Synthesis of New Pyrazolo[1,5‐a]pyrimidines as Potential Antibacterial Agents: In Vitro and In Silico Study

Abstract

AbstractIn this study, we aimed to establish two new series of pyrazolo[1,5‐a]pyrimidines starting from 1H‐pyrazole‐3,5‐diamine. The first series was prepared by reacting 1H‐pyrazole‐3,5‐diamine with the appropriate enaminones in pyridine at 120 °C for 5–6 h to produce 7‐arylpyrazolo[1,5‐a]pyrimidines in 87–94 % yields. Furthermore, α,β‐unsaturated ketones was reacted with 1H‐pyrazole‐3,5‐diamine in ethanolic potassium hydroxide solution at 80 °C for 4 h to produce a second series of regioisomeric 5,7‐diarylpyrazolo[1,5‐a]pyrimidines in 88–96 % yields. The antibacterial activity of new products was tested against six different bacterial strains. Substituting para‐arene units at C5 and/or C7 on the pyrazolo[1,5‐a]pyrimidine structure improved efficacy, with electron‐releasing substituents having the greatest impact. Some new pyrazolo[1,5‐a]pyrimidine were found to be more effective than ciprofloxacin, with minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values up to 2.2 and 4.4 μM, respectively. These compounds were deemed to have drug‐like properties according to SwissADME and drug‐likeness model scores.