Carlos José Vieira Simões,Zaida Catarina Lourenco de Almeida,Teresa Margarida Vasconcelos Dias de Pinho e Melo,Rui Manuel Pontes Meireles Ferreira de Brito,Dora Cristina Silva Costa,Ana Lúcia Cabral C
申请号：
US15736826
公开号：
US20180208570A1
申请日:
2016.06.15
申请国别(地区):
US
年份:
2018
代理人:
摘要：
The design and synthesis of a novel bis-furan scaffold tailored for high efficiency at inhibiting transthyretin amyloid formation is reported. In vitro results show that the discovered compounds are more efficient inhibitors of amyloid formation than tafamidis, a drug currently used in the treatment of familial amyloid polyneuropathy (FAP), despite their lower molecular weight and lipophilicity. Moreover, ex vivo experiments with the strongest inhibitor in the series, conducted in human blood plasma from normal and FAP Val30Met-transthyretin carriers, disclose remarkable affinity and selectivity profiles. The promises and challenges facing further development of this compound are discussed under the light of increasing evidence implicating transthyretin stability as a key factor not only in transthyretin amyloidoses and several associated co-morbidities, but also in Alzheimers disease.
