Discovery of novel A(3) adenosine receptor ligands based on chromone scaffold

• Tipo: Artigo em Revista Científica Internacional
• Data: 2012

Autores

Alexandra Gaspar (Autor) Outra; Joana Reis (Autor) Outra; Sonja Kachler (Autor) Outra; Silvia Paoletta (Autor) Outra; Eugenio Uriarte (Autor) Outra; Karl Norbert Klotz (Autor) Outra; Stefano Moro (Autor) Outra; Fernanda Borges (Autor) FCUP

Revista

Título: Biochemical Pharmacology

Vol. 84

ISSN: 0006-2952

Editora: Elsevier

Indexação

ISI Web of Knowledge - 45 Citações

Scopus - 43 Citações

Classificação Científica

FOS: Ciências exactas e naturais > Química

CORDIS: Ciências Físicas > Química > Química aplicada > Química farmacêutica

Outras Informações

ID Authenticus: P-002-8RH

Abstract (EN): A project focused on the discovery of new chemical entities (NCEs) as AR ligands that incorporate a benzo-gamma-pyrone [(4H)-1-benzopyran-4-one] substructure has been developed. Accordingly, two series of novel chromone carboxamides placed at positions C2 (compounds 2-13) and C3 (compounds 15-26) of the gamma-pyrone ring were synthesized using chromone carboxylic acids (compounds 1 or 14) as starting materials. From this study and on the basis of the obtained structure-activity relationships it was concluded that the chromone carboxamide scaffold represent a novel class of AR ligands. The most remarkable chromones were compounds 21 and 26 that present a better affinity for A(3)AR (K-i = 3680 nM and K-i = 3750 nM, respectively). Receptor-driven molecular modeling studies provide information on the binding/selectivity data of the chromone. The data so far acquired are instrumental for future optimization of chromone carboxamide as a selective A(3)AR antagonist. (c) 2012 Elsevier Inc. All rights reserved.

Idioma: Inglês

Tipo (Avaliação Docente): Científica