Discovery of (S)-N-{2-[1-(3-ethoxy-4-methoxyphenyl)-2-methanesulfonylethyl]-1, 3-dioxo-2, 3-dihydro-1 H-isoindol-4-yl} acetamide (apremilast), a potent and orally …

…, K Blease, J Leisten, MA Shirley, Y Tang…

Index: 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. Journal of Medicinal Chemistry, 2009 , vol. 52, # 6 p. 1522 - 1524

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Citation Number: 59

Abstract

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 ...