Butyl 2-(4-[1.1'-biphenyl]-4-yl-1H-imidazol-2-yl)ethylcarbamate, a potent sodium channel blocker for the treatment of neuropathic pain.
A series of 4-arylimidazole carbamates was synthesized and their binding affinities to the site-2 sodium (Na+) channel were determined. SAR studies led to the identification of compound 10, a potent Na+ channel blocker which was efficacious in pain models in vivo.
Liberatore
Anne-Marie
AM
Ipsen Research Laboratories, Institut Henri Beaufour, 5 avenue du Canada, 91966 Les Ulis Cedex, France. anne-marie.liberatore@ipsen.com
Schulz
Jocelyne
J
Favre-Guilmard
Christine
C
Pommier
Jacques
J
Lannoy
Jacques
J
Pawlowski
Emilia
E
Barthelemy
Marie-Anne
MA
Huchet
Marion
M
Auguet
Michel
M
Chabrier
Pierre-Etienne
PE
Bigg
Dennis
D
D000818:Animals; D001496:Batrachotoxins; D001667:Binding, Competitive / Q000187:drug effects; D002219:Carbamates / Q000138:chemical synthesis* / Q000494:pharmacology*; D002351:Carrageenan; D006801:Humans; D006930:Hyperalgesia / Q000139:chemically induced / Q000188:drug therapy; D007093:Imidazoles / Q000138:chemical synthesis* / Q000494:pharmacology*; D007202:Indicators and Reagents; D008861:Microsomes / Q000187:drug effects / Q000378:metabolism; D010146:Pain / Q000188:drug therapy* / Q000209:etiology*; D010523:Peripheral Nervous System Diseases / Q000150:complications*; D051381:Rats; D012964:Sodium / Q000378:metabolism; D026941:Sodium Channel Blockers / Q000138:chemical synthesis* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism; D014701:Veratridine / Q000494:pharmacology
D001496:Batrachotoxins; D002219:Carbamates; D007093:Imidazoles; D007202:Indicators and Reagents; D026941:Sodium Channel Blockers; C519764:butyl 2-(4-(1.1'-biphenyl)-4-yl-1H-imidazol-2-yl)ethylcarbamate; D014701:Veratridine; D002351:Carrageenan; D012964:Sodium