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
收藏
页码：427 / 432
页数：6
相关论文
共 24 条
  • [21] SYNTHESIS AND ANTITUMOR EVALUATION OF WATER-SOLUBLE TAXOL PHOSPHATES
    VYAS, DM
    WONG, H
    CROSSWELL, AR
    CASAZZA, AM
    KNIPE, JO
    MAMBER, SW
    DOYLE, TW
    [J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 1993, 3 (06) : 1357 - 1360
  • [22] HYPERSENSITIVITY REACTIONS FROM TAXOL
    WEISS, RB
    DONEHOWER, RC
    WIERNIK, PH
    OHNUMA, T
    GRALLA, RJ
    TRUMP, DL
    BAKER, JR
    VANECHO, DA
    VONHOFF, DD
    LEYLANDJONES, B
    [J]. JOURNAL OF CLINICAL ONCOLOGY, 1990, 8 (07) : 1263 - 1268
  • [23] MODIFIED TAXOLS .6. PREPARATION OF WATER-SOLUBLE PRODRUGS OF TAXOL
    ZHAO, ZY
    KINGSTON, DGI
    CROSSWELL, AR
    [J]. JOURNAL OF NATURAL PRODUCTS, 1991, 54 (06): : 1607 - 1611
  • [24] 1995, Patent No. 5411984
123