2. Academic Validation
  3. 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-alpha inhibitor

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-alpha inhibitor

  • J Med Chem. 2009 Mar 26;52(6):1522-4. doi: 10.1021/jm900210d.
Hon-Wah Man 1,  Peter Schafer,  Lu Min Wong,  Rebecca T Patterson,  Laura G Corral,  Heather Raymon,  Kate Blease,  Jim Leisten,  Michael A Shirley,  Yang Tang,  Darius M Babusis,  Roger Chen,  Dave Stirling,  George W Muller
Affiliations

Affiliation

  • 1 Drug Discovery Department, Celgene Corporation, 86 Morris Avenue, Summit, New Jersey 07901, USA. [email protected]
PMID: 19256507 DOI: 10.1021/jm900210d
Abstract

In this communication, we report the discovery of 1S (apremilast), a novel potent and orally active phosphodiesterase 4 (PDE4) and tumor necrosis factor-alpha 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.

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