New thiazole-based pyrazolo[1,5- <i>a</i> ]pyrimidine hybrids: One-pot synthesis of potential MRSA and VRE inhibitors
A.A. Ahmed, Ahmed E. M. Mekky, Sherif M. H. Sanad
Abstract
Synthesis of new heterocyclic hybrids that are capable of fighting methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE) strains is still a challenging task for organic chemists. In the current study, we examined the protocol involving the reaction of 2-(4-arylthiazol-2-yl)acetonitriles and benzaldehyde in pyridine at reflux for 2 h. The reaction mixture was then treated with 1H-pyrazole-3,5-diamines and heated at reflux for an additional 3-4 h. The reaction afforded 15 new thiazole-linked pyrimidines in good to excellent yields. Product 3e, which is linked to 4-methoxybenzyl and 4-(4-methoxyphenyl)thiazol-2-yl) units at C3 and C6, respectively, displayed the best antibacterial efficacy, especially against Staphylococcus aureus and Enterococcus faecalis, with an MIC/MBC up to 1.8/3.6 µM. Moreover, it possessed comparable efficacy to linezolid with an MIC/MBC of 3.6/7.3 µM against VRE ATCC:51299 and ATCC:51575, whereas it had an MIC/MBC of 7.3/14.6 µM against MRSA ATCC:33591 and ATCC:43300.