Design and synthesis of 6-amino-1,4-oxazepane-3,5-dione derivatives as novel broad spectrum anticonvulsants.
Based on the structural estimations of the typical anticonvulsant drugs, a series of 6-amino-1,4-oxazepane-3,5-dione derivatives, novel structures of 7-membered heterocyclic imides, which were hybridized with pharmacophores such as cyclic imide and N-CO-C-N group in their molecule were designed and synthesized. Their anticonvulsant activities were evaluated by the maximal electroshock induced seizure (MES) and subcutaneous pentylenetetrazole (PTZ) tests. Almost all the designed compounds except 1c and 1f showed comparable anticonvulsant activities in at least one of the anticonvulsant tests. Moreover, some of the tested compounds exhibited moderate anticonvulsant activities in both MES and PTZ tests. From these results, 6-amino-1,4-oxazepane-3,5-dione derivatives could be recommended as novel structures of broad spectrum anticonvulsants.
Sharma
Gitalee
G
College of Pharmacy, Kyungsung University, 110-1 Daeyeon-Dong, Nam-Gu, Busan 608-736, Republic of Korea.
Park
Jin Yup
JY
Park
Min Soo
MS
D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D020650:Combinatorial Chemistry Techniques; D015195:Drug Design; D004597:Electroshock / Q000009:adverse effects; D008297:Male; D051379:Mice; D015394:Molecular Structure; D010077:Oxazepines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D010433:Pentylenetetrazole / Q000493:pharmacokinetics; D012640:Seizures
D000927:Anticonvulsants; D010077:Oxazepines; D010433:Pentylenetetrazole