Synthesis and evaluation of two series of 4′-aza-carbocyclic nucleosides as adenosine A2A receptor agonists

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 A2A 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.

Graphical abstractTwo series of 4′-aza-carbocyclic nucleosides are described as adenosine A2A receptor agonists.Figure optionsDownload full-size imageDownload as PowerPoint slide