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

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 1995年 / 5卷 / 22期

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

页码：2741 / 2746

页数：6

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