Synthesis and biological evaluation of 2-oxonicotinonitriles and 2-oxonicotinonitrile based nucleoside analogues

Abstract

Drug resistance and emergence of new pathogens highlight the need for developing new therapeutic agents. We focused on 2-oxonicotinonitrile (2-ONN) as derivative of the natural product 2-pyridinone.(1) Herein, we describe the synthesis of 2-ONNs bearing two aryl groups, which we coupled with organohalides, including three glycosyl bromides, to prepare the nucleoside analogues. Coupling occurred mostly at the 2-ONN ring nitrogen to give the aimed targets, and in a few cases, it happened at the 2-oxo position giving O-alkylation products. Free 2-ONNs and their acetylated nucleosides were tested against a number of viruses. The nucleoside analogue 2a(Ac) showed good anti SARS-CoV and anti influenza A (H₅N₁) activities. Additionally, 7b had good activity against Gram positive bacterium, Bacillis subtilis.

An efficient synthesis of 4,6‐diarylnicotinonitrile‐acetamide hybrids via 1,2,3‐triazole linker as multitarget microbial inhibitors

“…Firstly, 2‐oxonicotinonitriles 1a‐f have been prepared via one‐pot condensation of aromatic aldehyde (namely, 4‐chlorobenzaldehyde, 4‐methoxybenzaldehyde, or 4‐nitrobenzaldehyde), ketone (2‐acetylthiophene, 2‐acetylpyridine, 2‐acetylphenanthrene, or 4‐hydroxyacetophenone), ethyl cyanoacetate, and an excess amount of ammonium acetate [28] (Scheme 1). The chemical structure of nucleobases 1a , 1b , and 1d has been described in the literature [28–30]. Currently, the structure of the new 2‐pyridones 1c , 1e , and 1f has been demonstrated from their spectral data.…”

Synthesis and Biological Evaluation of Glycosides and Acyclic Nucleosides Derived 2‐Oxonicotinonitriles

“…The antifungal activities of the 2‐ONN derivatives were assessed against Candida albicans ATCC 10231 and Aspergillus niger ATCC 16404. Agar‐diffusion method was used to assess the antibacterial and antifungal activity of the tested compounds. The diameter of inhibition zone of the bacterial and fungal growth in mm was used to assess the preliminary antimicrobial activity of the tested compounds .…”

“…Agar‐diffusion method was used to assess the antibacterial and antifungal activity of the tested compounds. The diameter of inhibition zone of the bacterial and fungal growth in mm was used to assess the preliminary antimicrobial activity of the tested compounds . Significant and broad antibacterial activity was observed for all tested compounds (Table ).…”

“…Previously, we have identified 2‐ONN derivatives with significant anti‐SARS and anti‐ Bacillis subtitis , activity ( 5 , 6 ; Fig. ) . The structural features of the later 2‐ONNs derivatives have a 1,3 relationship of the aryl substituents on the 2‐ONN core ring, at the C4 and the C6 positions, with a glycosyl or polar alkyl moieties at the ring nitrogen atom.…”

Recent Advances of Pyridinone in Medicinal Chemistry

“…Nucleoside analogs are well-known potent antiviral agents ( De Clercq 2004 ). Abou-Elkhair et al (2014 ) reported a scaffold of 2-oxonicotinonitrile (2-ONN)-based acetylated nucleosides. The hybrids were designed on the basis of many published biologically active 2-ONN derivatives.…”