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 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.
Beukers
Margot W
MW
Division of Medicinal Chemistry, LACDR, Gorlaeus Laboratories, P.O. Box 9502, 2300 RA Leiden, The Netherlands. beukers@chem.leidenuniv.nl
Chang
Lisa C W
LC
von Frijtag Drabbe Künzel
Jacobien K
JK
Mulder-Krieger
Thea
T
Spanjersberg
Ronald F
RF
Brussee
Johannes
J
IJzerman
Ad P
AP
D058908:Adenosine A2 Receptor Agonists; D019830:Adenosine-5'-(N-ethylcarboxamide) / Q000737:chemistry / Q000494:pharmacology*; D000631:Aminopyridines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D000242:Cyclic AMP / Q000096:biosynthesis; D006801:Humans; D007093:Imidazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship
C488438:2-amino-4-(4-hydroxyphenyl)-6-(1H-imidazol-2-ylmethylsulfanyl)pyridine-3,5-dicarbonitrile; D058908:Adenosine A2 Receptor Agonists; D000631:Aminopyridines; D007093:Imidazoles; D019830:Adenosine-5'-(N-ethylcarboxamide); D000242:Cyclic AMP