Discovery of 1, 2, 4-triazine derivatives as adenosine A2A antagonists using structure based drug design

…, K Hollenstein, E Hurrell, CJ Langmead…

Index: Congreve, Miles; Andrews, Stephen P.; Dore, Andrew S.; Hollenstein, Kaspar; Hurrell, Edward; Langmead, Christopher J.; Mason, Jonathan S.; Ng, Irene W.; Tehan, Benjamin; Zhukov, Andrei; Weir, Malcolm; Marshall, Fiona H. Journal of Medicinal Chemistry, 2012 , vol. 55, # 5 p. 1898 - 1903

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Citation Number: 157

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 A2A 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 ...