Potent agonists of the Hedgehog signaling pathway

  • Bioorg Med Chem Lett. 2009 Aug 1;19(15):4308-11. doi: 10.1016/j.bmcl.2009.05.096.
Shirley A Brunton  1 ,  John H A Stibbard ,  Lee L Rubin ,  Oivin M Guicherit ,  Lawrence I Kruse ,  Stephen Price ,  Raffaella di Lucrezia ,  Colin H MacKinnon ,  Alaric Avery ,  Yvonne Park ,  Danielle Buxton ,  Edward A Boyd
Affiliations
PMID: 19500978 DOI: 10.1016/j.bmcl.2009.05.096
Abstract

A family of biaryl substituted 1,4-diaminocyclohexanamides of 3-chlorobenzothiophene-2-carboxylic acid is reported as picomolar modulators of Hedgehog protein function. SAR for the 1,4-diaminocyclohexane group is shown to be exquisitely sensitive to substitution on the 4-amino group, and SAR for the 3-chlorobenzothiophene group is highly specific. Preliminary SAR studies of the biaryl substituent led to a picomolar compound with in vivo activity.

Products