Discovery of novel isothiazole inhibitors of the TrkA kinase: structure-activity relationship, computer modeling, optimization, and identification of highly potent antagonists.
Bioorg Med Chem Lett
; 16(13): 3444-8, 2006 Jul 01.
Article
em En
| MEDLINE
| ID: mdl-16632359
ABSTRACT
The design, synthesis, and biological evaluation of potent inhibitors of the TrkA kinase is presented. A homology model is created to aid in the enhancement of potency and selectivity of isothiazole inhibitors found during a high-throughput screen. Three different syntheses are utilized to make diverse analogs within this series. Aminoheterocycles are found to be good urea surrogates, whereas bicyclic substituents on the C3 thio group were found to be extremely potent TrkA inhibitors in kinase and cell assays.
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Base de dados:
MEDLINE
Assunto principal:
Tiazóis
/
Simulação por Computador
/
Receptor trkA
/
Inibidores Enzimáticos
Tipo de estudo:
Diagnostic_studies
Idioma:
En
Revista:
Bioorg Med Chem Lett
Ano de publicação:
2006
Tipo de documento:
Article
País de afiliação:
Estados Unidos