HRP20171859T1 - Pirazolil i pirimidinil triciklički enoni kao antioksidacijski modulatori upale - Google Patents

Pirazolil i pirimidinil triciklički enoni kao antioksidacijski modulatori upale Download PDF

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HRP20171859T1
HRP20171859T1 HRP20171859TT HRP20171859T HRP20171859T1 HR P20171859 T1 HRP20171859 T1 HR P20171859T1 HR P20171859T T HRP20171859T T HR P20171859TT HR P20171859 T HRP20171859 T HR P20171859T HR P20171859 T1 HRP20171859 T1 HR P20171859T1
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co2ch3
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Eric Anderson
Gary L. Bolton
Bradley Caprathe
Xin Jiang
Chitase Lee
William H. Roark
Melean Visnick
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Reata Pharmaceuticals, Inc.
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Claims (28)

1. Spoj s formulom: [image] naznačen time da: atomi označeni 1 i 2 su vezani ili preko dvostruke veze ili epoksidizirane dvostruke veze; n je 1 ili 2; m je 0 ili 1; X je -CN, -CF3, ili -C(O)Ra, pri čemu Ra je -OH, alkoksi(C≤6), alkilamino(C≤6), dialkilamino(C≤6), ili -NHS(O)2-alkil(C1-4); R1 i R2 su svaki neovisno vodik, hidroksi, halo, ili amino; ili alkil(C≤12), alkenil(C≤12), alkinil(C≤12), aril(C≤12), aralkil(C≤12), heteroaril(C≤12), heterocikloalkil(C≤12), acil(C≤12), alkoksi(C≤12), ariloksi(C≤12), aralkoksi(C≤12), heteroariloksi(C≤12), aciloksi(C≤12), alkilamino(C≤12), dialkilamino(C≤12), arilamino(C≤12), aralkilamino(C≤12), heteroaril-amino(C≤12), amido(C≤12), ili supstituirana verzija bilo koje od ovih skupina pri čemu jedan ili više vodikovih atoma je neovisno zamijenjen s -OH, -F, -Cl, -Br, -I, -NH2, -NO2, -CO2H, -CO2CH3, -CN, -SH, -OCH3, -OCH2CH3, -C(O)CH3, -N(CH3)2, -C(O)NH2, -OC(O)CH3, ili -S(O)2NH2; ili R1 i R2 se uzimaju zajedno i predstavljaju alkandiil(C≤12), alkendiil(C≤12), alkoksidiil(C≤12), alkilaminodiil(C≤12), ili supstituirana verzija bilo koje od ovih skupina pri čemu jedan ili više vodikovih atoma je neovisno zamijenjen s -OH, -F, -Cl, -Br, -I, NH2, -NO2, -CO2H, -CO2CH3, -CN, -SH, -OCH3, -OCH2CH3, -C(O)CH3, -N(CH3)2, -C(O)NH2, -OC(O)CH3, ili -S(O)2NH2; R3 je odsutan, vodik; ili alkil(C≤12), alkenil(C≤12), alkinil(C≤12), aril(C≤12), aralkil(C≤12), heteroaril(C≤12), heterocikloalkil(C≤12), acil(C≤12) ili supstituirana verzija bilo koje od ovih skupina pri čemu jedan ili više vodikovih atoma je neovisno zamijenjen s -OH, -F, -Cl, -Br, -I, -NH2, -NO2, -CO2H, -CO2CH3, -CN, -SH, -OCH3, -OCH2CH3, -C(O)CH3, -N(CH3)2, -C(O)NH2, -OC(O)CH3, ili -S(O)2NH2; ili R3 je uzet zajedno s R4 kako je dolje navedeno; pod uvjetom da R3 je odsutan kada i samo onda kada atom na koji je vezan tvori dio dvostruke veze; R4 je vodik, hidroksi, amino, halo, cijano, ili okso; ili alkil(C≤12), alkenil(C≤12), alkinil(C≤12), aril(C≤12), aralkil(C≤12), heteroaril(C≤12), heterociklo-alkil(C≤12), acil(C≤12), alkoksi(C≤12), ariloksi(C≤12), aralkoksi(C≤12), hetero-ariloksi(C≤12), aciloksi(C≤12), alkilamino(C≤12), dialkilamino(C≤12), arilamino(C≤12), aralkilamino(C≤12), heteroarilamino(C≤12), amido(C≤12), ili