title: T-type calcium channel blockers: spiro-piperidine azetidines and azetidinones-optimization, design and synthesis.
abstract: A series of spiro-azetidines and azetidinones has been evaluated as novel blockers of the T-type calcium channel (Ca(V)3.2) which is a new therapeutic target for the potential treatment of both inflammatory and neuropathic pain. Confirmation and optimization of the potency, selectivity and DMPK properties of leads will be described.
authors.affiliation: Department of Medicinal Chemistry, Merck Research Laboratory, Kenilworth, NJ 07033, USA. elizabeth.m.smith@spcorp.com
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Smith
authors.forename: Steve
authors.initials: S
authors.lastname: Sorota
authors.forename: Hyunjin M
authors.initials: HM
authors.lastname: Kim
authors.forename: Brian A
authors.initials: BA
authors.lastname: McKittrick
authors.forename: Terry L
authors.initials: TL
authors.lastname: Nechuta
authors.forename: Chad
authors.initials: C
authors.lastname: Bennett
authors.forename: Chad
authors.initials: C
authors.lastname: Knutson
authors.forename: Duane A
authors.initials: DA
authors.lastname: Burnett
authors.forename: Jane
authors.initials: J
authors.lastname: Kieselgof
authors.forename: Zheng
authors.initials: Z
authors.lastname: Tan
authors.forename: Diane
authors.initials: D
authors.lastname: Rindgen
authors.forename: Terry
authors.initials: T
authors.lastname: Bridal
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Zhou
authors.forename: Yu-Ping
authors.initials: YP
authors.lastname: Jia
authors.forename: Zoe
authors.initials: Z
authors.lastname: Dong
authors.forename: Debbie
authors.initials: D
authors.lastname: Mullins
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Zhang
authors.forename: Tony
authors.initials: T
authors.lastname: Priestley
authors.forename: Craig C
authors.initials: CC
authors.lastname: Correll
authors.forename: Deen
authors.initials: D
authors.lastname: Tulshian
authors.forename: Michael
authors.initials: M
authors.lastname: Czarniecki
authors.forename: William J
authors.initials: WJ
authors.lastname: Greenlee
mesh_terms: D000818:Animals; D001384:Azetidines / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use; D002121:Calcium Channel Blockers / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use; D020747:Calcium Channels, T-Type / Q000737:chemistry* / Q000378:metabolism; D015195:Drug Design; D006801:Humans; D010146:Pain / Q000188:drug therapy; D010880:Piperidines / Q000737:chemistry*; D011485:Protein Binding; D051381:Rats; D013141:Spiro Compounds / Q000737:chemistry*; D013329:Structure-Activity Relationship
chemical_list: C116379:2-azetidinone; D001384:Azetidines; D002121:Calcium Channel Blockers; D020747:Calcium Channels, T-Type; D010880:Piperidines; D013141:Spiro Compounds; C032727:piperidine