Structure-activity relationships of 8-cycloalkyl-1,3-dipropylxanthines as antagonists of adenosine receptors

J Med Chem. 1990 Jul;33(7):1906-10. doi: 10.1021/jm00169a012.


8-Substituted xanthines currently represent the most potent class of adenosine-receptor antagonists. A series of 8-substituted 1,3-dipropylxanthines was prepared and their potency as antagonists of A1 and A2 adenosine receptors of human platelets and rat adipocytes, respectively, were determined. No agents studied were as potent as 8-cyclopentyl-1,3-dipropylxanthine as antagonists of the A1 adenosine receptor, but 8-(2-methylcyclopropyl)-1,3-dipropylxanthine was at least 1000-fold more potent as an antagonist of A1 than of A2 adenosine receptors. While most substitutions on the 8-cycloalkyl moiety caused decreased potency to inhibit both A1 and A2 adenosine receptors, 8-[trans-4-(acetamidomethyl)cyclohexyl]-1,3-dipropylxanthine was nearly equipotent as an antagonist of the two receptors and appeared to be the most potent antagonist of A2 adenosine receptors reported to date.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 1-Methyl-3-isobutylxanthine / pharmacology
  • Adenylyl Cyclase Inhibitors*
  • Adenylyl Cyclases / blood
  • Adipose Tissue / enzymology
  • Alkylation
  • Animals
  • Blood Platelets / enzymology
  • Cell Membrane / enzymology
  • Humans
  • Indicators and Reagents
  • Kinetics
  • Molecular Structure
  • Rats
  • Receptors, Purinergic / drug effects*
  • Receptors, Purinergic / metabolism
  • Structure-Activity Relationship
  • Xanthines / chemical synthesis*
  • Xanthines / pharmacology


  • Adenylyl Cyclase Inhibitors
  • Indicators and Reagents
  • Receptors, Purinergic
  • Xanthines
  • Adenylyl Cyclases
  • 1-Methyl-3-isobutylxanthine