Artigo Acesso aberto Revisado por pares

Discovery of 1,2,4-Triazine Derivatives as Adenosine A 2A Antagonists using Structure Based Drug Design

2012; American Chemical Society; Volume: 55; Issue: 5 Linguagem: Inglês

10.1021/jm201376w

ISSN

1520-4804

Autores

Miles Congreve, Stephen P. Andrews, A.S. Dore, Kaspar Hollenstein, Edward Hurrell, Christopher J. Langmead, Jonathan S. Mason, Irene W. Ng, Benjamin G. Tehan, Andrei Zhukov, Malcolm Weir, Fiona H. Marshall,

Tópico(s)

Synthesis and Characterization of Heterocyclic Compounds

Resumo

Potent, ligand efficient, selective, and orally efficacious 1,2,4-triazine derivatives have been identified using structure based drug design approaches as antagonists of the adenosine A(2A) receptor. The X-ray crystal structures of compounds 4e and 4g bound to the GPCR illustrate that the molecules bind deeply inside the orthosteric binding cavity. In vivo pharmacokinetic and efficacy data for compound 4k are presented, demonstrating the potential of this series of compounds for the treatment of Parkinson's disease.

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