Substituted pyridazino[3,4-b][1,5]benzoxazepin-5(6H)ones as multidrug-resistance modulating agents

J Med Chem. 2004 Aug 26;47(18):4627-30. doi: 10.1021/jm040803n.

Abstract

Pyridazino[3,4-b][1,5]benzoxazepin-5(6H)ones substituted with propylene-linked basic side chains were synthesized and investigated for the ability to reverse multidrug resistance (MDR) at vincristine-pretreated HeLa-MDR1 cells. The substances were found to be effective chemosensitizers with activity comparable to that of the known MDR modulator verapamil. The observed antiproliferative effects were not caused by direct drug cytotoxicity.

MeSH terms

  • Cell Division / drug effects
  • Dibenzoxazepines / chemical synthesis*
  • Dibenzoxazepines / pharmacology
  • Drug Resistance, Multiple / drug effects*
  • HeLa Cells
  • Humans
  • Ketones / chemical synthesis
  • Ketones / pharmacology
  • Structure-Activity Relationship
  • Vincristine / pharmacology

Substances

  • Dibenzoxazepines
  • Ketones
  • Vincristine