NR2B-selective N-methyl-D-aspartate antagonists: synthesis and evaluation of 5-substituted benzimidazoles.

McCauley, John A; Theberge, Cory R; Romano, Joseph J; Billings, Susan B; Anderson, Kenneth D; Claremon, David A; Freidinger, Roger M; Bednar, Rodney A; Mosser, Scott D; Gaul, Stanley L; Connolly, Thomas M; Condra, Cindra L; Xia, Menghang; Cunningham, Michael E; Bednar, Bohumil; Stump, Gary L; Lynch, Joseph J; Macaulay, Alison; Wafford, Keith A; Koblan, Kenneth S; Liverton, Nigel J

McCauley, John A; Theberge, Cory R; Romano, Joseph J; Billings, Susan B; Anderson, Kenneth D; Claremon, David A; Freidinger, Roger M; Bednar, Rodney A; Mosser, Scott D; Gaul, Stanley L; Connolly, Thomas M; Condra, Cindra L; Xia, Menghang; Cunningham, Michael E; Bednar, Bohumil; Stump, Gary L; Lynch, Joseph J; Macaulay, Alison; Wafford, Keith A; Koblan, Kenneth S; Liverton, Nigel J.

Afiliación

McCauley JA; Department of Medicinal Chemistry, Merck Research Laboratories, West Point, PA 19486, USA. john_mccauley@merck.com

J Med Chem ; 47(8): 2089-96, 2004 Apr 08.

Article en En | MEDLINE | ID: mdl-15056006

ABSTRACT

ABSTRACT

Two classes of 5-substituted benzimidazoles were identified as potent antagonists of the NR2B subtype of the N-methyl-d-aspartate (NMDA) receptor. Selected compounds show very good selectivity versus the NR2A, NR2C, and NR2D subtypes of the NMDA receptor as well as versus hERG-channel activity and alpha(1)-adrenergic binding. Benzimidazole 37a shows excellent activity in the carrageenan-induced mechanical hyperalgesia assay in rats as well as good pharmacokinetic behavior in dogs.

Asunto(s)

Analgésicos/síntesis química; Bencimidazoles/síntesis química; Receptores de N-Metil-D-Aspartato/antagonistas & inhibidores; Analgésicos/farmacocinética; Analgésicos/farmacología; Animales; Bencimidazoles/farmacocinética; Bencimidazoles/farmacología; Encéfalo/metabolismo; Calcio/metabolismo; Carragenina; Línea Celular; Perros; Femenino; Humanos; Hiperalgesia/sangre; Hiperalgesia/inducido químicamente; Hiperalgesia/tratamiento farmacológico; Técnicas In Vitro; Masculino; Técnicas de Placa-Clamp; Ratas; Ratas Sprague-Dawley; Receptores de N-Metil-D-Aspartato/fisiología; Relación Estructura-Actividad

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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Bencimidazoles / Receptores de N-Metil-D-Aspartato / Analgésicos Tipo de estudio: Prognostic_studies Límite: Animals / Female / Humans / Male Idioma: En Revista: J Med Chem Asunto de la revista: QUIMICA Año: 2004 Tipo del documento: Article País de afiliación: Estados Unidos

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