Background: Tau aggregation inhibitors could treat Alzheimer disease.Results: Stable reduced forms of leucomethylthioninium (LMTX®) are active in blocking prion-like Tau aggregation in novel cellular models.Conclusion: The intracellular Ki (0.12 μm) is comparable with brain levels required for clinical benefit.Significance: LMTX® could treat Alzheimer disease.

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A series of tetrahydro-1,2,4,5-tetrazinan-3-ones have been prepared by the reaction of carbonic acid bis (1-methylhydrazide) with aromatic aldehydes. These were oxidised to oxoverdazyl free radicals and used immediately for ESR spectroscopy studies that indicate that the unpaired electron is delocalised over the verdazyl ring. The ESR spectra can be very well simulated considering hyperfine couplings with the four nitrogen atoms of the verdazyl ring and the six hydrogen atoms of the two methyl groups bonded to it.

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Other 6-membered heterocycles R 0670New Tetrahydro-1,2,4,5-tetrazinan-3-ones and Oxoverdazyl Free Radicals. -A series of new tetrahydrotetrazinones (III) (10 examples) is synthesized by reaction of bishydrazide (I) with aromatic aldehydes. Oxidation using NaIO4 affords the corresponding red-colored, stable 3-oxoverdazyl radicals (IV). -(PLATER*, M. J.; SINCLAIR, J. P.; KEMP, S.; GELBRICH, T.; HURSTHOUSE, M. B.; GOMEZ-GARCIA, C. J.; J. Chem. Res. 2006, 8, 515-520; Dep. Chem., Univ. Aberdeen, Aberdeen AB24 3UE, UK; Eng.) -H. Toeppel 52-173