Structural and biological investigation of ferrocene-substituted 3-methylidene-1,3-dihydro-2H-indol-2-ones
Structural and biological investigation of ferrocene-substituted 3-methylidene-1,3-dihydro-2H-indol-2-ones
复制标题
DOI：
10.1039/b816249b
复制
发表时间：
2009-01-01
影响因子：
4
通讯作者：
Hursthouse, Michael B.
中科院分区：
文献类型：
--
作者：
Spencer, John;Mendham, Andrew P.;Hursthouse, Michael B.
1，3-二氢-2H-吲哚-2-酮1与二茂铁甲醛2的Knovenagel缩合反应生成了几何异构体(E)-和(Z)-3-ferrocenylmethylidene-1，3-dihydro-2H-indol-2-one-3的约2：1混合物，总收率为67%，空气和溶液稳定的异构体通过制备性薄层色谱很容易分离，其结构在溶液中、通过H-1NMR谱和在固相中得到明确的确证；3的两种异构体对B16黑色素瘤和Vero细胞的体外毒性都在微摩尔范围内，并抑制了KVEGFR-2，IC50值约为200 nM。
The Knoevenagel condensation of 1,3-dihydro-2H-indol-2-one 1 with ferrocene carboxaldehyde 2 afforded an approximate 2: 1 mixture of the geometrical isomers (E)- and (Z)-3-ferrocenylmethylidene-1,3-dihydro-2H-indol-2-one 3 respectively in an overall 67% yield; the air and solution-stable isomers were readily separated by preparative thin layer chromatography and their structures were unequivocally elucidated in solution, by H-1 NMR spectroscopy, and in the solid phase, by X-ray crystallography; both isomers of 3 displayed in vitro toxicity against B16 melanoma and Vero cell lines in the micromolar range and inhibited the kinase VEGFR-2 with IC50 values of ca. 200 nM.