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

  • Bioorg Med Chem Lett. 2007 Mar 15;17(6):1773-8. doi: 10.1016/j.bmcl.2006.12.077.
Yasushi Miyazaki  1 ,  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
Affiliations
  • 1. GlaxoSmithKline, Tsukuba Research Laboratories, 43, Wadai, Tsukuba 300-4247, Ibaraki, Japan. [email protected]
PMID: 17276055 DOI: 10.1016/j.bmcl.2006.12.077
Abstract

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 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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