(1-(4-(Naphthalen-2-yl)pyrimidin-2-yl)piperidin-4-yl)methanamine: A Wingless β-Catenin Agonist That Increases Bone Formation Rate
| Autor: | Diane B. Hauze, Michael C. Sharp, Bheem M. Bhat, Paula Green, Colleen Milligan, Daniel M. Green, Jennifer Pirrello, Peter V.N. Bodine, Ronald L. Magolda, Adam M. Gilbert, Matthew D. Vera, Yogendra P. Kharode, Valerie E. Coleburn, Luciana De Araujo Felix, Mattew G. Bursavich, Nipa Alon, Jeanne J. Matteo, Jay Wrobel, Frederick J. Bex, Jeffrey C. Pelletier, Susan Lockhead, Joseph T. Lundquist, Richard J. Murrills, Ray Unwalla, Paul J. Yaworsky, Sally Selim, John F. Mehlmann, Ho-Sun Lam |
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| Rok vydání: | 2009 |
| Předmět: |
Models
Molecular Agonist medicine.drug_class Pharmacology Glycogen Synthase Kinase 3 Mice Piperidines Pharmacokinetics Osteogenesis Oral administration Catalytic Domain Cell Line Tumor Drug Discovery medicine Animals Humans beta Catenin Glycogen Synthase Kinase 3 beta Chemistry Wnt signaling pathway Small molecule In vitro Rats Wnt Proteins Pyrimidines Biochemistry Catenin Ovariectomized rat Molecular Medicine Signal Transduction |
| Zdroj: | Journal of Medicinal Chemistry. 52:6962-6965 |
| ISSN: | 1520-4804 0022-2623 |
| DOI: | 10.1021/jm9014197 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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