Bioorganic & Medicinal Chemistry Letters 2003-03-24

N-Phenyl-N-purin-6-yl ureas: the design and synthesis of p38alpha MAP kinase inhibitors.

Zehong Wan, Jeffrey C Boehm, Michael J Bower, Shouki Kassis, John C Lee, Baoguang Zhao, Jerry L Adams

Index: Bioorg. Med. Chem. Lett. 13(6) , 1191-4, (2003)

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Abstract

The design, synthesis and SAR of a series of 2,6,9-trisubstituted purine inhibitors of p38alpha kinase is reported. Synthetic routes were devised to allow for array synthesis in which all three points of diversity could be facilely explored. The binding of this novel series to p38alpha kinase, which was predicted to have several key interactions in common with SB-203580, was confirmed by X-ray crystallography of 19 (p38 IC(50)=82 nM).