Synthesis and Leukemia Cell Line K562 Inhibitory Activities of α-(Fluoro-substituted isoindolinone-2-yl)glutarimide Analogues

doi:10.6023/cjoc201412001

Chin. J. Org. Chem. ›› 2015, Vol. 35 ›› Issue (5): 1123-1130.DOI: 10.6023/cjoc201412001 Previous Articles Next Articles

Notes

α-(异吲哚啉酮-2-基)戊二酰亚胺含氟类似物的合成与白血病细胞K562抑制活性

陈衍炽, 任玉杰

上海应用技术学院化学与环境工程学院上海 201418

收稿日期:2014-12-01 修回日期:2014-12-25 发布日期:2015-01-14
通讯作者: 任玉杰 E-mail:clab@sit.edu.Cn
基金资助:
上海市科学技术委员会(No.13142201001)资助项目.

Synthesis and Leukemia Cell Line K562 Inhibitory Activities of α-(Fluoro-substituted isoindolinone-2-yl)glutarimide Analogues

Chen Yanchi, Ren Yujie

School of Chemical and Environmental Engineering, Shanghai Institute of Technology, Shanghai 201418

Received:2014-12-01 Revised:2014-12-25 Published:2015-01-14
Supported by:
Project supported by the Science and Technology Commission of Shanghai Municipality (No.13142201001).

1. Synthesis and Leukemia Cell Line K562 Inhibitory Activities of α-(Fluoro-substituted isoindolinone-2-yl)glutarimide Analogues.PDF(2735KB)

Abstract

A series of α-(fluoro-substituted isoindolinone-2-yl)glutarimide analogues 10a~10d, 13a~13b and 15 were synthesized from 3-amino-piperidine-2,6-dione hydrochloride (4) and different methyl 2-bromomethylbenzoate derivatives under alkaline condition, respectively. Furthermore, target compounds 14a and 14b were obtained via nitro reduction of 13a and 13b, respectively. The intermediate 4 was synthesized via amino-protection, cyclization and amino-deprotection using L-glutamine as the starting material. Different methyl 2-bromomethylbenzoate derivatives 9a~9d and 12a~12b were readily available via nitro reduction, Balz-Schiemann reaction, nitration reaction and bromination reaction strategies of nitro-substituted 2-methyl benzoic acid methyl esters. The structures of all compounds have been confirmed by ¹H NMR and HRMS spectra. The inhibitory activity against leukemia cell line K562 of seven target compounds was evaluated by thiazolyl blue tetrazolium bromide (MTT) method. The results indicated that the inhibitory activity to K562 cells of compound 10a was comparable with lenalidomide. Compound 15 exhibited strong inhibitory effect against K562 cells and with an inhibition rate of 99% at the concentration of 25 μg/mL.

Key words: α-(isoindolinone-2-yl)glutarimide, synthesis, leukemia, inhibitory activity

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Chen Yanchi, Ren Yujie. Synthesis and Leukemia Cell Line K562 Inhibitory Activities of α-(Fluoro-substituted isoindolinone-2-yl)glutarimide Analogues[J]. Chin. J. Org. Chem., 2015, 35(5): 1123-1130.

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α-(异吲哚啉酮-2-基)戊二酰亚胺含氟类似物的合成与白血病细胞K562抑制活性

Synthesis and Leukemia Cell Line K562 Inhibitory Activities of α-(Fluoro-substituted isoindolinone-2-yl)glutarimide Analogues

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