Medicinal Chemistry Research

, Volume 27, Issue 2, pp 642–652 | Cite as

Synthesis and anticonvulsant activity of some novel 7-(benzylamino) -1H-benzo[b][1,4]diazepine-2,4(3H, 5H)-dione derivatives

  • Yun-Peng Shao
  • Rong-Bi Han
  • Hui-Fan Wu
  • Feng-Yu Piao
Original Research
  • 74 Downloads

Abstract

A series of novel 7-(benzylamino)-1H-benzo[b][1,4]diazepine-2,4(3H, 5H)-dione derivatives were synthesized and screened for their anticonvulsant activities by the maximal electroshock (MES) test, subcutaneous pentylenetetrazol (scPTZ) test, and their neurotoxicity was evaluated by the rotarod neurotoxicity test (Tox). The study showed that the compound 8c (7-(4-fluorobenzylamino)-1,5-dimethyl-1H-benzo[b][1,4]diazepine-2,4(3H,5H)-dione) was the most promising compound, with median effective dose (ED50) of 36.5 mg/kg, and protective index (PI) values of 4.5 in the MES test. In the scPTZ test, compound 8c also exhibited better anticonvulsant activity (ED50 = 68.2 mg/kg), and the ED50 values of compounds 8c were smaller than that of the reference antiepileptic drugs carbamazepine (ED50 > 100 mg/kg), phenytoin (ED50 > 300 mg/kg), and sodium valproate (ED50 = 149 mg/kg). The possible structure activity relationship was discussed.

Keywords

1H-benzo[b][1,4]diazepine-2,4(3H,5H)-dione anticonvulsant activity structure-activity relationship 

Notes

Acknowledgements

This work was supported by the National Natural Science Foundation of China (No. 21162031).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no competing interests.

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Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  • Yun-Peng Shao
    • 1
  • Rong-Bi Han
    • 1
    • 2
  • Hui-Fan Wu
    • 1
  • Feng-Yu Piao
    • 1
    • 2
  1. 1.Department of Chemistry, College of ScienceYanbian UniversityYanjiPeople’s Republic of China
  2. 2.Key Laboratory of Natural Resources of Changbai Mountain & Functional Molecules (Yanbian University)Ministry of EducationYanjiPeople’s Republic of China

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