Synthesis of desaza analogues of annomontine and canthin-4-one alkaloids

Arch Pharm (Weinheim). 2015 Feb;348(2):125-31. doi: 10.1002/ardp.201400328.

Abstract

1-Acetylcarbazoles are readily converted to 3-desazacanthin-4-ones upon treatment with Bredereck's reagent, but in contrast to canthin-4-ones, these do not undergo ring transformation reactions with guanidine. Only after N-protection (methyl or 2-(trimethylsilyl)ethoxymethyl group), 2-desaza analogues of the alkaloid annomontine are accessible via the enaminoketones obtained by condensation with Bredereck's reagent. One of the annomontine analogues is an inhibitor of the Plasmodium falciparum CDC-like kinases (CLK) and shows antimalarial activity.

Keywords: Alkaloids; Antimalarial activity; Desaza analogues; Kinase inhibitor.

Publication types

  • Comparative Study

MeSH terms

  • Antimalarials / chemical synthesis*
  • Antimalarials / pharmacology*
  • Carbolines / chemical synthesis*
  • Carbolines / pharmacology*
  • Drug Design*
  • Molecular Structure
  • Plasmodium falciparum / drug effects*
  • Plasmodium falciparum / enzymology
  • Protein Kinase Inhibitors / chemical synthesis
  • Protein Kinase Inhibitors / pharmacology
  • Protein Serine-Threonine Kinases / antagonists & inhibitors
  • Protein Serine-Threonine Kinases / metabolism
  • Protein-Tyrosine Kinases / antagonists & inhibitors
  • Protein-Tyrosine Kinases / metabolism
  • Protozoan Proteins / antagonists & inhibitors
  • Protozoan Proteins / metabolism
  • Pyrimidines / chemical synthesis*
  • Pyrimidines / pharmacology*
  • Structure-Activity Relationship

Substances

  • Antimalarials
  • Carbolines
  • Protein Kinase Inhibitors
  • Protozoan Proteins
  • Pyrimidines
  • annomontine
  • Clk dual-specificity kinases
  • Protein-Tyrosine Kinases
  • Protein Serine-Threonine Kinases