title: 2-(Arylalkylamino)adenosin-5'-uronamides: a new class of highly selective adenosine A2 receptor ligands.
abstract: The synthesis and receptor-binding profiles at adenosine receptor subtypes for a series of 2-(arylalkylamino)-adenosin-5'-uronamides is described. Halogenated 2-phenethylamino analogues such as 3e show greater than 200-fold selectivity for the A2 receptor subtype on the basis of rat brain receptor binding. The general structure-activity relationship of this series of compounds is discussed both in terms of potency at A2 receptors as well as receptor subtype selectivity. It is possible to introduce a hydrophilic carboxyalkyl substituent to this series such as in CGS 21680A (3h) and still retain good potency and selectivity for A2 receptors. In addition, functional data in a perfused working rat heart model shows that these compounds possess full agonist properties at A2 receptors with 3h having a greater than 1500-fold separation between A2 (coronary vasodilatory) and A1 (negative chronotropic) receptor mediated events.
authors.affiliation: Research Department, CIBA-GEIGY Corporation, Summit, New Jersey 07901.
authors.forename: A J
authors.initials: AJ
authors.lastname: Hutchison
authors.forename: M
authors.initials: M
authors.lastname: Williams
authors.forename: R
authors.initials: R
authors.lastname: de Jesus
authors.forename: R
authors.initials: R
authors.lastname: Yokoyama
authors.forename: H H
authors.initials: HH
authors.lastname: Oei
authors.forename: G R
authors.initials: GR
authors.lastname: Ghai
authors.forename: R L
authors.initials: RL
authors.lastname: Webb
authors.forename: H C
authors.initials: HC
authors.lastname: Zoganas
authors.forename: G A
authors.initials: GA
authors.lastname: Stone
authors.forename: M F
authors.initials: MF
authors.lastname: Jarvis
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000378:metabolism; D003326:Coronary Circulation / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D007202:Indicators and Reagents; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D015394:Molecular Structure; D051381:Rats; D011919:Rats, Inbred Strains; D011983:Receptors, Purinergic / Q000378:metabolism*; D013329:Structure-Activity Relationship; D014664:Vasodilation / Q000187:drug effects
chemical_list: D007202:Indicators and Reagents; D008024:Ligands; D011983:Receptors, Purinergic; D000241:Adenosine