Development of pyrazolo[1,5-<i>a</i>]pyrimidine-based antibacterial agents
Ahmed E. M. Mekky, Nariman A. S. Taha, Nada G. Mohammed, Fatma R. M. Hussein, Esraa H. Abdelfattah, Aya A. Gamal Eldin, Alshimaa A. M. Abdelsalam, Sherif M. H. Sanad
Abstract
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 oC 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 °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 µM, 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.