SYNTHESIS AND STRUCTURE-ACTIVITY RELATIONSHIP STUDIES OF 2,3-DIHYDROIMIDAZO[2,1-A]ISOQUINOLINE ANALOGS AS ANTITUMOR AGENTS

5-Aryl-2,3-dihydroimidazo [2,1-a]isoquinolines were reported to have s trong antitumor activity and one of the derivatives such as (piperidin omethyl)phenyl]-2,3-dihydroimidazo[,1-a] isoquinoline (1, SDZ 62-434) was found to be more effective than the clinical cytostatic agent edel fosine (2) in in vitro and in 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 ac tivity. Among the 3-arylisoquinolin-1-one derivatives, 3-[4'-(piperidi nomethyl)phenyl] substituted analog had no antitumor activity but simp le phenyl substituted compound, such as 4, showed the most potent anti tumor activity in various human tumor cell lines.