Cyclopamine analogs bearing exocyclic methylenes are highly potent and acid-stable inhibitors of hedgehog signaling

Autor: Johann Moschner, Anna Chentsova, Nicole Eilert, Irene Rovardi, Philipp Heretsch, Athanassios Giannis
Jazyk: angličtina
Rok vydání: 2013
Předmět:
Zdroj: Beilstein Journal of Organic Chemistry, Vol 9, Iss 1, Pp 2328-2335 (2013)
Druh dokumentu: article
ISSN: 1860-5397
DOI: 10.3762/bjoc.9.267
Popis: The chemical synthesis and biological evaluation of new cyclopamine analogs bearing exocyclic methylenes in different positions is described. Bis-exo-cyclopamine 6 was identified as a potent inhibitor of the Gli1-dependent luciferase expression in Shh-LIGHTII cells. An extension of this study to F-ring-modified structures shows the necessity of a rigidly positioned nitrogen atom for bioactivity as well as the presence of the C21 methyl group for acid stability and bioactivity.
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