Synthesis of inhibitors of p90rsk

Details Synthesis of inhibitors of p90rsk Synthesis of inhibitors of p90rsk

C - Chemistry, Metallurgy

07

H

C07H 17/07 (2006.01) A61K 31/7048 (2006.01) A61P 35/00 (2006.01)

Patent

CA 2594542

The synthesis of the naturally occurring kaempferol glycoside SLO1O1-1, as well as analogs thereof, has been accomplished, as has its biochemical evaluation. SLO1O1-1 exhibits selective and potent p90 Rsk inhibitory activity at nanomolar concentrations without inhibiting the function of upstream kinases such as MEK, Raf, or PKC. The synthetic scheme of the invention verified the structural assignment of the natural product and has provided access to material sufficient for detailed biological evaluation.

Selon l'invention, on a réalisé la synthèse de glycoside de kaempférol naturel SL0101-1 et d'analogues de ce composé, de même que son évaluation biochimique. Le SL0101-1 présente une activité inhibitrice de la p90Rsk sélective et puissante à des concentrations nanomolaires sans inhibition de la fonction des kinases en amont telles que MEK, Raf ou PKC. Le système de synthèse de l'invention a permis de vérifier l'attribution structurale du produit naturel et a fourni un accès à la matière suffisant pour une évaluation biologique détaillée.

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