Synthesis, structural analysis and drug-likeness estimation of some imidazole derivatives

personАвтори: Al. Zlatkov, B. Tsvetkova, L. Andonova, P. Peykov


The xanthine skeleton, as a basic structure of a lot of physiologically active compounds, provides great opportunities for pharmacologically targeted synthesis of derivatives with various structures. Thus, using alkaline hydrolysis of methylxanthines theophylline (1), caffeine (2) and ethophylline (7), three 1-(un)substituted N-methyl-4-(methylamino)-1H-imidazole-5-carboxamides (5a,b and 8) were synthesized. The hydrolytic process was carried out at mild conditions without heating. Based on IR structural analysis, it was clearly established that under these reaction conditions the xanthine ring was cleaved at position 1,2 to form the corresponding 1-(un)substituted N-methyl-4-(methylamino)-1H-imidazole-5-carboxamides. In order to estimate the drug-likeness of compounds 5a,b and 8, a theoretical calculation of some molecular descriptors was made. The obtained values were compared to these of the starting biologically active xanthines 1, 2 and 7. The results indicate that a good oral bioavailability manifestation may be expected. The possible pharmacological effects and clarification of their potential as prodrugs will be studied in another research.

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