Yeşilada A, Gökhan N, Ozer I, Vural K, Erol K
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Hacettepe University, Ankara, Turkey.
Farmaco. 1996 Dec;51(12):775-80.
In this study a series of 5-methyl-8-N-substituted-thiocarbamoyl-7,8-diazabicyclo[4.3.0] non-6-enes derivatives previously synthesized and separated to their stereoisomers, were evaluated as BSAO inhibitors and screened pharmacologically for antidepressant activity, effect on anxiety and experimental parkinsonism by in vivo tests. The title compounds caused 30-40% inhibition irrespective of geometric isomerism as well as nature of substituent. On the other hand, their open chain derivative NBE (4-ethyl, p-methoxybenzylidenthiosemicarbazide) showed a marked enzyme inhibition and antidepressant effect. While the other group was inactive as antidepressant effect, these compounds have shown diastereoselective antitremor activity by inhibiting the tremors induced by oxotremorin in mice pretreated with dopaminergic antagonist haloperidol. The title compounds constitutes a new class of BSAO inhibitors and may serve as usefull leads for further investigation as specific BSAO inhibitors, antiparkinson, antidepressant and anticholinergic agents.
在本研究中，一系列先前合成并分离出其立体异构体的5-甲基-8-N-取代硫代氨基甲酰基-7,8-二氮杂双环[4.3.0]壬-6-烯衍生物，被评估为BSAO抑制剂，并通过体内试验对其抗抑郁活性、对焦虑的影响和实验性帕金森病进行了药理学筛选。无论几何异构体以及取代基的性质如何，标题化合物均能产生30%-40%的抑制作用。另一方面，它们的开链衍生物NBE（4-乙基，对甲氧基苄基亚硫脲）显示出显著的酶抑制和抗抑郁作用。虽然另一组作为抗抑郁作用无活性，但这些化合物通过抑制多巴胺能拮抗剂氟哌啶醇预处理的小鼠中由氧化震颤素诱导的震颤，表现出非对映选择性抗震颤活性。标题化合物构成了一类新的BSAO抑制剂，可作为进一步研究特定BSAO抑制剂、抗帕金森病、抗抑郁和抗胆碱能药物的有用先导物。