supstituirana verzija bilo koje od ovih skupina pri čemu jedan ili više vodikovih atoma je neovisno zamijenjen s -OH, -F, -Cl, -Br, -I, -NH2, -NO2, -CO2H, -CO2CH3, -CN, -SH, -OCH3, -OCH2CH3, -C(O)CH3, -N(CH3)2, -C(O)NH2, -OC(O)CH3, ili -S(O)2NH2; ili R4 je uzet zajedno s bilo R3 ili R5 kako je dolje navedeno; R5 je odsutan, vodik; ili alkil(C≤12), alkenil(C≤12), alkinil(C≤12), aril(C≤12), aralkil(C≤12), heteroaril(C≤12), heterocikloalkil(C≤12), acil(C≤12) ili supstituirana verzija bilo koje od ovih skupina pri čemu jedan ili više vodikovih atoma je neovisno zamijenjen s -OH, -F, -Cl, -Br, -I, -NH2, -NO2, -CO2H, -CO2CH3, -CN, -SH, -OCH3, -OCH2CH3, -C(O)CH3, -N(CH3)2, -C(O)NH2, -OC(O)CH3, ili -S(O)2NH2; ili R5 je uzet zajedno s R4 kako je dolje navedeno; pod uvjetom da R5 je odsutan kada i samo onda kada atom na koji je vezan tvori dio dvostruke veze; i R6 je vodik, hidroksi, amino, halo, cijano, ili okso; ili alkil(C≤12), alkenil(C≤12), alkinil(C≤12), aril(C≤12), aralkil(C≤12), heteroaril(C≤12), heterociklo-alkil(C≤12), acil(C≤12), alkoksi(C≤12), ariloksi(C≤12), aralkoksi(C≤12), hetero-ariloksi(C≤12), aciloksi(C≤12), alkilamino(C≤12), dialkilamino(C≤12), arilamino(C≤12), aralkilamino(C≤12), heteroarilamino(C≤12), amido(C≤12), ili supstituirana verzija bilo koje od ovih skupina pri čemu jedan ili više vodikovih atoma je neovisno zamijenjen s -OH, -F, -Cl, -Br, -I, -NH2, -NO2, -CO2H, -CO2CH3, -CN, -SH, -OCH3, -OCH2CH3, -C(O)CH3, -N(CH3)2, -C(O)NH2, -OC(O)CH3, ili -S(O)2NH2; pod uvjetom da kada R3 i R4 su uzeti zajedno, spoj je nadalje definiran s formulom Ia: [image] pri čemu R7 je vodik, hidroksi, amino, halo, ili cijano; ili alkil(C≤12), alkenil(C≤12), alkinil(C≤12), aril(C≤12), aralkil(C≤12), heteroaril(C≤12), heterocikloalkil(C≤12), acil(C≤12), alkoksi(C≤12), ariloksi(C≤12), aralkoksi(C≤12), heteroariloksi(C≤12), aciloksi(C≤12), alkilamino(C≤12), dialkil-amino(C≤12), arilamino(C≤12), aralkilamino(C≤12), heteroarilamino(C≤12), amido(C≤12), ili supstituirana verzija bilo koje od ovih skupina pri čemu jedan ili više vodikovih atoma je neovisno zamijenjen s -OH, -F, -Cl, -Br, -I, -NH2, -NO2, -CO2H, -CO2CH3, -CN, -SH, -OCH3, -OCH2CH3, -C(O)CH3, -N(CH3)2, -C(O)NH2, -OC(O)CH3, ili -S(O)2NH2; ili pod uvjetom da kada R4 i R5 su uzeti zajedno, spoj je nadalje definiran s formulom formula Ib: [image] pri čemu R8 je vodik, hidroksi, amino, halo, ili cijano; ili alkil(C≤12), alkenil(C≤12), alkinil(C≤12), aril(C≤12), aralkil(C≤12), heteroaril(C≤12), heterocikloalkil(C≤12), acil(C≤12), alkoksi(C≤12), ariloksi(C≤12), aralkoksi(C≤12), heteroariloksi(C≤12), aciloksi(C≤12), alkilamino(C≤12), dialkil-amino(C≤12), arilamino(C≤12), aralkilamino(C≤12), heteroarilamino(C≤12), amido(C≤12), ili supstituirana verzija bilo koje od ovih skupina pri čemu je jedan ili više vodikovih atoma neovisno zamijenjen s -OH, -F, -Cl, -Br, -I, -NH2, -NO2, -CO2H, -CO2CH3, -CN, -SH, -OCH3, -OCH2CH3, -C(O)CH3, -N(CH3)2, -C(O)NH2, -OC(O)CH3, ili -S(O)2NH2; ili njegova farmaceutski prihvatljiva sol ili tautomer.
