Discovery of Imidazopyridine Derivatives as Highly Potent Respiratory Syncytial Virus Fusion Inhibitors

Abstract

A series of imidazolepyridine derivatives were designed and synthesized according to the established docking studies. The imidazopyridine derivatives were found to have good potency and physical-chemical properties. Several highly potent compounds such as 8ji, 8jl, and 8jm were identified with single nanomolar activities. The most potent compound 8jm showed an IC 50 of 3 nM, lower microsome clearance and no CYP inhibition. The profile of 8jm appeared to be superior to BMS433771, and supported further optimization.

Drugs Against Neurodegenerative Diseases: Design and Synthesis of 6‐Amino–substituted Imidazo[1,2‐b]pyridazines as Acetylcholinesterase Inhibitors

“…Hetrocyclic ring nucleus with a bridgehead nitrogen atom bearing extra two nitrogen atoms such as, imidazo[1,2‐b] pyridazines, have emerged as a important pharmacophore of immense biological importance. These compounds have been found to be a new chemical entity exhibiting broad spectrum of biological activities viz., analgesic, anti‐inflammatory and antitumor activities, human picornavirus, macrofilaricidal activity, a potent inhibitor of acyclin‐dependent kinase, as a ligand for β‐amyloid plaques, IKKβ inhibitors, as novel VEGFR2 kinase inhibitors, antiproliferative activity, AchE inhibitory effects, anticancer, antiviral, antioxidant, anti‐inflammatory, antimicrobial and antiparkinsonian properties …”

Recent Developments in Transition‐Metal‐Catalyzed Regioselective Functionalization of Imidazo[1, 2‐a]pyridine

“…The methodology for the synthesis of this bio‐active scaffold includes cyclocondensations,oxidative couplings, rearrangements, C−H functionalizations,carbene‐transformations,multicomponent and tandem reactions among the different substrates [9–14] . Imidazo[1, 2‐ a ]pyridine possesses diverse biological activities such as antiviral, anti‐cancer, anti‐bacterial, anti‐inflammatory, antifungal, anti‐ulcer, antiallergic, and sedation [15–19] . Some pharmaceutical compounds containing imidazo[1, 2‐ a ]pyridine scaffold are necopidem, alpidem, zolpidem, saripidem, minodronic acid, zolimidine, olprinone (Figure 1).…”

“…Some pharmaceutical compounds containing imidazo[1, 2‐ a ]pyridine scaffold are necopidem, alpidem, zolpidem, saripidem, minodronic acid, zolimidine, olprinone (Figure 1). [15–18] Alpidem is an anxiolytic drug and it has the binding affinity for both the central benzodiazepine receptor (CBR) and the peripheral benzodiazepine receptor (PBR) which is associated with a regulated ion channel γ ‐aminobutyric acid A (GABA A )in the central nervous system [19,20] . The drug zolpidem is used to restore brain function after the brain injury of a person.…”

Design and Synthesis of 2-(1-Alkylaminoalkyl)pyrazolo[1,5-a]pyrimidines as New Respiratory Syncytial Virus Fusion Protein Inhibitors

“…Drugs that target several proteins of RSV have been developed; inhibitors of RSV F protein are also being developed as one class of anti-RSV agents. Inhibitors of RSV F protein include several classes of compounds, such as pyrazolo [1,5-a] pyrimidines, [41][42][43][44] benzimidazoles, [45][46][47] and piperazinyl-quinolines. 48) Among the RSV F protein inhibitors with the pyrazolo [1,5-a] pyrimidine scaffold, such as presatovir (GS-5806, 1) developed by Gilead, 41) and P3 (2) reported by Janssen, 44) 1 has advanced the furthest in clinical trials (Fig.…”