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

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

Affiliation

  • 1 GlaxoSmithKline, Tsukuba Research Laboratories, 43, Wadai, Tsukuba 300-4247, Ibaraki, Japan. yasushi.miyazaki@gsk.com
PMID: 17276055 DOI: 10.1016/j.bmcl.2006.12.077
Abstract

During our effort to develop dual VEGFR2/KDR/Flk-1 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/KDR/Flk-1 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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