2-(N-Acyl) and 2-N-acyl-N6-substituted analogues of adenosine and their affinity at the human adenosine receptors

A series of 2-(N-acyl) and 2-(N-acyl)-N6-alkyladenosine analogues have been synthesized from the intermediate 2-amino-6-chloroadenosine derivatives (2b and 7) and evaluated for their affinity at the human A1, A2A, and A3 receptors. We found that 2-(N-acyl) derivatives of adenosine showed relatively low affinity at A2A and A3 receptors, while the N6-cyclopentyl substituent in 4h and 4i induced high potency [A1 (Ki)=20.7 and 31.8 nM respectively] at the A1 receptor and resulted therefore in increased selectivity for this subtype. The general synthetic methods and their binding studies are presented herein.