RESUMEN
A series of thiazole based 5HT(7) ligands has been identified from screening. Optimisation of the pendent aryl group and modification of the core gave a related series of high affinity, selective thiopyridine based 5HT(7) ligands, the most active of which behaves as a partial agonist.
Asunto(s)
Piridinas/síntesis química , Piridinas/farmacología , Receptores de Serotonina/química , Receptores de Serotonina/metabolismo , Tiazoles/síntesis química , Tiazoles/farmacología , Células Cultivadas , Humanos , Ligandos , Serotonina/metabolismo , Agonistas de Receptores de Serotonina/química , Agonistas de Receptores de Serotonina/farmacología , Relación Estructura-Actividad , beta-Lactamasas/metabolismoRESUMEN
Novel (E)-N(1)-(benzyl)cinnamamidines were prepared and evaluated as NR2B subtype NMDA receptor ligands. Excellent affinity was achieved by appropriate substitution of either phenyl ring. The 2-methoxybenzyl compound 1h had approximately 1,000-fold lower IC(50) in NR2B than NR2A-containing cells. Replacement of the styryl unit by 2-naphthyl was well tolerated.
Asunto(s)
Amidinas/síntesis química , Receptores de N-Metil-D-Aspartato/antagonistas & inhibidores , Amidinas/metabolismo , Benzamidinas/síntesis química , Benzamidinas/metabolismo , Evaluación Preclínica de Medicamentos , Humanos , Naftalenos/síntesis química , Naftalenos/metabolismo , Unión Proteica , Ensayo de Unión Radioligante , Receptores de N-Metil-D-Aspartato/metabolismo , Relación Estructura-ActividadRESUMEN
A novel series of benzamidines was synthesized and shown to exhibit NR2B-subtype selective NMDA antagonist activity. Compound 31 is orally active in a carrageenan-induced rat hyperalgesia model of pain and shows no motor coordination side effects.
