: A chemically diverse set of 13 5-nitrofuran-tagged heterocyclic compounds has been prepared via the Groebke–Blackburn–Bienaymé multicomponent reaction. The testing of these
compounds against the so-called ESKAPE panel of pathogens identified an apparent lead compound—
N-cyclohexyl-2-(5-nitrofuran-2-yl)imidazo[1,2-a]pyridine-3-amine (4a)—which showed an excellent
profile against Enterobacter cloacae, Staphylococcus aureus, Klebsiella pneumoniae, and Enterococcus faecalis
(MIC 0.25, 0.06, 0.25 and 0.25 µg/mL, respectively). Its antibacterial profile and practically convenient
synthesis warrant further pre-clinical development. Certain structure-activity relationships were
established in the course of this study which were rationalized by the flexible docking experiments
in silico. The assessment of antitubercular potential of the compounds synthesized against drug
sensitive H37v strain of Mycobacterium tuberculosis revealed little potential of the imidazo-fused
products of the Groebke–Blackburn–Bienaymé multicomponent reaction as chemotherapeutic agents
against this pathogen.