ANTITUMOR-ACTIVITY OF 5-ARYL-2,3-DIHYDROIMIDAZO[2,1-A]ISOQUINOLINES

A series of 5-aryl-2,3-dihydroimidazo[2,1-alpha]isoquinolines previous ly reported to be platelet activating factor (PAF) receptor antagonist s 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 cyto toxicity against several tumor cell lines. )phenyl]-2,3-dihydroimidazo [2,1-alpha]isoquinoline (SDZ 62-434, 53) was more effective on a milli gram per kilogram basis than the clinical cytostatic agent edelfosine (1) in increasing survivors and decreasing tumor volume in the oral mo use Meth A fibrosarcoma assay. It was selected for further development and is currently in phase I clinical trials in cancer patients.