RESUMEN
High throughput screening of our compound library revealed a series of N-pyridyl-3-benzamides as low micromolar agonists of the human TRPV1 receptor. Synthesis of analogs in this series led to the discovery of a series of N-quinolin-3-yl-benzamides as low nanomolar antagonists of human TRPV1.
Asunto(s)
Benzamidas/síntesis química , Benzamidas/farmacología , Isoquinolinas/química , Piridinas/química , Canales Catiónicos TRPV/antagonistas & inhibidores , Canales Catiónicos TRPV/metabolismo , Animales , Benzamidas/química , Benzamidas/uso terapéutico , Reactivos de Enlaces Cruzados/química , Humanos , Hiperalgesia/tratamiento farmacológico , Estructura Molecular , Ratas , Relación Estructura-ActividadRESUMEN
The synthesis and structure-activity relationships of a novel series of aroylpyrrole alkylamides as potent selective bradykinin B(2) receptor antagonists are described. Several members of this series display nanomolar affinity at the B(2) receptor and show activity in an animal model of antinociception.
Asunto(s)
Alcanos/síntesis química , Alcanos/farmacología , Antagonistas de los Receptores de Bradiquinina , Pirroles/síntesis química , Pirroles/farmacología , Analgésicos/síntesis química , Analgésicos/farmacología , Animales , Indicadores y Reactivos , Irritantes/antagonistas & inhibidores , Caolín , Ratones , Dimensión del Dolor/efectos de los fármacos , Receptor de Bradiquinina B2 , Relación Estructura-ActividadRESUMEN
Two parallel synthetic methods were developed to explore the structure-activity relationships (SAR) of a series of potent opioid agonists. This series of tropanylidene benzamides proved extremely tolerant of structural variation while maintaining excellent opioid activity. Evaluation of several representative compounds from this series in the mouse hot plate test revealed potent antinociceptive effects upon oral administration.