Synthesis and anticonvulsant activity of some novel 7-(benzylamino) -1H-benzo[b][1,4]diazepine-2,4(3H, 5H)-dione derivatives
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.
Keywords1H-benzo[b][1,4]diazepine-2,4(3H,5H)-dione anticonvulsant activity structure-activity relationship
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.
- Bode JW (2006) Curr Opin Drug Discov Dev 9:765–775Google Scholar
- Eadie MJ, Vajda F (2012) Antiepileptic drugs. Springer, BerlinGoogle Scholar
- Guerrini G, A Costanzo, G Ciciani, F Bruni, S Selleri, C Costagli, F Besnard, B Costa, C Martini, GD Siena, P Malmberg-Aiello, Bioorg Med. Chem 14 (2006):758–775Google Scholar
- Jin DC, Zhang W, Piao* FY (2010) Chemistry 2:188–192Google Scholar