Investigation into the structure–activity relationship of novel concentration dependent, dual action T-type calcium channel agonists/antagonists

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.

This paper describes the synthesis and biological evaluation of a library of compounds that are based on the structure of compound 1, which has been shown to be a T-type calcium channel antagonist, as well as exhibits anti-proliferative activity against a variety of tumor cell lines. These new analogs of compound 1 not only show better antagonist activity toward calcium influx and anti-proliferation, at higher concentrations they also show an agonist activity toward calcium influx.Figure optionsDownload as PowerPoint slide