Development of anti-parkinsonism agent related to endogenous amines as pharmacophore

点击翻译按钮获取中文摘要

It has been known for about 5 years that tetrahydroisoquinoline(TIQ) derivatives may be related to the onset of parkinsonism. TIQ and 1-methyi-1, 2, 3, 4- tetrahydroisoquinoline (1MeTIQ) are endogenous amines coexisting in the brain of many species including humans. Mareover, 1MeTIQ has a preventive effect against parkinsonism in mice.Methyl derivative of TIQs were synthesized in preparative scale. And these pharmacological effects were investigated. From the structure-activity relationship, a methyl group attached 1 position is contributed to locomotive activity. The number of methyl groups is affected toxicity. These findings will be useful for further investigation to find out anti-parkinsonism agents.On the way of the investigation, we found that 1-benzyl-TIQ (1BnTIQ) had very strong neurotoxic character. This compound was also an endogeneous amine in human brain. The content of 1-BnTIQ in parkinsonians is higher than control subjects. So from these data, 1BnTIQ is a very suitable candidate for parkinsonism causing substance.