N. N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch, Russian Academy of Sciences, Lavrentjev Avenue 9, 630090 Novosibirsk, Russian Federation.
Bioorg Med Chem. 2013 Mar 1;21(5):1082-7. doi: 10.1016/j.bmc.2013.01.003. Epub 2013 Jan 11.
Earlier it was found, that (1R,2R,6S)-3-methyl-6-(prop-1-en-2-yl)cyclohex-3-ene-1,2-diol (1) possess high antiparkinsonian activity. The N-, O-, S- and C-derivatives at the C-9 position of diol 1 were synthesized in this work. The antiparkinsonian activity of these compounds was studied in MPTP mice models. As a rule, the introduction of substituents containing nitrogen atoms at the C-9 position led to a considerable decrease or loss of antiparkinsonian activity. A derivative of 2-aminoadamantane 8 significantly decreased the locomotor activity time, thus enhancing the symptoms of the parkinsonian syndrome. However the introduction of butyl or propylthio substituents at the C-9 position of diol 1 did not diminish the antiparkinsonian activity comparing to parent compound. This information is important when choosing a route for immobilization of compound 1 to find possible targets.
早些时候发现，（1R,2R,6S）-3-甲基-6-（1-丙烯-2-基）环己-3-烯-1,2-二醇（1）具有很高的抗帕金森病活性。本工作合成了二醇 1 在 C-9 位的 N-、O-、S-和 C-衍生物。这些化合物的抗帕金森病活性在 MPTP 小鼠模型中进行了研究。通常，在 C-9 位引入含氮原子的取代基会导致抗帕金森病活性显著降低或丧失。2-氨基金刚烷 8 的衍生物显著缩短了运动时间，从而加重了帕金森综合征的症状。然而，与母体化合物相比，二醇 1 的 C-9 位引入丁基或丙基硫取代基并没有降低其抗帕金森病活性。当选择固定化合物 1 的途径以寻找可能的靶标时，这些信息很重要。
