RESUMEN

2-Arylbenzoxazole 5 was identified as a hit from a fluorescence-based high-throughput screen for CETP inhibitors. The synthesis and SAR investigation employing array synthesis of the A- and B-rings are described.

Asunto(s)

Benzoxazoles/síntesis química , Benzoxazoles/farmacología , Proteínas de Transferencia de Ésteres de Colesterol/antagonistas & inhibidores , Benzoxazoles/química , Proteínas de Transferencia de Ésteres de Colesterol/metabolismo , Humanos , Modelos Moleculares , Estructura Molecular , Relación Estructura-Actividad

RESUMEN

A structure-activity relationship study of the amine portion of the calcilytic compound NPS-2143 resulted in the discovery of substituted 2-benzylpyrrolidines as replacements for the 1,1-dimethyl-2-naphthalen-2-yl-ethylamine. When compared to NPS-2143, a newly discovered compound, 3h, exhibited similar potency as a calcium-sensing receptor (CaR) antagonist and a superior human ether-a-go-go related gene (hERG) profile.

Asunto(s)

Propanoles/síntesis química , Receptores Sensibles al Calcio/antagonistas & inhibidores , Señalización del Calcio/efectos de los fármacos , Canal de Potasio ERG1 , Canales de Potasio Éter-A-Go-Go , Humanos , Concentración 50 Inhibidora , Naftalenos/farmacología , Técnicas de Placa-Clamp , Canales de Potasio con Entrada de Voltaje/antagonistas & inhibidores , Propanoles/farmacología , Relación Estructura-Actividad