Identification of novel adenosine A2A receptor antagonists by virtual screening

Christopher J Langmead, Stephen P Andrews, Miles Congreve, James C Errey, Edward Hurrell, Fiona H Marshall, Jonathon S Mason, Christine M Richardson, Nathan Robertson, Andrei Zhukov, Malcolm Weir

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100 Citations (Scopus)

Abstract

Virtual screening was performed against experimentally enabled homology models of the adenosine A 2A receptor, identifying a diverse range of ligand efficient antagonists (hit rate 9 ). By use of ligand docking and Biophysical Mapping (BPM), hits 1 and 5 were optimized to potent and selective lead molecules (11-13 from 5, pK I = 7.5-8.5, 13- to >100-fold selective versus adenosine A 1; 14-16 from 1, pK I = 7.9-9.0, 19- to 59-fold selective).
Original languageEnglish
Pages (from-to)1904 - 1909
Number of pages6
JournalJournal of Medicinal Chemistry
Volume55
Issue number5
DOIs
Publication statusPublished - 2012
Externally publishedYes

Cite this

Langmead, C. J., Andrews, S. P., Congreve, M., Errey, J. C., Hurrell, E., Marshall, F. H., Mason, J. S., Richardson, C. M., Robertson, N., Zhukov, A., & Weir, M. (2012). Identification of novel adenosine A2A receptor antagonists by virtual screening. Journal of Medicinal Chemistry, 55(5), 1904 - 1909. https://doi.org/10.1021/jm201455y