Synthesis and structure-activity relationships of 1,2,3,4-tetrahydropyrido[2,3-b]pyrazines as potent and selective inhibitors of the anaplastic lymphoma kinase.
Bioorg Med Chem
; 18(12): 4351-62, 2010 Jun 15.
Article
em En
| MEDLINE
| ID: mdl-20483621
ABSTRACT
Dysregulation of the anaplastic lymphoma kinase (ALK) is implicated in a variety of cancers. A series of tetrahydropyrido[2,3-b]pyrazines was constructed as ring-constrained analogs of a known aminopyridine kinase scaffold. Chemistry was developed to rapidly elaborate the SAR, structural elements impacting ALK inhibitory activity were exploited, and kinase selective analogs were identified that inhibit ALK with IC(50) values approximately 10 nM (enzyme) and approximately 150 nM (cell).
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Base de dados:
MEDLINE
Assunto principal:
Pirazinas
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Proteínas Tirosina Quinases
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Inibidores de Proteínas Quinases
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Antineoplásicos
Idioma:
En
Ano de publicação:
2010
Tipo de documento:
Article