Journal article

Novel Irreversible Agonists Acting at the A(1) Adenosine Receptor

Manuela Jorg, Alisa Glukhova, Alaa Abdul-Ridha, Elizabeth A Vecchio, Anh TN Nguyen, Patrick M Sexton, Paul J White, Lauren T May, Arthur Christopoulos, Peter J Scammells

Journal of Medicinal Chemistry | AMER CHEMICAL SOC | Published : 2016


The A1 adenosine receptor (A1AR) is an important G protein-coupled receptor that regulates a range of physiological functions. Herein we report the discovery of novel irreversible agonists acting at the A1AR, which have the potential to serve as useful research tools for studying receptor structure and function. A series of novel adenosine derivatives bearing electrophilic substituents was synthesized, and four compounds, 8b, 15a, 15b, and 15d, were shown to possess similar potency and efficacy to the reference high efficacy agonist, NECA, in an assay of ERK1/2 phosphorylation assay. Insensitivity to antagonist addition in a real-time, label-free, xCELLigence assay was subsequently used to i..

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Awarded by National Health and Medical Research Council of Australia (NHMRC)

Funding Acknowledgements

We thank Dr. Michael Crouch (TGR Biosciences) for generously providing the ERK1/2 phosphorylation assay kit. This work was funded by Project Grants APP1084246 and APP1084487 of the National Health and Medical Research Council of Australia (NHMRC). A.C. is a Senior Principal Research Fellow, and P.M.S. a Principal Research Fellow, of the NHMRC.