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

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

Affiliation

  • 1 IRBM-Merck Research Laboratories Rome, Via Pontina km 30,600, Pomezia 00040, Rome, Italy. gabriella_dessole@merck.com
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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