Title of article :
Synthesis, SAR, and Evaluation of 4-[2,4-Difluoro-5-(cyclopropylcarbamoyl)phenylamino]pyrrolo[2,1-f][1,2,4]triazine-based VEGFR-2 kinase inhibitors
Author/Authors :
Zhen-wei Cai، نويسنده , , Donna Wei، نويسنده , , Robert M. Borzilleri، نويسنده , , Ligang Qian، نويسنده , , Amrita Kamath، نويسنده , , Steven Mortillo، نويسنده , , Barri Wautlet، نويسنده , , Benjamin J. Henley، نويسنده , , Robert Jeyaseelan Sr.، نويسنده , , John Tokarski، نويسنده , , John T. Hunt، نويسنده , , Rajeev S. Bhide، نويسنده , , Joseph Fargnoli، نويسنده , , Louis J. Lombardo، نويسنده ,
Abstract :
Introduction of the 2,4-difluoro-5-(cyclopropylcarbamoyl)phenylamino group at the C-4 position of the pyrrolo[2,1-f][1,2,4] triazine scaffold led to the discovery of a novel sub-series of inhibitors of VEGFR-2 kinase activity. Subsequent SAR studies on the 1,3,5-oxadiazole ring appended to the C-6 position of this new sub-family of pyrrolotriazines resulted in the identification of low nanomolar inhibitors of VEGFR-2. Antitumor efficacy was observed with compound 37 against L2987 human lung carcinoma xenografts in athymic mice.
Keywords :
VEGFR-2 , Kinase inhibitors , 4]triazine , 2
