RESUMEN
Cilnidipine is a 1,4-dihydropyridine derived L/N-type calcium channel dual blocker possessing neuroprotective and analgesic effects which are related to its N-type calcium channel inhibitory activity. In order to find specific N-type calcium channel blockers with the least effects on cardiovascular system, we performed structure-activity relationship study on APJ2708, which is a derivative of cilnidipine, and found a promising N-type calcium channel blocker 21b possessing analgesic effect in vivo with a 1600-fold lower activity against L-type calcium channels than that of cilnidipine.
Asunto(s)
Bloqueadores de los Canales de Calcio/farmacología , Canales de Calcio Tipo N/efectos de los fármacos , Dihidropiridinas/farmacología , Animales , Bloqueadores de los Canales de Calcio/síntesis química , Bloqueadores de los Canales de Calcio/química , Dihidropiridinas/síntesis química , Dihidropiridinas/química , Formaldehído/química , Estructura Molecular , Dolor/inducido químicamente , Dolor/tratamiento farmacológico , Dimensión del Dolor/efectos de los fármacos , Ratas , Relación Estructura-ActividadRESUMEN
O-glucuronides and O-glucosides of a series of pyrazoles analogues were synthesized and evaluated for their SGLT inhibitory activity in brush border membrane vehicles (BBMVs) of rat kidney. O-glucosides of certain pyrazole analogues inhibited the transport of [(14)C]-glucose in BBMVs, and induced glucosuria in Wistar rats by intravenous injection.
