Carbamate substituted 2-amino-4,6-diphenylpyrimidines as adenosine receptor antagonists

Bioorg Med Chem Lett. 2016 Feb 1;26(3):734-738. doi: 10.1016/j.bmcl.2016.01.004. Epub 2016 Jan 5.

Abstract

A novel series of carbamate substituted 2-amino-4,6-diphenylpyrimidines was evaluated as potential dual adenosine A1 and A2A receptor antagonists. The majority of the synthesised compounds exhibited promising dual affinities, with A1Ki values ranging from 0.175 to 10.7 nM and A2AKi values ranging from 1.58 to 451 nM. The in vivo activity illustrated for 3-(2-amino-6-phenylpyrimidin-4-yl)phenyl morpholine-4-carboxylate (4c) is indicative of the potential of these compounds as therapeutic agents in the treatment of Parkinson's disease, although physicochemical properties may require optimisation.

Keywords: 2-Aminopyrimidine; Adenosine A(1) and A(2A) receptor; Antagonist; Dual.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine A1 Receptor Antagonists / chemistry*
  • Adenosine A2 Receptor Antagonists / chemistry*
  • Binding Sites
  • Carbamates / chemistry
  • Humans
  • Hydrogen Bonding
  • Hydrophobic and Hydrophilic Interactions
  • Kinetics
  • Molecular Docking Simulation
  • Protein Binding
  • Protein Structure, Tertiary
  • Pyrimidines / chemistry*
  • Pyrimidines / metabolism
  • Receptor, Adenosine A1 / chemistry
  • Receptor, Adenosine A1 / metabolism
  • Receptor, Adenosine A2A / chemistry
  • Receptor, Adenosine A2A / metabolism
  • Structure-Activity Relationship

Substances

  • Adenosine A1 Receptor Antagonists
  • Adenosine A2 Receptor Antagonists
  • Carbamates
  • Pyrimidines
  • Receptor, Adenosine A1
  • Receptor, Adenosine A2A