Synthesis and SAR of inhibitors of protein kinase CK2: novel tricyclic quinoline analogs.
Bioorg Med Chem Lett
; 22(1): 45-8, 2012 Jan 01.
Article
em En
| MEDLINE
| ID: mdl-22169261
ABSTRACT
Protein kinase CK2 is a potential drug target for many diseases including cancer and inflammation disorders. The crystal structure of clinical candidate CX-4945 1 with CK2 revealed an indirect interaction with the protein through hydrogen bonding between the NH of the 3-chlorophenyl amine and a water molecule. Herein, we investigate the relevance of this hydrogen bond by preparing several novel tricyclic derivatives lacking a NH moiety at the same position. This SAR study allowed the discovery of highly potent CK2 inhibitors.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Quinolinas
/
Caseína Quinase II
/
Antineoplásicos
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article