title: Synthesis and SAR of 4-aminocyclopentapyrrolidines as orally active N-type calcium channel inhibitors for inflammatory and neuropathic pain.
abstract: A novel series of N-type calcium channel inhibitors have been discovered. Optimization of potency and HT-ADME properties provides 4-aminocyclopentapyrrolidines with analgesic efficacy after oral dosing.
authors.affiliation: Neuroscience Research, AbbVie, 1 N Waukegan Road, North Chicago, IL 60064, United States. xenia.b.searle@abbvie.com
authors.forename: Xenia
authors.initials: X
authors.lastname: Beebe
authors.forename: Clinton M
authors.initials: CM
authors.lastname: Yeung
authors.forename: Daria
authors.initials: D
authors.lastname: Darczak
authors.forename: Shashank
authors.initials: S
authors.lastname: Shekhar
authors.forename: Timothy A
authors.initials: TA
authors.lastname: Vortherms
authors.forename: Loan
authors.initials: L
authors.lastname: Miller
authors.forename: Ivan
authors.initials: I
authors.lastname: Milicic
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Swensen
authors.forename: Chang Z
authors.initials: CZ
authors.lastname: Zhu
authors.forename: Patricia
authors.initials: P
authors.lastname: Banfor
authors.forename: Jill M
authors.initials: JM
authors.lastname: Wetter
authors.forename: Kennan C
authors.initials: KC
authors.lastname: Marsh
authors.forename: Michael F
authors.initials: MF
authors.lastname: Jarvis
authors.forename: Victoria E
authors.initials: VE
authors.lastname: Scott
authors.forename: Michael R
authors.initials: MR
authors.lastname: Schrimpf
authors.forename: Chih-Hung
authors.initials: CH
authors.lastname: Lee
mesh_terms: D000284:Administration, Oral; D000700:Analgesics / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism / Q000627:therapeutic use*; D000818:Animals; D002121:Calcium Channel Blockers / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism / Q000627:therapeutic use*; D020864:Calcium Channels, N-Type / Q000378:metabolism*; D006801:Humans; D008861:Microsomes / Q000378:metabolism; D009437:Neuralgia / Q000188:drug therapy*; D051381:Rats; D013329:Structure-Activity Relationship
chemical_list: D000700:Analgesics; D002121:Calcium Channel Blockers; D020864:Calcium Channels, N-Type
keywords: Analgesia; Enantiomeric synthesis; Microsomal stability; N-type calcium channels; SAR