- Novel 2,3,4,5-tetrahydro-benzo[d]azepine derivatives of 2,4-diaminopyrimidine, selective and orally bioavailable ALK inhibitors with antitumor efficacy in ALCL mouse models.
Novel 2,3,4,5-tetrahydro-benzo[d]azepine derivatives of 2,4-diaminopyrimidine, selective and orally bioavailable ALK inhibitors with antitumor efficacy in ALCL mouse models.
Bioorganic & medicinal chemistry letters (2010-11-16)
Eugen F Mesaros, Jason P Burke, Jonathan D Parrish, Benjamin J Dugan, Andrew V Anzalone, Thelma S Angeles, Mark S Albom, Lisa D Aimone, Matthew R Quail, Weihua Wan, Lihui Lu, Zeqi Huang, Mark A Ator, Bruce A Ruggeri, Mangeng Cheng, Gregory R Ott, Bruce D Dorsey
PMID21074994
ABSTRACT
The synthesis and biological evaluation of potent and selective anaplastic lymphoma kinase (ALK) inhibitors from a novel class of 2,4-diaminopyrimidines, incorporating 2,3,4,5-tetrahydro-benzo[d]azepine fragments, is described. An orally bioavailable analogue (18) that displayed antitumor efficacy in ALCL xenograft models in mice was identified and extensively profiled.
MATERIALS