Targeting adenosine receptors with coumarins: synthesis and binding activities of amide and carbamate derivatives

Authors


Maria João Matos, Departamento de Química Orgánica, Facultad de Farmacia, Universidad de Santiago de Compostela, Spain. E-mail: mariajoao.correiapinto@rai.usc.es

Abstract

Objectives  With the aim of finding the structural features governing binding activity and selectivity against adenosine receptors (ARs), several 3-subtituted coumarins with amide (compounds 36) and carbamate (79) functions were synthesized. To study its possible influence on the binding activity and selectivity, a hydroxyl substituent was also introduced at position 4 of the coumarin moiety.

Methods  A new series of coumarins (39) were synthesized and evaluated by radioligand binding studies towards ARs.

Key findings  None of the 4-hydroxy derivatives (4, 8 and 9) showed binding affinity for any of the ARs. None of the compounds interacted with the hA2B AR (Ki > 100 000 nm). Compounds 3, 5, 6 and 7 had different activity profiles with dissimilar binding affinity and selectivity towards human A1, A2A and A3 ARs.

Conclusions  The most remarkable derivative is compound 7, which presents the best affinity and selectivity for the A3 adenosine receptor (Ki = 5500 nm).

Ancillary