Abstract
Using the PASS programme computer prediction of the biological activity of 1-Ar-4-R-[1,2,4]triazolo[4,3-a] quinazolin-5(4H)-ones has been performed; it has allowed to identify the types of the biological activity of the compounds studied and sort out the most promising compounds 5{1-20} with the potential anti-asthmatic and anti-allergic activity. Prediction of the acute toxicity of 1-Ar-4-R-[1,2,4]triazolo[4,3-a]quinazolin-5(4H)-ones 5{1-20} has been carried out by the GUSAR software, which allows to refer them to slightly toxic (toxicity class 4) or practically nontoxic (toxicity class 5) substances. The synthesis of the most promising compounds 5{1-20} studied іn silico for the biological activity and the acute toxicity has been conducted by interaction of the corresponding 2-hydrazinoquinazolin-4(3H)-ones 1{1-5} with imidazolides 3{1, 2} of aromatic acids 2{1, 2}, or with aromatic aldehydes 4{1, 2} followed by oxidation in the presence of FeCl3. The structure of the compounds 5{1-20}synthesized has been proven by the data of the elemental analysis and 1H NMR spectroscopy. The compounds obtained are promising objects for further investigations as slightly toxic or nontoxic substances with the potential anti-asthmatic and anti-allergic activity.
Highlights
Analysis of the computer prediction results for the virual library of 1-Ar-4-R-[1,2,4]triazolo[4,3-a] quinazolin-5(4H)-ones by the PASS software showed the possibility of searching substances possessing the anti-asthmatic and anti-allergic activity among these compounds and allowed to generate the library of the most promising compounds 5{1-20} for further research (Table 1) [18]
The data of computer prediction of the biological activity obtained are fully consistent with the fact that [1,2,4]triazolo[4,3-a]quinazolin-5(4H)-one derivatives are similar in their chemical structure to the chemical structures described as promising nonsedative H1-antihistaminic drugs [1,2,3,4,5,6,7,8,9,10,11]
The research results іn silico by the GUSAR software gave the possbility to predict the acute toxicity values for different routes of administration of 1-Ar-4-R[1,2,4]triazolo[4,3-a]quinazolin-5(4H)-ones 5{1-20} (Table 2)
Summary
For design of the virual library of 1-Ar-4-R-[1,2,4] triazolo[4,3-a]quinazolin-5(4H)-ones two randomization points in position 1 and 4 of [1,2,4]triazolo[4,3-a]quinazolin-5(4H)-one were chosen. The synthesis of 1-Ar-4-R-[1,2,4]triazolo[4,3-a] quinazolin-5(4H)-ones without hydroxyls 5{1, 4, 5, 8, 9, 12, 13, 16, 17, 20} was carried out by interaction of the corresponding 2-hydrazinoquinazolin-4(3H)ones 1{1-5} previously synthesized according to the improved method [21] with imidazolides 3{1, 2} of aromatic acids 2{1, 2} preliminary obtained via carbonyldiimidazole (CDI). This way allows obtaining the final products in good yields, but is not suitable for hydroxyl-containing compounds due to adverse reactions. Formation of the [1,2,4]triazolo[4,3-a]quinazolin-5(4H)-ones condenced system leads to shift of Н-6 protons signals to 8.22-8.26 ppm, and it is in good correlation with the known data [22]
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