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Solvent-free microwave-assisted synthesis of novel pyrazolo[4′,3′:5,6]pyrido[2,3-d]pyrimidines with potential antifungal activity

Year: 2015

Type: article

Abstract: Novel fused pyrazolo[4′,3′:5,6]pyrido[2,3- d ]pyrimidines 5 were prepared by a solvent-free microwave assisted reaction of heterocyclic o -aminonitriles 3 and cyanopyridines 4 in the presence of t BuOK as catalyst. This protocol provides a versatile procedure for the synthesis of the title compounds with the advantages of easy work-up, mild reaction conditions and good yields. All compounds were also tested for antifungal properties against two clinically important fungi; Candida albicans and Cryptococcus neoformans . Several compounds showed moderate activity against both fungi , being 5a the most active compound. Analysis of the antifungal behavior of properly grouped compounds allowed to determine that the position of the N in the pyrimidyl moiety per se does not play a role in the activity. In turn, the type of 4-R substituent appears to influence the activity. In addition to the above considerations, the lipophilicity of compounds measured as log P showed to be not related to the activity and regarding the dipole moment ( D ), no net correlation was observed, although it is the most active compounds (% inhibition >50%) that have a D ⩾ 7.5, mainly against C. albicans .

Source: Arabian Journal of Chemistry

DOI: 10.1016/j.arabjc.2015.03.002