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Bioorg Med Chem Lett. 2007 May 15;17(10):2863-8. Epub 2007 Feb 25.

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

Author information

1
Vascular Research Team, Johnson & Johnson Pharmaceutical Research & Development, Spring House, PA 19477-0776, USA. hzhang@prdus.jnj.com

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.

PMID:
17350261
DOI:
10.1016/j.bmcl.2007.02.059
[Indexed for MEDLINE]

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