Structure-based discovery of C-2 substituted imidazo-pyrrolopyridine JAK1 inhibitors with improved selectivity over JAK2.
Bioorg Med Chem Lett
; 22(24): 7627-33, 2012 Dec 15.
Article
en En
| MEDLINE
| ID: mdl-23107482
ABSTRACT
Herein we describe our successful efforts in obtaining C-2 substituted imidazo-pyrrolopyridines with improved JAK1 selectivity relative to JAK2 by targeting an amino acid residue that differs between the two isoforms (JAK1 E966; JAK2 D939). Efforts to improve cellular potency by reducing the polarity of the inhibitors are also detailed. The X-ray crystal structure of a representative inhibitor in complex with the JAK1 enzyme is also disclosed.
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1
Banco de datos:
MEDLINE
Asunto principal:
Piridinas
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Pirroles
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Inhibidores de Proteínas Quinasas
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Janus Quinasa 1
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Janus Quinasa 2
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Descubrimiento de Drogas
Límite:
Animals
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Humans
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Male
Idioma:
En
Año:
2012
Tipo del documento:
Article