title: TRPV1 antagonist with high analgesic efficacy: 2-Thio pyridine C-region analogues of 2-(3-fluoro-4-methylsulfonylaminophenyl)propanamides.
abstract: A series of 2-thio pyridine C-region analogues of 2-(3-fluoro-4-methylsulfonylaminophenyl)propanamides were investigated as hTRPV1 antagonists. Among them, compound 24S showed stereospecific and excellent TRPV1 antagonism of capsaicin-induced activation. Further, it demonstrated strong anti-allodynic in a rat neuropathic pain model. Consistent with its action in vitro being through TRPV1, compound 24S blocked capsaicin-induced hypothermia in mice. Docking analysis of 24S with our hTRPV1 homology model was performed to identify its binding mode.
authors.affiliation: Laboratory of Medicinal Chemistry, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 151-742, Republic of Korea.
authors.forename: Tae-Hwan
authors.initials: TH
authors.lastname: Ha
authors.forename: Hyungchul
authors.initials: H
authors.lastname: Ryu
authors.forename: Sung-Eun
authors.initials: SE
authors.lastname: Kim
authors.forename: Ho Shin
authors.initials: HS
authors.lastname: Kim
authors.forename: Jihyae
authors.initials: J
authors.lastname: Ann
authors.forename: Phuong-Thao
authors.initials: PT
authors.lastname: Tran
authors.forename: Van-Hai
authors.initials: VH
authors.lastname: Hoang
authors.forename: Karam
authors.initials: K
authors.lastname: Son
authors.forename: Minghua
authors.initials: M
authors.lastname: Cui
authors.forename: Sun
authors.initials: S
authors.lastname: Choi
authors.forename: Peter M
authors.initials: PM
authors.lastname: Blumberg
authors.forename: Robert
authors.initials: R
authors.lastname: Frank
authors.forename: Gregor
authors.initials: G
authors.lastname: Bahrenberg
authors.forename: Klaus
authors.initials: K
authors.lastname: Schiene
authors.forename: Thomas
authors.initials: T
authors.lastname: Christoph
authors.forename: Sven
authors.initials: S
authors.lastname: Frormann
authors.forename: Jeewoo
authors.initials: J
authors.lastname: Lee
mesh_terms: D000577:Amides / Q000737:chemistry* / Q000378:metabolism / Q000627:therapeutic use; D000700:Analgesics / Q000737:chemistry* / Q000378:metabolism / Q000627:therapeutic use; D000818:Animals; D044482:Benzeneacetamides / Q000737:chemistry* / Q000378:metabolism / Q000627:therapeutic use; D001665:Binding Sites; D004195:Disease Models, Animal; D006801:Humans; D051379:Mice; D062105:Molecular Docking Simulation; D009437:Neuralgia / Q000188:drug therapy; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011725:Pyridines / Q000737:chemistry*; D051381:Rats; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000737:chemistry* / Q000378:metabolism / Q000627:therapeutic use; D050916:TRPV Cation Channels / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000577:Amides; D000700:Analgesics; D044482:Benzeneacetamides; C000588460:N-((2-(cyclohexylthio)-6-(trifluoromethyl)pyridin-3-yl)methyl)-2-(3-fluoro-4-(methylsulfonamido)phenyl)propanamide; D011725:Pyridines; D013449:Sulfonamides; D050916:TRPV Cation Channels; C494482:TRPV1 protein, human; C023666:pyridine
keywords: Analgesic; Capsaicin; Resiniferatoxin; TRPV1 antagonists
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