Medicinal Chemistry of the A3 Adenosine Receptor: Agonists, Antagonists, and Receptor Engineering View Full Text


Ontology type: schema:Chapter      Open Access: True


Chapter Info

DATE

2009-05-28

AUTHORS

Kenneth A. Jacobson , Athena M. Klutz , Dilip K. Tosh , Andrei A. Ivanov , Delia Preti , Pier Giovanni Baraldi

ABSTRACT

A(3) adenosine receptor (A(3)AR) ligands have been modified to optimize their interaction with the A(3)AR. Most of these modifications have been made to the N(6) and C2 positions of adenine as well as the ribose moiety, and using a combination of these substitutions leads to the most efficacious, selective, and potent ligands. A(3)AR agonists such as IB-MECA and Cl-IB-MECA are now advancing into Phase II clinical trials for treatments targeting diseases such as cancer, arthritis, and psoriasis. Also, a wide number of compounds exerting high potency and selectivity in antagonizing the human (h)A(3)AR have been discovered. These molecules are generally characterized by a notable structural diversity, taking into account that aromatic nitrogen-containing monocyclic (thiazoles and thiadiazoles), bicyclic (isoquinoline, quinozalines, (aza)adenines), tricyclic systems (pyrazoloquinolines, triazoloquinoxalines, pyrazolotriazolopyrimidines, triazolopurines, tricyclic xanthines) and nucleoside derivatives have been identified as potent and selective A(3)AR antagonists. Probably due to the "enigmatic" physiological role of A(3)AR, whose activation may produce opposite effects (for example, concerning tissue protection in inflammatory and cancer cells) and may produce effects that are species dependent, only a few molecules have reached preclinical investigation. Indeed, the most advanced A(3)AR antagonists remain in preclinical testing. Among the antagonists described above, compound OT-7999 is expected to enter clinical trials for the treatment of glaucoma, while several thiazole derivatives are in development as antiallergic, antiasthmatic and/or antiinflammatory drugs. More... »

PAGES

123-159

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/978-3-540-89615-9_5

DOI

http://dx.doi.org/10.1007/978-3-540-89615-9_5

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1041153893

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/19639281


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Turtle is a human-readable linked data format.

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RDF/XML is a standard XML format for linked data.

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