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

Autor: Dessole G; IRBM-Merck Research Laboratories Rome, Via Pontina km 30,600, Pomezia 00040, Rome, Italy. gabriella_dessole@merck.com, Branca D, Ferrigno F, Kinzel O, Muraglia E, Palumbi MC, Rowley M, Serafini S, Steinkühler C, Jones P
Jazyk: angličtina
Zdroj: Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2009 Aug 01; Vol. 19 (15), pp. 4191-5. Date of Electronic Publication: 2009 Jun 02.
DOI: 10.1016/j.bmcl.2009.05.112
Abstrakt: 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.
Databáze: MEDLINE
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