MRSA Inhibitory Activity of Some New Pyrazolo1,5‐apyrimidines Linked to Arene and/or Furan or Thiophene Units

Methicillin‐resistant Staphylococcus aureus (MRSA) is a major contributor to hospital‐acquired infections and is highly resistant to treatment. Ongoing research focuses on developing new antimicrobial medications to prevent the spread of resistance. A facile method was employed to efficiently synthesize new pyrazolo1,5‐apyrimidines in 84‐93% yields by reacting 4‐benzyl‐1H‐pyrazole‐3,5‐diamine with the respective α,β‐unsaturated ketones. The reaction was carried out in ethanol containing 1.2 equivalents of potassium hydroxide at reflux for 5‐6 h. The new products are attached to a para‐substituted aryl group with variable electronic properties at pyrazolopyrimidine‐C5, in addition to one of three units at C7, namely phenyl, thiophen‐2‐yl, or furan‐2‐yl units. A wide spectrum of antibacterial activity was displayed by the new pyrimidines against six different bacterial strains. In general, pyrimidines attached to furan‐2‐yl units at C7, in addition to another aryl unit at C5, attached to 4‐Me or 4‐OMe groups, demonstrate significant antibacterial activity, particularly against S. aureus strain. They had MIC/MBC of 2.5/5.1 and 2.4/4.9 µM, respectively, which exceeded that of ciprofloxacin. Moreover, they demonstrate more effective MRSA inhibitory activity than linezolid, with MIC/MBC values up to 4.9/19.7 and 2.4/19.7 µM against MRSA ATCC:33591 and ATCC:43300 strains, respectively.