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

Farmaco. 2005 Aug;60(8):643-51. doi: 10.1016/j.farmac.2005.04.012.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine A1 Receptor Antagonists
  • Adenosine A2 Receptor Antagonists
  • Adenosine A3 Receptor Antagonists*
  • Animals
  • Binding Sites
  • Drug Design*
  • Drug Evaluation, Preclinical
  • Humans
  • Models, Molecular
  • Molecular Structure
  • Protein Conformation
  • Protein Structure, Secondary
  • Purines* / chemical synthesis
  • Purines* / chemistry
  • Purines* / pharmacology
  • Rats
  • Structure-Activity Relationship

Substances

  • Adenosine A1 Receptor Antagonists
  • Adenosine A2 Receptor Antagonists
  • Adenosine A3 Receptor Antagonists
  • Purines