Synthesis of New Bis(pyrazolo[1,5-a]pyrimidines) Linked to Different Spacers as Potential MurB Inhibitors

An efficient protocol was adopted to efficiently prepare three new series of bis(pyrazolo[1,5-a]pyrimidines) linked to different spacers. The new bis(pyrazolo[1,5-a]pyrimidines) were prepared in 80-90 % yields by reacting the respective bis(enaminones) and 4-(4-substituted benzyl)-1H-pyrazole-3,5-diamines in pyridine at reflux temperature for 5-7 h. The new products showed a wide spectrum of antibacterial activity against six different bacterial strains. In general, propane- and butane-linked bis(pyrazolo[1,5-a]pyrimidines), which are attached to 3-(4-methyl- or 4-methoxybenzyl) units, had the best antibacterial activity with minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values up to 2.5 and 5.1 mu M, respectively. Additionally, the previous products demonstrated promising MurB inhibitory activity with IC50 values up to 7.2 mu M.

Automated summary

An efficient protocol was used to synthesize three new series of bis(pyrazolo[1,5-a]pyrimidines) linked to different spacers. The new compounds exhibited a wide range of antibacterial activity against six bacterial strains. The propane- and butane-linked bis(pyrazolo[1,5-a]pyrimidines) attached to 3-(4-methyl- or 4-methoxybenzyl) units showed the best antibacterial activity, with MIC and MBC values up to 2.5 and 5.1 µM, respectively. The previous compounds also demonstrated promising MurB inhibitory activity with IC50 values up to 7.2 µM.