2,6-Diaryl-4-phenacylaminopyrimidines as potent and selective adenosine A_2A antagonists with reduced hERG liability

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• 作者：Manisha Moorjani ; Xiaohu Zhang ; Yongsheng Chen ; Emily Lin ; Jaimie K. Rueter ; Raymond S. Gross ; Marion C. Lanier ; John E. Tellew ; John P. Williams ; S ; ra M. Lechner ; Siobhan Malany ; Mark Santos ; Paddi E
• 关键词：A_2A antagonists ; Adenosine receptor ; Parkinson’ ; s disease ; Phenacylaminopyrimidines ; hERG
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：2008
• 出版时间：15 February 2008
• 年：2008
• 卷：18
• 期：4
• 页码：1269-1273
• 全文大小：159 K

文摘

In this report, the design and synthesis of a series of pyrimidine based adenosine A_2A antagonists are described. The strategy and outcome of expanding SAR exploration to attenuate hERG and improve selectivity over A₁ are discussed. Compound 33 exhibited excellent potency, selectivity over A₁, and reduced hERG liability.