Synthesis and evaluation of two series of 4'-aza-carbocyclic nucleosides as adenosine A2A receptor agonists

Bioorg Med Chem Lett. 2010 Feb 1;20(3):1219-24. doi: 10.1016/j.bmcl.2009.11.131. Epub 2009 Dec 1.

Abstract

The synthesis of two series of 4'-aza-carbocyclic nucleosides are described in which the 4'-substituent is either a reversed amide, relative to the carboxamide of NECA, or an N-bonded heterocycle. Using established purine substitution patterns, potent and selective examples of agonists of the human adenosine A(2A) receptor have been identified from both series. The propionamides 14-18 and the 4-hydroxymethylpyrazole 32 were determined to be the most potent and selective examples from the 4'-reversed amide and 4'-N-bonded heterocyclic series, respectively.

Publication types

  • Comparative Study

MeSH terms

  • Adenosine A2 Receptor Agonists*
  • Animals
  • Aza Compounds / chemical synthesis*
  • Aza Compounds / metabolism
  • Aza Compounds / pharmacology
  • CHO Cells
  • Carboxylic Acids / chemical synthesis*
  • Carboxylic Acids / metabolism
  • Carboxylic Acids / pharmacology
  • Cricetinae
  • Cricetulus
  • Drug Evaluation, Preclinical / methods
  • Humans
  • Nucleosides / chemical synthesis*
  • Nucleosides / metabolism
  • Nucleosides / pharmacology
  • Pyrimidine Nucleotides / chemical synthesis*
  • Pyrimidine Nucleotides / metabolism
  • Pyrimidine Nucleotides / pharmacology
  • Rats
  • Receptor, Adenosine A2A / metabolism

Substances

  • Adenosine A2 Receptor Agonists
  • Aza Compounds
  • Carboxylic Acids
  • Nucleosides
  • Pyrimidine Nucleotides
  • Receptor, Adenosine A2A