title: Discovery of diphenyl lactam derivatives as N-type calcium channel blockers.
abstract: A novel series of diphenyl lactam containing calcium channel blockers is described. Extensive SAR studies resulted in compounds with low molar activity and good plasma exposure after oral dosing. Compounds 2, 6 and 7 demonstrated significant efficacy in the capsaicin model of secondary hyperalgesia following oral administration.
authors.affiliation: Abbott Laboratories, Global Pharmaceutical Research and Development, Abbott Park, IL 60064, USA. george.doherty@abbott.com
authors.forename: George A
authors.initials: GA
authors.lastname: Doherty
authors.forename: Pramila
authors.initials: P
authors.lastname: Bhatia
authors.forename: Timothy A
authors.initials: TA
authors.lastname: Vortherms
authors.forename: Kennan C
authors.initials: KC
authors.lastname: Marsh
authors.forename: Jill M
authors.initials: JM
authors.lastname: Wetter
authors.forename: Helmut
authors.initials: H
authors.lastname: Mack
authors.forename: Victoria E
authors.initials: VE
authors.lastname: Scott
authors.forename: Michael F
authors.initials: MF
authors.lastname: Jarvis
authors.forename: Andrew O
authors.initials: AO
authors.lastname: Stewart
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001713:Biphenyl Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D002121:Calcium Channel Blockers / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D020864:Calcium Channels, N-Type / Q000378:metabolism*; D055808:Drug Discovery; D020128:Inhibitory Concentration 50; D007769:Lactams / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D015394:Molecular Structure; D010879:Piperazines / Q000737:chemistry; D051381:Rats; D012995:Solubility
chemical_list: D001713:Biphenyl Compounds; D002121:Calcium Channel Blockers; D020864:Calcium Channels, N-Type; D007769:Lactams; D010879:Piperazines; C534047:1-(6,6-bis(4-fluorophenyl)hexyl)-4-(3,4,5-trimethoxybenzyl)piperazine; C010574:biphenyl