Cheon S H, Park J S, Jeong S H, Chung B H, Choi B G, Cho W J, Kang B H, Lee C O
College of Pharmacy, Chonnam National University, 300 Yongbong-Dong Buk-Ku, 500-757, Kwangju, Korea.
Arch Pharm Res. 1997 Apr;20(2):138-43. doi: 10.1007/BF02974000.
5-Aryl-2,3-dihydroimidazo[2,1-a]isoquinolines were reported to have strong antitumor activity and one of the derivatives such as 5-[4'-(piperidinomethyl)phenyl]-2,3-dihydroimidazo[2,1-a] isoquinoline (1, SDZ 62-434) was found to be more effective than the clinical cytostatic agent edelfosine (2) inin vitro andin vivo assays. Currently SDZ 62-434 is in clinical trials in Europe. The structure-activity relationship studies of SDZ 62-434 showed that compounds with substitution on ring A were less active than the lead compound. Ring B in SDZ 62-434 was essential for the activity because compounds without B ring had no antitumor activity. Among the 3-arylisoquinolin-1-one derivatives, 3-[4'-(piperidonomethyl)phenyl] substituted analog had no antitumor activity but simple phenyl substituted compound, such as4, showed the most potent antitumor activity in various human tumor cell lines.
据报道，5-芳基-2,3-二氢咪唑并[2,1-a]异喹啉具有很强的抗肿瘤活性，其中一种衍生物，如5-[4'-(哌啶甲基)苯基]-2,3-二氢咪唑并[2,1-a]异喹啉（1，SDZ 62-434），在体外和体内试验中被发现比临床使用的细胞生长抑制剂依地福新（2）更有效。目前，SDZ 62-434正在欧洲进行临床试验。对SDZ 62-434的构效关系研究表明，A环上有取代基的化合物比先导化合物的活性低。SDZ 62-434中的B环对活性至关重要，因为没有B环的化合物没有抗肿瘤活性。在3-芳基异喹啉-1-酮衍生物中，3-[4'-(哌啶酮甲基)苯基]取代的类似物没有抗肿瘤活性，但简单的苯基取代化合物，如4，在各种人类肿瘤细胞系中显示出最强的抗肿瘤活性。
