Abstract A series of novel (−)-verbenone hydrazones was designed and synthesized via condensation of terpenoid with hydrazides derived from phenoxyacetic acid. The structure of target compounds was confirmed by 1H-NMR and 13C-NMR analysis, Raman and FT-IR spectroscopy, electrospray ionization method and fast atom bombardment (FAB) mass spectrometry. Thermal properties of (−)-verbenone hydrazones 3a–3e were estimated by differential scanning calorimetry and their purity by HPLC coupled to mass spectrometry. Verbenone hydrazones were revealed to exist as Z/E geometrical isomers about C═N bond and cis/trans amide conformers. Verbenone derivatives were estimated as potential anticonvulsant agents after their oral administration against pentylenetetrazole and maximal electroshock-induced seizures in mice. Analgesic effect of hydrazones was studied by topical application on models of allyl isothiocyanate and capsaicin-induced pain. The present findings indicate that verbenone hydrazones contribute to seizure protection both at short (6 h) and long (24 h) time periods by blocking chemical- and electroshock-induced convulsions. Binding of compounds 3a–3e to TRPA1/TRPV1 ion channels was suggested as a feasible mechanism explaining their significant analgesic activity.

中文翻译：

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(-)-verbenone 腙的设计、合成和药理学特征

摘要 通过萜类化合物与苯氧乙酸衍生的酰肼类化合物的缩合反应，设计并合成了一系列新型(-)-马鞭草酮腙。目标化合物的结构通过1H-NMR和13C-NMR分析、拉曼和FT-IR光谱、电喷雾电离法和快速原子轰击(FAB)质谱法证实。(-)-verbenone 腙 3a-3e 的热性质通过差示扫描量热法估计，其纯度通过 HPLC 与质谱联用进行估计。马鞭草腙被发现作为关于 C=N 键和顺/反酰胺构象异构体的 Z/E 几何异构体存在。马鞭草衍生物被认为是潜在的抗惊厥剂，在它们口服给药对抗戊四唑和最大电击诱发的小鼠癫痫发作后。通过在异硫氰酸烯丙酯和辣椒素引起的疼痛模型上局部应用来研究腙的镇痛作用。目前的研究结果表明，马鞭草腙通过阻断化学和电击引起的惊厥，在短 (6 小时) 和长 (24 小时) 时间段内有助于癫痫发作保护。化合物 3a-3e 与 TRPA1/TRPV1 离子通道的结合被认为是解释其显着镇痛活性的可行机制。