Progress in the development of small molecules as new human A(3) adenosine receptor ligands based on the 3-thiophenylcoumarin core

• Type: Article in International Scientific Journal
• Date: 2016

Authors

Klotz, KN (Author) Other; Fernanda Borges (Author) FCUP; Matos, MJ (Author) Other; Vilar, S (Author) Other; Kachler, S (Author) Other; Vazquez Rodriguez, S (Author) Other; Varela, C (Author) Other; Delogu, G (Author) Other; Hripcsak, G (Author) Other; Santana, L (Author) Other; Uriarte, E (Author) Other

Journal

Title: MedChemComm

Vol. 7

Pages: 845-852

ISSN: 2040-2503

Publisher: Royal Society of Chemistry

Indexing

ISI Web of Knowledge - 4 Citations

Scopus - 4 Citations

Other information

Authenticus ID: P-00K-GYB

DOI: 10.1039/c5md00573f

Abstract (EN): Adenosine receptors (AR) are GPCRs involved in several biochemical processes. Agents able to selectively modulate the activity of these receptors represent promising multifunctional agents to delay or slow the progression of a large range of diseases. Here, differently substituted 3-thiophenylcoumarins are described that exert affinity towards human AR subtypes. Among the compounds synthesized, the 3-(4-bromothiophenyl) derivative 11 showed the highest affinity and selectivity for the hA(3) AR (K-i = 740 nM). Interestingly, the current study revealed that small structural changes in this scaffold allow modulating the AR affinity, suggesting that this scaffold has desirable properties for the development of promising classes of hA(1), hA(2A), and/or hA(3) AR ligands. Further docking calculations in the hA(3) AR identified the hypothetical binding mode of the most active and selective compounds. In addition, theoretical evaluation of some physicochemical properties highlighted the potential of these compounds as drug candidates. The data so far acquired is the first step for further optimization of these 3-thiophenylcoumarins as hA(3) AR selective ligands.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 8