Author/Authors :
Blaise Lippa، نويسنده , , Goss S. Kauffman، نويسنده , , Joel Arcari، نويسنده , , Tricia Kwan، نويسنده , , Jinshan Chen، نويسنده , , William Hungerford، نويسنده , , Samit Bhattacharya، نويسنده , , Xumiao Zhao، نويسنده , , Courtney Williams، نويسنده , , Jun Xiao، نويسنده , , Leslie Pustilnik، نويسنده , , Chunyan Su، نويسنده , , James D. Moyer، نويسنده , , Ling Ma، نويسنده , , Mary Campbell، نويسنده , , Stefanus Steyn، نويسنده ,
Abstract :
The synthesis and biological evaluation of potent and selective inhibitors of the erbB2 kinase is presented. Based on the 4-anilinoquinazoline chemotype, the syntheses of several new series of erbB2 inhibitors are described with quinazoline and pyrido[4,3-d]pyrimidine cores. The vast majority of these compounds are found to be >100× selective over the closely related EGFR kinase. Two lead compounds are further shown to have low clearance and moderate bioavailability in rat.
Keywords :
Anilinoquinazoline , kinase , erbB2 , HER2 , cancer
