New, Non-Adenosine, High-Potency Agonists for the Human Adenosine A2B Receptor with an Improved Selectivity Profile Compared to the Reference Agonist N-Ethylcarboxamidoadenosine

The adenosine A2B 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-dicarbon...

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Bibliographic Details
Published in:Journal of medicinal chemistry 2004-07, Vol.47 (15), p.3707-3709
Main Authors: Beukers, Margot W, Chang, Lisa C. W, von Frijtag Drabbe Künzel, Jacobien K, Mulder-Krieger, Thea, Spanjersberg, Ronald F, Brussee, Johannes, IJzerman, Ad P
Format: Article
Language:English
Subjects:
Adenosine A2 Receptor Agonists
Adenosine-5'-(N-ethylcarboxamide) - chemistry
Adenosine-5'-(N-ethylcarboxamide) - pharmacology
Aminopyridines - chemical synthesis
Aminopyridines - chemistry
Aminopyridines - pharmacology
Animals
Biological and medical sciences
CHO Cells
Cricetinae
Cyclic AMP - biosynthesis
Humans
Imidazoles - chemical synthesis
Imidazoles - chemistry
Imidazoles - pharmacology
Medical sciences
Neuropharmacology
Neurotransmitters. Neurotransmission. Receptors
Peptidergic system (neuropeptide, opioid peptide, opiates...). Adenosinergic and purinergic systems
Pharmacology. Drug treatments
Structure-Activity Relationship
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Summary:The adenosine A2B 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 EC50 = 12 nM and 45-fold selectivity over the adenosine A3 receptor but lacking selectivity versus the A1 and A2A subtypes. Compound 18, LUF5835, the 3-hydroxyphenyl analogue, is a full agonist with EC50 = 10 nM.
ISSN:0022-2623
1520-4804
DOI:10.1021/jm049947s