K-252a derivatives which enhance neurotrophin-induced activity

C - Chemistry – Metallurgy – 07 – D

Patent

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C07D 487/14 (2006.01) A61K 31/40 (2006.01) A61K 31/55 (2006.01) C07D 498/22 (2006.01)

Patent

CA 2171561

Disclosed are derivatives of the indolocarbazole alkaloid K- 252a of formulae (I-VI), useful for enhancing neurotrophin-induced activity of neurotrophin responsive cells. A particularly preferred neurotrophin is NT-3, and a particularly preferred neurotrophin responsive cell is one which comprises a trk receptor. The enhanced neurotrophin-induced activity occasioned by the disclosed K-252a derivatives may be determined by the following assays: ChAT activity; DRG neuronal survival; or cell division (mitogenesis).

L'invention se rapporte à des dérivés de l'alcaloïde indolocarbazole K-252a des formules (I-VI) qui sont utilisés pour accroître l'activité induite par la neurotrophine des cellules sensibles à la neurotrophine. Une neurotrophine préférée est la NT-3, et une cellule sensible à la neurotrophine préférée est une cellule qui comprend un récepteur trk. L'activité améliorée induite par la neurotrophine et occasionnée par les dérivés de K-252a décrits peut être déterminée par les processus suivants: activité ChAT; durée de vie des neurones des ganglions de la racine dorsale (DRG); ou division cellulaire (mitogénèse).

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