Semicarbazone-based inhibitors of cathepsin K, are they prodrugs for aldehyde inhibitors?
Bioorg Med Chem Lett
; 16(4): 978-83, 2006 Feb 15.
Article
en En
| MEDLINE
| ID: mdl-16290936
ABSTRACT
Starting from potent aldehyde inhibitors with poor drug properties, derivatization to semicarbazones led to the identification of a series of semicarbazone-based cathepsin K inhibitors with greater solubility and better pharmacokinetic profiles than their parent aldehydes. Furthermore, a representative semicarbazone inhibitor attenuated bone resorption in an ex vivo rat calvarial bone resorption model. However, based on enzyme inhibition comparisons at neutral pH, semicarbazone hydrolysis rates, and 13C NMR experiments, these semicarbazones probably function as prodrugs of aldehydes.
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Banco de datos:
MEDLINE
Asunto principal:
Semicarbazonas
/
Catepsinas
/
Aldehídos
/
Inhibidores Enzimáticos
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Bioorg Med Chem Lett
Asunto de la revista:
BIOQUIMICA
/
QUIMICA
Año:
2006
Tipo del documento:
Article
País de afiliación:
Estados Unidos