Hit to lead studies on (hetero) arylpyrimidines—agonists of the canonical Wnt-β-catenin cellular messaging system

…, Y Kharode, G Krishnamurthy, M Kirisits…

Index: Gilbert, Adam M.; Bursavich, Matthew G.; Alon, Nippa; Bhat, Bheem M.; Bex, Frederick J.; Cain, Michael; Coleburn, Valerie; Gironda, Virginia; Green, Paula; Hauze, Diane B.; Kharode, Yogendra; Krishnamurthy, Girija; Kirisits, Matthew; Lam, Ho-Sun; Liu, Yao-Bin; Lombardi, Sabrina; Matteo, Jeanne; Murrills, Richard; Robinson, John A.; Selim, Sally; Sharp, Michael; Unwalla, Raymond; Varadarajan, Usha; Zhao, Weiguang; Yaworsky, Paul J. Bioorganic and Medicinal Chemistry Letters, 2010 , vol. 20, # 1 p. 366 - 370

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Citation Number: 7

Abstract

A series of (hetero) arylpyrimidines agonists of the Wnt-β-catenin cellular messaging system have been prepared. These compounds show activity in U2OS cells transfected with Wnt-3a, TCF-luciferase, Dkk-1 and tk-Renilla. Selected compounds show minimal GSK-3β inhibition indicating that the Wnt-β-catenin agonism activity most likely comes from interaction at Wnt- 3a/Dkk-1. Two examples 1 and 25 show in vivo osteogenic activity in a mouse calvaria ...