Development of a Robust Process for the Preparation of High-Quality 4‑Methylene­piperidine Hydrochloride

An efficient route for the preparation of 4-methylenepiperidine hydrochloride <b>1</b> was designed, and then a process feasible for large-scale production was developed with a total yield of 83.5% at a purity of 99.9%

Discovery of N‑Substituted Oseltamivir Derivatives as Potent and Selective Inhibitors of H5N1 Influenza Neuraminidase

To discover group-1-specific neuraminidase (NA) inhibitors that are especially involved in combating the H5N1 virus, two series of oseltamivir derivatives were designed and synthesized by targeting the 150-cavity. Among these, compound <b>20l</b> was the most potent N1-selective inhibitor, with IC₅₀ values of 0.0019, 0.0038, and 0.0067 μM against NAs from three H5N1 viruses. These values are better than those of oseltamivir carboxylate. Compound <b>32</b> was another potent N1-selective inhibitor that exhibited a 12-fold increase in activity against the H274Y mutant relative to oseltamivir carboxylate. Molecular docking studies revealed that the 150-cavity was an auxiliary binding site that may contribute to the high selectivity of these compounds. The present work is a significant breakthrough in the discovery of potent group-1-specific neuraminidase inhibitors, which may be further investigated for the treatment of infection by the H5N1 virus