Discovery of a Highly Potent, Orally Active Mitosis/Angiogenesis Inhibitor R1530 for the Treatment of Solid Tumors

被引：20

作者：

Liu, Jin-Jun ^{[1
]}

Higgins, Brian ^{[2
]}

Ju, Grace ^{[2
]}

Kolinsky, Kenneth ^{[2
]}

Luk, Kin-Chun ^{[1
]}

Packman, Kathryn ^{[2
]}

Pizzolato, Giacomo ^{[1
]}

Ren, Yi ^{[3
]}

Thakkar, Kshitij ^{[1
]}

Tovar, Christian ^{[2
]}

Zhang, Zhuming ^{[1
]}

Woykulich, Peter M. ^{[1
]}

机构：

[1] Hoffmann La Roche Inc, Discovery Chem, Nutley, NJ 07110 USA

[2] Hoffmann La Roche Inc, Discovery Oncol, Nutley, NJ 07110 USA

[3] Hoffmann La Roche Inc, Chem Synth, Nutley, NJ 07110 USA

来源：

ACS MEDICINAL CHEMISTRY LETTERS | 2013年 / 4卷 / 02期

关键词：

pyrazolobenzodiazepines; mitosis/angiogenesis inhibitor; antitumor effect; VGFr-2; FGFr and PDGFr-beta; ORTHO-SUBSTITUTION-REACTION; ORGANIC-SYNTHESIS; ANGIOGENESIS; CANCER; AMINOHALOBORANE; COMBINATION; THERAPY;

D O I：

10.1021/ml300351e

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A new series of 7,8-disubstituted pyrazolobenzodiazepines based on the lead compound 1 have been synthesized and evaluated for their effects on mitosis and angiogenesis. Described herein is the design, synthesis, SAR, and antitumor activity of these compounds leading to the identification of R1530, which was selected for clinical evaluation.

引用

页码：259 / 263

页数：5

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