Synthesis and SAR of succinamide peptidomimetic inhibitors of cathepsin S.
Bioorg Med Chem Lett
; 17(10): 2899-903, 2007 May 15.
Article
em En
| MEDLINE
| ID: mdl-17382545
ABSTRACT
Peptidic, non-covalent inhibitors of lysosomal cysteine protease cathepsin S (1 and 2) were investigated due to low oral bioavailability, leading to an improved series of peptidomimetic inhibitors. Utilizing phenyl succinamides as the P2 residue increased the oral exposure of this lead series of compounds, while retaining selective inhibition of the cathepsin S isoform. Concurrent investigation of the P1 and P2 subsites resulted in the discovery of several potent and selective inhibitors of cathepsin S with good pharmacokinetic properties due to the elimination of saturated aliphatic P2 residues.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Inibidores de Proteases
/
Catepsinas
/
Amidas
Limite:
Animals
Idioma:
En
Revista:
Bioorg Med Chem Lett
Ano de publicação:
2007
Tipo de documento:
Article