Design and Synthesis of Polyheterocyclic Compounds Containing Pyrazolopyridopyrimidine Nucleus with Antimicrobial Activities

This study reports the design, synthesis, and antibacterial evaluation of a library of novel polyheterocyclic derivatives featuring a unique fused pyrimidopyridopyrazole moiety. A cyclocondensation reaction between an amino−pyrazolopyridopyrimidine precursor and malonates afforded a series of pyrimidopyridopyrazolopyrimidine derivatives. Further diversification was achieved through nucleophilic cyclocondensation, yielding a collection of complex polyheterocyclic systems encompassing various ring structures. All synthesized compounds were rigorously characterized using spectroscopic techniques and elemental analysis. The antibacterial activity of the newly synthesized compounds was assessed against a panel of Gram‐positive and Gram‐negative bacteria. Notably, several compounds exhibited promising antibacterial activity, highlighting their potential as leads for the development of novel antibiotics. This work introduces novel polyheterocyclic derivatives featuring a fused pyrimidopyridopyrazole core, synthesized through cyclocondensation reactions with amino‐pyrazolopyridopyrimidine precursors and various malonates. These compounds, characterized by spectroscopic techniques, exhibit significant antibacterial activity against both Gram‐positive and Gram‐negative bacteria, underscoring their potential as novel antibiotic leads.