Adenosine deaminase inhibitors: synthesis, diastereoisomeric resolution and biological activity of 1-(2-hydroxy-3-nonyl)-1,2,4-triazole-3-carboxamide

Farmaco. 1997 Jun-Jul;52(6-7):429-33.

Abstract

The synthesis and the diastereoisomeric resolution of 9-(2-hydroxy-3-nonyl)-1,2,4-triazole-3-carboxamide (8e and 8t) were undertaken in order to investigate the structural requirements of the adenosine deaminase inhibitory site, through simplification of the purine moiety of 9-(2-hydroxy-3-nonyl)adenine (1a, EHNA). The new compounds resulted to be good inhibitors of the enzyme, the erythro isomer being more potent than the threo one (8e, Ki = 0.11 microM vs 8t, Ki = 1.4 microM). However, the triazole derivatives did not show enhancement of inhibitory activity in comparison with the previously reported imidazole analogue 1b (Ki = 0.035 microM).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Deaminase Inhibitors*
  • Animals
  • Cattle
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / pharmacology*
  • Fatty Alcohols / chemistry
  • Fatty Alcohols / pharmacology*
  • Molecular Structure
  • Stereoisomerism
  • Triazoles / chemistry
  • Triazoles / pharmacology*

Substances

  • 1-(2-hydroxy-3-nonyl)-1,2,4-triazole-3-carboxamide
  • Adenosine Deaminase Inhibitors
  • Enzyme Inhibitors
  • Fatty Alcohols
  • Triazoles