Paper
Design,synthesis and α-glucosidase inhibitory activity of 3-(4-methylsulfonylamido/acetylamido)benzoyl-2H-1-benzopyran-2-one derivatives
Published 2010 · Wang Xiao-yan
Chinese Journal of Medicinal Chemistry
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Abstract
Aim In the course of study on the non-sugar α-glucosidase inhibitors,3-(4-phenylsulfonylamido)benzoyl-2H-1-benzopyran-2-one derivatives were found to be good α-glucosidase inhibitors.In order to investigate the structure-activity relationship of this type of compounds,4-phenylsulfonylamido group was replaced with 4-methylsulfonylamido and 4-acetylamido,respectively.3-(4-Methylsulfonylamido/acetylamido) benzoyl-2H-1-benzopyran-2-one derivatives were designed and synthesized,and their α-glucosidase inhibitory activity was assayed.Methods Treatment of 4-nitrobenzoic acid with thionyl chloride gave 4-nitrobenzoyl chloride,which was reacted with ethyl acetoacetate and followed by hydrolysis to afford ethyl 3-(4-nitrophenyl)-3-oxopropanoate.Then it was hydrogenated over Pd/C catalyst and acylated with methylsulfonyl chloride and acetyl chloride to give two key intermediates ethyl 3-(4-(methylsulfonylamido)phenyl)-3-oxopropanoate and ethyl 3-(4-acetylamido)phenyl)-3-oxopropanoate,respectively.Lastly the target compounds were obtained by the reaction of either key intermediate with the corresponding substituted salicylic aldehyde via Knoevernagel condensation and cyclization.The α-glucosidase inhibitory activity of the target compounds was evaluated on yeast α-glucosidase.Results 22 Target compounds were obtained and their structures were confirmed by 1H-NMR and IR.Most 3-(4-methylsulfonylamido/ acetylamido)benzoyl-2H-1-benzopyran-2-one derivatives did not show α-glucosidase inhibitory activity,only compound 3-(4-methylsulfonylamido)benzoyl-6,8-di-tert-butyl-2H-1-benzopyran-2-one(10f) showed good α-glucosidase inhibitory activity with an IC50 value of 10.16 μmol·L-1.Conclusion In 3-benzoyl-2H-1-benzopyran-2-one derivatives,methylsulfonylamido/acetylamido group at the position 4 of benzoyl moiety was unfavorable for α-glucosidase inhibitory,and the structure-activity relationship of 3-(4-amino)benzoyl-2H-1-benzopyran-2-one derivatives should be investigated further.
In Vitro Study3-(4-methylsulfonylamido/acetylamido)benzoyl-2H-1-benzopyran-2-one derivatives show good -glucosidase inhibitory activity, with compound 10f showing the best activity.
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