Bioorganic & Medicinal Chemistry Letters 2003-05-19

2,4-disubstituted pyrimidines: a novel class of KDR kinase inhibitors.

Peter J Manley, Adrienne E Balitza, Mark T Bilodeau, Kathleen E Coll, George D Hartman, Rosemary C McFall, Keith W Rickert, Leonard D Rodman, Kenneth A Thomas

Index: Bioorg. Med. Chem. Lett. 13(10) , 1673-7, (2003)

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Abstract

2,4-Disubstituted pyrimidines were synthesized as a novel class of KDR kinase inhibitors. Evaluation of the SAR of the screening lead compound 1 (KDR IC(50)=105 nM, Cell IC(50)=8% inhibition at 500 nM) led to the potent 3,5-dimethylaniline derivative 2d (KDR IC(50)=6 nM, cell IC(50)=19 nM).