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ID: ALA1139135
Journal: Bioorg Med Chem Lett
Title: Orally active 4-amino-5-diarylurea-furo[2,3-d]pyrimidine derivatives as anti-angiogenic agent inhibiting VEGFR2 and Tie-2.
Authors: Miyazaki Y, Tang J, Maeda Y, Nakano M, Wang L, Nolte RT, Sato H, Sugai M, Okamoto Y, Truesdale AT, Hassler DF, Nartey EN, Patrick DR, Ho ML, Ozawa K.
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.
CiteXplore: 17276055