| 主权项 |
1. A FoxM1 gene splicing modifier selected from a compound of formula (I) or a compound of formula (VI) wherein A is 2-hydroxy-phenyl which is substituted with:
0, 1, 2, or 3 substituents independently selected from C1-4 alkyl, oxo, oxime, hydroxy, halo-C1-4 alkyl, dihalo-C1-4 alkyl, trihalo-C1-4 alkyl, C1-4 alkoxy, C1-4 alkoxy-C3-7 cycloalkyl, halo-C1-4 alkoxy, dihalo-C1-4 alkoxy, trihalo-C1-4 alkoxy, hydroxy, cyano, halogen, amino, mono-C1-4 alkylamino, di-C1-4 alkylamino, heteroaryl, C1-4 alkyl substituted with hydroxy, C1-4 alkoxy substituted with aryl, amino, —C(O)NH—C1-4alkyl-heteroaryl, —NHC(O)—C1-4 alkylheteroaryl, C1-4 alkyl-C(O)NH-heteroaryl, C1-4alkyl-NHC(O)-heteroaryl, C3-7 cycloalkyl, 5-7 membered cycloalkenyl, or 5, 6 or 9 membered heterocycle containing 1 or 2 heteroatoms independently, selected from S, O and N,wherein two C1-4 alkyl groups can combine with the atoms to which they are bound to form a 5-6 membered ring;wherein heteroaryl has 5, 6 or 9 ring atoms, 1, 2 or 3 ring heteroatoms selected from N, O and S, and is substituted with 0, 1, or 2 substituents independently selected from oxo, hydroxy, nitro, halogen, C1-4 alkyl, C1-4 alkenyl, C1-4 alkoxy, C3-7 cycloalkyl, C1-4 alkyl-OH, trihalo-C1-4 alkyl, mono-C1-4 alkylamino, di-C1-4 alkylamino, —C(O)NH2, —NH2, NO2, hydroxy-C1-4alkylamino, hydroxy-C1-4 alkyl, 4-7 membered heterocycle-C1-4 alkyl, amino-C1-4 alkyl, mono-C1-4alkylamino-C1-4 alkyl, and di-C1-4alkylamino-C1-4 alkyl; or A is 2-naphthyl optionally substituted at the 3 position with hydroxy and additionally substituted with 0, 1, or 2 substituents selected from hydroxy, cyano, halogen, C1-4 alkyl, C2-4 alkenyl, C1-5 alkoxy, wherein the alkoxy is unsubstituted or substituted with hydroxy, C1-4 alkoxy, amino, —NHC(O)—C1-4 alkyl, —NHC(O)O—C1-4 alkyl, C1-4 alkylene-4-7 membered heterocycle, 4-7 membered heterocycle, mono-C1-4 alkylamino, and di-C1-4 alkylamino; or A is 6 membered heteroaryl having 1-3 ring nitrogen atoms and which is substituted by phenyl or a heteroaryl having 5 or 6 ring atoms, 1 or 2 ring heteroatoms independently selected from N, O and S and is substituted with 0, 1, or 2 substituents independently selected from C1-4 alkyl, mono-C1-4 alkylamino, di-C1-4 alkylamino, hydroxy-C1-4 alkylamino, hydroxy-C1-4 alkyl, amino-C1-4 alkyl and mono-C1-4 alkylamino-C1-4 alkyl, and di-C1-4alkylamino-C1-4 alkyl; or A is bicyclic heteroaryl having 9 to 10 ring atoms, 1, 2, or 3 ring heteroatoms independently selected from N, O or S, and which is substituted with 0, 1, or 2 substituents independently selected from cyano, oxime, halogen, hydroxy, C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-4 alkoxy, C1-4 alkoxy substituted with hydroxy, amino, mono-C1-4 alkylamino, and di-C1-4 alkylamino; or A is tricyclic heteroaryl having 12 or 13 ring atoms, 1, 2, or 3 ring heteroatoms independently selected from N, O or S, and which is substituted with 0, 1, or 2 substituents independently selected from cyano, halogen, hydroxy, C1-4 alkyl, C1-4 alkenyl, C2-4 alkynyl, C1-4 alkoxy, C1-4 alkoxy substituted with hydroxy, amino, mono-C1-4 alkylamino, di-C1-4 alkylamino, and heteroaryl having 5, 6 or 9 ring atoms, 1, 2 or 3 ring heteroatoms selected from N, O and S, and which is substituted with 0, 1, or 2 substituents independently selected from oxo, hydroxy, nitro, halogen, C1-4 alkyl, C1-4 alkenyl, C1-4 alkoxy, C3-7 cycloalkyl, C1-4 alkyl-OH, trihalo-C1-4 alkyl, mono-C1-4 alkylamino, di-C1-4 