Discovery of N-[(1-aryl-1H-indazol-5-yl)methyl]amides derivatives as smoothened antagonists for inhibition of the hedgehog pathway

  • Bioorg Med Chem Lett. 2009 Aug 1;19(15):4191-5. doi: 10.1016/j.bmcl.2009.05.112.
Gabriella Dessole  1 ,  Danila Branca ,  Federica Ferrigno ,  Olaf Kinzel ,  Ester Muraglia ,  Maria Cecilia Palumbi ,  Michael Rowley ,  Sergio Serafini ,  Christian Steinkühler ,  Philip Jones
Affiliations
  • 1. IRBM-Merck Research Laboratories Rome, Via Pontina km 30,600, Pomezia 00040, Rome, Italy. [email protected]
PMID: 19540115 DOI: 10.1016/j.bmcl.2009.05.112
Abstract

We report the synthesis and biological evaluation of N-[(1-aryl-1H-indazol-5-yl)methyl]amide derivatives as Smoothened antagonists and inhibitors of the Hedgehog pathway. Identification of the lead structure 1 by HTS, followed by SAR study on the amide and aryl portions led to the discovery of antagonists with nanomolar activity.

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