2-(3,5-Dichlorophenyl)-1,3-benzoxazole-6-carboxylic acid--1-deoxy-1-(methylamino)hexitol (1/1)

BeschreibungIn November 2011, the European Commission approved tafamidis meglumine (Fx-1006A, PF-06291826) for the treatment of transthyretin familial amyloid polyneuropathy (TTR-FAP) in adult patients with stage 1 symptomatic polyneuropathy. Tafamidis stabilizes both the wild type and mutant forms of TTR tetramer and prevents tetramer dissociation by noncooperatively binding to the two thyroxine binding sites. Tafamidis is the first approved medicine for TTR-FAP. The Kd values for tafamidis for the two thyroxine binding sites on TTR, as determined by isothermal titration calorimetry, were 3 nM and 278 nM, respectively. In another in vitro study using wild type TTR, V30M mutant TTR, and V122I mutant TTR, it was shown that tafamidis inhibited fibril formation in a concentration-dependent manner reaching EC50 at a tafamidis:TTR stoichiometry of 50 was in the range of 2.7–3.2 μM, corresponding to a tafamidis:TTR stoichiometry range of 0.75–0.9). Tafamidis has been synthesized by coupling 4-amino-3- hydroxybenzoic acid with 3,5-dichlorobenzoyl chloride followed by dehydration using p-toluenesulfonic acid.

VerwendenTafamidis Meglumine is used as a potential therapeutics for COVID-19 and related viral infections