Discovery of 1,2,4-Triazine
Derivatives as Adenosine
A<sub>2A</sub> Antagonists using Structure Based Drug Design
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Abstract
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<sub>2A</sub> receptor.
The X-ray crystal structures of compounds <b>4e</b> and <b>4g</b> bound to the GPCR illustrate that the molecules bind deeply
inside the orthosteric binding cavity. In vivo pharmacokinetic and
efficacy data for compound <b>4k</b> are presented, demonstrating
the potential of this series of compounds for the treatment of Parkinson’s
disease