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Recent Developments in Adenosine A2A Receptor Ligands

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Adenosine Receptors in Health and Disease

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 193))

Abstract

The development of potent and selective agonists and antagonists of adenosine receptors (ARs) has been a target of medicinal chemistry research for several decades, and recently the US Food and Drug Administration has approved LexiscanTM, an adenosine derivative substituted at the 2 position, for use as a pharmacologic stress agent in radionuclide myocardial perfusion imaging. Currently, some other adenosine A2A receptor (A2AAR) agonists and antagonists are undergoing preclinical testing and clinical trials. While agonists are potent antiinflammatory agents also showing hypotensive effects, antagonists are being developed for the treatment of Parkinson’s disease.

However, since there are still major problems in this field, including side effects, low brain penetration (for the targeting of CNS diseases), short half-life, or lack of in vivo effects, the design and development of new AR ligands is a hot research topic.

This review presents an update on the medicinal chemistry of A2AAR agonists and antagonists, and stresses the strong need for more selective ligands at the human A2AAR subtype, in particular in the case of agonists.

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Abbreviations

ADA:

Adenosine deaminase

Ado:

Adenosine

AK:

Adenosine kinase

AR:

Adenosine receptor

CCPA:

2-Chloro-N 6-cyclopentyladenosine

CHA:

N 6-Cyclohexyladenosine

CHO:

Chinese hamster ovarian

CNS:

Central nervous system

CPA:

N 6-Cyclopentyladenosine

HEAdo:

2-(Hexyn-1-yl)adenosine

HENECA:

2-Hexynyl-NECA

MECA:

N-Methylcarboxamidoadenosine

NECA:

N-Ethylcarboxamidoadenosine

PEAdo:

2-Phenylethynyladenosine

PENECA:

2-PhenylethynylNECA

PHPAdo:

2-Phenylhydroxypropynyladenosine

PHPNECA:

2-PhenyhydroxypropynylNECA

PIA:

N 6-(2-Phenylisopropyl)adenosine

QSAR:

Quantitative structure–activity relationships

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Authors and Affiliations

  1. Dipartimento di Scienze Chimiche, Università di Camerino, via S. Agostino 1, 62032, Camerino (MC), Italy

    Gloria Cristalli

  2. University of Bonn, Pharmaceutical Institute, Pharmaceutical Chemistry I, An der Immenburg 4, 53121, Bonn, Germany

    Christa E. Müller

  3. Dipartimento di Scienze Chimiche, Universit`a di Camerino, via S. Agostino 1, 62032, Camerino (MC), Italy

    Rosaria Volpini

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  1. Gloria Cristalli
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  2. Christa E. Müller
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  3. Rosaria Volpini
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Correspondence to Gloria Cristalli .

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  1. Endacea, Inc.,, Davis Drive 2, Research Triangle Park, 27709-2076, U.S.A.

    Constance N. Wilson

  2. Health Sciences Center, West Virginia University, Health Sciences S. 2267, Morgantown, 26506-9104, U.S.A.

    S. Jamal Mustafa

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Cristalli, G., Müller, C.E., Volpini, R. (2009). Recent Developments in Adenosine A2A Receptor Ligands. In: Wilson, C., Mustafa, S. (eds) Adenosine Receptors in Health and Disease. Handbook of Experimental Pharmacology, vol 193. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-89615-9_3

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