RESUMO
This paper describes the synthesis and biological evaluation of a series of straight chain analogs of a compound (1) that was previously synthesized in our research program. These compounds, which are T-type calcium channel antagonists, exhibits potent anti-proliferative activity against a variety of cancer cells. A structure-activity relationship of these analogs against a variety of cancer cells has provided insight into a logical pharmacophore for this series of compounds. Furthermore, this series of compounds has presented itself as a set of novel, concentration dependent, dual action agonists/antagonists for the T-type calcium channel.
Assuntos
Agonistas dos Canais de Cálcio/química , Agonistas dos Canais de Cálcio/farmacologia , Bloqueadores dos Canais de Cálcio/química , Bloqueadores dos Canais de Cálcio/farmacologia , Canais de Cálcio Tipo T/efeitos dos fármacos , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Relação Estrutura-AtividadeRESUMO
This paper describes the synthesis of several novel T-type calcium channel antagonists that inhibit calcium influx into the cell, which in turn regulates unknown aspects of the cell cycle pathway that are responsible for cellular proliferation. A library of compounds was synthesized and a brief structure activity relationship will be described. From these studies we have identified a compound (1) that displays anti-proliferative activity in the low micromolar range across a variety of cancer cell lines.