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Identification of novel adenosine A(2A) 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).

SUBMITTER: Langmead CJ

PROVIDER: S-EPMC3308209 | biostudies-literature | 2012 Mar

REPOSITORIES: biostudies-literature

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Identification of novel adenosine A(2A) receptor antagonists by virtual screening.

Langmead Christopher J CJ Andrews Stephen P SP Congreve Miles M Errey James C JC Hurrell Edward E Marshall Fiona H FH Mason Jonathan S JS Richardson Christine M CM Robertson Nathan N Zhukov Andrei A Weir Malcolm M

Journal of medicinal chemistry 20120223 5

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). ...[more]

PMID: 22250781

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