Synthesis and Neurotoxicity of Tetrahydroisoquinoline Derivatives for Studying Parkinson's Disease
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- Abe Kenji
- Department of Neuroscience, Showa Pharmaceutical University
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- Saitoh Toshiaki
- Department of Medicinal Chemistry, Showa Pharmaceutical University
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- Horiguchi Yoshie
- Department of Medicinal Chemistry, Showa Pharmaceutical University
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- Utsunomiya Iku
- Department of Neuroscience, Showa Pharmaceutical University
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- Taguchi Kyoji
- Department of Neuroscience, Showa Pharmaceutical University
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説明
Parkinson's disease involves the progressive degeneration of dopaminergic neurons in the substantia nigra. However, the etiology of the disease remains to be elucidated. Endogenous amines, such as 1,2,3,4-tetrahydroisoquinoline (TIQ) derivatives present in the mammalian brain, are known to participate in the pathogenesis of Parkinson's disease. These endogenous neurotoxins have been extensively studied because of their structural resemblance to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), an agent widely used for generating animal models of Parkinson's disease-like symptoms. Investigations of the synthesis and pharmacological properties of TIQ derivatives are expected to contribute to the development of new therapeutic agents for treating Parkinson's disease. In the present study, we describe more efficient synthesis methods for TIQ derivatives via Pummerer-type cyclization of the substrate N-acyl sulfoxide. Furthermore, the modified Pummerer reaction provided a convenient and efficient method for synthesizing various TIQs. TIQ and its derivative, 1-benzyl-TIQ, can induce parkinsonism in primates and rodents. On the other hand, one TIQ derivative, 1-methyl-TIQ, has been shown to prevent MPTP, TIQ, and 1-benzyl-TIQ induced behavioral abnormalities. Therefore, TIQ derivatives are considered to play an important role in both the onset and prevention of Parkinson's disease. In this article, we focus on the synthesis and pharmacological aspects of 1,2,3,4-tetrahydroisoquinoline derivatives in Parkinson's disease.
収録刊行物
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- Biological & Pharmaceutical Bulletin
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Biological & Pharmaceutical Bulletin 28 (8), 1355-1362, 2005
公益社団法人 日本薬学会
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詳細情報 詳細情報について
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- CRID
- 1390282679604452224
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- NII論文ID
- 10016666239
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- NII書誌ID
- AA10885497
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- ISSN
- 13475215
- 09186158
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- NDL書誌ID
- 7372212
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- PubMed
- 16079473
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- 本文言語コード
- en
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- データソース種別
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- JaLC
- NDL
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- PubMed
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