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
| Autor: | Peter H. Schafer, Rebecca T. Patterson, D. I. Stirling, Michael A. Shirley, Kate Blease, Lu Min Wong, George W. Muller, Laura G. Corral, Heather Raymon, Darius Babusis, Hon-Wah Man, Yang Tang, Roger Shen-Chu Chen, Jim Leisten |
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| Rok vydání: | 2009 |
| Předmět: |
Phosphodiesterase Inhibitors
Tumor Necrosis Factor-alpha Stereochemistry Administration Oral Stereoisomerism Rats Thalidomide Sulfone Phthalimide Structure-Activity Relationship chemistry.chemical_compound chemistry Oral administration Drug Discovery medicine Animals Humans Molecular Medicine Structure–activity relationship Tumor necrosis factor alpha Phosphodiesterase 4 Inhibitors Apremilast Imide Acetamide medicine.drug |
| Zdroj: | Journal of Medicinal Chemistry. 52:1522-1524 |
| ISSN: | 1520-4804 0022-2623 |
| DOI: | 10.1021/jm900210d |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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