1022964-01-7Relevant articles and documents
Fused bicyclic derivatives of 2,4-diaminopyrimidine as c-Met inhibitors
Weinberg, Linda R.,Albom, Mark S.,Angeles, Thelma S.,Husten, Jean,Lisko, Joseph G.,McHugh, Robert J.,Milkiewicz, Karen L.,Murthy, Seetha,Ott, Gregory R.,Theroff, Jay P.,Tripathy, Rabindranath,Underiner, Ted L.,Zificsak, Craig A.,Dorsey, Bruce D.
supporting information; experimental part, p. 164 - 167 (2011/03/17)
The HGF-c-Met signaling axis is an important paracrine mediator of epithelial-mesenchymal cell interactions involving the regulation of multiple cellular activities including cell motility, mitogenesis, morphogenesis, and angiogenesis. Dysregulation of c-Met signaling (e.g., overexpression or increased activation) is associated with the development of a wide range of tumor types; thus, inhibiting the HGF-c-Met pathway is predicted to lead to anti-tumor effects in many cancers. Elaboration of a 2-arylaminopyrimidine scaffold led to a series of potent c-Met inhibitors bearing a C4-2-amino-N-methylbenzamide group. Specifically, a series of C2-benzazepinone analogs demonstrated potent inhibition of c-Met in enzymatic and cellular assays. Kinase selectivity could be tuned by varying the nature of the alkyl group on the benzazepinone nitrogen.
