Journal
JOURNAL OF MEDICINAL CHEMISTRY
Volume 52, Issue 22, Pages 6962-6965Publisher
AMER CHEMICAL SOC
DOI: 10.1021/jm9014197
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- Tarek Mansour
- John Ellingboe
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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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