Synthesis and TNF expression inhibitory properties of new thalidomide analogues derived via Heck cross coupling

A library of new thalidomide analogues containing an olefin functionality were synthesised using a Heck cross coupling reaction from their aryl halogenated precursor. All analogues were tested for their ability to inhibit the synthesis of the proinflammatory cytokine Tumour Necrosis Factor (TNF). Compounds 22, 29, 33 and 37 were the most effective in this assay inhibiting TNF expression 50%, 69%, 52% and 50%, respectively.

Graphical abstractA series of novel thalidomide and N-phenylphthalimides were synthesised from their halide precursors using a Heck cross coupling reaction. This library of compounds was assessed for their ability to alter TNF production through measuring inhibition of TNF transcriptional activity.Figure optionsDownload full-size imageDownload as PowerPoint slide