title: Synthesis, biological studies and molecular modeling investigation of 1,3-dimethyl-2,4-dioxo-6-methyl-8-(substituted) 1,2,3,4-tetrahydro [1,2,4]-triazolo [3,4-f]-purines as potential adenosine receptor antagonists.
abstract: A new series of potential adenosine receptor antagonists with a [1,2,4]-triazolo-[3,4-f]-purine structure have been synthesized, and their affinities at the four adenosine receptor subtypes (A1, A2A, A2B and A3) have been evaluated. The design was based on the demonstrated approach to novel A3 adenosine receptor antagonists of adding a third ring to the xanthine structure. Unfortunately, all the synthesized compounds were completely inactive at all four adenosine receptor subtypes independently of their substitutions. Preliminary molecular modeling investigation has demonstrated that only a low degree of steric and electrostatic complementarity has been observed for all the new synthesized triazolo-purines with respect to other structurally related A3 receptor antagonists. This analysis yielded valuable information about structure-activity relationships and further design of potential adenosine receptor antagonists.
authors.affiliation: Dipartimento di Scienze Farmaceutiche, Università di Trieste, Piazzale Europa 1, I-34127, Trieste, Italy.
authors.forename: Giorgia
authors.initials: G
authors.lastname: Pastorin
authors.forename: Chiara
authors.initials: C
authors.lastname: Bolcato
authors.forename: Barbara
authors.initials: B
authors.lastname: Cacciari
authors.forename: Sonja
authors.initials: S
authors.lastname: Kachler
authors.forename: Karl-Norbert
authors.initials: KN
authors.lastname: Klotz
authors.forename: Christian
authors.initials: C
authors.lastname: Montopoli
authors.forename: Stefano
authors.initials: S
authors.lastname: Moro
authors.forename: Giampiero
authors.initials: G
authors.lastname: Spalluto
mesh_terms: D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D001665:Binding Sites; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D006224:Cricetinae; D003412:Cricetulus; D003500:Cyclization; D008958:Models, Molecular; D015394:Molecular Structure; D011485:Protein Binding; D058915:Purinergic P1 Receptor Antagonists; D011687:Purines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D058915:Purinergic P1 Receptor Antagonists; D011687:Purines; D014230:Triazoles; D000262:Adenylyl Cyclases