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

Yasushi Miyazaki,Jun Tang,Yutaka Maeda,Masato Nakano,Liping Wang,Robert T Nolte,Hideyuki Sato,Masaki Sugai,Yuji Okamoto,Anne T Truesdale,Daniel F Hassler,Eldridge N Nartey,Denis R Patrick,Maureen L Ho,Kazunori Ozawa

Bioorganic & Medicinal Chemistry Letters（2007）

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摘要

Dual VEGFR2 and Tie-2 inhibitors as anti-angiogenic agents were identified. Compound 8a exhibited strong inhibitory activities against VEGFR2 and Tie-2 in both enzyme and cellular assays, demonstrated high pharmacokinetic 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.

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关键词

Kinase inhibitor,Angiogenesis,VEGFR2,Tie-2,Receptor tyrosine kinase

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