2. Academic Validation
  3. New, non-adenosine, high-potency agonists for the human adenosine A2B receptor with an improved selectivity profile compared to the reference agonist N-ethylcarboxamidoadenosine

New, non-adenosine, high-potency agonists for the human adenosine A2B receptor with an improved selectivity profile compared to the reference agonist N-ethylcarboxamidoadenosine

  • J Med Chem. 2004 Jul 15;47(15):3707-9. doi: 10.1021/jm049947s.
Margot W Beukers 1,  Lisa C W Chang,  Jacobien K von Frijtag Drabbe Künzel,  Thea Mulder-Krieger,  Ronald F Spanjersberg,  Johannes Brussee,  Ad P IJzerman
Affiliations

Affiliation

  • 1 Division of Medicinal Chemistry, LACDR, Gorlaeus Laboratories, P.O. Box 9502, 2300 RA Leiden, The Netherlands. [email protected]
PMID: 15239649 DOI: 10.1021/jm049947s
Abstract

The adenosine A(2B) receptor is the least well characterized of the four known Adenosine Receptor subtypes because of the absence of potent, selective agonists. Here, we present five non-adenosine agonists. Among them, 2-amino-4-(4-hydroxyphenyl)-6-(1H-imidazol-2-ylmethylsulfanyl)pyridine-3,5-dicarbonitrile, 17, LUF5834, is a high-efficacy partial agonist with EC(50) = 12 nM and 45-fold selectivity over the adenosine A(3) receptor but lacking selectivity versus the A(1) and A(2A) subtypes. Compound 18, LUF5835, the 3-hydroxyphenyl analogue, is a full agonist with EC(50) = 10 nM.

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