SYNTHESIS AND ANTITUMOR-ACTIVITY OF STRUCTURAL ANALOGS OF THE EPIPODOPHYLLOTOXINS

被引:34
作者
KLEIN, LL
YEUNG, CM
CHU, DT
MCDONALD, EJ
CLEMENT, JJ
PLATTNER, JJ
机构
[1] Anti-Infective Division, Abbott Laboratories, Abbott Park
关键词
D O I
10.1021/jm00107a016
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
Several ring-contracted analogues of the antitumor agent etoposide have been prepared. The synthesis of the simple indanyl system 3 is described along with two bicyclic systems of general structure 4 prepared through a stereoselective allylation of the keto-ester 6. A cis-fused lactone analogue 5, which is isomeric with the etoposide aglycone, has been synthesized via a dialkylation of the indene-2-carboxylate anion. Regiochemical and stereochemical results of these alkylations are described. The cytotoxicity of these derivatives toward several tumor cell lines is described and generally follows the structure-activity relationships known for the agent podophyllotoxin (2).
引用
收藏
页码:984 / 992
页数:9
相关论文
共 25 条
[1]  
ASO Y, 1989, CHEM PHARM BULL, V37, P422
[2]  
BEARD AR, 1987, ANTI-CANCER DRUG DES, V2, P247
[3]   ANTITUMOR AGENTS .99. SYNTHETIC RING C AROMATIZED PODOPHYLLOTOXIN ANALOGS AS POTENTIAL INHIBITORS OF HUMAN DNA TOPOISOMERASE-II [J].
BEERS, SA ;
IMAKURA, Y ;
DAI, HJ ;
LI, DH ;
CHENG, YC ;
LEE, KH .
JOURNAL OF NATURAL PRODUCTS, 1988, 51 (05) :901-905
[4]  
Bures M., UNPUB
[5]   NON-ENOLIZABLE PODOPHYLLOTOXIN DERIVATIVES [J].
GENSLER, WJ ;
MURTHY, CD ;
TRAMMELL, MH .
JOURNAL OF MEDICINAL CHEMISTRY, 1977, 20 (05) :635-644
[6]  
HANAYA K, 1978, NIPPON KAGAKU KAISHI, V2, P238
[7]   STEREOSELECTIVE SYNTHESIS OF AN ANALOG OF PODOPHYLLOTOXIN BY AN INTRAMOLECULAR DIELS-ALDER REACTION [J].
JUNG, ME ;
LAM, PY ;
MANSURI, MM ;
SPELTZ, LM .
JOURNAL OF ORGANIC CHEMISTRY, 1985, 50 (07) :1087-1105
[8]   MITOSIS INHIBITING NATURAL PRODUCTS .24. SYNTHESIS AND ANTIMITOTIC ACTIVITY OF GLYCOSIDIC LIGNAN DERIVATIVES RELATED TO PODOPHYLLOTOXIN [J].
KELLERJU.C ;
KUHN, M ;
WARTBURG, AV ;
STAHELIN, H .
JOURNAL OF MEDICINAL CHEMISTRY, 1971, 14 (10) :936-&
[9]  
Klein Lilviu, UNPUB
[10]  
KOHLBRENNER WE, UNPUB