Houlihan W J, Munder P G, Handley D A, Cheon S H, Parrino V A
Sandoz Research Institute, Sandoz Pharmaceuticals Corporation, East Hanover, New Jersey 07936.
J Med Chem. 1995 Jan 20;38(2):234-40. doi: 10.1021/jm00002a004.
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.
先前报道的一系列5-芳基-2,3-二氢咪唑并[2,1-a]异喹啉被评估其作为血小板活化因子（PAF）受体拮抗剂的潜在抗肿瘤活性。几种化合物，如5-（4'-叔丁基苯基）（65）、5-[4'-（三甲基甲硅烷基）苯基]（69）和5-（4'-环己基苯基）（71）类似物对几种肿瘤细胞系显示出非常好的细胞毒性。在口服小鼠Meth A纤维肉瘤试验中，5-[4'-（哌啶甲基）苯基]-2,3-二氢咪唑并[2,1-a]异喹啉（SDZ 62-434，53）在每千克毫克的基础上比临床细胞生长抑制剂依地福新（1）在增加存活者和减小肿瘤体积方面更有效。它被选择用于进一步开发，目前正在癌症患者中进行I期临床试验。
