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.
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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)
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Chemical References |
- Antineoplastic Agents
- Isoquinolines
- Platelet Activating Factor
- Platelet Membrane Glycoproteins
- Receptors, Cell Surface
- Receptors, G-Protein-Coupled
- platelet activating factor receptor
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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)
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