title: Structure-activity relationship at the leucine side chain in a series of N,N-dialkyldipeptidyl-amines as N-type calcium channel blockers.
abstract: 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.
authors.affiliation: Department of Chemistry, Parke-Davis Pharmaceutical Research, Division of Warner-Lambert Company, Ann Arbor, MI 48105, USA.
authors.forename: T R
authors.initials: TR
authors.lastname: Ryder
authors.forename: L Y
authors.initials: LY
authors.lastname: Hu
authors.forename: M F
authors.initials: MF
authors.lastname: Rafferty
authors.forename: S M
authors.initials: SM
authors.lastname: Lotarski
authors.forename: D M
authors.initials: DM
authors.lastname: Rock
authors.forename: S J
authors.initials: SJ
authors.lastname: Stoehr
authors.forename: C P
authors.initials: CP
authors.lastname: Taylor
authors.forename: M L
authors.initials: ML
authors.lastname: Weber
authors.forename: G P
authors.initials: GP
authors.lastname: Miljanich
authors.forename: E
authors.initials: E
authors.lastname: Millerman
authors.forename: B G
authors.initials: BG
authors.lastname: Szoke
mesh_terms: 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
chemical_list: 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