RESUMEN
The preparation and structure-activity-relationships of novel pyrrolidine-carboxamides and oxadiazoles are described. Compounds in this series were found to be potent hNK(1) antagonists in vitro and efficacious in vivo with minimal interactions with P(450) liver enzymes. Oxadiazole analog 22 was determined to have excellent hNK(1) binding affinity, functional activity, and a good PD response in vivo.
Asunto(s)
Alcaloides/farmacología , Antivirales/farmacología , Virus de la Hepatitis B/efectos de los fármacos , Menispermaceae/química , Oxadiazoles/farmacología , Pirrolidinas/farmacología , Alcaloides/química , Antivirales/química , Línea Celular , Cromatografía por Intercambio Iónico , Antígenos de Superficie de la Hepatitis B/metabolismo , Antígenos e de la Hepatitis B/metabolismo , Humanos , Espectroscopía de Resonancia Magnética , Modelos Moleculares , Conformación Molecular , Oxadiazoles/química , Pirrolidinas/química , Espectrometría de Masa por Ionización de ElectrosprayRESUMEN
A series of 2-aminoquinoline compounds was prepared and evaluated in MCH1R binding and functional antagonist assays. Small dialkyl, methylalkyl, methylcycloalkyl, and cyclic amines were tolerated at the quinoline 2-position. The in vivo efficacy of compound 12 was explored and compared to that of a related inactive analog to determine their effects on food intake and body weight in rodents.
