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(S)-N-[1-(3-morpholin-4-ylphenyl)ethyl]- 3-phenylacrylamide: an orally bioavailable KCNQ2 opener with significant activity in a cortical spreading depression model of migraine.

Wu, Yong-Jin; Boissard, Christopher G; Greco, Corinne; Gribkoff, Valentin K; Harden, David G; He, Huan; L'Heureux, Alexandre; Kang, Shing Hong; Kinney, Gene G; Knox, Ronald J; Natale, Joanne; Newton, Amy E; Lehtinen-Oboma, Sanna; Sinz, Michael W; Sivarao, Digavalli V; Starrett, John E; Sun, Li-Qiang; Tertyshnikova, Svetlana; Thompson, Mark W; Weaver, David; Wong, Henry S; Zhang, Lei; Dworetzky, Steven I.

J Med Chem ; 46(15): 3197-200, 2003 Jul 17.

Article in English | MEDLINE | ID: mdl-12852750

ABSTRACT

(S)-N-[1-(3-Morpholin-4-ylphenyl)ethyl]-3-phenylacrylamide (2) was synthesized as an orally bioavailable KCNQ2 potassium channel opener. In a rat model of migraine, 2 demonstrated significant oral activity in reducing the total number of cortical spreading depressions induced by potassium chloride.

Subject(s)

Acrylamides/chemical synthesis , Cerebral Cortex/drug effects , Migraine Disorders/physiopathology , Morpholines/chemical synthesis , Potassium Channels/drug effects , Acrylamides/chemistry , Acrylamides/pharmacology , Administration, Oral , Animals , Biological Availability , Cell Line , Cerebral Cortex/physiopathology , Disease Models, Animal , Dogs , Humans , Ion Channel Gating , KCNQ2 Potassium Channel , Migraine Disorders/metabolism , Morpholines/chemistry , Morpholines/pharmacology , Oocytes/drug effects , Oocytes/physiology , Patch-Clamp Techniques , Potassium Channels/physiology , Potassium Channels, Voltage-Gated , Rats , Rats, Sprague-Dawley , Stereoisomerism , Structure-Activity Relationship , Xenopus laevis

ABSTRACT

Subject(s)

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