Novel 5-Nitrofuran-Tagged Imidazo-Fused Azines and Azoles Amenable by the Groebke–Blackburn–Bienaymé Multicomponent Reaction: Activity Profile against ESKAPE Pathogens and Mycobacteria

Abstract

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.

HPW-Catalyzed environmentally benign approach to imidazo[1,2-a]pyridines

“…Imidazo[1,2- a ]pyridine is a privileged structure that plays an important role in organic synthesis and in the pharmaceutical industry. This scaffold is present in drugs with several biological activities, such as antiviral [ 1 ], anticonvulsant [ 2 ], antibacterial [ 3 ], antipyretic [ 4 ], antituberculosis [ 5 ], anticancer [ 6 ], anthelmintic [ 5 ], antifungal [ 7 ], analgesic [ 8 ], antiulcer [ 9 ], antiprotozoal [ 10 ], antitumor [ 11 ], and anti-inflammatory [ 12 ]. Examples of commercial drugs are depicted in Figure 1 [ 13 ] and include alpidem (anxiety disorders), minodronic acid (osteoporosis), miroprofen (non-steroidal anti-inflammatory drug, NSAID), necopidem (insomnia), olprinone (acute heart failure), saripidem (type A GABA receptor agonist), zolimidine (gastroesophageal reflux disease), and zolpidem (insomnia).…”

Green Synthesis and Molecular Docking Study of Some New Thiazoles Using Terephthalohydrazide Chitosan Hydrogel as Ecofriendly Biopolymeric Catalyst

“…On the other hand, thiazole and thiadiazole derivatives constitute crucial frameworks in the realm of medicinal chemistry. An exploration of the literature highlights their significant role encompassing a diverse array of biological effects [44][45][46][47][48], notably including antimicrobial properties [49][50][51][52][53].…”