title: New, non-adenosine, high-potency agonists for the human adenosine A2B receptor with an improved selectivity profile compared to the reference agonist N-ethylcarboxamidoadenosine.
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.
authors.affiliation: Division of Medicinal Chemistry, LACDR, Gorlaeus Laboratories, P.O. Box 9502, 2300 RA Leiden, The Netherlands. beukers@chem.leidenuniv.nl
authors.forename: Margot W
authors.initials: MW
authors.lastname: Beukers
authors.forename: Lisa C W
authors.initials: LC
authors.lastname: Chang
authors.forename: Jacobien K
authors.initials: JK
authors.lastname: von Frijtag Drabbe Künzel
authors.forename: Thea
authors.initials: T
authors.lastname: Mulder-Krieger
authors.forename: Ronald F
authors.initials: RF
authors.lastname: Spanjersberg
authors.forename: Johannes
authors.initials: J
authors.lastname: Brussee
authors.forename: Ad P
authors.initials: AP
authors.lastname: IJzerman
mesh_terms: 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
chemical_list: 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