Chromophore-modified antineoplastic imidazoacridinones. Synthesis and activity against murine leukemias

J Med Chem. 1992 Jan 24;35(2):378-82. doi: 10.1021/jm00080a026.


The synthesis of 8-hydroxy and 8-methoxy analogues of some substituted 5-aminoimidazoacridinones (4) is described. The synthesis was carried out by a three-step sequence from the corresponding 1-chloro-4-nitro-9(10H)-acridinone precursors (1). The annulation of the imidazolo ring onto the aminoacridinone chromophore was accomplished by heating the required aminoacridinone (3) with formic acid or, in the case of 1-methyl derivatives, with N,N-dimethylacetamide. Potent cytotoxic activity against L1210 leukemia, as well as antitumor activity against P388 leukemia in mice, was demonstrated for the 8-hydroxy analogues. The corresponding 8-methoxy derivatives were not cytotoxic. However, in some cases, they showed significant in vivo antileukemic activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aminoacridines / chemical synthesis*
  • Aminoacridines / therapeutic use
  • Animals
  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / therapeutic use
  • Imidazoles / chemical synthesis
  • Imidazoles / therapeutic use
  • Leukemia L1210 / drug therapy
  • Leukemia P388 / drug therapy
  • Leukemia, Experimental / drug therapy*
  • Male
  • Mice
  • Structure-Activity Relationship
  • Tumor Cells, Cultured


  • Aminoacridines
  • Antineoplastic Agents
  • Imidazoles