Discovery and structure-based design of 4,6-diaminonicotinamides as potent and selective IRAK4 inhibitors.
Bioorg Med Chem Lett
; 27(21): 4908-4913, 2017 11 01.
Article
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| MEDLINE
| ID: mdl-28947151
ABSTRACT
The identification of small molecule inhibitors of IRAK4 for the treatment of autoimmune diseases has been an area of intense research. We discovered novel 4,6-diaminonicotinamides which potently inhibit IRAK4. Optimization efforts were aided by X-ray crystal structures of inhibitors bound to IRAK4. Structure activity relationship (SAR) studies led to the identification of compound 29 which exhibited sub-micromolar potency in a LTA stimulated cellular assay.
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Bases de datos:
MEDLINE
Asunto principal:
Diseño de Fármacos
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Niacinamida
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Inhibidores de Proteínas Quinasas
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Quinasas Asociadas a Receptores de Interleucina-1
Idioma:
En
Revista:
Bioorg Med Chem Lett
Año:
2017
Tipo del documento:
Article