Semisynthetic cyclopamine analogues as potent and orally bioavailable hedgehog pathway antagonists. Academic Article uri icon

Overview

MeSH

  • Administration, Oral
  • Molecular Structure
  • Structure-Activity Relationship

MeSH Major

  • Hedgehog Proteins
  • Signal Transduction
  • Veratrum Alkaloids

abstract

  • Herein is reported the synthesis of a novel class of hedgehog antagonists derived from cyclopamine. The acid sensitive D-ring of cyclopamine was homologated utilizing a sequence of chemoselective cyclopropanation and stereoselective acid-catalyzed rearrangement. Further modification of the A/B-ring homoallylic alcohol to the conjugated ketone led to the discovery of new cyclopamine analogues with improved pharmaceutical properties and in vitro potency (EC 50) ranging from 10 to 1000 nM.

publication date

  • November 13, 2008

has subject area

  • Administration, Oral
  • Hedgehog Proteins
  • Molecular Structure
  • Signal Transduction
  • Structure-Activity Relationship
  • Veratrum Alkaloids

Research

keywords

  • Journal Article

Identity

Language

  • eng

Digital Object Identifier (DOI)

  • 10.1021/jm8008508

PubMed ID

  • 18842035

Additional Document Info

start page

  • 6646

end page

  • 6649

volume

  • 51

number

  • 21