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新型N-(烷基/取代芳基)-N'-[4-(5-环己基氨基)-1,3,4-噻二唑-2-基]苯基硫脲的合成及其抗惊厥活性

Synthesis and anticonvulsant activity of new N-(alkyl/sub-stituted aryl)-N'-[4-(5-cyclohexylamino)-1,3,4-thiadiazole-2-yl)phenyl]thioureas.

作者信息

Karakus Sevgi, Koçyiğit-Kaymakcioğlu Bedia, Toklu Hale Z, Aricioglu Feyza, Rollas Sevim

机构信息

Department of Pharmaceutical Chemistry, Marmara University, Faculty of Pharmacy, Istanbul, Turkey.

出版信息

Arch Pharm (Weinheim). 2009 Jan;342(1):48-53. doi: 10.1002/ardp.200800118.

Abstract

A series of novel thiourea derivatives carrying the 5-cylohexylamino-1,3,4-thiadiazole moiety was synthesized and their anticonvulsant activity was evaluated. Structures of the synthesized compounds have been confirmed by IR, 1H-NMR, and elemental analysis. All of the compounds were administered at a dose of 50 mg/kg. Some of the active compounds have different effects in pentylenetetrazole (PTZ) and maximal electroshock (MES) tests, indicating the therapeutical potential in petit mal seizures, but not in grand mal seizures. Compounds 10, 11, 13, and 14 carrying 2-methylphenyl, 4-chlorophenyl, allyl, and 4-methylphenyl on the thiourea pharmacophore, increased the survival rate in the PTZ model. The ED50 values of the active compounds 10, 11, 13, and 14 were found 68.42, 43.75, 18.75 and 25 mg/kg, respectively.

摘要

合成了一系列带有5-环己基氨基-1,3,4-噻二唑部分的新型硫脲衍生物,并评估了它们的抗惊厥活性。通过红外光谱、1H-核磁共振和元素分析确定了合成化合物的结构。所有化合物均以50mg/kg的剂量给药。一些活性化合物在戊四氮(PTZ)和最大电休克(MES)试验中有不同的作用,表明其对失神性癫痫有治疗潜力,但对大发作癫痫无治疗潜力。在硫脲药效基团上带有2-甲基苯基、4-氯苯基、烯丙基和4-甲基苯基的化合物10、11、13和14在PTZ模型中提高了存活率。活性化合物10、11、13和14的半数有效剂量(ED50)值分别为68.42、43.75、18.75和25mg/kg。

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