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Synthesis of novel (benzimidazolyl)isoquinolinols and evaluation as adenosine A1 receptor tools

G protein-coupled receptors (GPCRs) constitute the largest family of transmembrane receptors in eukaryotes. The adenosine A(1) receptor (A(1)AR) is a class A GPCR that is of interest as a therapeutic target particularly in the treatment of cardiovascular disease and neuropathic pain. Increased knowl...

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Detalles Bibliográficos
Autores principales: Singh, Sameek, Cooper, Samantha L., Glenn, Jacqueline R., Beresford, Jessica, Percival, Lydia R., Tyndall, Joel D. A., Hill, Stephen J., Kilpatrick, Laura E., Vernall, Andrea J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Royal Society of Chemistry 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9080270/
https://www.ncbi.nlm.nih.gov/pubmed/35542203
http://dx.doi.org/10.1039/c7ra13148h
Descripción
Sumario:G protein-coupled receptors (GPCRs) constitute the largest family of transmembrane receptors in eukaryotes. The adenosine A(1) receptor (A(1)AR) is a class A GPCR that is of interest as a therapeutic target particularly in the treatment of cardiovascular disease and neuropathic pain. Increased knowledge of the role A(1)AR plays in mediating these pathophysiological processes will help realise the therapeutic potential of this receptor. There is a lack of enabling tools such as selective fluorescent probes to study A(1)AR, therefore we designed a series of (benzimidazolyl)isoquinolinols conjugated to a fluorescent dye (31–35, 42–43). An improved procedure for the synthesis of isoquinolinols from tetrahydroisoquinolinols via oxidation with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) and atmospheric oxygen is reported. This synthetic method offers advantages over previous metal-based methods for the preparation of isoquinolinols and isoquinolines, which are important scaffolds found in many biologically active compounds and natural products. We report the first synthesis of the (benzimidazolyl)isoquinolinol compound class, however the fluorescent conjugates were not successful as A(1)AR fluorescent ligands.