Preparation of kinase-biased compounds in the search for lead inhibitors of kinase targets.
Med Res Rev
; 25(3): 310-30, 2005 May.
Article
en En
| MEDLINE
| ID: mdl-15593285
This work describes the preparation of approximately 13,000 compounds for rapid identification of hits in high-throughput screening (HTS). These compounds were designed as potential serine/threonine or tyrosine kinase inhibitors. The library consists of various scaffolds, e.g., purines, oxindoles, and imidazoles, whereby each core scaffold generally includes the hydrogen bond acceptor/donor properties known to be important for kinase binding. Several of these are based upon literature kinase templates, or adaptations of them to provide novelty. The routes to their preparation are outlined. A variety of automation techniques were used to prepare >500 compounds per scaffold. Where applicable, scavenger resins were employed to remove excess reagents and when necessary, preparative high performance liquid chromatography (HPLC) was used for purification. These compounds were screened against an 'in-house' kinase panel. The success rate in HTS was significantly higher than the corporate compound collection.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Diseño de Fármacos
/
Inhibidores de Proteínas Quinasas
Idioma:
En
Revista:
Med Res Rev
Año:
2005
Tipo del documento:
Article
País de afiliación:
Reino Unido
Pais de publicación:
Estados Unidos