Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10594027 | Bioorganic & Medicinal Chemistry Letters | 2011 | 6 Pages |
Abstract
Smoothened (Smo) antagonists are emerging as new therapies for the treatment of neoplasias with aberrantly reactivated hedgehog (Hh) signaling pathway. A novel series of 4-[3-(quinolin-2-yl)-1,2,4-oxadiazol-5-yl]piperazinyl ureas as smoothened antagonists was recently described, herein the series has been further optimized through the incorporation of a basic amine into the urea. This development resulted in identification of some exceptionally potent smoothened antagonists with low serum shifts, however, reductive ring opening on the 1,2,4-oxadiazole in rats limits the applicability of these compounds in in vivo studies.
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Authors
Ester Muraglia, Jesus M. Ontoria, Danila Branca, Gabriella Dessole, Alberto Bresciani, Massimiliano Fonsi, Claudio Giuliano, Laura Llauger Bufi, Edith Monteagudo, Maria Cecilia Palumbi, Caterina Torrisi, Michael Rowley, Christian Steinkühler,