Artigo Revisado por pares

Practical Synthesis of a p38 MAP Kinase Inhibitor

2008; American Chemical Society; Volume: 74; Issue: 2 Linguagem: Inglês

10.1021/jo802186m

ISSN

1520-6904

Autores

Michał Achmatowicz, Oliver R. Thiel, Philip Wheeler, Charles Bernard, Jinkun Huang, Robert D. Larsen, Margaret M. Faul,

Tópico(s)

Synthesis and biological activity

Resumo

p38 MAP kinase inhibitors have attracted considerable interest as potential agents for the treatment of inflammatory diseases. Herein, we describe a concise and efficient synthesis of inhibitor 1 that is based on a phthalazine scaffold. Highlights of our approach include a practical synthesis of a 1,6-disubstituted phthalazine building block 24 as well as the one-pot formation of boronic acid 27. Significant synthetic work to understand the reactivity principles of the intermediates helped in selection of the final synthetic route. Subsequent optimization of the individual steps of the final sequence led to a practical synthesis of 1.

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