Your browser doesn't support javascript.
loading
Discovery of a Novel Class of Imidazo[1,2-a]Pyridines with Potent PDGFR Activity and Oral Bioavailability.
Hicken, Erik J; Marmsater, Fred P; Munson, Mark C; Schlachter, Stephen T; Robinson, John E; Allen, Shelley; Burgess, Laurence E; DeLisle, Robert Kirk; Rizzi, James P; Topalov, George T; Zhao, Qian; Hicks, Julie M; Kallan, Nicholas C; Tarlton, Eugene; Allen, Andrew; Callejo, Michele; Cox, April; Rana, Sumeet; Klopfenstein, Nathalie; Woessner, Richard; Lyssikatos, Joseph P.
Afiliación
  • Hicken EJ; Department of Drug Discovery, Array BioPharma , 3200 Walnut Street, Boulder, Colorado 80301, United States.
  • Marmsater FP; Department of Drug Discovery, Array BioPharma , 3200 Walnut Street, Boulder, Colorado 80301, United States.
  • Munson MC; Department of Drug Discovery, Array BioPharma , 3200 Walnut Street, Boulder, Colorado 80301, United States.
  • Schlachter ST; Department of Drug Discovery, Array BioPharma , 3200 Walnut Street, Boulder, Colorado 80301, United States.
  • Robinson JE; Department of Drug Discovery, Array BioPharma , 3200 Walnut Street, Boulder, Colorado 80301, United States.
  • Allen S; Department of Drug Discovery, Array BioPharma , 3200 Walnut Street, Boulder, Colorado 80301, United States.
  • Burgess LE; Department of Drug Discovery, Array BioPharma , 3200 Walnut Street, Boulder, Colorado 80301, United States.
  • DeLisle RK; Department of Drug Discovery, Array BioPharma , 3200 Walnut Street, Boulder, Colorado 80301, United States.
  • Rizzi JP; Department of Drug Discovery, Array BioPharma , 3200 Walnut Street, Boulder, Colorado 80301, United States.
  • Topalov GT; Department of Drug Discovery, Array BioPharma , 3200 Walnut Street, Boulder, Colorado 80301, United States.
  • Zhao Q; Department of Drug Discovery, Array BioPharma , 3200 Walnut Street, Boulder, Colorado 80301, United States.
  • Hicks JM; Department of Drug Discovery, Array BioPharma , 3200 Walnut Street, Boulder, Colorado 80301, United States.
  • Kallan NC; Department of Drug Discovery, Array BioPharma , 3200 Walnut Street, Boulder, Colorado 80301, United States.
  • Tarlton E; Department of Drug Discovery, Array BioPharma , 3200 Walnut Street, Boulder, Colorado 80301, United States.
  • Allen A; Department of Drug Discovery, Array BioPharma , 3200 Walnut Street, Boulder, Colorado 80301, United States.
  • Callejo M; Department of Drug Discovery, Array BioPharma , 3200 Walnut Street, Boulder, Colorado 80301, United States.
  • Cox A; Department of Drug Discovery, Array BioPharma , 3200 Walnut Street, Boulder, Colorado 80301, United States.
  • Rana S; Department of Drug Discovery, Array BioPharma , 3200 Walnut Street, Boulder, Colorado 80301, United States.
  • Klopfenstein N; Department of Drug Discovery, Array BioPharma , 3200 Walnut Street, Boulder, Colorado 80301, United States.
  • Woessner R; Department of Drug Discovery, Array BioPharma , 3200 Walnut Street, Boulder, Colorado 80301, United States.
  • Lyssikatos JP; Department of Drug Discovery, Array BioPharma , 3200 Walnut Street, Boulder, Colorado 80301, United States.
ACS Med Chem Lett ; 5(1): 78-83, 2014 Jan 09.
Article en En | MEDLINE | ID: mdl-24900776
ABSTRACT
The in silico construction of a PDGFRß kinase homology model and ensuing medicinal chemistry guided by molecular modeling, led to the identification of potent, small molecule inhibitors of PDGFR. Subsequent exploration of structure-activity relationships (SAR) led to the incorporation of a constrained secondary amine to enhance selectivity. Further refinements led to the integration of a fluorine substituted piperidine, which resulted in significant reduction of P-glycoprotein (Pgp) mediated efflux and improved bioavailability. Compound 28 displayed oral exposure in rodents and had a pronounced effect in a pharmacokinetic-pharmacodynamic (PKPD) assay.
Palabras clave
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Prognostic_studies Idioma: En Revista: ACS Med Chem Lett Año: 2014 Tipo del documento: Article País de afiliación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Prognostic_studies Idioma: En Revista: ACS Med Chem Lett Año: 2014 Tipo del documento: Article País de afiliación: Estados Unidos