title: Synthesis and anticonvulsant activity of 1-(8-(benzyloxy)quinolin-2-yl)-6-substituted-4,6-diazaspiro[2,4]heptane-5,7-diones.
abstract: In the present study on the development of new anticonvulsants, 16 new1-(8-(benzyloxy)quinolin-2-yl-6-substituted-4,6-diazaspiro[2,4]heptane-5,7-diones were synthesized and tested for anticonvulsant activity using the maximal electroshock (MES), subcutaneous pentylenetetrazole (scPTZ) screens, which are the most widely employed seizure models for early identification of candidate anticonvulsants. Their neurotoxicity was determined applying the rotorod test. Two compounds 8e and 8j showed promising anticonvulsant activities in both models employed for anticonvulsant evaluation. The most active compound 8e showed the MES-induced seizures with ED(50) value of 8.6 mg/kg and TD(50) value of 365.3 mg/kg after intraperitoneally injection to mice, which provided compound 8e with a protective index (TD(50)/ED(50)) of 26.8 in the MES test.
authors.affiliation: State Key Laboratory of Virology, Ministry of Education Laboratory of Combinatorial Biosynthesis and Drug Discovery, Wuhan University School of Pharmaceutical Science, Luojiashan Road, Wuhan 430071, China.
authors.forename: Xianran
authors.initials: X
authors.lastname: He
authors.forename: Min
authors.initials: M
authors.lastname: Zhong
authors.forename: Tao
authors.initials: T
authors.lastname: Zhang
authors.forename: Jin
authors.initials: J
authors.lastname: Yang
authors.forename: Zhongyuan
authors.initials: Z
authors.lastname: Wu
authors.forename: Yuling
authors.initials: Y
authors.lastname: Xiao
authors.forename: Hao
authors.initials: H
authors.lastname: Guo
authors.forename: Guofu
authors.initials: G
authors.lastname: Qiu
authors.forename: Xianming
authors.initials: X
authors.lastname: Hu
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001681:Biological Assay; D004597:Electroshock; D006536:Heptanes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D013058:Mass Spectrometry; D051379:Mice; D015394:Molecular Structure; D011804:Quinolines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D012640:Seizures / Q000188:drug therapy*; D013141:Spiro Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D018675:Toxicity Tests / Q000379:methods
chemical_list: D000927:Anticonvulsants; D006536:Heptanes; D011804:Quinolines; D013141:Spiro Compounds