T-type calcium channel blockers: spiro-piperidine azetidines and azetidinones-optimization, design and synthesis.
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.
Smith
Elizabeth M
EM
Department of Medicinal Chemistry, Merck Research Laboratory, Kenilworth, NJ 07033, USA. elizabeth.m.smith@spcorp.com
Sorota
Steve
S
Kim
Hyunjin M
HM
McKittrick
Brian A
BA
Nechuta
Terry L
TL
Bennett
Chad
C
Knutson
Chad
C
Burnett
Duane A
DA
Kieselgof
Jane
J
Tan
Zheng
Z
Rindgen
Diane
D
Bridal
Terry
T
Zhou
Xiaoping
X
Jia
Yu-Ping
YP
Dong
Zoe
Z
Mullins
Debbie
D
Zhang
Xiaoping
X
Priestley
Tony
T
Correll
Craig C
CC
Tulshian
Deen
D
Czarniecki
Michael
M
Greenlee
William J
WJ
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
C116379:2-azetidinone; D001384:Azetidines; D002121:Calcium Channel Blockers; D020747:Calcium Channels, T-Type; D010880:Piperidines; D013141:Spiro Compounds; C032727:piperidine