2. Spoj prema zahtjevu 1, nadalje definiran s formulom: [image] naznačen time da: n je 1 ili 2; X je -CN, -CF3, ili -C(O)Ra, pri čemu Ra je -OH, alkoksi(C≤6), alkilamino(C≤6), dialkilamino(C≤6), ili -NHS(O)2-alkil(C1-4); R1 i R2 su svaki neovisno vodik, hidroksi, halo, ili amino; ili alkil(C≤12), alkenil(C≤12), alkinil(C≤12), aril(C≤12), aralkil(C≤12), heteroaril(C≤12), heterocikloalkil(C≤12), acil(C≤12), alkoksi(C≤12), ariloksi(C≤12), aralkoksi(C≤12), heteroariloksi(C≤12), aciloksi(C≤12), alkilamino(C≤12), dialkilamino(C≤12), arilamino(C≤12), aralkilamino(C≤12), heteroaril-amino(C≤12), amido(C≤12), ili supstituirana verzija bilo koje od ovih skupina pri čemu jedan ili više vodikovih atoma je neovisno zamijenjen s -OH, -F, -Cl, -Br, -I, -NH2, -NO2, -CO2H, -CO2CH3, -CN, -SH, -OCH3, -OCH2CH3, -C(O)CH3, -N(CH3)2, -C(O)NH2, -OC(O)CH3, ili -S(O)2NH2; ili R1 i R2 se uzimaju zajedno i predstavljaju alkandiil(C≤12), alkendiil(C≤12), alkoksidiil(C≤12), alkilaminodiil(C≤12), ili supstituirana verzija bilo koje od ovih skupina pri čemu jedan ili više vodikovih atoma je neovisno zamijenjen s -OH, -F, -Cl, -Br, -I, -NH2, -NO2, -CO2H, -CO2CH3, -CN, -SH, -OCH3, -OCH2CH3, -C(O)CH3, -N(CH3)2, -C(O)NH2, -OC(O)CH3, ili -S(O)2NH2; R3 je odsutan, vodik; ili alkil(C≤12), alkenil(C≤12), alkinil(C≤12), aril(C≤12), aralkil(C≤12), heteroaril(C≤12), heterocikloalkil(C≤12), acil(C≤12) ili supstituirana verzija bilo koje od ovih skupina pri čemu jedan ili više vodikovih atoma je neovisno zamijenjen s -OH, -F, -Cl, -Br, -I, -NH2, -NO2, -CO2H, -CO2CH3, -CN, -SH, -OCH3, -OCH2CH3, -C(O)CH3, -N(CH3)2, -C(O)NH2, -OC(O)CH3, ili -S(O)2NH2; pod uvjetom da R3 je odsutan kada i samo onda kada atom na koji je vezan tvori dio dvostruke veze; R5 je odsutan, vodik; ili alkil(C≤12), alkenil(C≤12), alkinil(C≤12), aril(C≤12), aralkil(C≤12), heteroaril(C≤12), heterocikloalkil(C≤12), acil(C≤12) ili supstituirana verzija bilo koje od ovih skupina pri čemu jedan ili više vodikovih atoma je neovisno zamijenjen s -OH, -F, -Cl, -Br, -I, -NH2, -NO2, -CO2H, -CO2CH3, -CN, -SH, -OCH3, -OCH2CH3, -C(O)CH3, -N(CH3)2, -C(O)NH2, -OC(O)CH3, ili -S(O)2NH2; pod uvjetom da R5 je odsutan kada i samo onda kada atom na koji je vezan tvori dio dvostruke veze; i R6 je vodik, hidroksi, amino, halo, ili cijano; ili alkil(C≤12), alkenil(C≤12), alkinil(C≤12), aril(C≤12), aralkil(C≤12), heteroaril(C≤12), heterociklo-alkil(C≤12), acil(C≤12), alkoksi(C≤12), ariloksi(C≤12), aralkoksi(C≤12), hetero-ariloksi(C≤12), aciloksi(C≤12), alkilamino(C≤12), dialkilamino(C≤12), arilamino(C≤12), aralkilamino(C≤12), heteroarilamino(C≤12), amido(C≤12), ili