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
  • [1] Lanthanide trifluoromethanesulfonate catalysed selective acylation of 10-deacetylbaccatin III
    Damen, EWP
    Braamer, L
    Scheeren, HW
    [J]. TETRAHEDRON LETTERS, 1998, 39 (33) : 6081 - 6082
  • [2] Synthesis and biological activity of beta-glucuronyl carbamate-based prodrugs of paclitaxel as potential candidates for ADEPT
    deBont, DBA
    Leenders, RGG
    Haisma, HJ
    vanderMeulenMuileman, I
    Scheeren, HW
    [J]. BIOORGANIC & MEDICINAL CHEMISTRY, 1997, 5 (02) : 405 - 414
  • [3] SYNTHESIS OF CONGENERS AND PRODRUGS .3. WATER-SOLUBLE PRODRUGS OF TAXOL WITH POTENT ANTITUMOR-ACTIVITY
    DEUTSCH, HM
    GLINSKI, JA
    HERNANDEZ, M
    HAUGWITZ, RD
    NARAYANAN, VL
    SUFFNESS, M
    ZALKOW, LH
    [J]. JOURNAL OF MEDICINAL CHEMISTRY, 1989, 32 (04) : 788 - 792
  • [4] HIGHLY WATER-SOLUBLE TAXOL DERIVATIVES - 2'-POLYETHYLENEGLYCOL ESTERS AS POTENTIAL PRODRUGS
    GREENWALD, RB
    PENDRI, A
    BOLIKAL, D
    GILBERT, CW
    [J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 1994, 4 (20) : 2465 - 2470
  • [5] HIGHLY WATER-SOLUBLE TAXOL DERIVATIVES - 7-POLYETHYLENE GLYCOL CARBAMATES AND CARBONATES
    GREENWALD, RB
    PENDRI, A
    BOLIKAL, D
    [J]. JOURNAL OF ORGANIC CHEMISTRY, 1995, 60 (02) : 331 - 336
  • [6] DIRECT, STEREOSELECTIVE SYNTHESIS OF THE PROTECTED PACLITAXEL (TAXOL) SIDE-CHAIN AND HIGH-YIELD TRANSFORMATION TO PACLITAXEL
    KANAZAWA, AM
    DENIS, JN
    GREENE, AE
    [J]. JOURNAL OF THE CHEMICAL SOCIETY-CHEMICAL COMMUNICATIONS, 1994, (22) : 2591 - 2592
  • [7] COMPARISON OF THE SULFORHODAMINE-B PROTEIN AND TETRAZOLIUM (MTT) ASSAYS FOR INVITRO CHEMOSENSITIVITY TESTING
    KEEPERS, YP
    PIZAO, PE
    PETERS, GJ
    VANARKOTTE, J
    WINOGRAD, B
    PINEDO, HM
    [J]. EUROPEAN JOURNAL OF CANCER, 1991, 27 (07) : 897 - 900
  • [8] SYNTHESIS AND EVALUATION OF SOME WATER-SOLUBLE PRODRUGS AND DERIVATIVES OF TAXOL WITH ANTITUMOR-ACTIVITY
    MATHEW, AE
    MEJILLANO, MR
    NATH, JP
    HIMES, RH
    STELLA, VJ
    [J]. JOURNAL OF MEDICINAL CHEMISTRY, 1992, 35 (01) : 145 - 151
  • [9] *NAT CANC I, 1983, 125973 NCI DIV CANC
  • [10] Nicolaou K. C., 1994, ANGEW CHEM, V106, P38
123