Synthesis and pharmacological evaluation of novel 1,3,8- and 1,3,7,8-substituted xanthines as adenosine receptor antagonists

Bioorg Med Chem. 2010 Mar 1;18(5):2001-9. doi: 10.1016/j.bmc.2010.01.028. Epub 2010 Jan 15.

Abstract

A number of novel xanthines bearing a variety of substituents at positions 1, 3, 7 and 8 were prepared and evaluated for their binding affinity to the human adenosine receptor A(1), A(2A), A(2B) and A(3) subtypes. Several of the 1,3,8- and 1,3,7,8-substituted xanthines showed moderate-to-high affinity at human A(2B) and A(1) receptors, with the most active compound (14q) having a pK(i) of 7.57 nM for hA(2B) receptors and a selectivity over hA(2A) receptors of 8.1-fold and hA(1) receptors of 3.7-fold.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine A1 Receptor Antagonists
  • Adenosine A2 Receptor Antagonists
  • Adenosine A3 Receptor Antagonists
  • Anti-Inflammatory Agents / chemical synthesis*
  • Anti-Inflammatory Agents / chemistry
  • Anti-Inflammatory Agents / pharmacology
  • Cell Line
  • HeLa Cells
  • Humans
  • Purinergic P1 Receptor Antagonists*
  • Receptor, Adenosine A1 / metabolism
  • Receptor, Adenosine A2A / metabolism
  • Receptor, Adenosine A2B / metabolism
  • Receptor, Adenosine A3 / metabolism
  • Receptors, Purinergic P1 / metabolism
  • Structure-Activity Relationship
  • Xanthines / chemical synthesis
  • Xanthines / chemistry*
  • Xanthines / pharmacology

Substances

  • Adenosine A1 Receptor Antagonists
  • Adenosine A2 Receptor Antagonists
  • Adenosine A3 Receptor Antagonists
  • Anti-Inflammatory Agents
  • Purinergic P1 Receptor Antagonists
  • Receptor, Adenosine A1
  • Receptor, Adenosine A2A
  • Receptor, Adenosine A2B
  • Receptor, Adenosine A3
  • Receptors, Purinergic P1
  • Xanthines