supstituirana verzija bilo koje od ovih skupina pri čemu jedan ili više vodikovih atoma je neovisno zamijenjen s -OH, -F, -Cl, -Br, -I, -NH2, -NO2, -CO2H, -CO2CH3, -CN, -SH, -OCH3, -OCH2CH3, -C(O)CH3, -N(CH3)2, -C(O)NH2, -OC(O)CH3, ili -S(O)2NH2; ili njegova farmaceutski prihvatljiva sol ili tautomer.
3. Spoj prema zahtjevu 1, nadalje definiran s formulom: [image] naznačen time da: R1 i R2 su svaki neovisno vodik, hidroksi, halo, ili amino; ili alkil(C≤12), alkenil(C≤12), alkinil(C≤12), aril(C≤12), aralkil(C≤12), heteroaril(C≤12), heterocikloalkil(C≤12), acil(C≤12), alkoksi(C≤12), ariloksi(C≤12), aralkoksi(C≤12), heteroariloksi(C≤12), aciloksi(C≤12), alkilamino(C≤12), dialkilamino(C≤12), arilamino(C≤12), aralkilamino(C≤12), heteroaril-amino(C≤12), amido(C≤12), ili supstituirana verzija bilo koje od ovih skupina pri čemu jedan ili više vodikovih atoma je neovisno zamijenjen s -OH, -F, -Cl, -Br, -I, -NH2, -NO2, -CO2H, -CO2CH3, -CN, -SH, -OCH3, -OCH2CH3, -C(O)CH3, -N(CH3)2, -C(O)NH2, -OC(O)CH3, ili -S(O)2NH2; ili R1 i R2 se uzimaju zajedno i predstavljaju alkandiil(C≤12), alkendiil(C≤12), alkoksidiil(C≤12), alkilaminodiil(C≤12), ili supstituirana verzija bilo koje od ovih skupina pri čemu jedan ili više vodikovih atoma je neovisno zamijenjen s -OH, -F, -Cl, -Br, -I, -NH2, -NO2, -CO2H, -CO2CH3, -CN, -SH, -OCH3, -OCH2CH3, -C(O)CH3, -N(CH3)2, -C(O)NH2, -OC(O)CH3, ili -S(O)2NH2; R3 je odsutan, vodik; ili alkil(C≤12), alkenil(C≤12), alkinil(C≤12), aril(C≤12), aralkil(C≤12), heteroaril(C≤12), heterocikloalkil(C≤12), acil(C≤12) ili supstituirana verzija bilo koje od ovih skupina pri čemu jedan ili više vodikovih atoma je neovisno zamijenjen s -OH, -F, -Cl, -Br, -I, -NH2, -NO2, -CO2H, -CO2CH3, -CN, -SH, -OCH3, -OCH2CH3, -C(O)CH3, -N(CH3)2, -C(O)NH2, -OC(O)CH3, ili -S(O)2NH2; pod uvjetom da R3 je odsutan kada i samo onda kada atom na koji je vezan tvori dio dvostruke veze; R5 je odsutan, vodik; ili alkil(C≤12), alkenil(C≤12), alkinil(C≤12), aril(C≤12), aralkil(C≤12), heteroaril(C≤12), heterocikloalkil(C≤12), acil(C≤12) ili supstituirana verzija bilo koje od ovih skupina pri čemu jedan ili više vodikovih atoma je neovisno zamijenjen s -OH, -F, -Cl, -Br, -I, -NH2, -NO2, -CO2H, -CO2CH3, -CN, -SH, -OCH3, -OCH2CH3, -C(O)CH3, -N(CH3)2, -C(O)NH2, -OC(O)CH3, ili -S(O)2NH2; pod uvjetom da R5 je odsutan kada i samo onda kada atom na koji je vezan tvori dio