Transthyretin stabilization

Details Transthyretin stabilization Transthyretin stabilization

A - Human Necessities

61

K

A61K 31/34 (2006.01) C07D 307/91 (2006.01)

Patent

CA 2566688

Dibenz.omicron.furan-4,6-dicarboxylic acid core structures having an aromatic substituent appended onto the at the C1 position using three different types of linkages are disclosed herein and shown to afford exceptional amyloidogenesis inhibitors that display increased affinity and greatly increased binding selectivity to TTR over all the other plasma proteins, relative to lead compound 1. It is further disclosed herein that these compounds function by imposing kinetic stabilization on the TTR tetramer.

L'invention concerne des structures de noyaux d'acide dibenzofuran-4,6-dicarboxylique comprenant un substituant aromatique ajouté en position C1 au moyen de trois types de liaisons différents, ces structures permettant d'obtenir d'excellents inhibiteurs de l'amyloïdogenèse présentant une affinité accrue et une sélectivité largement supérieure vis-à-vis de la TTR en comparaison avec toutes les autres protéines plasmatiques pour ce qui est du composé principal (1). En outre, selon l'invention, ces composé fonctionnent par introduction d'une stabilisation cinétique sur le tétramère TTR.

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