Indazoles as potential c-Met inhibitors: design, synthesis and molecular docking studies.
Eur J Med Chem
; 65: 112-8, 2013 Jul.
Article
em En
| MEDLINE
| ID: mdl-23702473
ABSTRACT
Deregulation of the receptor tyrosine kinase c-Met has been implicated in several human cancers and is considered as an attractive target for small molecule drug discovery. In this study, a series of indazoles were designed, synthesized and evaluated as novel c-Met inhibitors. The results showed that the majority of the compounds exhibited significant inhibition on c-Met and compound 4d showed highest activity against c-Met with IC50 value of 0.17 µM in TR-FRET-based assay and IC50 value of 5.45 µM in cell-based assay as compared to other tested compounds. Molecular docking experiments verified the results and explained the molecular mechanism of pretty activities to c-Met.
Palavras-chave
AQKULDWMVLPKPM-RQNOJGIXSA-N; ASSDAYRAIJUAKP-UHFFFAOYSA-N; Bioisosterism principles; IOEGMAJBPLCGLZ-RQNOJGIXSA-N; Indazole; Isomer; KFHKXMBLOGYCPH-OGESRWMOSA-N; KUZAYSZLNQTGIG-UHFFFAOYSA-N; LNULRIFOOHDLKU-UHFFFAOYSA-N; Molecular docking; QONCLFMRNBSJDL-UHFFFAOYSA-N; SGCGRBMTXZLJBR-OGESRWMOSA-N; Suzuki coupling reaction; VMWYPUTZWINMTO-UHFFFAOYSA-N; VXDNOGKPNKBTFZ-UHFFFAOYSA-N; c-Met inhibitor
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Desenho de Fármacos
/
Proteínas Proto-Oncogênicas c-met
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Inibidores de Proteínas Quinases
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Indazóis
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article