Abstract
Aim. The aim of present study was to conduct modelling of the virtual library of 4-aryl-5-oxo-4,5-dihydro[1,2,4]triazolo[4,3-a]quinazoline-8-carboxamides, to determine the most probable biological activity spectrum and the acute toxicity of studied compounds by PASS and GUSAR software, sort out the most perspective substances and develop preparative protocols for their synthesis.Methods. Using the PASS program computer prediction of the biological activity of 4-aryl-5-oxo-4,5-dihydro[1,2,4]triazolo[4,3-a]quinazoline-8-carboxamides has been performed. Prediction of the acute toxicity has been carried out by the GUSAR software. The structure of the compounds synthesized has been proven by elemental analysis and 1H NMR spectroscopy data.Results. The synthesis of 4-aryl-5-oxo-4,5-dihydro[1,2,4]triazolo[4,3-a]quinazoline-8-carboxamides has been conducted starting from corresponding methyl 3-aryl-4-oxo-2-thioxo-1,2,3,4-tetrahydroquinazoline-7-carboxylates, which were converted into corresponding 3-aryl-2-hydrazino-4-oxo-3,4-dihydroquinazoline-7-carbohydrazides by treatment with hydrazine hydrate. Heating of these 2-hydrazinoquinazolin-4(3H)-ones with acetylacetone was resulted in 4-aryl-8-[(3,5-dimethyl-1H-pyrazol-1-yl)carbonyl]-1-methyl[1,2,4]triazolo[4,3-a]quinazolin-5(4H)-ones formation. Following substitution of pyrazole moiety by interaction of these compounds with primary amines led to destinated 4-aryl-5-oxo-4,5-dihydro[1,2,4]triazolo[4,3-a]quinazoline-8-carboxamides. The PASS program computer prediction of the biological activity of 4-aryl-5-oxo-4,5-dihydro[1,2,4]triazolo[4,3-a]quinazoline-8-carboxamides has allowed identifying the types of activity of studied compounds and sorting out the leaders with potential antineurotic activity, which are perspective for male reproductive and erectile dysfunction treatment. Prediction of the acute toxicity has been carried out by the GUSAR software, which allowed to refer them to slightly toxic (class 4) or practically nontoxic (class 5) substances.Conclusions. The obtained compounds are perspective objects for further investigations as slightly toxic (nontoxic) substances with potential antineurotic activity, which are perspective for male reproductive and erectile dysfunction treatment
Highlights
Derivatives of [1,2,4]triazolo[4,3-a]quinazolin5(4H)-one, which are representatives of the important class of condensed heterocycles possessing wide range of the biological activity, attract particular interest in development of innovative drug substances.2
Formulation of the problem in a general way, the relevance of the theme and its connection with important scientific and practical issues The possibility to synthesize a large amount of [1,2,4]triazolo[4,3-a]quinazolin-5(4H)-one derivatives leads to the necessity for the rational presynthetic selection the most perspective compounds from defined variety
Allocation of unsolved parts of the general problem, which is dedicated to the article The presence of amide group may have a significant impact on biological behavior of compounds
Summary
The PASS program computer prediction of the biological activity of 4-aryl-5-oxo-4,5-dihydro[1,2,4]triazolo[4,3a]quinazoline-8-carboxamides has allowed identifying the types of activity of studied compounds and sorting out the leaders with potential antineurotic activity, which are perspective for male reproductive and erectile dysfunction treatment. Комп’ютерне прогнозування біологічної активності 4-арил-5-оксо-4,5-дигідро[1,2,4]триазоло[4,3-a]хіназолін-8карбоксамідів за допомогою програми PASS дозволило визначити напрямок активності досліджуваних сполук та виділити серед них лідерів з потенційною антиневротичною активністю, які можуть бути перспективними для лікування чоловічих репродуктивних захворювань та еректильних дисфункцій. Отримані сполуки є перспективними об’єктами для подальших досліджень як малотоксичні (нетоксичні) речовини з потенційною антиневротичною активністю, які можуть бути перспективними для лікування чоловічих репродуктивних захворювань та еректильних дисфункцій Ключові слова: синтез, 4-арил-5-оксо-4,5-дигідро[1,2,4]триазоло[4,3-a]хіназолін-8-карбоксаміди, комп’ютерне прогнозування, біологічна активність, гостра токсичність
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