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

共 24 条

[1] Lanthanide trifluoromethanesulfonate catalysed selective acylation of 10-deacetylbaccatin III [J].

Damen, EWP ;

Braamer, L ;

Scheeren, HW .

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 [J].

deBont, DBA ;

Leenders, RGG ;

Haisma, HJ ;

vanderMeulenMuileman, I ;

Scheeren, HW .

BIOORGANIC & MEDICINAL CHEMISTRY, 1997, 5 (02) :405-414

[3] SYNTHESIS OF CONGENERS AND PRODRUGS .3. WATER-SOLUBLE PRODRUGS OF TAXOL WITH POTENT ANTITUMOR-ACTIVITY [J].

DEUTSCH, HM ;

GLINSKI, JA ;

HERNANDEZ, M ;

HAUGWITZ, RD ;

NARAYANAN, VL ;

SUFFNESS, M ;

ZALKOW, LH .

JOURNAL OF MEDICINAL CHEMISTRY, 1989, 32 (04) :788-792

[4] HIGHLY WATER-SOLUBLE TAXOL DERIVATIVES - 2'-POLYETHYLENEGLYCOL ESTERS AS POTENTIAL PRODRUGS [J].

GREENWALD, RB ;

PENDRI, A ;

BOLIKAL, D ;

GILBERT, CW .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 1994, 4 (20) :2465-2470

[5] HIGHLY WATER-SOLUBLE TAXOL DERIVATIVES - 7-POLYETHYLENE GLYCOL CARBAMATES AND CARBONATES [J].

GREENWALD, RB ;

PENDRI, A ;

BOLIKAL, D .

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 [J].

KANAZAWA, AM ;

DENIS, JN ;

GREENE, AE .

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 [J].

KEEPERS, YP ;

PIZAO, PE ;

PETERS, GJ ;

VANARKOTTE, J ;

WINOGRAD, B ;

PINEDO, HM .

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 [J].

MATHEW, AE ;

MEJILLANO, MR ;

NATH, JP ;

HIMES, RH ;

STELLA, VJ .

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

← 1 2 3 →