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 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.
Cheon
S H
SH
College of Pharmacy, Chonnam National University, 300 Yongbong-Dong Buk-Ku, 500-757, Kwangju, Korea.
Park
J S
JS
Jeong
S H
SH
Chung
B H
BH
Choi
B G
BG
Cho
W J
WJ
Kang
B H
BH
Lee
C O
CO