Discovery and characterization of 4'-(2-furyl)-N-pyridin-3-yl-4,5'-bipyrimidin-2'-amine (LAS38096), a potent, selective, and efficacious A2B adenosine receptor antagonist

J Med Chem. 2007 May 31;50(11):2732-6. doi: 10.1021/jm061333v. Epub 2007 May 1.

Abstract

A novel series of N-heteroaryl 4'-(2-furyl)-4,5'-bipyrimidin-2'-amines has been identified as potent and selective A(2B) adenosine receptor antagonists. In particular, compound 5 showed high affinity for the A(2B) receptor (Ki = 17 nM), good selectivity (IC(50): A(1) > 1000 nM, A(2A) > 2500 nM, A3 > 1000 nM), displayed a favorable pharmacokinetic profile in preclinical species, and showed efficacy in functional in vitro models.

MeSH terms

  • Adenosine A2 Receptor Antagonists*
  • Animals
  • Cell Line
  • Cricetinae
  • Cricetulus
  • Dogs
  • Furans / chemical synthesis*
  • Furans / pharmacokinetics
  • Furans / pharmacology
  • Mice
  • Pyridines / chemical synthesis*
  • Pyridines / pharmacokinetics
  • Pyridines / pharmacology
  • Pyrimidines / chemical synthesis*
  • Pyrimidines / pharmacokinetics
  • Pyrimidines / pharmacology
  • Radioligand Assay
  • Rats
  • Structure-Activity Relationship

Substances

  • 4'-(2-furyl)-N-pyridin-3-yl-4,5'-bipyrimidin-2'-amine
  • Adenosine A2 Receptor Antagonists
  • Furans
  • Pyridines
  • Pyrimidines