Orally active 4-amino-5-diarylurea-furo[2,3-d]pyrimidine derivatives as anti-angiogenic agent inhibiting VEGFR2 and Tie-2

被引：32
作者：
Miyazaki, Yasushi
Tang, Jun
Maeda, Yutaka
Nakano, Masato
Wang, Liping
Nolte, Robert T.
Sato, Hideyuki
Sugai, Masaki
Okamoto, Yuji
Truesdale, Anne T.
Hassler, Daniel F.
Nartey, Eldridge N.
Patrick, Denis R.
Ho, Maureen L.
Ozawa, Kazunori
机构：
[1] GlaxoSmithKline Inc, Tsukuba Res Labs, Tsukuba, Ibaraki 3004247, Japan
[2] GlaxoSmithKline Inc, Res Triangle Pk, NC 27709 USA
[3] GlaxoSmithKline Inc, Collegeville, PA 19426 USA
来源：
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2007年 / 17卷 / 06期
关键词：
kinase inhibitor; angiogenesis; VEGFR2; Tie-2; receptor tyrosine kinase;
D O I：
10.1016/j.bmcl.2006.12.077
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
During our effort to develop dual VEGFR2 and Tie-2 inhibitors as anti-angiogenic agents for cancer therapy, we discovered 4-amino-5-(4-((2-fluoro-5-(trifluoromethyl)phenyl)-aminocarbonylamino)phenyl)furo[2,3-d]pyrimidine (8a) possessing strong inhibitory activity at both the enzyme and cellular level against VEGFR2 and Tie-2. Compound 8a demonstrated high pharmaco-kinetic exposure through oral administration, and showed marked tumor growth inhibition and anti-angiogenic activity in mouse HT-29 xenograft model via once-daily oral administration. (c) 2006 Elsevier Ltd. All rights reserved.
引用
收藏
页码：1773 / 1778
页数：6
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