946490-32-0Relevant academic research and scientific papers
PREPARATION OF 7-ALKENYL-3 QUINOLINECARBONITRILES VIA A PALLADIUM MEDIATED COUPLING REACTION
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Page/Page column 9, (2009/04/24)
The present invention is directed to a process for preparing compounds of formula (I): wherein A, R1-R3, X, s, t, u, m and Z are defined herein, comprising the step of reacting a reagent of formula (II): in the presence of Pd(O) meta
4-Anilino-7-alkenylquinoline-3-carbonitriles as potent MEK1 kinase inhibitors
Berger, Dan M.,Dutia, Minu,Powell, Dennis,Floyd, Middleton B.,Torres, Nancy,Mallon, Robert,Wojciechowicz, Donald,Kim, Steven,Feldberg, Larry,Collins, Karen,Chaudhary, Inder
experimental part, p. 9202 - 9211 (2009/04/11)
A series of substituted 7-alkenyl 4[3-chloro-4-(1-methyl-1H-imidazol-2-ylsulfanyl)]anilino-3-quinolinecarbonitrile analogs were synthesized and evaluated as MEK1 kinase inhibitors. The synthetic details, structure-activity relationships, biological activity, and selected oral exposure studies of these analogs are described. From these studies, compound 5m was chosen as a strong candidate for further evaluation. The selectivity of 5m was ascertained against a panel of 17 kinases, where activity was observed against EGFR, Src, Lyn, and IR kinases. Western blot studies in WM-266 cells demonstrated that 5m inhibited phosphorylation of ERK, while additional kinase pathways tested showed no inhibition at up to 10 μM of 5m. PK studies, as well as a xenograft and in vivo biomarker studies are described for 5m.
