Discovery, Design, and Optimization of Isoxazole Azepine BET Inhibitors
ACS Medicinal Chemistry Letters2013Vol. 4(9), pp. 835–840
Citations Over TimeTop 10% of 2013 papers
Victor Gehling, Michael C. Hewitt, Rishi G. Vaswani, Yves Leblanc, Alexandre Côté, Christopher G. Nasveschuk, Alexander M. Taylor, Jean-Christophe Harmange, James E. Audia, Eneida Pardo, Shivangi Joshi, Péter Sandy, Jennifer A. Mertz, Robert J. Sims, Louise Bergeron, Barbara M. Bryant, S.F. Bellon, Florence Poy, Hariharan Jayaram, Ravichandran Sankaranarayanan, Sreegouri Yellapantula, Nandana Bangalore Srinivasamurthy, Swarnakumari Birudukota, Brian K. Albrecht
Abstract
The identification of a novel series of small molecule BET inhibitors is described. Using crystallographic binding modes of an amino-isoxazole fragment and known BET inhibitors, a structure-based drug design effort lead to a novel isoxazole azepine scaffold. This scaffold showed good potency in biochemical and cellular assays and oral activity in an in vivo model of BET inhibition.
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