NOVEL C-4 PACLITAXEL (TAXOL(R)) ANALOGS - POTENT ANTITUMOR AGENTS

被引:35
作者
CHEN, SH [1 ]
WEI, JM [1 ]
LONG, BH [1 ]
FAIRCHILD, CA [1 ]
CARBONI, J [1 ]
MAMBER, SW [1 ]
ROSE, WC [1 ]
JOHNSTON, K [1 ]
CASAZZA, AM [1 ]
KADOW, JF [1 ]
FARINA, V [1 ]
VYAS, DM [1 ]
DOYLE, TW [1 ]
机构
[1] BRISTOL MYERS SQUIBB CO,PHARMACEUT RES INST,WALLINGFORD,CT 06492
关键词
D O I
10.1016/0960-894X(95)00453-Z
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
A large number of C-4 paclitaxel analogs have been prepared in the course of our systematic C-4 modification. These include C-4 esters, carbonates, carbamates as well as a C-4 deacetyl derivative. All of these analogs were evaluated in a tubulin polymerization assay as well as in a cytotoxicity assay against a human colon cancer cell line. The potent analogs emerging from these in vitro assays were further evaluated in vivo. With the exception of paclitaxel side chain bearing C-4 carbamates and C-4 aromatic esters, most of the C-4 aliphatic esters and carbonates were found to possess comparable or superior activity to paclitaxel in vitro. Several C-4 aliphatic esters and carbonates also exhibited in vivo activities against i.p. implanted murine M-109 lung carcinoma.
引用
收藏
页码:2741 / 2746
页数:6
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