title: 2-n-Butyl-9-methyl-8-[1,2,3]triazol-2-yl-9H-purin-6-ylamine and analogues as A2A adenosine receptor antagonists. Design, synthesis, and pharmacological characterization.
abstract: Two types of adenosine receptor ligands were designed, i.e., 9H-purine and 1H-imidazo[4,5-c]pyridines, to obtain selective A(2A) antagonists, and we report here their synthesis and binding affinities for the four adenosine receptor subtypes A(1), A(2A), A(2B) and A(3). The design was carried out on the basis of the molecular modeling of a number of potent adenosine receptor antagonists described in the literature. Three compounds (25b-d) showed an interesting affinity and selectivity for the A(2A) subtype. One of them, i.e., ST1535 (2-n-butyl-9-methyl-8-[1,2,3]triazol-2-yl-9H-purin-6-ylamine, 25b) (K(i) A(2A) = 6.6 nM, K(i) A(1)/A(2A) = 12; K(i) A(2B)/A(2A) = 58; K(i) A(3)/A(2A) > 160), was selected for in vivo study and shown to induce a dose-related increase in locomotor activity, suggestive of an A(2A) antagonist type of activity.
authors.affiliation: Istituto di Chimica Farmaceutica, Università degli Studi di Urbino Carlo Bo, Piazza del Rinascimento 6, 61029 Urbino (PU), Italy. Patrizia.Minetti@sigma-tau.it
authors.forename: Patrizia
authors.initials: P
authors.lastname: Minetti
authors.forename: Maria Ornella
authors.initials: MO
authors.lastname: Tinti
authors.forename: Paolo
authors.initials: P
authors.lastname: Carminati
authors.forename: Massimo
authors.initials: M
authors.lastname: Castorina
authors.forename: Maria Assunta
authors.initials: MA
authors.lastname: Di Cesare
authors.forename: Stefano
authors.initials: S
authors.lastname: Di Serio
authors.forename: Grazia
authors.initials: G
authors.lastname: Gallo
authors.forename: Orlando
authors.initials: O
authors.lastname: Ghirardi
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Giorgi
authors.forename: Luca
authors.initials: L
authors.lastname: Giorgi
authors.forename: Giovanni
authors.initials: G
authors.lastname: Piersanti
authors.forename: Francesca
authors.initials: F
authors.lastname: Bartoccini
authors.forename: Giorgio
authors.initials: G
authors.lastname: Tarzia
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D058917:Adenosine A2 Receptor Antagonists; D000818:Animals; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D015195:Drug Design; D006801:Humans; D007093:Imidazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D008297:Male; D008958:Models, Molecular; D009043:Motor Activity / Q000187:drug effects; D011687:Purines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011869:Radioligand Assay; D051381:Rats; D011916:Rats, Inbred F344; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
chemical_list: C506291:2-n-butyl-9-methyl-8-(1,2,3)triazol-2-yl-9H-purin-6-ylamine; D058917:Adenosine A2 Receptor Antagonists; D007093:Imidazoles; D011687:Purines; D014230:Triazoles; D000225:Adenine