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Medicinal Chemistry of A2B Adenosine Receptors

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The Adenosine Receptors

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

Abstract

A2B adenosine receptors (A2BARs) are in the focus of interest as drug targets in (immuno)oncology since antagonists show anti-proliferative, anti-angiogenic, anti-metastatic, and immunostimulatory properties. Additional (potential) indications for A2BAR antagonists include inflammatory (pulmonary, colon) and autoimmune diseases, pain, fibrosis, infectious diseases, diabetes, and more. Agonists were found to exhibit cardioprotective properties. The A2BAR is most closely related to the A2AAR subtype. Both are Gs protein-coupled receptors, but the A2BAR is additionally coupled to Gq proteins. A2BAR expression is upregulated under pathological conditions (hypoxia, inflammation, ischemia) and on many cancer cells. A2BARs form stable heteromeric complexes with A2AARs when co-expressed, and thereby completely block A2AAR signaling. There is still a lack of potent, selective, and fully efficacious A2BAR agonists, while structurally diverse potent and selective competitive antagonists for A2BARs have become available. The first positive and negative allosteric modulators for A2BARs were recently described. For the labeling of A2BARs, antagonist radioligands have been developed, and recently the first potent and selective fluorescent ligands were reported.

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Acknowledgments

We are grateful to the Federal Ministry of Education and Research (BMBF), Germany, for the support of a project on the development of A2BAR antagonists as diagnostics for PET imaging within the BioPharma initiative (Neuroallianz, project D11B). We thank A.C. Schiedel for the design of Fig. 6.4.

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Authors and Affiliations

  1. PharmaCenter Bonn, Pharmaceutical Institute, Pharmaceutical Chemistry I, University of Bonn, Bonn, Germany

    Christa E. Müller, Sonja Hinz & Vigneshwaran Namasivayam

  2. Department of Chemistry, Faculty of Science, Sultan Qaboos University, Muscat, Oman

    Younis Baqi

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  4. Vigneshwaran Namasivayam
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Correspondence to Christa E. Müller .

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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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Müller, C.E., Baqi, Y., Hinz, S., Namasivayam, V. (2018). Medicinal Chemistry of A2B Adenosine Receptors. 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_6

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