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

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 c...

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Bibliographic Details
Published in:Farmaco (Società chimica italiana : 1989) 2005-08, Vol.60 (8), p.643-651
Main Authors: Pastorin, G., Bolcato, C., Cacciari, B., Kachler, S., Klotz, K.-N., Montopoli, C., Moro, S., Spalluto, G.
Format: Article
Language:English
Subjects:
Adenosine A1 Receptor Antagonists
Adenosine A2 Receptor Antagonists
Adenosine A3 Receptor Antagonists
Adenosine receptors
Animals
Antagonists
Binding Sites
Cycloaddition
Drug Design
Drug Evaluation, Preclinical
G-protein-coupled receptors
Humans
Models, Molecular
Molecular Structure
Protein Conformation
Protein Structure, Secondary
Purines - chemical synthesis
Purines - chemistry
Purines - pharmacology
Rats
Structure-Activity Relationship
Xanthine
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Summary: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.
ISSN:0014-827X
1879-0569
DOI:10.1016/j.farmac.2005.04.012