Paclitaxel esters of malic acid as prodrugs with improved water solubility

被引：49

作者：

Damen, EWP

Wiegerinck, PHG

Braamer, L

Sperling, D

de Vos, D

Scheeren, HW ^{[1
]}

机构：

[1] Catholic Univ Nijmegen, Dept Organ Chem, NSR Ctr Mol Struct Design & Synth, NL-6525 ED Nijmegen, Netherlands

[2] Pharmachem BV Haarlem, NL-2003 RN Haarlem, Netherlands

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2000年 / 8卷 / 02期

关键词：

D O I：

10.1016/S0968-0896(99)00301-6

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The synthesis of paclitaxel esters of malic acid is described. These compounds were found to have improved water solubility and are stable in solution at neutral pH. The C2' modified compounds behave as prodrugs, that is, paclitaxel is generated upon exposure to human plasma, whereas the C7 modified derivatives do not. 2'-Malyl paclitaxel sodium salt demonstrated enhanced antitumour activity and less toxicity in a P388 murine leukaemia in vivo model when compared to paclitaxel. (C) 2000 Elsevier Science Ltd. All rights reserved.

引用

页码：427 / 432

页数：6

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