Synthesis and evaluation of two series of 4′-aza-carbocyclic nucleosides as adenosine A_2A receptor agonists

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• 作者：David Beattie ; Andrew Brearley ; Zarin Brown ; Steven J. Charlton ; Brian Cox ; Robin A. Fairhurst ; John R. Fozard ; Peter Gedeck ; Paul Kirkham ; Koremu Meja ; Lana Nanson ; James Neef ; Helen Oakman ; Gillian
• 关键词：Adenosine A2A receptor agonists ; Carbocyclic nucleosides ; Anti-inflammatory
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：2010
• 出版时间：1 February 2010
• 年：2010
• 卷：20
• 期：3
• 页码：1219-1224
• 全文大小：347 K

文摘

The synthesis of two series of 4′-aza-carbocyclic nucleosides are described in which the 4′-substituent is either a reversed amide, relative to the carboxamide of NECA, or an N-bonded heterocycle. Using established purine substitution patterns, potent and selective examples of agonists of the human adenosine A_2A receptor have been identified from both series. The propionamides 14–18 and the 4-hydroxymethylpyrazole 32 were determined to be the most potent and selective examples from the 4′-reversed amide and 4′-N-bonded heterocyclic series, respectively.