N6-substituted C5'-modified adenosines as A1 adenosine receptor agonists.
Adenosines bearing 5'-modification in conjunction with an N6-substituent have previously been shown to act as partial agonists at the A1 adenosine receptor. Our current work investigates the effect of modifying the 5'-position in conjunction with efficacious bicyclic and tricyclic N6-substituents. Several highly potent agonists for the A1 adenosine receptor were identified; however, all of these compounds behaved as full agonists. In keeping with previous reports, 5'-halogen and 5'-sulfide derivatives of N6-(endo-norborn-2-yl)adenosine were, in general, low nanomolar agonists of the A1 adenosine receptor. The known partial agonist, N6-cyclopentyl-5'-deoxy-5'-ethylthioadenosine (2), also behaved as a full agonist in our assay.
Ashton
T D
TD
Department of Medicinal Chemistry, Victorian College of Pharmacy, Monash University, 381 Royal Parade, Parkville, Vic. 3052, Australia.
Baker
Stephen P
SP
Hutchinson
Sally A
SA
Scammells
Peter J
PJ
D000241:Adenosine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology*; D058907:Adenosine A1 Receptor Agonists; D006574:Heterocyclic Compounds, 2-Ring; D006575:Heterocyclic Compounds, 3-Ring; D006801:Humans; D013329:Structure-Activity Relationship
D058907:Adenosine A1 Receptor Agonists; D006574:Heterocyclic Compounds, 2-Ring; D006575:Heterocyclic Compounds, 3-Ring; D000241:Adenosine