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

doi:10.1021/jm201455y

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

Research output: Contribution to journal › Article › Research › peer-review

127 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 language	English
Pages (from-to)	1904 - 1909
Number of pages	6
Journal	Journal of Medicinal Chemistry
Volume	55
Issue number	5
DOIs	https://doi.org/10.1021/jm201455y
Publication status	Published - 2012
Externally published	Yes

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10.1021/jm201455y

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title = "Identification of novel adenosine A2A receptor antagonists by virtual screening",

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).",

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

year = "2012",

doi = "10.1021/jm201455y",

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T1 - Identification of novel adenosine A2A receptor antagonists by virtual screening

AU - Langmead, Christopher J

AU - Andrews, Stephen P

AU - Congreve, Miles

AU - Errey, James C

AU - Hurrell, Edward

AU - Marshall, Fiona H

AU - Mason, Jonathon S

AU - Richardson, Christine M

AU - Robertson, Nathan

AU - Zhukov, Andrei

AU - Weir, Malcolm

PY - 2012

Y1 - 2012

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AB - 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).

UR - http://pubs.acs.org/doi/pdfplus/10.1021/jm201455y

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DO - 10.1021/jm201455y

M3 - Article

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JO - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

IS - 5

ER -

Identification of novel adenosine A2A receptor antagonists by virtual screening

Abstract

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