title: Structure-activity relationship of N-methyl-N-aralkyl-peptidylamines as novel N-type calcium channel blockers.
abstract: Selective N-type voltage sensitive calcium channel (VSCC) blockers have shown efficacy in several animal models of stroke and pain. In the process of searching for small molecule N-type calcium channel blockers, we have identified a series of N-methyl-N-aralkyl-peptidylamines with potent functional activity at N-type VSCCs. The most active compound discovered in this series is PD 173212 (11, IC50 = 36 nM in the IMR-32 assays). SAR and pharmacological evaluation of this series are described.
authors.affiliation: Parke-Davis Pharmaceutical Research, Division of Warner-Lambert Company, Ann Arbor, MI 48105, USA.
authors.forename: L Y
authors.initials: LY
authors.lastname: Hu
authors.forename: T R
authors.initials: TR
authors.lastname: Ryder
authors.forename: M F
authors.initials: MF
authors.lastname: Rafferty
authors.forename: D J
authors.initials: DJ
authors.lastname: Dooley
authors.forename: J J
authors.initials: JJ
authors.lastname: Geer
authors.forename: S M
authors.initials: SM
authors.lastname: Lotarski
authors.forename: G P
authors.initials: GP
authors.lastname: Miljanich
authors.forename: E
authors.initials: E
authors.lastname: Millerman
authors.forename: D M
authors.initials: DM
authors.lastname: Rock
authors.forename: S J
authors.initials: SJ
authors.lastname: Stoehr
authors.forename: B G
authors.initials: BG
authors.lastname: Szoke
authors.forename: C P
authors.initials: CP
authors.lastname: Taylor
authors.forename: M G
authors.initials: MG
authors.lastname: Vartanian
mesh_terms: D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology* / Q000627:therapeutic use; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism*; D004151:Dipeptides / Q000737:chemistry / Q000494:pharmacology*; D004195:Disease Models, Animal; D006801:Humans; D051379:Mice; D012640:Seizures / Q000188:drug therapy; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
chemical_list: D002121:Calcium Channel Blockers; D015220:Calcium Channels; D004151:Dipeptides; C121650:PD 173212