26975-77-9Relevant articles and documents
Synthesis and Anticonvulsant Activity of 2-Iminohydantoins
Kwon, Chul-Hoon,Iqbal, Muhammad Tahir,Wurpel, John N. D.
, p. 1845 - 1849 (2007/10/02)
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 than the unsubstituted counterparts.Evaluation of the individual enantiomers of the chiral iminohydantoins showed that the anticonvulsant activity resided primarily in the S isomers.In this study, (S)-(+)-1-carbobenzoxy-5-isobutyl-2-iminohydantoin (9a) was the most active member.This compound was not nearly as active as phenythoin against electrically induced convulsions, but was also active against pentylenetetrazole-induced seizures, suggesting a broader clinical potential.The closest analogue of phenytoin, viz., 5,5-diphenyl-2-iminohydantoin (1), failed to show any significant activity.Methylation on N-3 or the imino nitrogen of 1 also did not provide a compound with substantial activity. 2-Thiophenytoin was not active against electoshock seizures and showed only a weak activity against pentylenetetrazole.This study suggested that the structure-activity relationship of 2-iminohydantoins was quite different from that of 2-hydantoins.
