- An iodinated derivative of moclobemide as potential radioligand for brain MAO-A exploration
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In vivo evaluation of MAO-A would be of great value for the diagnosis and follow-up of therapy of depression. In order to perform this exploration by SPECT, we developed an iodinated derivative of the reversible MAO-A inhibitor, moclobemide. Ro 11-9900 was synthesized and analysed by IR, NMR and HPLC. Radioiodination was carried out by nucleophilic exchange of [125I] on the brominated precursor, and yielded [125I]-Ro 11-9900 with high specific activity. In vitro experiments on rat brain homogenates showed that Ro 11-9900 had poor inhibitory activity on MAO-A, as already described for moclobemide. By contrast, in vivo biodistribution in the rat brain showed that [125I]-Ro 11-9900 accumulated in a region corresponding to the localization of-locus coeruleus known for its high density of MAO-A. Moreover, preinjection of the irreversible MAO-A inhibitor clorgyline (10 mg.kg-1) prevented accumulation of radioactivity by 40 to 60% and we found that the radioactivity in the brain corresponded exclusively to [125I]-Ro 11-9900 and not to a metabolite. [125I]-Ro 11-9900 was highly accumulated in the pineal gland, both on MAO-A and on MAO-B sites. We concluded that the unmetabolized iodinated derivative of moclobemide, Ro 11-9900, preferentially labeled MAO-A in vivo in the rat brain. This compound would therefore be a potential tracer for evaluation of MAO-A by SPECT.
- Rafii,Chalon,Ombetta,Frangin,Pourcelot,Besnard,Bodard,Guilloteau
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- A Visible-Light-Driven, Metal-free Route to Aromatic Amides via Radical Arylation of Isonitriles
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The photochemical metal-free carboamidation of aryl radicals has been exploited for the preparation of aromatic amides, including hetero- and polyaromatic derivatives, under visible light irradiation of arylazo sulfones in the presence of isocyanides in aqueous acetonitrile. The process was useful for the smooth preparation of the antidepressant moclobemide. (Figure presented.).
- Malacarne, Marco,Protti, Stefano,Fagnoni, Maurizio
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supporting information
p. 3826 - 3830
(2017/11/15)
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- PYRIDINYLQUINAZ0LINAMINE DERIVATIVES AND THEIR USE AS B-RAF INHIBITORS
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The invention relates to chemical compounds of the formula (I) or pharmaceutically acceptable salts thereof, which possess B-Raf inhibitory activity and are accordingly useful for their anti cancer activity and thus in methods of treatment of the human or animal body. The invention also relates to processes for the manufacture of said chemical compounds, to pharmaceutical compositions containing them and to their use in the manufacture of medicaments of use in the production of an anti-cancer effect in a warm blooded animal such as man.
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Page/Page column 73
(2010/11/30)
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- Morpholino containing benzamides
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Benzamides of the formula STR1 wherein X is halogen, trifluoromethyl or C3-4 -alkyl and Y is hydrogen, halogen or nitro, and N-oxides thereof, prepared inter alia from N-(2-aminoethyl)-morpholine and an acid of the formula STR2 wherein X and Y are as hereinbefore set forth, are described. The end products are useful in the treatment of depressive conditions, that is, are useful as antidepressants.
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