Antitumor activity of 5-aryl-2,3-dihydroimidazo[2,1-a]isoquinolines.

Abstract

A series of 5-aryl-2,3-dihydroimidazo[2,1-a]isoquinolines previously reported to be platelet activating factor (PAF) receptor antagonists were evaluated for potential antitumor activity. Several compounds, such as the 5-(4'-tert-butylphenyl) (65), 5-[4'-(trimethylsilyl)phenyl] (69), and 5-(4'-cyclohexylphenyl) (71) analogs showed very good cytotoxicity against several tumor cell lines. 5-[4'-(Piperidinomethyl)phenyl]-2,3-dihydroimidazo[2,1- a]isoquinoline (SDZ 62-434, 53) was more effective on a milligram per kilogram basis than the clinical cytostatic agent edelfosine (1) in increasing survivors and decreasing tumor volume in the oral mouse Meth A fibrosarcoma assay. It was selected for further development and is currently in phase I clinical trials in cancer patients.

• Authors: W J Houlihan, P G Munder, D A Handley, S H Cheon, V A Parrino
• Journal: Journal of medicinal chemistry (J Med Chem) Vol. 38 Issue 2 Pg. 234-40 (Jan 20 1995) ISSN: 0022-2623 [Print] United States
• PMID: 7830265 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents
• Isoquinolines
• Platelet Activating Factor
• Platelet Membrane Glycoproteins
• Receptors, Cell Surface
• Receptors, G-Protein-Coupled
• platelet activating factor receptor

Topics

• Animals
• Antineoplastic Agents
• Binding, Competitive
• Humans
• In Vitro Techniques
• Isoquinolines (chemical synthesis, pharmacology)
• Magnetic Resonance Spectroscopy
• Mice
• Platelet Activating Factor (metabolism)
• Platelet Membrane Glycoproteins (antagonists & inhibitors, metabolism)
• Receptors, Cell Surface
• Receptors, G-Protein-Coupled
• Tumor Cells, Cultured (drug effects)