Details

Autor(en) / Beteiligte

• Man, Hon-Wah
• Schafer, Peter
• Wong, Lu Min
• Patterson, Rebecca T
• Corral, Laura G
• Raymon, Heather
• Blease, Kate
• Leisten, Jim
• Shirley, Michael A
• Tang, Yang
• Babusis, Darius M
• Chen, Roger
• Stirling, Dave
• Muller, George W

Titel

Discovery of (S)-N-{2-[1-(3-Ethoxy-4-methoxyphenyl)-2-methanesulfonylethyl]-1,3-dioxo-2,3-dihydro-1H-isoindol-4-yl}acetamide (Apremilast), a Potent and Orally Active Phosphodiesterase 4 and Tumor Necrosis Factor-α Inhibitor

Ist Teil von

• Journal of medicinal chemistry, 2009-03, Vol.52 (6), p.1522-1524

Ort / Verlag

American Chemical Society

Erscheinungsjahr

2009

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• In this communication, we report the discovery of 1S (apremilast), a novel potent and orally active phosphodiesterase 4 (PDE4) and tumor necrosis factor-α inhibitor. The optimization of previously reported 3-(1,3-dioxo-1,3-dihydroisoindol-2-yl)-3-(3,4-dimethoxyphenyl)propionic acid PDE4 inhibitors led to this series of sulfone analogues. Evaluation of the structure−activity relationship of substitutions on the phthalimide group led to the discovery of an acetylamino analogue 1S, which is currently in clinical trials.