spectrophotometry, thin-layer chromatography and chemical reactions. RESULTS AND CONCLUSIONS: As the result of the work performed, the spectral characteristics of the analben substance in various solvents have been studied, the optimal conditions for determining related impurities have been selected using the method of thin-layer chromatography. The spectrophotometric method for quantitative determination of Analben in the tablets under study has been developed; the solvent, concentration and wavelength have been chosen. The validation characteristics of the quantitative determination method have been studied and it has been determined that linearity is observed in the range of concentrations from 0.16 µg/ml to 0.24 µg/ml (±20%), the systematic error of the method (0.33%) is practically insignificant, the relative confidence interval for the value Z (0.62%) is less than the critical value for convergence of results (1.66%).