Discovery of 1,2,4-Triazine Derivatives as Adenosine A2A Antagonists using Structure Based Drug Design
Journal of Medicinal Chemistry2012Vol. 55(5), pp. 1898–1903
Citations Over TimeTop 1% of 2012 papers
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
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(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.
Related Papers
- → Fragment-based lead discovery: leads by design(2005)339 cited
- → Fragment-Based Drug Discovery Applied to Hsp90. Discovery of Two Lead Series with High Ligand Efficiency(2010)185 cited
- → A Practical Use of Ligand Efficiency Indices Out of the Fragment-Based Approach: Ligand Efficiency-Guided Lead Identification of Soluble Epoxide Hydrolase Inhibitors(2010)72 cited
- → Caffeine intake induces an alteration in human neutrophil A2A adenosine receptors(2005)33 cited
- → Novel adenosine A2A receptor ligands: A synthetic, functional and computational investigation of selected literature adenosine A2A receptor antagonists for extending into extracellular space(2013)28 cited