1,2,4-Triazolo[1,5-a]quinoxaline derivatives: synthesis and biological evaluation as adenosine receptor antagonists

Farmaco. 2004 Feb;59(2):71-81. doi: 10.1016/j.farmac.2003.09.005.

Abstract

Since most of the reported adenosine receptor antagonists are 2-(hetero)aryl-substituted tricyclic heteroaromatic derivatives, in the present study we report the synthesis and the biological evaluation of a new set of 4-amino-1,2,4-triazolo[1,5-a]quinoxalines containing at position-2 an ethyl carboxylate group or a hydrogen atom. The structure-activity relationships on these compounds were in accordance with those of a previously reported series of analogous size and shape, thus suggesting a similar A(1)-binding mode. In particular, the binding data indicate that alkylation of the 4-amino group of these derivatives lead to potent A(1)-receptor antagonists. Moreover, as new results, this study has pointed out that the ethyl 2-carboxylate group can advantageously replace the 2-(hetero)aryl ring of previously reported triazoloquinoxaline derivatives, affording an ameliorated interaction with the A(1)-receptor subtype.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine / analogs & derivatives
  • Adenosine / pharmacology
  • Adenosine A1 Receptor Antagonists
  • Adenosine A2 Receptor Antagonists
  • Adenosine A3 Receptor Antagonists
  • Animals
  • Binding, Competitive / drug effects
  • CHO Cells
  • Cattle
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / metabolism
  • Cricetinae
  • Humans
  • In Vitro Techniques
  • Indicators and Reagents
  • Kinetics
  • Magnetic Resonance Spectroscopy
  • Neostriatum / metabolism
  • Purinergic P1 Receptor Antagonists*
  • Quinoxalines / chemical synthesis*
  • Quinoxalines / pharmacology*
  • Spectrophotometry, Infrared
  • Structure-Activity Relationship
  • Triazoles / chemical synthesis*
  • Triazoles / pharmacology*

Substances

  • 1,2,4-Triazolo(1,5-a)quinoxaline
  • Adenosine A1 Receptor Antagonists
  • Adenosine A2 Receptor Antagonists
  • Adenosine A3 Receptor Antagonists
  • Indicators and Reagents
  • Purinergic P1 Receptor Antagonists
  • Quinoxalines
  • Triazoles
  • N(6)-cyclohexyladenosine
  • Adenosine