Bifunctional coumarin derivatives that inhibit transthyretin amyloidogenesis and serve as fluorescent transthyretin folding sensors

We describe coumarin derivatives that are non-fluorescent in aqueous buffers and that very selectively bind to transthyretin (TTR) in complex biological environments potently inhibiting TTR amyloidogenesis while also exhibiting sensitive off-on fluorescent sensing of the properly folded quaternary structure of TTR.