Structure-activity relationship at the leucine side chain in a series of N,N-dialkyldipeptidyl-amines as N-type calcium channel blockers.
Exploration of the SAR around the leucine side chain in a series of N,N-dialkyldipeptidylamines with potent functional activity at N-type VSCC is presented. A novel analog is disclosed which possesses improved aqueous solubility, in vivo activity in an audiogenic seizure model, and reversible blockade in electrophysiological assays.
Ryder
T R
TR
Department of Chemistry, Parke-Davis Pharmaceutical Research, Division of Warner-Lambert Company, Ann Arbor, MI 48105, USA.
Hu
L Y
LY
Rafferty
M F
MF
Lotarski
S M
SM
Rock
D M
DM
Stoehr
S J
SJ
Taylor
C P
CP
Weber
M L
ML
Miljanich
G P
GP
Millerman
E
E
Szoke
B G
BG
D000473:Alkanes / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D020864:Calcium Channels, N-Type / Q000187:drug effects / Q000378:metabolism*; D004151:Dipeptides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D004594:Electrophysiology; D007930:Leucine / Q000737:chemistry*; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D012995:Solubility; D013329:Structure-Activity Relationship; D020960:omega-Conotoxins / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
D000473:Alkanes; D002121:Calcium Channel Blockers; D020864:Calcium Channels, N-Type; D004151:Dipeptides; D009842:Oligopeptides; D020960:omega-Conotoxins; C121649:PD 151307; C078452:ziconotide; D007930:Leucine