Preclinical pharmacology and possible mechanism of action of the novel antitumor agent 5-(4'-piperidinomethylphenyl)-2,3-dihydroimidazo [2,1-a]isoquinoline

Arzneimittelforschung. 1995 Oct;45(10):1133-7.

Abstract

SDZ 62-434 (CAS 115621-95-9, 5-(4'-piperidinomethylphenyl)-2,3-dihydroimidazo [2,1-a]isoquinoline dihydrochloride), a member of a novel class of antitumor agents, exhibited direct and macrophage-induced cytotoxicity against a variety of murine tumor cell lines. It is more effective than edelfosine in increasing survivors and reducing tumor volume in the oral mouse Meth A fibrosarcoma model. Preliminary studies suggest that an undefined cytotoxic effect, macrophage activation and possible effects on signal transduction may account for its antitumor mechanism of action. SDZ 62-434 is currently in Phase I clinical trials as a potential antitumor agent.

MeSH terms

  • Allantoin / metabolism
  • Animals
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / toxicity
  • Bronchodilator Agents / pharmacology
  • Cell Survival / drug effects
  • Chick Embryo
  • Dogs
  • Drug Screening Assays, Antitumor
  • Fibroblasts / drug effects
  • Fibroblasts / metabolism
  • Guinea Pigs
  • Hemodynamics / drug effects
  • Hemolysis / drug effects
  • Humans
  • Imidazoles / pharmacology*
  • Imidazoles / toxicity
  • In Vitro Techniques
  • Isoquinolines / pharmacology*
  • Isoquinolines / toxicity
  • Macrophage Activation / drug effects
  • Male
  • Mice
  • Mice, Inbred Strains
  • Neoplasm Transplantation
  • Platelet Aggregation / drug effects
  • Rats
  • Rats, Sprague-Dawley
  • Signal Transduction / drug effects
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents
  • Bronchodilator Agents
  • Imidazoles
  • Isoquinolines
  • SDZ 62-434
  • Allantoin