Synthesis and in-vitro biological activity of macrocyclic urea Chk1 inhibitors.
Bioorg Med Chem Lett
; 17(23): 6499-504, 2007 Dec 01.
Article
em En
| MEDLINE
| ID: mdl-17931867
ABSTRACT
A variety of macrocyclic urea compounds were prepared as potent Chk1 inhibitors by modifying the C5 position of the benzene ring of the macrocyclic urea with ether moieties, aliphatic carbon chains, amide and halides. Enzymatic activity less than 20nM was observed in 29 of 40 compounds. Compounds 14, 46d, and 48j provided the best overall results in the cellular assays as they abrogated doxorubicin-induced cell cycle arrest (IC(50)=3.31, 3.08, and 3.13microM) and enhanced doxorubicin cytotoxicity (IC(50)=0.54, 1.27, and 0.96microM) while displaying no single agent activity, respectively.
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Base de dados:
MEDLINE
Assunto principal:
Proteínas Quinases
/
Ureia
/
Compostos Macrocíclicos
/
Inibidores de Proteínas Quinases
Limite:
Humans
Idioma:
En
Ano de publicação:
2007
Tipo de documento:
Article