There is provided novel cinnamide derivatives of Formula I:
##STR1##
wherein R is C.sub.1-4 alkyl or trifluoromethyl; R.sup.1 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, C.sub.1-4 alkyl, C.sub.1-4 alkoxy,
trifluoromethyl, trifluoromethoxy and nitro; R.sup.2 and R.sup.3 are each
independently selected from the group consisting of hydrogen, C.sub.1-4
alkyl, and halogen; R.sup.4 is selected from the group consisting of
di(C.sub.1-4 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 C.sub.1-4 alkyl, aminomethyl,
hydroxymethyl, chloro or fluoro; R.sup.5 is hydrogen, chloro or fluoro; or
R.sup.4 and R.sup.5 taken together are --CH.dbd.CH--CH.dbd.CH-- or
--X(CH.sub.2).sub.m Y-- in which X and Y are each independently selected
from the group consisting of CH.sub.2, (CH.sub.2).sub.n N(R.sup.9)-- and
O, wherein m is 1 or 2; n is 0 or 1; and R.sup.6, R.sup.7, and R.sup.8 are
each independently selected from hydrogen, chloro and fluoro; and R.sup.9
is selected from the group consisting of hydrogen, C.sub.1-4 alkyl,
hydroxyethyl, C.sub.1-4 alkoxyethyl, cyclopropylmethyl, --CO.sub.2
(C.sub.1-4 alkyl), and --CH.sub.2 CH.sub.2 NR.sup.10 R.sup.11 in which
R.sup.10 and R.sup.11 are each independently hydrogen or C.sub.1-4 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.
Hay derivados proporcionados del cinnamide de la novela del fórmula I: ## del ## STR1 en donde R es el alkyl C.sub.1-4 o trifluoromethyl; R.sup.1 se selecciona del pyridinyl que consiste en del grupo, quinolinyl, thienyl, furanyl, 1,4-benzodioxanyl, 1,3-benzodioxolyl, chromanyl, indanyl, biphenylyl, fenilo y el fenilo substituido en que dijo fenilo substituido se substituye con un o dos sustitutos cada uno independientemente seleccionar- del halógeno que consiste en del grupo, C.sub.1-4 alkyl, C.sub.1-4 alkoxy, trifluoromethyl, trifluoromethoxy y nitro; R.sup.2 y R.sup.3 son cada uno seleccionado independientemente del hidrógeno del grupo, del alkyl C.sub.1-4, y del halógeno que consisten en; R.sup.4 se selecciona del grupo que consiste en el alkyl)amino di(C.sub.1-4, el trifluoromethoxy y morpholin-4-yl, pyridinyl, pyrimidinyl, piperazinyl opcionalmente substituidos, y pyrazinyl con un o dos sustitutos en los cuales el sustituto dicho se seleccione independientemente del grupo que consiste en el alkyl C.sub.1-4, el aminomethyl, hidroximetílico, cloro o fluoro; R.sup.5 es hidrógeno, cloro o fluoro; o R.sup.4 y R.sup.5 tomados juntos son -- CH.dbd.CH -- CH.dbd.CH -- o -- X(CH.sub.2).sub.m Y -- en es qué X y Y cada uno seleccionó independientemente del grupo que consistía en CH.sub.2, (CH.sub.2).sub.n N(R.sup.9) -- y O, en donde m es 1 o 2; n es 0 o 1; y R.sup.6, R.sup.7, y R.sup.8 son cada uno seleccionado independientemente del hidrógeno, cloro y del fluoro; y R.sup.9 se selecciona del grupo que consiste en el hidrógeno, C.sub.1-4 alkyl, hidroxietílico, C.sub.1-4 alkoxyethyl, cyclopropylmethyl, -- CO.sub.2 (alkyl C.sub.1-4), y -- CH.sub.2 CH.sub.2 NR.sup.10 R.sup.11 en el cual R.sup.10 y R.sup.11 estén cada uno independientemente hidrógeno o el alkyl C.sub.1-4, que son abrelatas de los canales del potasio de KCNQ y son útiles en el tratamiento de los desórdenes que son responsivos a la abertura de los canales del potasio de KCNQ.
