Synthesis and Anti-Inflammatory Activity of 3-Aryloxylindolizine Derivatives via Sonogashira Coupling/<i>5-endo-trig</i> Cycloisomerization Domino Strategy

Abstract

With the aim of obtaining potential IL-6 inhibitor for the treatment of rheumatoid arthritis, four 3-aryloxylindolizine derivatives were synthesized from the 2-bromopyridine and aryl propargyl ether through the Sonogashira coupling/5-endo-trigcycloisomerization domino strategy. These compounds were characterized by NMR, IR, EI-MS and elemental analysis. Their biological activities were evaluated by the bacterial lipopolysaccharide (LPS) stimulation of mouse cells on the RAW264.7 inflammation model. All the compounds revealed good anti-inflammatory activities with the inhibitions of 71~82% against IL-6 at 100 μM. The bioactive 3-aryloxylindolizines might be used as potential anti-inflammatory drugs.

Facile Synthesis, Characterization and Anti-Inflammatory Effect of 3-Aminoindolizine Derivatives

“…The identification of inhibitory agents targeting interleukin (IL)-6 is currently of interest in anti-inflammatory drug discovery [4], as a result, a series of anti-inflammatory 3-alkyloxyl and 3-aryloxyl substituted indolizines were designed and synthesized in our earlier reports [5]. With the aim of searching for new bioactive indolizines against chronic inflammatory diseases and studying their structure-activity relationships, a general and straightforward methodology to rapidly prepare structurally diverse 3-aminoindolizine derivatives were introduced in this work.…”