Synthesis of potent taxoids for tumor-specific delivery using monoclonal antibodies

被引：14

作者：

Miller, ML

Roller, EE

Wu, XY

Leece, BA

Goldmacher, VS

Chari, RVJ

Ojima, I

机构：

[1] ImmunoGen Inc, Cambridge, MA 02139 USA

[2] SUNY Stony Brook, Dept Chem, Stony Brook, NY 11794 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2004年 / 14卷 / 15期

关键词：

taxoid; antibody conjugate; tumor specific; targeted delivery;

D O I：

10.1016/j.bmcl.2004.05.027

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The targeted delivery of taxoids, in the form of taxane-antibody immunoconjugates, requires the preparation of taxoids containing moieties suitable for their conjugation to monoclonal antibodies. A series of taxoids incorporating a disulfide-containing linker at various positions of the taxoid framework have been prepared to investigate the most suitable position for conjugation. A second series of taxoids modified at the C-2 position aimed at increasing the potency of these taxanes has also been prepared. (C) 2004 Elsevier Ltd. All rights reserved.

引用

收藏

页码：4079 / 4082

页数：4

相关论文

共 20 条

[11] Eradication of large colon tumor xenografts by targeted delivery of maytansinoids [J].

Liu, CN ;

Tadayoni, BM ;

Bourret, LA ;

Mattocks, KM ;

Derr, SM ;

Widdison, WC ;

Kedersha, NL ;

Ariniello, PD ;

Goldmacher, VS ;

Lambert, JM ;

Blattler, WA ;

Chari, RVJ .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1996, 93 (16) :8618-8623

[12]

Newman Roland, 2002, P225

[13] CHEMICAL SYNTHESIS AND BIOLOGICAL EVALUATION OF C-2 TAXOIDS [J].

NICOLAOU, KC ;

RENAUD, J ;

NANTERMET, PG ;

COULADOUROS, EA ;

GUY, RK ;

WRASIDLO, W .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1995, 117 (09) :2409-2420

[14] Synthesis and structure-activity relationships of new second-generation taxoids [J].

Ojima, I ;

Wang, T ;

Miller, ML ;

Lin, SN ;

Borella, CP ;

Geng, XD ;

Pera, P ;

Bernacki, RJ .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 1999, 9 (24) :3423-3428

[15] Syntheses and structure-activity relationships of the second-generation antitumor taxoids: Exceptional activity against drug-resistant cancer cells [J].

Ojima, I ;

Slater, JC ;

Michaud, E ;

Kuduk, SD ;

Bounaud, PY ;

Vrignaud, P ;

Bissery, MC ;

Veith, JM ;

Pera, P ;

Bernacki, RJ .

JOURNAL OF MEDICINAL CHEMISTRY, 1996, 39 (20) :3889-3896

[16] Tumor-specific novel taxoid-monoclonal antibody conjugates [J].

Ojima, I ;

Geng, XD ;

Wu, XY ;

Qu, CX ;

Borella, CP ;

Xie, HS ;

Wilhelm, SD ;

Leece, BA ;

Bartle, LM ;

Goldmacher, VS ;

Chari, RVJ .

JOURNAL OF MEDICINAL CHEMISTRY, 2002, 45 (26) :5620-5623

[17] Synthesis and structure-activity relationships of nonaromatic taxoids: Effects of alkyl and alkenyl ester groups on cytotoxicity [J].

Ojima, I ;

Kuduk, SD ;

Pera, P ;

Veith, JM ;

Bernacki, RJ .

JOURNAL OF MEDICINAL CHEMISTRY, 1997, 40 (03) :279-285

[18] Syntheses and structure-activity relationships of taxoids derived from 14 beta-hydroxy-10-deacetylbaccatin III [J].

Ojima, I ;

Slater, JC ;

Kuduk, SD ;

Takeuchi, CS ;

Gimi, RH ;

Sun, CM ;

Park, YH ;

Pera, P ;

Veith, JM ;

Bernacki, RJ .

JOURNAL OF MEDICINAL CHEMISTRY, 1997, 40 (03) :267-278

[19]

Suffness M., 1995, TAXOL SCI APPL

[20] PLANT ANTITUMOR AGENTS .6. ISOLATION AND STRUCTURE OF TAXOL, A NOVEL ANTILEUKEMIC AND ANTITUMOR AGENT FROM TAXUS-BREVIFOLIA [J].

WANI, MC ;

TAYLOR, HL ;

WALL, ME ;

COGGON, P ;

MCPHAIL, AT .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1971, 93 (09) :2325-&