Novel Abietane Type Sugar Triazole Hybrids and Amides against SARS‐CoV‐2 Spike Glycoprotein and Influenza A Virus

Abietane type diterpenic (dehydroabietic, 2,3‐dihydroquinopimaric and maleopimaric) acids were converted by the acid chloride method into a series of aliphatic and heterocyclic amine spacered conjugates. A number of structurally novel derivatives holding 1,2,3‐triazole moieties were designed and synthesized by treating of the propargylated amides and esters with a sugar azides using the Cu(I)‐catalyzed click chemistry approach. The synthesized N‐containing diterpene derivatives were tested for their potential inhibition of influenza A/PuertoRico/8/34 (H1N1) virus in MDCK cell culture and SARS‐CoV‐2 pseudovirus in BHK‐21‐hACE2 cells. Among tested forty‐five compounds ten derivatives were the most efficacious against influenza virus A with IC₅₀ 0.7–63.4 μM together with high selectivity index SI value from 11 from 94. Dihydroquinopimaric acid N‐ethylpiperazine‐amide and dehydroabietic acid 1,2,3‐triazoles spacered with glucose and lactose showed anti‐SARS‐CoV‐2 pseudovirus activity with EC₅₀ values of 1.79–25.46 μM. Molecular docking and dynamics modeling investigated the binding mode of the lead compounds into the binding pocket of influenza A virus M2 protein and the RBD domain of SARS‐CoV‐2 spike glycoprotein.