title: Arylglycine derivatives as potent transient receptor potential melastatin 8 (TRPM8) antagonists.
abstract: A series of arylglycine-based analogs was synthesized and tested for TRPM8 antagonism in a cell-based functional assay. Following structure-activity relationship studies in vitro, a number of compounds were identified as potent TRPM8 antagonists and were subsequently evaluated in an in vivo pharmacodynamic assay of icilin-induced 'wet-dog' shaking in which compound 12 was fully effective. TRPM8 antagonists of the type described here may be useful in treating pain conditions wherein cold hypersensitivity is a dominant feature.
authors: Janssen Research & Development, L.L.C., Welsh & McKean Roads, Spring House, PA 19477, USA. bzhu@its.jnj.com
authors: Bin
authors: B
authors: Zhu
authors: Mingde
authors: M
authors: Xia
authors: Xiaoqing
authors: X
authors: Xu
authors: Donald W
authors: DW
authors: Ludovici
authors: Manomi
authors: M
authors: Tennakoon
authors: Mark A
authors: MA
authors: Youngman
authors: Jay M
authors: JM
authors: Matthews
authors: Scott L
authors: SL
authors: Dax
authors: Raymond W
authors: RW
authors: Colburn
authors: Ning
authors: N
authors: Qin
authors: Tasha L
authors: TL
authors: Hutchinson
authors: Mary Lou
authors: ML
authors: Lubin
authors: Michael R
authors: MR
authors: Brandt
authors: Dennis J
authors: DJ
authors: Stone
authors: Christopher M
authors: CM
authors: Flores
authors: Mark J
authors: MJ
authors: Macielag
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005998:Glycine / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology*; D057809:HEK293 Cells; D006801:Humans; D015394:Molecular Structure; D011744:Pyrimidinones / Q000494:pharmacology; D051381:Rats; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D050053:TRPM Cation Channels / Q000819:agonists / Q000037:antagonists & inhibitors*
chemical_list: D011744:Pyrimidinones; D050053:TRPM Cation Channels; C425966:TRPM8 protein, human; C498947:Trpm8 protein, rat; C490483:icilin; D005998:Glycine