N6-Cycloalkyl-2-substituted adenosine derivatives as selective, high affinity adenosine A1 receptor agonists

A series of new selective, high affinity A1-AdoR agonists is reported. Compound 23 that incorporated a carboxylic acid functionality in the 4-position of the pyrazole ring displayed KiL value of 1 nM for the A1-AdoR and >5000-fold selectivity over the A3 and A2A-AdoRs. In addition, compound 19 that incorporated a carboxamide functionality in the 4-position of the pyrazole ring displayed subnanomolar affinity for the A1-AdoR (KiL = 0.6 nM) and >600-fold selectivity over the A3 and A2A-AdoRs.

The synthesis, binding affinity and selectivity of 2,6-disubstituted adenosine derivatives for the A1-AdoR is reported.Figure optionsDownload as PowerPoint slide