Pd-catalyzed post-Ugi intramolecular cyclization to the synthesis of isoquinolone-pyrazole hybrid pharmacophores & discover their antimicrobial and DFT studies

A novel microwave assisted ligand-free palladium-catalyzed post Ugi reaction for the synthesis of isoquinolone and pyrazole mixed pharmacophore derivatives was achieved from isocyanide and pyrazole substituted amide molecules (synthesized by using Ugi reaction). Benzaldehyde, aniline, t-butyl isocyanide and a variety of pyrazole carboxylic acids are being used as starting materials for the Ugi-MCR to generate diverse amide precursors, which in turn provided an access to the synthesis of various isoquinolone-pyrazole hybrid derivatives in moderate to good yields through the isocyanide insertion and successive intramolecular cyclization. The newly synthesized target compounds were characterized by 1H NMR, 13C NMR, HRMS, and elemental analysis. In vitro antimicrobial activity of the prepared molecules was studied against various pathogenic strains; the results obtained were further described with the help of DFT and molecular orbital calculations. Compound 6e and 6g revealed good antimicrobial activity compared to standard drugs kanamycin and amphotericin B.