2. Academic Validation
  3. (1-(4-(Naphthalen-2-yl)pyrimidin-2-yl)piperidin-4-yl)methanamine: a wingless beta-catenin agonist that increases bone formation rate

(1-(4-(Naphthalen-2-yl)pyrimidin-2-yl)piperidin-4-yl)methanamine: a wingless beta-catenin agonist that increases bone formation rate

  • J Med Chem. 2009 Nov 26;52(22):6962-5. doi: 10.1021/jm9014197.
Jeffrey C Pelletier 1,  Joseph T Lundquist 4th,  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
Affiliations

Affiliation

  • 1 Chemical Sciences, Drug Safety & Metabolism, Wyeth Research, 500 Arcola Road, Collegeville, Pennsylvania 19426, USA. Pelletj@wyeth.com
PMID: 19856966 DOI: 10.1021/jm9014197
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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