title: Structure-activity relationships of diphenylpiperazine N-type calcium channel inhibitors.
abstract: A novel series of compounds derived from the previously reported N-type calcium channel blocker NP118809 (1-(4-benzhydrylpiperazin-1-yl)-3,3-diphenylpropan-1-one) is described. Extensive SAR studies resulted in compounds with IC(50) values in the range of 10-150 nM and selectivity over the L-type channels up to nearly 1200-fold. Orally administered compounds 5 and 21 exhibited both anti-allodynic and anti-hyperalgesic activity in the spinal nerve ligation model of neuropathic pain.
authors.affiliation: Neuromed Pharmaceuticals Ltd, 301-2389 Health Sciences Mall, Vancouver, BC, Canada.
authors.forename: Hassan
authors.initials: H
authors.lastname: Pajouhesh
authors.forename: Zhong-Ping
authors.initials: ZP
authors.lastname: Feng
authors.forename: Yanbing
authors.initials: Y
authors.lastname: Ding
authors.forename: Lingyun
authors.initials: L
authors.lastname: Zhang
authors.forename: Hossein
authors.initials: H
authors.lastname: Pajouhesh
authors.forename: Jerrie-Lynn
authors.initials: JL
authors.lastname: Morrison
authors.forename: Francesco
authors.initials: F
authors.lastname: Belardetti
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Tringham
authors.forename: Eric
authors.initials: E
authors.lastname: Simonson
authors.forename: Todd W
authors.initials: TW
authors.lastname: Vanderah
authors.forename: Frank
authors.initials: F
authors.lastname: Porreca
authors.forename: Gerald W
authors.initials: GW
authors.lastname: Zamponi
authors.forename: Lester A
authors.initials: LA
authors.lastname: Mitscher
authors.forename: Terrance P
authors.initials: TP
authors.lastname: Snutch
mesh_terms: D000284:Administration, Oral; D000700:Analgesics / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D001559:Benzhydryl Compounds / 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*; D006801:Humans; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D010879:Piperazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D013329:Structure-Activity Relationship; D014867:Water / Q000737:chemistry
chemical_list: C549646:1-(4-benzhydrylpiperazin-1-yl)-3,3-diphenylpropan-1-one; D000700:Analgesics; D001559:Benzhydryl Compounds; D002121:Calcium Channel Blockers; D020864:Calcium Channels, N-Type; D010879:Piperazines; D014867:Water