S-fluoxetine

There are currently no antiviral drugs available to treat or prevent life-threatening human non-poliovirus enterovirus infections, such as those caused by CV-B3, EV-A71 or EV-D68. Our aim is to develop novel inhibitors that target the non-structural ATPase/Helicase 2C protein, which is involved in the RNA replication process that is essential for enterovirus replication, among other functions. In this study, we describe the optimization of (S)-fluoxetine, a promising hit identified through drug repurposing that binds to an allosteric site on the CV-B3 2C ATPase domain. Our optimization process was guided by rational design, X-ray crystallographic structures, computational docking, and validation by enzyme and cell-based assays, leading to several new inhibitors, among which compound 53 (CV-B3 EC₅₀ = 0.5 μM and EV-D68 EC₅₀ = 0.4 μM), a novel anti-enterovirus with higher selectivity indexes than (S)-fluoxetine.

A new class of compounds, β-dithiocarbamate enamines, has been prepared for the first time via a new and environmentally friendly two-step one-pot procedure.In this protocol, the enamines were first obtained via Michael addition of carbonyl alkynes and amines, which were then reacted with aminodithioacids generated from amines and carbon disulfide and iodine to afford various (Z)-β-dithiocarbamate enamines in moderate to excellent yields (46%-90% yields).This method does not require any transition metal catalysts, bases or hazardous solvents and can be operated under mild conditions.Furthermore, good functional group tolerance, broad substrate scope, ease of performance, scalability and high chem. selectivity make this reaction attractive, demonstrating its practical synthetic value for the late-stage functionalization of natural products and pharmaceuticals.Antifungal activity anal. showed that Et (Z)-1-(((3-ethoxy-1-(3-methyl-1,3,4,9-tetrahydro-2H-pyrido[3,4-b]indol-2-yl)-3-oxoprop-1-en-2-yl)thio)carbonothioyl)piperidine-3-carboxylat has drug-like properties and good biol. activities.This approach opens a new avenue towards β-allylamine derivatives