Synthesis and Anticonvulsant Activity of 2-Iminohydantoins

V. K. Singh1., B. B. Subudhi2.
1
Department of Pharmaceutical Chemistry, Columbia Institute of Pharmacy, Raipur, (C.G)
2
Department of Pharmaceutical Chemistry, SOA University, Bhuwaneshwar, (Orissa)

A series of 2-Iminohydantoins selectively substituted at position C-5 and their 1-carbobenzoxy derivatives have
been synthesized, and their anticonvulsant activity was evaluated in mice. In general, the more lipophilic 1-
carbobenzoxy iminohydantoins were more potent. In this study (S)-(+)-1-carbobenzoxy-5-Sustituted phenyl-2-
iminohydantoins derivatives were provide the most substantial anticonvulsant activity against maximal
electroshock seizure (MES) test and pentylenetetrazol(ScPTZ) test with the dose range of 30-150 mg kg -1.
Compound 3, 4 and 7 were found to active against MES test and compound 3, 4, 5 and 7 were found to active
against ScPTZ. This compound was not nearly as active as phenytoin against electrically induced convulsions,
but was also active against pentylenetetrazole-induced seizures, suggesting a broader clinical potential. All
significantly active compounds possessed aryl groups in the carbamate moiety. These results suggest that
substituent at C-5 and N-1 oxycarbonyl side chain in the 2- iminohydantoin molecule plays an important role in
providing anticonvulsant activity, and that an aryl substituent with a proper size further enhances PTZ
anticonvulsant activity while maintaining MES activity.
Graphical abstract:
O
R R'

R1
O N1 5
4 O
2 3
N
X

H X= O Hydantoin
X= NH 2-Iminohydantoin

Key words: anticonvulsants; 2-iminohydantoins; synthesis; drug design