(1-(4-(Naphthalen-2-yl)pyrimidin-2-yl)piperidin-4-yl)methanamine: A Wingless β-Catenin Agonist That Increases Bone Formation Rate
Journal of Medicinal Chemistry2009Vol. 52(22), pp. 6962–6965
Citations Over TimeTop 25% of 2009 papers
Jeffrey C. Pelletier, Joseph T. Lundquist, A. Gilbert, N. Alon, Frederick J. Bex, Bheem M. Bhat, Matthew G. Bursavich, Valerie E. Coleburn, Luciana A. Felix, Daniel M. Green, Paula Green, Diane B. Hauze, Yogendra P. Kharode, Ho‐Sun Lam, Susan Lockhead, Ronald L. Magolda, Jeanne J. Matteo, John F. Mehlmann, Colleen Milligan, Richard J. Murrills, Jennifer Pirrello, Sally A. Selim, Michael Sharp, Ray Unwalla, Matthew D. Vera, Jay Wrobel, Paul J. Yaworsky, Peter V.N. Bodine
Abstract
A high-throughput screening campaign to discover small molecule leads for the treatment of bone disorders concluded with the discovery of a compound with a 2-aminopyrimidine template that targeted the Wnt beta-catenin cellular messaging system. Hit-to-lead in vitro optimization for target activity and molecular properties led to the discovery of (1-(4-(naphthalen-2-yl)pyrimidin-2-yl)piperidin-4-yl)methanamine (5, WAY-262611). Compound 5 has excellent pharmacokinetic properties and showed a dose dependent increase in the trabecular bone formation rate in ovariectomized rats following oral administration.
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