Discovery of aminoquinazoline derivatives as human A(2A) adenosine receptor antagonists

Bioorg Med Chem Lett. 2016 Feb 15;26(4):1348-54. doi: 10.1016/j.bmcl.2015.11.048. Epub 2015 Dec 1.

Abstract

Novel bicyclic adenosine A(2A) antagonists with an aminoquinazoline moiety were designed and synthesized. The optimization of the initial lead compound based on in vitro and in vivo activity has led to the discovery of a potent and selective class of adenosine A(2A) antagonists. The structure-activity relationships of this novel series of bicyclic aminoquinazoline derivatives as adenosine A(2A) antagonists are described in detail.

Keywords: Adenosine A(2A) receptor antagonist; Aminoquinazoline; Parkinson’s disease.

MeSH terms

  • Adenosine A2 Receptor Antagonists / chemical synthesis
  • Adenosine A2 Receptor Antagonists / chemistry*
  • Adenosine A2 Receptor Antagonists / pharmacokinetics
  • Animals
  • Binding Sites
  • Drug Design
  • Half-Life
  • Humans
  • Inhibitory Concentration 50
  • Molecular Docking Simulation
  • Protein Structure, Tertiary
  • Quinazolines / chemical synthesis
  • Quinazolines / chemistry*
  • Quinazolines / pharmacokinetics
  • Rats
  • Receptor, Adenosine A2A / chemistry*
  • Receptor, Adenosine A2A / metabolism
  • Structure-Activity Relationship

Substances

  • Adenosine A2 Receptor Antagonists
  • Quinazolines
  • Receptor, Adenosine A2A