title: Preclinical pharmacology and possible mechanism of action of the novel antitumor agent 5-(4'-piperidinomethylphenyl)-2,3-dihydroimidazo [2,1-a]isoquinoline.
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.
authors.affiliation: Atherosclerosis and Vascular Biology, Preclinical Research, Sandoz Pharmaceuticals Corporation, East Hanover, NJ USA.
authors.forename: W J
authors.initials: WJ
authors.lastname: Houlihan
authors.forename: P G
authors.initials: PG
authors.lastname: Munder
authors.forename: D A
authors.initials: DA
authors.lastname: Handley
authors.forename: G A
authors.initials: GA
authors.lastname: Nemecek
mesh_terms: D000481:Allantoin / Q000378:metabolism; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000633:toxicity; D001993:Bronchodilator Agents / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D002642:Chick Embryo; D004285:Dogs; D004354:Drug Screening Assays, Antitumor; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006168:Guinea Pigs; D006439:Hemodynamics / Q000187:drug effects; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology* / Q000633:toxicity; D066298:In Vitro Techniques; D007546:Isoquinolines / Q000494:pharmacology* / Q000633:toxicity; D008262:Macrophage Activation / Q000187:drug effects; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009368:Neoplasm Transplantation; D010974:Platelet Aggregation / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D001993:Bronchodilator Agents; D007093:Imidazoles; D007546:Isoquinolines; C081240:SDZ 62-434; D000481:Allantoin