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Structure-based design, synthesis, and anticonvulsant activity of isatin-1-N-phenylacetamide derivatives

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Abstract

In an effort to develop the potent anticonvulsant agents, a series of novel isatin-1-N-phenylacetamide derivatives was synthesized and screened for their in vivo anticonvulsant activity against maximal electroshock test and evaluated for their neurotoxicity by the rotarod test at the same dose levels. Ten compounds exhibited the anticonvulsant activity. 2-(5-Methyl-2,3-dioxoindolin-1-yl)-N-phenylacetamide (4b) was found to be the most potent compound of the series with an ED50 of 91.3 mg/kg, TD50 of >1,000 mg/kg, a higher protective index (PI = TD50/ED50, >11) was gained than the reference drug phenobarbital and carbamazepine. The essential structural features responsible for interaction with receptor site are established within a suggested pharmacophore.

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Acknowledgments

This work was supported by the National Natural Science Foundation of China (No. 30960458) and the Natural Science Foundation of Zhejiang Province of China (No. LY12C19005; No. LY13C200006). This work was supported by the Major Science and Technology Project of Zhejiang Province of China (No. 2012C11015-2), the Public Welfare of Zhejiang Province of China (No. 2012C21068), and Zhejiang Marine Biotechnology Innovation Team (ZMBIT) (No. 2010R50029).

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Authors and Affiliations

  1. School of Food, Drug and Medicine, Zhejiang Ocean University, Zhoushan, 316000, People’s Republic of China

    Chao Xie, Li-Ming Tang, Li-Ping Guan & Cheng-Yan Pan

  2. Xiamen University School of Pharmaceutical Sciences, Xiang’an South Road, Xiamen, 361102, People’s Republic of China

    Fu-Nan Li

  3. Analysis and Test Center, Yanbian University, Yanji, 133002, People’s Republic of China

    Si-Hong Wang

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  1. Chao Xie
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  2. Li-Ming Tang
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Correspondence to Li-Ping Guan or Si-Hong Wang.

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Xie, C., Tang, LM., Li, FN. et al. Structure-based design, synthesis, and anticonvulsant activity of isatin-1-N-phenylacetamide derivatives. Med Chem Res 23, 2161–2168 (2014). https://doi.org/10.1007/s00044-013-0811-1

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  • DOI: https://doi.org/10.1007/s00044-013-0811-1

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