dvostruke veze; i R6 je vodik, hidroksi, amino, halo, ili cijano; ili alkil(C≤12), alkenil(C≤12), alkinil(C≤12), aril(C≤12), aralkil(C≤12), heteroaril(C≤12), heterociklo-alkil(C≤12), acil(C≤12), alkoksi(C≤12), ariloksi(C≤12), aralkoksi(C≤12), hetero-ariloksi(C≤12), aciloksi(C≤12), alkilamino(C≤12), dialkilamino(C≤12), arilamino(C≤12), aralkilamino(C≤12), heteroarilamino(C≤12), amido(C≤12), ili supstituirana verzija bilo koje od ovih skupina pri čemu jedan ili više vodikovih atoma je neovisno zamijenjen s -OH, -F, -Cl, -Br, -I, -NH2, -NO2, -CO2H, -CO2CH3, -CN, -SH, -OCH3, -OCH2CH3, -C(O)CH3, -N(CH3)2, -C(O)NH2, -OC(O)CH3, ili -S(O)2NH2; ili njegova farmaceutski prihvatljiva sol ili tautomer.
4. Spoj prema zahtjevu 3, nadalje definiran s formulom: [image] naznačen time da: R1 i R2 su svaki neovisno vodik, hidroksi, halo, ili amino; ili alkil(C≤12), alkenil(C≤12), alkinil(C≤12), aril(C≤12), aralkil(C≤12), heteroaril(C≤12), heterocikloalkil(C≤12); acil(C≤12), alkoksi(C≤12), ariloksi(C≤12), aralkoksi(C≤12), heteroariloksi(C≤12), aciloksi(C≤12), alkilamino(C≤12), dialkilamino(C≤12), arilamino(C≤12), aralkilamino(C≤12), heteroaril-amino(C≤12), amido(C≤12), ili supstituirana verzija bilo koje od ovih skupina pri čemu jedan ili više vodikovih atoma je neovisno zamijenjen s -OH, -F, -Cl, -Br, -I, -NH2, -NO2, -CO2H, -CO2CH3, -CN, -SH, -OCH3, -OCH2CH3, -C(O)CH3, -N(CH3)2, -C(O)NH2, -OC(O)CH3, ili -S(O)2NH2; R3 je vodik; ili alkil(C≤12), alkenil(C≤12), alkinil(C≤12), aril(C≤12), aralkil(C≤12), heteroaril(C≤12), heterocikloalkil(C≤12), acil(C≤12) ili supstituirana verzija bilo koje od ovih skupina pri čemu jedan ili više vodikovih atoma je neovisno zamijenjen s -OH, -F, -Cl, -Br, -I, -NH2, -NO2, -CO2H, -CO2CH3, -CN, -SH, -OCH3, -OCH2CH3, -C(O)CH3, -N(CH3)2, -C(O)NH2, -OC(O)CH3, ili -S(O)2NH2; i R6 je vodik, hidroksi, amino, halo, ili cijano; ili alkil(C≤12), alkenil(C≤12), alkinil(C≤12), aril(C≤12), aralkil(C≤12), heteroaril(C≤12), heterociklo-alkil(C≤12), acil(C≤12), alkoksi(C≤12), ariloksi(C≤12), aralkoksi(C≤12), hetero-ariloksi(C≤12), aciloksi(C≤12), alkilamino(C≤12), dialkilamino(C≤12), arilamino(C≤12), aralkilamino(C≤12), heteroarilamino(C≤12), amido(C≤12), ili supstituirana verzija bilo koje od ovih skupina pri čemu jedan ili više vodikovih atoma je neovisno zamijenjen s -OH, -F, -Cl, -Br, -I, -NH2, -NO2, -CO2H, -CO2CH3, -CN, -SH, -OCH3, -OCH2CH3, -C(O)CH3, -N(CH3)2, -C(O)NH2, -OC(O)CH3, ili -S(O)2NH2; ili njegova farmaceutski prihvatljiva sol ili tautomer.
