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

Abstract

A series of 2-( N-acyl) and 2-( N-acyl)- N 6-alkyladenosine analogues have been synthesized from the intermediate 2-amino-6-chloroadenosine derivatives ( 2b and 7) and evaluated for their affinity at the human A 1, A 2A, and A 3 receptors. We found that 2-( N-acyl) derivatives of adenosine showed relatively low affinity at A 2A and A 3 receptors, while the N 6-cyclopentyl substituent in 4h and 4i induced high potency [A 1 ( K i)=20.7 and 31.8 nM respectively] at the A 1 receptor and resulted therefore in increased selectivity for this subtype. The general synthetic methods and their binding studies are presented herein.