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.
McCalmont
William F
WF
Department of Chemistry, University of Virginia, Charlottesville, VA 22904-4319, USA. wfm3s@virginia.edu
Patterson
Jaclyn R
JR
Lindenmuth
Michael A
MA
Heady
Tiffany N
TN
Haverstick
Doris M
DM
Gray
Lloyd S
LS
Macdonald
Timothy L
TL
D002120:Calcium Channel Agonists / Q000737:chemistry* / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000737:chemistry* / Q000494:pharmacology*; D020747:Calcium Channels, T-Type / Q000187:drug effects*; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D013329:Structure-Activity Relationship
D002120:Calcium Channel Agonists; D002121:Calcium Channel Blockers; D020747:Calcium Channels, T-Type