1,3-Dipropyl-8-(1-phenylacetamide-1H-pyrazol-3-yl)-xanthine derivatives as highly potent and selective human A(2B) adenosine receptor antagonists

Bioorg Med Chem. 2008 Mar 1;16(5):2419-30. doi: 10.1016/j.bmc.2007.11.058. Epub 2007 Nov 28.

Abstract

A new series of 1,3-dipropyl-8-(1-phenylacetamide-1H-pyrazol-3-yl)-xanthine derivatives has been identified as potent A(2B) adenosine receptor antagonists. The products have been evaluated for their binding affinities for the human A(2B), A(1), A(2A), and A(3) adenosine receptors. N-(4-chloro-phenyl)-2-[3-(2,6-dioxo-1,3-dipropyl-2,3,6,7-tetrahydro-1H-purin-8-yl)-5-methyl-pyrazol-1-yl] (11c) showed a high affinity for the human A(2B) adenosine receptor K(i)=7nM and good selectivity (A(1), A(2A), A(3)/A(2B)>140). Synthesis and SAR of this novel class of compounds is presented herein.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine A2 Receptor Antagonists*
  • Humans
  • Magnetic Resonance Spectroscopy
  • Molecular Structure
  • Pyrazoles / chemical synthesis*
  • Pyrazoles / chemistry
  • Pyrazoles / pharmacology*
  • Receptor, Adenosine A2B / metabolism*
  • Structure-Activity Relationship
  • Xanthines / chemical synthesis*
  • Xanthines / chemistry
  • Xanthines / pharmacology*

Substances

  • 1,3-dipropyl-8-(1-phenylacetamide-1H-pyrazol-3-yl)-xanthine
  • Adenosine A2 Receptor Antagonists
  • Pyrazoles
  • Receptor, Adenosine A2B
  • Xanthines