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ID: ALA1139192

Journal: Bioorg Med Chem Lett

Title: Novel bis(indolyl)maleimide pyridinophanes that are potent, selective inhibitors of glycogen synthase kinase-3.

Authors: Zhang HC, Boñaga LV, Ye H, Derian CK, Damiano BP, Maryanoff BE.

Abstract: Novel bis(indolyl)maleimide pyridinophanes 3, 9a, 9b, 10a, 10b, and 11 were prepared by cobalt-mediated [2+2+2] cycloaddition of an appropriate alpha,omega-diyne with an N,N-dialkylcyanamide. These macrocyclic heterophanes were found to be potent, selective inhibitors of glycogen synthase kinase-3beta. An X-ray structure of a co-crystal of GSK-3beta and 3 (IC(50)=3nM) depicts the hydrogen bonding and hydrophobic interactions in the ATP-binding pocket of this serine/threonine protein kinase.

CiteXplore: 17350261

DOI: 10.1016/j.bmcl.2007.02.059