5. Spoj prema zahtjevu 3, nadalje definiran s formulom: [image] naznačen time da: R1 i R2 su svaki neovisno vodik, hidroksi, halo, ili amino; ili alkil(C≤12), alkenil(C≤12), alkinil(C≤12), aril(C≤12), aralkil(C≤12), heteroaril(C≤12), heterocikloalkil(C≤12), acil(C≤12), alkoksi(C≤12), ariloksi(C≤12), aralkoksi(C≤12), heteroariloksi(C≤12), aciloksi(C≤12), alkilamino(C≤12), dialkilamino(C≤12), arilamino(C≤12), aralkilamino(C≤12), heteroaril-amino(C≤12), amido(C≤12), ili supstituirana verzija bilo koje od ovih skupina pri čemu jedan ili više vodikovih atoma je neovisno zamijenjen s -OH, -F, -Cl, -Br, -I, -NH2, -NO2, -CO2H, -CO2CH3, -CN, -SH, -OCH3, -OCH2CH3, -C(O)CH3, -N(CH3)2, -C(O)NH2, -OC(O)CH3, ili -S(O)2NH2; ili R1 i R2 se uzimaju zajedno i predstavljaju alkandiil(C≤12), alkendiil(C≤12), alkoksidiil(C≤12), alkilaminodiil(C≤12), ili supstituirana verzija bilo koje od ovih skupina pri čemu jedan ili više vodikovih atoma je neovisno zamijenjen s -OH, -F, -Cl, -Br, -I, -NH2, -NO2, -CO2H, -CO2CH3, -CN, -SH, -OCH3, -OCH2CH3, -C(O)CH3, -N(CH3)2, -C(O)NH2, -OC(O)CH3, ili -S(O)2NH2; R5 je vodik; ili alkil(C≤12), alkenil(C≤12), alkinil(C≤12), aril(C≤12), aralkil(C≤12), heteroaril(C≤12), heterocikloalkil(C≤12), acil(C≤12) ili supstituirana verzija bilo koje od ovih skupina pri čemu jedan ili više vodikovih atoma je neovisno zamijenjen s -OH, -F, -Cl, -Br, -I, -NH2, -NO2, -CO2H, -CO2CH3, -CN, -SH, -OCH3, -OCH2CH3, -C(O)CH3, -N(CH3)2, -C(O)NH2, -OC(O)CH3, ili -S(O)2NH2; i R6 je vodik, hidroksi, amino, halo, ili cijano; ili alkil(C≤12), alkenil(C≤12), alkinil(C≤12), aril(C≤12), aralkil(C≤12), heteroaril(C≤12), heterocikloalkil(C≤12), acil(C≤12), alkoksi(C≤12), ariloksi(C≤12), aralkoksi(C≤12), heteroariloksi(C≤12), aciloksi(C≤12), alkilamino(C≤12), dialkilamino(C≤12), arilamino(C≤12), aralkilamino(c≤12), heteroarilamino(c≤12), amido(C≤12), ili supstituirana verzija bilo koje od ovih skupina pri čemu jedan ili više vodikovih atoma je neovisno zamijenjen s -OH, =F, -Cl, -Br, -I, -NH2, -NO2, -CO2H, -CO2CH3, -CN, -SH, -OCH3, -OCH2CH3, -C(O)CH3, -N(CH3)2, -C(O)NH2, -OC(O)CH3, ili -S(O)2NH2; ili njegova farmaceutski prihvatljiva sol ili tautomer.
