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Synthesis of New Bis(pyrazolo[1,5‐<i>a</i>]pyrimidines) Linked to Different Spacers as Potential MurB Inhibitors

Sherif M. H. Sanad, Alshimaa A. M. Abdelsalam, Aya A. Gamal Eldin, Esraa H. Abdelfattah, Fatma R. M. Hussein, Nada G. Mohammed, Nariman A. S. Taha, Ahmed E. M. Mekky

2023Chemistry & Biodiversity12 citationsDOIOpen Access PDF

Abstract

Abstract An efficient protocol was adopted to efficiently prepare three new series of bis(pyrazolo[1,5‐ a ]pyrimidines) linked to different spacers. The new bis(pyrazolo[1,5‐ a ]pyrimidines) were prepared in 80–90 % yields by reacting the respective bis(enaminones) and 4‐(4‐substituted benzyl)‐1 H ‐pyrazole‐3,5‐diamines in pyridine at reflux temperature for 5–7 h. The new products showed a wide spectrum of antibacterial activity against six different bacterial strains. In general, propane‐ and butane‐linked bis(pyrazolo[1,5‐ a ]pyrimidines), which are attached to 3‐(4‐methyl‐ or 4‐methoxybenzyl) units, had the best antibacterial activity with minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values up to 2.5 and 5.1 μM, respectively. Additionally, the previous products demonstrated promising MurB inhibitory activity with IC 50 values up to 7.2 μM.

Topics & Concepts

ChemistryStereochemistryCombinatorial chemistryComputational chemistrySynthesis and biological activityCytokine Signaling Pathways and InteractionsBioactive Compounds and Antitumor Agents