Cinnamide derivatives as KCNQ potassium channel modulators
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 &#8212;CH&boxH;CH&#8212;CH&boxH;CH&#8212; or &#8212;X(CH2)mY&#8212; in which X and Y are each independently selected from the group consisting of CH2, (CH2)nN(R9)&#8212; 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, &#8212;CO2(C1-4alkyl), and &#8212;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.
Bristol-Myers Squibb Company
C A C C C C C C A A A C C C C C C C A C C A C C C C C A A A A
C07C A61P C07D C07D C07D C07D C07D C07D A61P A61P A61P C07D C07C C07D C07D C07D C07D C07D A61P C07D C07D A61P C07D C07D C07D C07D C07D A61P A61P A61P A61P
inventional inventional inventional inventional inventional inventional inventional inventional inventional inventional inventional inventional inventional inventional inventional inventional inventional inventional inventional inventional inventional inventional inventional inventional inventional inventional inventional inventional inventional inventional inventional
Gene G. Jean-Paul Li-Quang Alexandre Pierre Piyasena Huan Jie Steven I. Yong-Jin
Kinney Daris Sun L'Heureux Dextraze Hewawasam He Chen Dworetzky Wu