6. Spoj prema zahtjevu 1, nadalje definiran kao: [image] naznačen time da: R1 i R2 su svaki neovisno vodik, hidroksi, halo, ili amino; ili alkil(C≤12), alkenil(C≤12), alkinil(C≤12), aril(C≤12), aralkil(C≤12), heteroaril(C≤12), heterocikloalkil(C≤12), acil(C≤12), alkoksi(C≤12), ariloksi(C≤12), aralkoksi(C≤12), heteroariloksi(C≤12), aciloksi(C≤12), alkilamino(C≤12), dialkilamino(C≤12), arilamino(C≤12), aralkilamino(C≤12), heteroarilamino(C≤12), amido(C≤12), ili supstituirana verzija bilo koje od ovih skupina pri čemu jedan ili više vodikovih atoma je neovisno zamijenjen s -OH, -F, -Cl, -Br, -I, -NH2, -NO2, -CO2H, -CO2CH3, -CN, -SH, -OCH3, -OCH2CH3, -C(O)CH3, -N(CH3)2, -C(O)NH2, -OC(O)CH3, ili-S(O)2NH2; R4 je vodik, hidroksi, amino, halo, ili cijano; ili alkil(C≤12), alkenil(C≤12), alkinil(C≤12), aril(C≤12), aralkil(C≤12), heteroaril(C≤12), heterocikloalkil(C≤12), acil(C≤12), alkoksi(C≤12), ariloksi(C≤12), aralkoksi(C≤12), heteroariloksi(C≤12), aciloksi(C≤12), alkilamino(C≤12), dialkilamino(C≤12), arilamino(C≤12), aralkilamino(C≤12), heteroarilamino(C≤12), amido(C≤12), ili supstituirana verzija bilo koje od ovih skupina pri čemu jedan ili više vodikovih atoma je neovisno zamijenjen s -OH, -F, -Cl, -Br, -I, -NH2, -NO2, -CO2H, -CO2CH3, -CN, -SH, -OCH3, -OCH2CH3, -C(O)CH3, -N(CH3)2, -C(O)NH2, -OC(O)CH3, ili -S(O)2NH2; R6 je vodik, hidroksi, amino, halo, ili cijano; ili alkil(C≤12), alkenil(C≤12), alkinil(C≤12), aril(C≤12), aralkil(C≤12), heteroaril(C≤12), heterocikloalkil(C≤12), acil(C≤12), alkoksi(C≤12), ariloksi(C≤12), aralkoksi(C≤12), heteroariloksi(C≤12), aciloksi(C≤12), alkilamino(C≤12), dialkilamino(C≤12), arilamino(C≤12), aralkilamino(C≤12), heteroarilamino(C≤12), amido(C≤12), ili supstituirana verzija bilo koje od ovih skupina pri čemu jedan ili više vodikovih atoma je neovisno zamijenjen s -OH, -F, -Cl, -Br, -I, -NH2, -NO2, -CO2H, -CO2CH3, -CN, -SH, -OCH3, -OCH2CH3, -C(O)CH3, -N(CH3)2, -C(O)NH2, -OC(O)CH3, ili -S(O)2NH2; ili njegova farmaceutski prihvatljiva sol ili tautomer.
