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A2A Adenosine Receptor: Structures, Modeling, and Medicinal Chemistry

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The Adenosine Receptors

Part of the book series: The Receptors ((REC,volume 34))

Abstract

Many selective agonists and antagonists of the A2A adenosine receptor (AR) have been reported, while allosteric modulators specific for this receptor are still needed. Many heterocyclic chemotypes have been discovered as A2AAR antagonists, while most of the known AR agonists are nucleosides or 3,5-dicyanopyridine derivatives. A few A2AAR ligands have been in clinical trials as antihypertensives, anti-inflammatory or diagnostic compounds (agonists), and as drugs for treating Parkinson’s disease and cancer (antagonists). The A2AAR has become one of the most widely investigated G protein-coupled receptor (GPCR) structures using X-ray crystallography and also biophysical techniques such as NMR. Thus, the design of agonists, antagonists, and allosteric modulators has become structure-based, with numerous examples of in silico approaches, including virtual ligand screening (VLS), leading to the discovery of both novel agonists and antagonists.

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Authors and Affiliations

  1. Department of Chemical and Pharmaceutical Sciences, University of Ferrara, Ferrara, Italy

    Stefania Baraldi, Pier Giovanni Baraldi & Paola Oliva

  2. National Institute of Diabetes and Digestive and Kidney Disease, National Institutes of Health, Bethesda, MA, USA

    Kiran S. Toti, Antonella Ciancetta & Kenneth A. Jacobson

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  1. Stefania Baraldi
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  2. Pier Giovanni Baraldi
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  3. Paola Oliva
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  4. Kiran S. Toti
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  5. Antonella Ciancetta
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  6. Kenneth A. Jacobson
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Correspondence to Kenneth A. Jacobson .

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  1. Department of Medical Sciences, University of Ferrara, Ferrara, Italy

    Pier Andrea Borea

  2. Department of Medical Sciences, University of Ferrara, Ferrara, Italy

    Katia Varani

  3. Department of Medical Sciences, University of Ferrara, Ferrara, Italy

    Stefania Gessi

  4. Department of Medical Sciences, University of Ferrara, Ferrara, Italy

    Stefania Merighi

  5. Department of Medical Sciences, University of Ferrara, Ferrara, Italy

    Fabrizio Vincenzi

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Baraldi, S., Baraldi, P.G., Oliva, P., Toti, K.S., Ciancetta, A., Jacobson, K.A. (2018). A2A Adenosine Receptor: Structures, Modeling, and Medicinal Chemistry. In: Borea, P., Varani, K., Gessi, S., Merighi, S., Vincenzi, F. (eds) The Adenosine Receptors. The Receptors, vol 34. Humana Press, Cham. https://doi.org/10.1007/978-3-319-90808-3_5

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