| Literature DB >> 19856966 |
Jeffrey C Pelletier1, Joseph T Lundquist, Adam M Gilbert, Nipa Alon, Frederick J Bex, Bheem M Bhat, Mattew G Bursavich, Valerie E Coleburn, Luciana A Felix, Daniel M Green, Paula Green, Diane B Hauze, Yogendra P Kharode, Ho-Sun Lam, Susan R Lockhead, Ronald L Magolda, Jeanne J Matteo, John F Mehlmann, Colleen Milligan, Richard J Murrills, Jennifer Pirrello, Sally Selim, Michael C Sharp, Ray J Unwalla, Matthew D Vera, Jay E Wrobel, Paul 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.Entities:
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Year: 2009 PMID： 19856966 DOI： 10.1021/jm9014197
Source DB: PubMed Journal: J Med Chem ISSN： 0022-2623 Impact factor: 7.446