Journal of Medicinal Chemistry p. 2689 - 2700 (1993)
Update date:2022-08-03
Topics:
Wall, Monroe E.
Wani, Mansukh C.
Nicholas, Allan W.
Manikumar, Govindarajan
Tele, Chhagan
et al.
A large number of camptothecin (CPT) analogs have been prepared in the 20S, 20RS, and 20R configurations with a number of ring A substituents.Topoisomerase I (T-I) inhibition data (IC50) have been obtained by standard procedures.In general, substitution at the 9 or 10 positions with amino, halogeno, or hydroxyl groups in compounds with 20S configuration results in compounds with enhanced T-1 inhibition.Compounds in the 20RS configuration were less active in vitro and in vivo and those in the 20R configuration were inactive.Compounds with 10,11-methylenedioxy substitution on ring A displayed a marked increase in potency in the T-I inhibition assay.The activities of some of the analogs as determined in a variety of in vivo assays including the L-1210 mouse leukemia assay were, in general, in accord with T-I inhibition.A number of water-soluble analogs such as 20-glycinate esters, 9-glycinamides, or hydrolyzed lactone salts were prepared and tested in in vitro and in vivo assays.In general, these compounds were less active than CPT both in terms of T-I inhibition and life prolongation in the L-1210 assay.However, certain 20-glycinate esters showed good in vivo activity after iv administration.
View MoreSHANXI JINJIN CHEMICAL INDUSTRIAL CO.,LTD
website:http://www.jinjingroup.com
Contact:4009982989
Address:Economic And Technological Development Zone,Hejin?City,Shanxi Province?,China
WEIFANG DERUN CHEMICAL CO.,LTD
Contact:86-536-8956886
Address:weifang
taicang liyuan chemical co,.ltd
website:http://www.tcliyuanchem.com/productse.php
Contact:86-512-53539583
Address:Room 804,Huaxu Building,No.95,Renmin South Road,Taicang city,Jiangsu Province,China
Contact:+86-535-8888888
Address:No.161 Haishi Rd.
PharmaResources(Kaiyuan)CO,.Ltd
Contact:+86-21-50720028
Address:No.3, Beihuan Road, Economic Development District, Kaiyuan City, Tieling City, Liaoning Province, China 112300
Doi:10.1002/jlcr.2963
(2012)Doi:10.1007/BF01150742
(1992)Doi:10.1039/c39950001013
(1995)Doi:10.1021/ja00987a021
(1967)Doi:10.1134/S1070363212040275
(2012)Doi:10.1016/S0040-4039(00)60636-6
(1993)