Identification of Novel Adenosine A2A Receptor Antagonists by Virtual Screening

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• 作者：Christopher J. Langmead ; Stephen P. Andrews ; Miles Congreve ; James C. Errey ; Edward Hurrell ; Fiona H. Marshall ; Jonathan S. Mason ; Christine M. Richardson ; Nathan Robertson ; Andrei Zhukov ; Malcolm Weir
• 刊名：Journal of Medicinal Chemistry
• 出版年：2012
• 出版时间：March 8, 2012
• 年：2012
• 卷：55
• 期：5
• 页码：1904-1909
• 全文大小：277K
• 年卷期：v.55,no.5(March 8, 2012)
• ISSN：1520-4804

文摘

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鈥?b>13 from 5, pK_I = 7.5鈥?.5, 13- to >100-fold selective versus adenosine A₁; 14鈥?b>16 from 1, pK_I = 7.9鈥?.0, 19- to 59-fold selective).