Development of pyrazolo[1,5-a]pyrimidine-based antibacterial agents

In the present study, a facile method was adopted to efficiently prepare new pyrazolo[1,5-a]pyrimidin-2-amines linked to arene units in good to excellent yields. A mixture of acetophenones and DMF-DMA was heated at 120 C-o for 3-4 h. The crude enaminones were collected, and then reacted, without isolation, with the respective 4-(4-substituted benzyl)-1H-pyrazole-3,5-diamines in pyridine at 120 degrees C for 4-6 h. At the end of protocol, the target products are obtained in 87-95% yields. The new products showed a wide spectrum of antibacterial activity. In general, products attached to 3-(4-methoxybenzyl) units exceeded their analogues attached to 3-(4-chlorobenzyl) units in antibacterial activity. Moreover, 3-(4-methoxybenzyl)-linked pyrazolo[1,5-a]pyrimidines, which are attached to 7-p-tolyl and 7-(4-methoxyphenyl) units, had the best antibacterial activity with MIC/MBC values of 2.8/5.6 and 2.6/5.3 mu M, respectively. As predicted by SwissADME as well as drug-likeness model score, all new pyrazolo[1,5-a]pyrimidines could be considered as drug-like derivatives.

Automated summary

A simple method was used to prepare pyrazolo[1,5-a]pyrimidin-2-amines linked to arene units with high yields. The crude enaminones were collected and reacted with 4-(4-substituted benzyl)-1H-pyrazole-3,5-diamines in pyridine. The resulting products showed a wide spectrum of antibacterial activity, with the compounds linked to 3-(4-methoxybenzyl) units exhibiting better activity.