2-[N'-(3-arylallylidene)hydrazino]adenosines showing A2a adenosine agonist properties and vasodilation activity.
A series of 2-[N'-(3-arylallylidene)hydrazino]adenosines were prepared and studied in binding and functional assays to assess their potency for the A2a compared with the A1 adenosine receptor. These analogs possess A2a receptor affinity in the low nanomolar range associated with weak interaction with the A1 receptor. Among the compounds, in rat tissues, 2-[N'-[3-(4-nitrophenyl)allylidene] hydrazinoadenosine (5g) had the most potent affinity for the A2a receptor, the K(i) value being 23 nM. The type and position of substituents on the phenyl ring show a moderate influence on biological activity, allowing the conclusion that the latter is mostly due to the allylidenehydrazino side chain. From functional experiments 2-[N'-(2-furylmethylidene)hydrazino]adenosine (4b), 2-[N'-(3-phenylallylidene)hydrazino]adenosine (5a) and 2-[N'-[3-(2-furyl)allylidene]hydrazino]adenosine (5b) appeared to be potent in inducing vasorelaxation (an A2a-mediated response) without appreciable effects on the heart rate (an A1-mediated action). While the lack of effects on heart rate is clearly explained by the poor affinity for A1 receptors, more difficult appears the interpretation of vasorelaxant properties displayed by some compounds. Affinity for A2a has a major role, but other types of interactions, yet to be identified, may play a part.
Viziano
M
M
Instituto di Chimica Organica, Facoltà di Farmacia, Università di Milano, Italy.
Ongini
E
E
Conti
A
A
Zocchi
C
C
Seminati
M
M
Pocar
D
D
D000241:Adenosine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000187:drug effects; D006834:Hydrazines / Q000737:chemistry / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D058906:Purinergic P1 Receptor Agonists; D051381:Rats; D017207:Rats, Sprague-Dawley; D043705:Receptor, Adenosine A2A; D018047:Receptors, Purinergic P1 / Q000378:metabolism; D013329:Structure-Activity Relationship; D014665:Vasodilator Agents / Q000737:chemistry / Q000494:pharmacology*
D006834:Hydrazines; D058906:Purinergic P1 Receptor Agonists; D043705:Receptor, Adenosine A2A; D018047:Receptors, Purinergic P1; D014665:Vasodilator Agents; D000241:Adenosine