Author/Authors :
Yasushi Miyazaki، نويسنده , , Jun Tang، نويسنده , , Yutaka Maeda، نويسنده , , Masato Nakano، نويسنده , , Liping Wang، نويسنده , , Robert T. Nolte، نويسنده , , Hitoshi Sugawara and Hideyuki Sato، نويسنده , , Masaki Sugai، نويسنده , , Yuji Okamoto، نويسنده , , Anne T. Truesdale، نويسنده , , Daniel F. Hassler، نويسنده , , Eldridge N. Nartey، نويسنده , , Denis R. Patrick، نويسنده , , Maureen L. Ho، نويسنده , , Kazunori Ozawa، نويسنده ,
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.
Keywords :
Receptor tyrosine kinase , Tie-2 , VEGFR2 , angiogenesis , Kinase inhibitor
