1. Academic Validation
  2. (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
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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