Synthesis and potential anticonvulsant activity of new N-3-substituted 5,5-cyclopropanespirohydantoins.
Thirteen new 5-cyclopropanespirohydantoins with various N-3 substituents were synthesized and their pharmacological activity was determined with the objective to better understand their structure-activity relationship (SAR) for anticonvulsant activity. The anticonvulsant effects of these compounds were evaluated by maximal electroshock seizure (MES) test and subcutaneous pentylenetetrazole (scPTZ) test models in mice. All compounds substituted with cyclopropyl group at fifth position of hydantoin ring showed better protection against MES test. Compounds 5b, 5d, 5e, 5g and 5j were found to be the most potent compounds of this series and compared with the reference drug phenytoin sodium in MES test. Compound 5j also showed equipotent activity with the standard drug sodium valproate at the doses of 20 and 40 mg kg(-1) in scPTZ test.
Zhu
Qifeng
Q
State Key Laboratory of Virology, College of Pharmacy, Wuhan University, Wuhan 430072, China.
Pan
Yuanhu
Y
Xu
Zaixu
Z
Li
Ruimin
R
Qiu
Guofu
G
Xu
Wenjin
W
Ke
Xianbing
X
Wu
Lamei
L
Hu
Xianming
X
D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis* / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical; D006827:Hydantoins / Q000138:chemical synthesis* / Q000494:pharmacology; D051379:Mice; D051381:Rats; D012640:Seizures / Q000188:drug therapy / Q000517:prevention & control; D013141:Spiro Compounds; D013329:Structure-Activity Relationship
D000927:Anticonvulsants; D006827:Hydantoins; D013141:Spiro Compounds