Diels-Alder adducts of 3-N-substituted derivatives of (−)-Cytisine as influenza A/H1N1 virus inhibitors; stereodifferentiation of antiviral properties and preliminary assessment of action mechanism

Synthesis of Camphecene and Cytisine Conjugates Using Click Chemistry Methodology and Study of Their Antiviral Activity

“…The compound 13 described in the present study represents the hybrid of camphor and another cage moiety, cytisine, connected to each other with long triazole‐containing linker. Recently, cytisine derivatives have been shown to act on late stages of influenza infection . In contrast, camphor derivatives were active at early stages of viral cycle due to their targeting to the hemagglutinin, the protein working at the very beginning of viral reproduction.…”

“…On the other hand, the lead compound 13 contains the (−)‐cytisine fragment. Results of ‘time‐of‐addition’ experiments (A (H1N1)pdm09) demonstrate activity of Diels−Alder adduct of N‐substituted derivative of (−)‐cytisine at the late stage of the life cycle of the virus, while it was added the period of 6–10 h p.i. This suggests that interaction of 13 with NA is likely.…”

“…Recently, cytisine derivatives have been shown to act on late stages of influenza infection. [28] In contrast, camphor derivatives were active at early stages of viral cycle due to their targeting to the hemagglutinin, the protein working at the very beginning of viral reproduction. Due to low similarity of 13 to previously described derivatives of both camphor and cytisine, further expansion of chemical libraries and study of similar derivatives should be performed for detailed QSAR analysis.…”

Catalytic Enantioselective Diels Alder Reaction: Application in the Synthesis of Antiviral Agents

“…Using the Nicolaou words, the DAR has afforded numerous and unparalleled solutions to a diverse range of synthetic puzzles provided by nature in the form of natural products [49]. Even if there are several examples of the application of this reaction applied to natural compounds endowing antiviral activity-referred, for example, to anti-influenza (-)-Cytisine derivatives [77] and Sorbicatechol [78] to the Anti-HIV agent Siamenol [79] herein we report one selected example in which the asymmetric DAR protocol was applied, using chiral diene in the presence of LA to the synthesis of anti-influenza wickerol.…”

Recent Advances in the Chemistry of Saturated Annulated Nitrogen-Containing Polycyclic Compounds

“…The complete reduction of compound 101 d enabled the synthesis of saturated triamine 102 in 66% yield ( Scheme 26 ). It was shown that (–)-cytisine derivatives of this type exhibited a moderate antiviral activity against the H1N1 serotype influenza A virus [ 55 ].…”