| Literature DB >> 18842035 |
Martin R Tremblay1, Marta Nevalainen, Somarajan J Nair, James R Porter, Alfredo C Castro, Mark L Behnke, Lin-Chen Yu, Margit Hagel, Kerry White, Kerrie Faia, Louis Grenier, Matthew J Campbell, Jill Cushing, Caroline N Woodward, Jennifer Hoyt, Michael A Foley, Margaret A Read, Jens R Sydor, Jeffrey K Tong, Vito J Palombella, Karen McGovern, Julian Adams.
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.Entities:
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Year: 2008 PMID： 18842035 DOI： 10.1021/jm8008508
Source DB: PubMed Journal: J Med Chem ISSN： 0022-2623 Impact factor: 7.446