Brunton SA, Stibbard JH, Rubin LL, Guicherit OM, Kruse LI, Price S, di Lucrezia R, MacKinnon CH, Avery A, Park Y, Buxton D, Boyd EA. Potent agonists of the Hedgehog signaling pathway. Bioorg Med Chem Lett. 2009 Aug 01; 19(15):4308-11.

Citation

Brunton SA, Stibbard JH, Rubin LL, Guicherit OM, Kruse LI, Price S, di Lucrezia R, MacKinnon CH, Avery A, Park Y, Buxton D, Boyd EA. 2009. Potent agonists of the Hedgehog signaling pathway. Bioorganic & medicinal chemistry letters. 19(15):4308-11. Pubmed: 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.

Related Faculty

Lee Rubin, Ph.D.

Rubin Lab

Lee Rubin investigates the key molecular mediators of a variety of neurodegenerative diseases, with the ultimate goal of finding effective preclinical therapeutic candidates.