期刊
JOURNAL OF MEDICINAL CHEMISTRY
卷 58, 期 18, 页码 7241-7257出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.jmedchem.5b00440
关键词
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资金
- Japan Society for the Promotion of Science (JSPS) through the Funding Program for Next Generation World-Leading Researchers (NEXT Program)
- Council for Science and Technology Policy (CSTP)
- MEXT [15H01555]
- JSPS Research Fellowships for Young Scientists
- Grants-in-Aid for Scientific Research [14J05961, 15H01555, 15H04271] Funding Source: KAKEN
In order to explore novel tau-imaging agents that can selectively detect neurofibrillary tangles in Alzheimer's disease (AD) brains, we designed and synthesized a series of heterocyclic phenylethenyl and (3-pyridinyl)ethenyl derivatives with or without a dimethyl amino group. In in vitro autoradiography using AD brain sections, all radioiodinated ligands with a dimethyl amino group bound to A beta deposits in the sections. In contrast, the ligands without a dimethyl amino group showed different patterns of radioactivity accumulation in the sections depending on the kind of heterocycle contained in their molecules. Particularly, a phenylethenyl benzimidazole derivative ([I-125]64) showed marked radioactivity accumulation in the temporal lobe which corresponded with the distribution of tau deposits. [I-125]64 also showed the most favorable pharmacokinetics in normal mouse brains (3.69 and 0.06% ID/g at 2 and 60 min postinjection, respectively) among all ligands in this study. Taken together, these results suggest that [I-123]64 may be a new candidate tau-imaging agent.
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