Syntheses and in silico pharmacokinetic predictions of glycosylhydrazinyl-pyrazolo[1,5-c]pyrimidines and pyrazolo[1,5-c]triazolo[4,3-a]pyrimidines as anti-proliferative agents

Abstract

New glycosylhydrazinyl-pyrazolo[1,5-c]pyrimidines were synthesized by the reaction of respective 5-aryl-7-hydrazino-2-phenylpyrazolo[1,5-c]pyrimidines (1a-d) with glucose, galactose, and xylose in ethanol. Their glycopyranosyl structures were reasoned to be in chair conformations and each have hydrazine moiety in the β-configuration. Also, pyrazolo[1,5-c]triazolo[4,3-a]pyrimidines derivatives were synthesized by the reaction of 1a-d with benzoic acid in the presence of phosphorousoxy chloride or by the reaction with benzaldehyde derivatives followed by cyclization in the presence of bromine. All structures of the compounds were confirmed from their IR, 1H, 13C, DPET-135°, 1H-1H COSY, 1H-13C HMQC, 13C-1H HMBC spectra and microanalysis. The synthesized compounds showed inhibition of proliferation of MCF-7 human breast cancer cells with IC50 values ranging from 0.56 to 8.86 µg/ml. Some of the most active compounds showed acceptable predicted pharmacokinetics and drug-likeness properties.