Synthesis of New Imidazopyridine Nucleoside Derivatives Designed as Maribavir Analogues

Abstract

The strong inhibition of Human Cytomegalovirus (HCMV) replication by benzimidazole nucleosides, like Triciribine and Maribavir, has prompted us to expand the structure–activity relationships of the benzimidazole series, using as a central core the imidazo[4,5-b]pyridine scaffold. We have thus synthesized a number of novel amino substituted imidazopyridine nucleoside derivatives, which can be considered as 4-(or 7)-aza-d-isosters of Maribavir and have evaluated their potential antiviral activity. The target compounds were synthesized upon glycosylation of suitably substituted 2-aminoimidazopyridines, which were prepared in six steps starting from 2-amino-6-chloropyridine. Even if the new compounds possessed only a slight structural modification when compared to the original drug, they were not endowed with interesting antiviral activity. Even so, three derivatives showed promising cytotoxic potential.

Novel Pyrazolo[3,4-c]pyridine Antagonists with Nanomolar affinity for A1 / A3 Adenosine Receptors: Binding Kinetics and Exploration of their Binding Profile Using Mutagenesis Experiments, MD simulations and TI/MD calculations

“…The tested compounds belong to our in-house compounds library and were aromatic nitrogen heterocycles with originally purposed for antiproliferative activity, 37,46,47 against angiogenesis, 48 as fluorescence tracers in cells, 49 against hepatitis B virus, 50 and nucleosides originally tested against adenosine deaminase, 51 hepatitis C virus, 52 and human cytomegalovirus. 53 We found that pyrazolo [3,4-c]pyridine, is a novel heterocyclic ring that bind ARs having antagonistic activity to A1R and A3R with potential for further development. We investigated experimentally for the identified two classes of pyrazolo [3,4-c]pyridines their (a) pharmacological profile using functional assays, (b) binding interactions and binding kinetic profile using, correspondingly, molecular dynamics (MD) simulations and mutagenesis experiments, and competition binding experiments with the NanoBRET 20 (Nano Bioluminescence resonance energy transfer) method.…”

The efficient CO2 fixation catalyzed by K‐doped g‐C3N4 catalyst for synthesizing benzimidazoles at atmospheric pressure

“…Benzimidazole and its derivatives have been widely applied in drug synthesis and biological activity 12 . Benzimidazole is used as an intermediate for many essential drug molecules, including omeprazole, 13 cyclobendazole, 14 maribavir, 15 etc. Generally, benzimidazole and its derivatives are synthesized by reacting o ‐phenylenediamine with carboxylic acids, esters and aldehydes.…”

Manufacturing of ultra-thin redox-active polymer films using the layer-by-layer method and co-polymerization of vinyl viologen units

“…Suitable organic molecules widely utilized as electro-, thermo-, and photo-sensitive building blocks in numerous materials are 4,4 -bipyridine derivatives, known as viologens [22]. The viologens have excellent redox ability and can act as suitable electron acceptors because of Lewis acidity and πdeficiency to form charge-transfer (CT) complexes with electron-rich species [23].…”