title: Synthesis, biological and modeling studies of 1,3-di-n-propyl-2,4-dioxo-6-methyl-8-(substituted) 1,2,3,4-tetrahydro [1,2,4]-triazolo [3,4-f]-purines as adenosine receptor antagonists.
abstract: A new series of potential adenosine receptor antagonists with a [1,2,4]-triazolo-[3,4-f]-purine structure bearing at the 1 and 3 position n-propyl groups have been synthesized, and their affinities at the four human adenosine receptor subtypes (A(1), A(2A), A(2B) and A(3)) have been evaluated. In this case the presence of n-propyl groups seems to induce potency at the A(2A) and A(3) adenosine receptor subtypes as opposed to our previously reported series bearing methyl substituents at the 1 and 3 positions. In particular the non-acylated derivative 17 showed affinity at these two receptor subtypes in the micromolar range. Indeed, preliminary molecular modeling investigations according to the experimental binding data indicate a modest steric and electrostatic antagonist-receptor complementarity.
authors.affiliation: Dipartimento di Scienze Farmaceutiche, Università di Trieste, Piazzale Europa 1, 34127 Trieste, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Pastorin
authors.forename: C
authors.initials: C
authors.lastname: Bolcato
authors.forename: B
authors.initials: B
authors.lastname: Cacciari
authors.forename: S
authors.initials: S
authors.lastname: Kachler
authors.forename: K-N
authors.initials: KN
authors.lastname: Klotz
authors.forename: C
authors.initials: C
authors.lastname: Montopoli
authors.forename: S
authors.initials: S
authors.lastname: Moro
authors.forename: G
authors.initials: G
authors.lastname: Spalluto
mesh_terms: D058916:Adenosine A1 Receptor Antagonists; D058917:Adenosine A2 Receptor Antagonists; D058918:Adenosine A3 Receptor Antagonists; D000818:Animals; D001665:Binding Sites; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D011687:Purines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D013329:Structure-Activity Relationship
chemical_list: D058916:Adenosine A1 Receptor Antagonists; D058917:Adenosine A2 Receptor Antagonists; D058918:Adenosine A3 Receptor Antagonists; D011687:Purines