COMPUTER PREDICTION AND SYNTHESIS OF NEW OXAZOLES BASED ON AN 8-THIOSUBSTITUTED 1,3,7-TRIMETHYLXANTHINE SKELETON

Alexander Zlatkov; Javor Mitkov; Maya Georgieva

doi:10.12955/cbup.v6.1317

Alexander Zlatkov Medical University, Faculty of Pharmacy, Department of Pharmaceutical Chemistry, Sofia
Javor Mitkov Medical University, Faculty of Pharmacy, Department of Pharmaceutical Chemistry, Sofia
Maya Georgieva Medical University, Faculty of Pharmacy, Department of Pharmaceutical Chemistry, Sofia

DOI: https://doi.org/10.12955/cbup.v6.1317

Keywords: 8-thiosubstituted 1, 3, 7-trimethylxanthine, oxazoles, PASS online, substrate/metabolite specificity prediction

Abstract

The synthesis of new oxazole derivatives was carried out under Davidson synthesis conditions from O-acylacyloins with an 8-thiosubstituted 1,3,7-trimethylxanthine skeleton and ammonium acetate in a 1:10 ratio in glacial acetic acid media. The starting O-acylacyloins were obtained as products from the interaction of the sodium salt of 2-(1,3,7-trimethyl-2,6-dioxo-2,3,6,7-tetrahydro-1H-purin-8-ylthio)acetic acid and a-haloketones. The structures of the new compounds were proven by microanalyses and spectral data. The PASS online web application was used to predict the biological activity spectra of the obtained derivatives and to determine the most promising biological effects for further experimental testing. Thus, it has been shown that the synthesized compounds are a promising class for the creation of substances with a wide range of biological activity. The substrate/metabolite specificity of the tested compounds was also predicted using SMP web-service. The studied compounds were considered to perform most probably with CYP2 substrate activity.

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