A novel series of positive modulators of the AMPA receptor : structure-based lead optimization

Jamieson, Craig and Campbell, Robert A. and Cumming, Iain A. and Gillen, Kevin J. and Gillespie, Jonathan and Kazemier, Bert and Kiczun, Michael and Lamont, Yvonne and Lyons, Amanda J. and Maclean, John K.F. and Martin, Frederic and Moir, Elizabeth M. and Morrow, John A. and Pantling, John and Rankovic, Zoran and Smith, Lynn (2010) A novel series of positive modulators of the AMPA receptor : structure-based lead optimization. Bioorganic and Medicinal Chemistry Letters, 20 (20). pp. 6072-6075. ISSN 0960-894X

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    Abstract

    Starting from lead compound 1, we demonstrate how x-ray structural data can be used to understand SAR and expediently optimize bioavailability in a novel series of AMPA receptor modulators, furnishing 5 with improved bioavailability and robust in vivo activity.