A New Way to 2,3,4-Trisubstituted Benzo[h]quinolines: Synthesis, Consecutive Reactions and Cellular Activities

The reaction of mercaptoacetic acid esters with pentachloro-2-nitro-1,3-butadiene provides appropriate precursors for the synthesis of 2,3,4-trisubstituted benzo[h]quinolines. These heterocycles are easily accessible via a single-step reaction with 1-naphthyl- or 1-anthracenylamine, respectively. Due to steric bulk and high electron density ring closure to benzo[h]quinolines takes place, exclusively. Such highly substituted annelated pyridine systems can be modified in subsequent, selective reactions to build up new N-heterocycles with promising microbiological properties. Antibacterial and antiproliferative assays against four cell mammalian cell lines demonstrate that some of the sulfur-substituted benzo[h]quinolines analogs display potent phenotypic bioactivities in the single-digit micromolar range.