Transthyretin-IN-3 (compound 6) is a synthetically designed benzofuran analogue. It selectively binds with transthyretin in plasma, inhibiting amyloid aggregation with an IC50 of 5.0±0.2 μM. By incorporating a chlorine substituent at a specific position, Transthyretin-IN-3 effectively targets the thyroxine binding site of TTR, preventing the dissociation of TTR tetramers into unstable monomers.

The compound Transthyretin-IN-3, when administered intravenously (0.1 mg/kg) and orally (0.1 mg/kg) at an 8-hour interval, exhibits an oral bioavailability (BA) of 66.8% in Sprague-Dawley (SD) rats, aligning with the effectiveness of current therapeutics. Pharmacokinetic parameters for SD rats are as follows: for intravenous administration, the dose is 0.1 mg/kg, C0max is 1718 ng/mL, CLtot is 20.6 mL/h/kg, Vdss is 112 mL/kg, and the AUC0_8 is 3726 ng•h/mL. For oral dosing, with the same dose, C0max is 395 ng/mL, and the AUC0_8 is 2524 ng•h/mL, resulting in a BA of 67.7%.