Title of article :
Tricyclic azepine derivatives: Pyrimido[4,5-b]-1,4-benzoxazepines as a novel class of epidermal growth factor receptor kinase inhibitors
Author/Authors :
Leon Smith II، نويسنده , , Evgueni L. Piatnitski، نويسنده , , Alexander S. Kiselyov، نويسنده , , Xiaohu Ouyang، نويسنده , , Clara Xiaoling Chen، نويسنده , , Sabina Burdzovic-Wizemann، نويسنده , , Yongjiang Xu، نويسنده , , Ying Wang، نويسنده , , Robin L. Rosler، نويسنده , , Sheetal N. Patel، نويسنده , , Hui-Hsien Chiang، نويسنده , , Daniel L. Milligan، نويسنده , , John Columbus، نويسنده , , Wai C. Wong، نويسنده , , Jacqueline F. Doody، نويسنده , , Yaron R. Hadari، نويسنده ,
Abstract :
A novel class of pyrimido[4,5-b]-1,4-benzoxazepines is described as inhibitors of epidermal growth factor receptor (EGFR) tyrosine kinase. Two compounds display potent EGFR inhibitory activity of less than 1 μM in cellular phosphorylation assays (IC50 0.47–0.69 μM) and are highly selective against a small kinase panel. Such compounds demonstrate anti-EGFR activity within a class that is different from any known EGFR inhibitor scaffolds. They also provide a basis for the design of kinase inhibitors with the desired selectivity profile.
Keywords :
Kinase selectivity , kinase inhibitor , Benzoxazepine , epidermal growth factor receptor
