Synthesis, structure, and activity of diclofenac analogues as transthyretin amyloid fibril formation inhibitors.
J Med Chem
; 45(2): 321-32, 2002 Jan 17.
Article
em En
| MEDLINE
| ID: mdl-11784137
ABSTRACT
Twelve analogues of diclofenac (1), a nonsteroidal antiinflammatory drug and known inhibitor of transthyretin (TTR) amyloid formation, were prepared and evaluated as TTR amyloid formation inhibitors. High activity was exhibited by five of the compounds. Structure-activity relationships reveal that a carboxylic acid is required for activity, but changes in its position as well as the positions of other substituents are tolerated. High-resolution X-ray crystal structures of four of the active compounds bound to TTR were obtained. These demonstrate the significant flexibility with which TTR can accommodate ligands within its two binding sites.
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Base de dados:
MEDLINE
Assunto principal:
Pré-Albumina
/
Anti-Inflamatórios não Esteroides
/
Diclofenaco
/
Amiloide
Idioma:
En
Revista:
J Med Chem
Assunto da revista:
QUIMICA
Ano de publicação:
2002
Tipo de documento:
Article
País de afiliação:
Estados Unidos