Synthesis of new bis(pyrazolo[1,5- <i>a</i> ]pyrimidines) linked to different spacers with potential MurB inhibitory activity utilizing 1 <i>H</i> -pyrazole-3,5-diamines
A.A. Ahmed, Ahmed E. M. Mekky, Sherif M. H. Sanad
Abstract
Recently, there has been an increased interest in developing new antibacterial agents that target the MurB inhibition, which is necessary for bacterial survival. We developed a two-step tandem protocol to synthesize 15 new bis(pyrazolo[1,5-a]pyrimidines), which are attached to alkane cores by amide linkages. The protocol involved reacting the appropriate bis(2-cyanoacetamides) with dimethylformamide-dimethylacetal in toluene at 80 °C for 3-4 h. The crude bis(2-cyano-3-(dimethylamino)acrylamides) was collected, then reacted with 3,5-diamino-1H-pyrazoles. The reaction gave the desired products in 82-92% yields after 5-6 h of heating at reflux in pyridine. Bis(2,7-diamino-3-(4-methoxybenzyl)pyrazolo[1,5-a]pyrimidine-6-carboxamides) demonstrated comparable efficacy to ciprofloxacin. Their MIC and MBC ranged from 2.8-3.0 and 5.7-6.0 µM, respectively, against S. aureus and E. coli. Moreover, these products displayed promising MurB inhibitory activity with IC50 ranging from 7.8 to 8.0 µM.