7. Spoj prema zahtjevu 1, naznačen time da su atomi označeni 1 i 2 spojeni preko dvostruke veze.
8. Spoj prema jednom od zahtjeva 1, 2 i 7, naznačen time da X je -CN.
9. Spoj prema jednom od zahtjeva 1-8, naznačen time da R1 ili R2 je alkil(C≤8).
10. Spoj prema zahtjevu 9, naznačen time da R1 i R2 su svaki metil.
11. Spoj prema zahtjevu 9, naznačen time da R1 je metil i R2 je vodik.
12. Spoj prema jednom od zahtjeva 1-3 i 7-11, naznačen time da R3 je odsutan.
13. Spoj prema jednom od zahtjeva 1 i 6-12, naznačen time da R4 je vodik.
14. Spoj prema jednom od zahtjeva 1 i 7-12, naznačen time da R4 je okso.
15. Spoj prema jednom od zahtjeva 1 i 6-12, naznačen time da R4 je alkil(C≤8), aril(C≤8), acil(C≤8), alkoksi(C≤8) ili supstituirana verzija bilo koje od ovih skupina pri čemu jedan ili više vodikovih atoma je neovisno zamijenjen s -OH, -F, -Cl, -Br, -I, -NH2, -NO2, -CO2H, -CO2CH3, -CN, -SH, -OCH3, -OCH2CH3, -C(O)CH3, -N(CH3)2, -C(O)NH2, -OC(O)CH3, ili -S(O)2NH2.
16. Spoj prema jednom od zahtjeva 1-3 i 7-15, naznačen time da R5 je odsutan.
17. Spoj prema jednom od zahtjeva 1-3, 5, i 7-15, naznačen time da R5 je vodik.
18. Spoj prema jednom od zahtjeva 1-3, 5, i 7-15, naznačen time da R5 je alkil(C≤8), aril(C≤8), acil(C≤8), ili supstituirana verzija bilo koje od ovih skupina pri čemu jedan ili više vodikovih atoma je neovisno zamijenjen s -OH, -F, -Cl, -Br, -I, -NH2, -NO2, -CO2H, -CO2CH3, -CN, -SH, -OCH3, -OCH2CH3, -C(O)CH3, -N(CH3)2, -C(O)NH2, -OC(O)CH3, ili -S(O)2NH2.
19. Spoj prema jednom od zahtjeva 1-18, naznačen time da R6 je vodik.
20. Spoj prema jednom od zahtjeva 1-19, naznačen time da R6 je halo.
21. Spoj prema jednom od zahtjeva 1-19, naznačen time da R6 je alkil(C≤6) ili supstituirani alkil(C≤6) pri čemu jedan ili više vodikovih atoma je neovisno zamijenjen s -OH, -F, -Cl, -Br, -I, -NH2, -NO2, -CO2H, -CO2CH3, -CN, -SH, -OCH3, -OCH2CH3, -C(O)CH3, -N(CH3)2, -C(O)NH2, -OC(O)CH3, ili -S(O)2NH2.
22. Spoj prema jednom od zahtjeva 1-21, naznačen time da R6 je aril(C≤8), heteroaril(C≤8) ili supstituirana verzija bilo koje od tih skupina pri čemu jedan ili više vodikovih atoma je neovisno zamijenjen s -OH, -F, -Cl, -Br, -I, -NH2, -NO2, -CO2H, -CO2CH3, -CN, -SH, -OCH3, -OCH2CH3, -C(O)CH3, -N(CH3)2, -C(O)NH2, -OC(O)CH3, ili -S(O)2NH2.
23. Spoj prema jednom od zahtjeva 1-18, naznačen time da R6 je alkoksi(C≤8).
24. Spoj prema zahtjevu 1, naznačen time da je nadalje definiran kao: [image] [image] [image] [image] [image] [image] [image] [image] [image] [image] [image] ili [image]
25. Spoj prema zahtjevu 1, naznačen time da je nadalje definiran kao: [image] [image] [image] [image] [image] [image] [image] [image] [image] [image] [image] [image] [image] ili [image]
26. Spoj s formulom: [image] [image] [image] ili [image]
27. Spoj s formulom: [image]
28. Farmaceutski pripravak naznačen time da sadrži: a) spoj prema bilo kojem od zahtjeva 1-27; b) optički izomer spoja, pri čemu optički izomer je enantiomer spoja; i c) pomoćno sredstvo.
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