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

• Type: Article in International Scientific Journal
• Date: 2013

Authors

Joao Matos, MJ (Author) Other; gaspar, alexandra (Author) Other; kachler, sonja (Author) Other; klotz, karl-norbert (Author) Other; borges, fernanda (Author) FCUP; santana, lourdes (Author) Other; uriarte, eugenio (Author) Other

Journal

Title: Journal of Pharmacy and Pharmacology

Vol. 65

Pages: 30-34

ISSN: 0022-3573

Publisher: Oxford University Press

Indexing

ISI Web of Knowledge - 14 Citations

Scopus - 13 Citations

Scientific classification

FOS: Natural sciences > Chemical sciences

CORDIS: Physical sciences > Chemistry > Applied chemistry > Pharmaceutical chemistry

Other information

Authenticus ID: P-002-264

DOI: 10.1111/j.2042-7158.2012.01571.x

Abstract (EN): 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).

Language: English

Type (Professor's evaluation): Scientific