Synthesis, Crystallization, and Biological Evaluation of an Orally Active Prodrug of Gemcitabine

被引：89

作者：

Bender, David M. ^{[1
]}

Bao, Jingqi ^{[1
]}

Dantzig, Anne H. ^{[1
]}

Diseroad, William D. ^{[1
]}

Law, Kevin L. ^{[1
]}

Magnus, Nicholas A. ^{[1
]}

Peterson, Jeffrey A. ^{[1
]}

Perkins, Everett J. ^{[1
]}

Pu, Yangwei J. ^{[1
]}

Reutzel-Edens, Susan M. ^{[1
]}

Remick, David M. ^{[1
]}

Starling, James J. ^{[1
]}

Stephenson, Gregory A. ^{[1
]}

Vaid, Radhe K. ^{[1
]}

Zhang, Deyi ^{[1
]}

McCarthy, James R. ^{[1
]}

机构：

[1] Eli Lilly & Co, Lilly Res Labs, Indianapolis, IN 46285 USA

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2009年 / 52卷 / 22期

关键词：

2'; 2'-DIFLUORODEOXYCYTIDINE; 5'-TRIPHOSPHATE; ANTITUMOR-ACTIVITY; DOSE-RATE; ACCUMULATION; INFUSION; CANCER; DESIGN; TRIAL; DNA;

D O I：

10.1021/jm901181h

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The design, synthesis, and biological characterization of an orally active prodrug (3) of gemcitabine are described. Additionally, the identification of a novel co-crystal solid form of the compound is presented. Valproate amide 3 is orally bioavailable and releases gemcitabine into the systemic circulation after passing through the intestinal mucosa. The compound has entered clinical trials and is being evaluated as a potential new anticancer agent.

引用

页码：6958 / 6961

页数：4

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