Chinese Journal of Organic Chemistry >
Synthesis and Leukemia Cell Line K562 Inhibitory Activities of α-(Fluoro-substituted isoindolinone-2-yl)glutarimide Analogues
Received date: 2014-12-01
Revised date: 2014-12-25
Online published: 2015-01-14
Supported by
Project supported by the Science and Technology Commission of Shanghai Municipality (No.13142201001).
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.
Chen Yanchi , Ren Yujie . Synthesis and Leukemia Cell Line K562 Inhibitory Activities of α-(Fluoro-substituted isoindolinone-2-yl)glutarimide Analogues[J]. Chinese Journal of Organic Chemistry, 2015 , 35(5) : 1123 -1130 . DOI: 10.6023/cjoc201412001
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