A novel nitro-substituted seco-CI: Application as a reductively activated adept prodrug

被引：29

作者：

Tercel, M ^{[1
]}

Denny, WA ^{[1
]}

Wilson, WR ^{[1
]}

机构：

[1] UNIV AUCKLAND,DEPT PATHOL,SECT ONCOL,AUCKLAND 1,NEW ZEALAND

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 1996年 / 6卷 / 22期

关键词：

D O I：

10.1016/S0960-894X(96)00508-2

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

An alternative synthesis of seco-CI alkylating agents bearing a nitrogen substituent at C-6 is reported. The nitro compound 3 prepared by this route exhibits a 400-fold increase in cytotoxicity against UV4 cells in the presence of a nitroreductase enzyme from Escherichia coli B, suggesting it as a potential prodrug for use in antibody-directed enzyme prodrug therapy. Copyright (C) 1996 Elsevier Science Ltd

引用

页码：2741 / 2744

页数：4

共 16 条

[1] THE BIOACTIVATION OF 5-(AZIRIDIN-1-YL)-2,4-DINITROBENZAMIDE (CB1954) .1. PURIFICATION AND PROPERTIES OF A NITROREDUCTASE ENZYME FROM ESCHERICHIA-COLI - A POTENTIAL ENZYME FOR ANTIBODY-DIRECTED ENZYME PRODRUG THERAPY (ADEPT) [J].

ANLEZARK, GM ;

MELTON, RG ;

SHERWOOD, RF ;

COLES, B ;

FRIEDLOS, F ;

KNOX, RJ .

BIOCHEMICAL PHARMACOLOGY, 1992, 44 (12) :2289-2295

[2] BIOACTIVATION OF DINITROBENZAMIDE MUSTARDS BY AN ESCHERICHIA-COLI-B NITROREDUCTASE [J].

ANLEZARK, GM ;

MELTON, RG ;

SHERWOOD, RF ;

WILSON, WR ;

DENNY, WA ;

PALMER, BD ;

KNOX, RJ ;

FRIEDLOS, F ;

WILLIAMS, A .

BIOCHEMICAL PHARMACOLOGY, 1995, 50 (05) :609-618

[3] ANTIBODY-DIRECTED ENZYME PRODRUG THERAPY [J].

BAGSHAWE, KD .

CLINICAL PHARMACOKINETICS, 1994, 27 (05) :368-376

[4] DUOCARMYCIN PYRINDAMYCIN DNA ALKYLATION PROPERTIES AND IDENTIFICATION, SYNTHESIS, AND EVALUATION OF AGENTS INCORPORATING THE PHARMACOPHORE OF THE DUOCARMYCIN PYRINDAMYCIN ALKYLATION SUBUNIT - IDENTIFICATION OF THE CC-1065-DUOCARMYCIN COMMON PHARMACOPHORE [J].

BOGER, DL ;

ISHIZAKI, T ;

ZARRINMAYEH, H ;

MUNK, SA ;

KITOS, PA ;

SUNTORNWAT, O .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1990, 112 (24) :8961-8971

[5]

Hansch C., 1979, Substituent constants for correlation analysis in chemistry and biology

[6] A NOVEL ENEDIYNE PRODRUG FOR ANTIBODY-DIRECTED ENZYME PRODRUG THERAPY (ADEPT) USING ESCHERICHIA-COLI-B NITROREDUCTASE [J].

HAY, MP ;

WILSON, WR ;

DENNY, WA .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 1995, 5 (23) :2829-2834

[7] TUMOR TARGETING - ACTIVATION OF PRODRUGS BY ENZYME-MONOCLONAL ANTIBODY CONJUGATES [J].

HUENNEKENS, FM .

TRENDS IN BIOTECHNOLOGY, 1994, 12 (06) :234-239

[8] DESIGN OF ANTITUMOR PRODRUGS - SUBSTRATES FOR ANTIBODY-TARGETED ENZYMES [J].

JUNGHEIM, LN ;

SHEPHERD, TA .

CHEMICAL REVIEWS, 1994, 94 (06) :1553-1566

[9] THE BIOACTIVATION OF 5-(AZIRIDIN-1-YL)-2,4-DINITROBENZAMIDE (CB1954) .2. A COMPARISON OF AN ESCHERICHIA-COLI NITROREDUCTASE AND WALKER DT DIAPHORASE [J].

KNOX, RJ ;

FRIEDLOS, F ;

SHERWOOD, RF ;

MELTON, RG ;

ANLEZARK, GM .

BIOCHEMICAL PHARMACOLOGY, 1992, 44 (12) :2297-2301

[10] THE BIOACTIVATION OF CB-1954 AND ITS USE AS A PRODRUG IN ANTIBODY-DIRECTED ENZYME PRODRUG THERAPY (ADEPT) [J].

KNOX, RJ ;

FRIEDLOS, F ;

BOLAND, MP .

CANCER AND METASTASIS REVIEWS, 1993, 12 (02) :195-212

← 1 2 →