Development of novel adenosine receptor ligands based on the 3-amidocoumarin scaffold

• Tipo: Artigo em Revista Científica Internacional
• Data: 2015

Autores

Maria J Matos (Autor) Outra; Santiago Vilar (Autor) Outra; Sonja Kachler (Autor) Outra; Maria Celeiro (Autor) Outra; Saleta Vazquez Rodriguez (Autor) Outra; Lourdes Santana (Autor) Outra; Eugenio Uriarte (Autor) Outra; George Hripcsak (Autor) Outra; Fernanda Borges (Autor) FCUP; Karl Norbert Klotz (Autor) Outra

Revista

Título: Bioorganic Chemistry

Vol. 61

ISSN: 0045-2068

Editora: Elsevier

Indexação

ISI Web of Knowledge - 10 Citações

Scopus - 10 Citações

Classificação Científica

FOS: Ciências exactas e naturais > Química

Outras Informações

ID Authenticus: P-00G-B0K

Abstract (EN): With the aim of finding new adenosine receptor (AR) ligands presenting the 3-amidocoumarin scaffold, a study focusing on the discovery of new chemical entities was carried out. The synthesized compounds 1-8 were evaluated in radioligand binding (A(1), A(2A) and A(3)) and adenylyl cyclase activity (A(2B)) assays in order to determine their affinity for human AR subtypes. The 3-benzamide derivative 4 showed the highest affinity of the whole series and was more than 30-fold selective for the A(3) AR (K-i = 3.24 mu M). The current study supported that small structural changes in this scaffold allowed modulating the affinity resulting in novel promising classes of A(1), A(2A), and/or A(3) AR ligands. We also performed docking calculations in hA(2A) and hA(3) to identify the hypothetical binding mode for the most active compounds. In addition, some ADME properties were calculated in order to better understand the potential of these compounds as drug candidates. (C) 2015 Elsevier Inc. All rights reserved.

Idioma: Inglês

Tipo (Avaliação Docente): Científica