Novel C-3N-urea, amide, and carbamate dihydroindazolo[5,4-a] pyrrolo[3,4-c]carbazole analogs as potent TIE-2 and VEGF-R2 dual inhibitors

被引：19

作者：

Becknell, Nadine C. ^{[1
]}

Zulli, Allison L. ^{[1
]}

Angeles, Thelma S. ^{[1
]}

Yang, Shi ^{[1
]}

Albom, Mark S. ^{[1
]}

Aimone, Lisa D. ^{[1
]}

Robinson, Candy ^{[1
]}

Chang, Hong ^{[1
]}

Hudkins, Robert L. ^{[1
]}

机构：

[1] Cephalon Inc, W Chester, PA 19380 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2006年 / 16卷 / 20期

关键词：

antiangiogenenic therapy; anti-tumor; tyrosine kinases; TIE-2; VEGF-R2;

D O I：

10.1016/j.bmcl.2006.07.066

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A novel series of C-3 urea, amide, and carbamate fused dihydroindazolocarbazole (DHI) analogs are reported as highly potent dual inhibitors of TIE-2 and VEGF-R2 receptor tyrosine kinases with excellent cellular potency. Structure-activity relationship (SAR) studies indicate the optimal N-13 alkyl substitutions are n-propyl and i-butyl. The isopropyl carbamate 39 displayed good dual enzyme, cell potency, and rat pharmacokinetic properties for advancement to in vivo evaluation. (c) 2006 Elsevier Ltd. All rights reserved.

引用

页码：5368 / 5372

页数：5