A New Way to 2,3,4-Trisubstituted Benzo[<i>h</i>]quinolines: Synthesis, Consecutive Reactions and Cellular Activities <xref rid="fn1-molecules-2227845" ref-type="fn">†</xref>

Abstract

The reaction of mercaptoacetic acid esters with pentachloro-2-nitro-1,3-butadiene provides the appropriate precursors for the synthesis of 2,3,4-trisubstituted benzo[h]quinolines. These heterocycles are easily accessible via a single-step reaction with naphthalen-1-amine or anthracen-1-amine as the precursor. Due to the steric bulk and high electron density ring, the ring closure of 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. The antibacterial and antiproliferative assays against four mammalian cell lines demonstrate that some of the sulfur-substituted benzo[h]quinoline analogs display potent phenotypic bioactivities in the single-digit micromolar range.

Keywords

• synthetic methods
• 2-nitroperchlorobutadiene
• benzoquinolines
• cyclization
• amines
• sulfides