Design and synthesis of piperidine farnesyltransferase inhibitors with reduced glucuronidation potential.
Bioorg Med Chem
; 15(3): 1363-82, 2007 Feb 01.
Article
em En
| MEDLINE
| ID: mdl-17127066
ABSTRACT
The design and synthesis of a novel piperidine series of farnesyltransferase (FTase) inhibitors with reduced potential for metabolic glucuronidation are described. The various substitution and exchange of the phenyl group at the C-2 position of the previously described 2-(4-hydroxy)phenyl-3-nitropiperidine 1a (FTase IC(50)=5.4nM) resulted in metabolically stable compounds with potent FTase inhibition (14a IC(50)=4.3nM, 20a IC(50)=3.0nM, and 50a IC(50)=16nM). Molecular modeling studies of these compounds complexed with FTase and farnesyl pyrophosphate are also described.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Piperidinas
/
Desenho de Fármacos
/
Alquil e Aril Transferases
/
Glucuronídeos
/
Inibidores Enzimáticos
Limite:
Animals
Idioma:
En
Revista:
Bioorg Med Chem
Assunto da revista:
BIOQUIMICA
/
QUIMICA
Ano de publicação:
2007
Tipo de documento:
Article
País de afiliação:
Japão