477313-05-6Relevant articles and documents
(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 Jr., John E.,Sun, Li-Qiang,Tertyshnikova, Svetlana,Thompson, Mark W.,Weaver, David,Wong, Henry S.,Zhang, Lei,Dworetzky, Steven I.
, p. 3197 - 3200 (2003)
(S)-N-[1-(3-Morpholin-4-ylphenyl)ethyl]-3-phenyl-acrylamide (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.
Cinnamide derivatives as KCNQ potassium channel modulators
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, (2008/06/13)
There is provided novel cinnamide derivatives of Formula I wherein R is C1-4 alkyl or trifluoromethyl; R1 is selected from the group consisting of pyridinyl, quinolinyl, thienyl, furanyl, 1,4-benzodioxanyl, 1,3-benzodioxolyl, chromanyl, indanyl, biphenylyl, phenyl and substituted phenyl in which said substituted phenyl is substituted with one or two substituents each independently selected-from the group consisting of halogen, C1-4 alkyl, C1-4 alkoxy, trifluoromethyl, trifluoromethoxy and nitro; R2 and R3 are each independently selected from the group consisting of hydrogen, C1-4 alkyl, and halogen; R4 is selected from the group consisting of di(C1-4 alkyl)amino, trifluoromethoxy and optionally substituted morpholin-4-yl, pyridinyl, pyrimidinyl, piperazinyl, and pyrazinyl with one or two substituents in which said substituent is independently selected from the group consisting of C1-4 alkyl, aminomethyl, hydroxymethyl, chloro or fluoro; R5 is hydrogen, chloro or fluoro; or R4 and R5 taken together are —CH═CH—CH═CH— or —X(CH2)mY— in which X and Y are each independently selected from the group consisting of CH2, (CH2)nN(R9)— and O, wherein m is 1 or 2; n is 0 or 1; and R6, R7, and R8 are each independently selected from hydrogen, chloro and fluoro; and R9 is selected from the group consisting of hydrogen, C1-4 alkyl, hydroxyethyl, C1-4 alkoxyethyl, cyclopropylmethyl, —CO2(C1-4alkyl), and —CH2CH2NR10R11 in which R10 and R11 are each independently hydrogen or C1-4 alkyl, which are openers of the KCNQ potassium channels and are useful in the treatment of disorders which are responsive to the opening of the KCNQ potassium channels.