alkylamino, —C(O)NH2, —NH2, —NO2, hydroxy-C1-4 alkylamino, hydroxy-C1-4 alkyl, 4-7 membered heterocycle-C1-4 alkyl, amino-C1-4 alkyl, mono-C1-4 alkylamino-C1-4 alkyl and di-C1-4 alkylamino-C1-4 alkyl; or A is phenyl which is substituted with 0, 1, 2, or 3 substituents independently selected from C1-4 alkyl, oxo, oxime, hydroxy, halo-C1-4 alkyl, dihalo-C1-4 alkyl, trihalo-C1-4 alkyl, C1-4 alkoxy, C1-4 alkoxy-C3-7 cycloalkyl, halo-C1-4 alkoxy, dihalo-C1-4 alkoxy, trihalo-C1-4 alkoxy, cyano, halogen, amino, mono-C1-4 alkylamino, di-C1-4 alkylamino, heteroaryl, C1-4 alkyl substituted with hydroxy, C1-4 alkoxy substituted with aryl, —C(O)NH—C1-4 alkyl-heteroaryl, —NHC(O)—C1-4 alkylheteroaryl, C1-4 alkyl-C(O)NH-heteroaryl, C1-4 alkyl-NHC(O)-heteroaryl, C3-7 cycloalkyl, 5-7 membered cycloalkenyl or 5, 6 or 9 membered heterocycle containing 1 or 2 heteroatoms, independently, selected from S, O and N;
wherein two C1-4 alkyl groups can combine with the atoms to which they are bound to form a 5-6 membered ring;wherein heteroaryl has 5, 6 or 9 ring atoms, 1, 2 or 3 ring heteroatoms selected from N, O and S and is substituted with 0, 1, or 2 substituents independently selected from oxo, hydroxy, nitro, halogen, C1-4 alkyl, C1-4 alkenyl, C1-4 alkoxy, C3-7 cycloalkyl, C1-4 alkyl-OH, trihalo-C1-4 alkyl, mono-C1-4 alkylamino, di-C1-4 alkylamino, —C(O)NH2, —NH2,—NO2, hydroxy-C1-4 alkylamino, hydroxy-C1-4 alkyl, 4-7 memberered heterocycle-C1-4 alkyl, amino-C1-4 alkyl, mono-C1-4 alkylamino-C1-4 alkyl, and di-C1-4 alkylamino-C1-4 alkyl; B is a group of the formula wherein
m, n and p are independently selected from 0 or 1;R, R1, R2, R3, and R4 are independently selected from the group consisting of hydrogen and C1-4 alkyl, wherein alkyl is optionally substituted with hydroxy, amino, mono-C1-4 akylamino or di-C1-4 akylamino;R5 and R6 are independently selected from hydrogen and fluorine; orR and R3, taken in combination form a fused 5 or 6 membered heterocyclic ring having 0 or 1 additional ring heteroatoms selected from N, O or S; orR1 and R3, taken in combination form a C1-3 alkylene group; orR1 and R5, taken in combination form a C1-3 alkylene group; orR3 and R4, taken in combination with the carbon atom to which they attach, form a spirocyclic C3-6 cycloalkyl;X is CRARB, O, NR7 or a bond;R7 is hydrogen, or C1-4 alkyl;RA and RB are independently selected from hydrogen and C1-4 alkyl, or RA and RB, taken in combination, form a divalent C2-5 alkylene group;Z is CR8 or N; with the proviso that when Z is N, X is a bond;R8 is hydrogen or taken in combination with R6 form a double bond; or B is a group of the formula wherein
p and q are independently selected from the group consisting of 0, 1, and 2;R9 and R13 are independently selected from hydrogen and C1-4 alkyl;R10 and R14 are independently selected from hydrogen, amino, mono-C1-4 alkylamino, di-C1-4 alkylamino, and C1-4 alkyl optionally substituted with hydroxy, amino, mono-C1-4 alkylamino or di-C1-4 alkylamino;R11 is hydrogen, C1-4 alkyl, amino, mono-C1-4 alkylamino, or di-C1-4 alkylamino;R12 is hydrogen or C1-4 alkyl; orR9 and R11 taken in combination form a saturated azacycle having 4 to 7 ring atoms which is optionally substituted with one to three C1-4 alkyl groups; orR11 and R12, taken in combination form a saturated azacycle having 4 to 7 ring atoms which is optionally substituted with one to three C1-4 alkyl groups. or a pharmaceutically acceptable salt thereof; for use in the treatment, prevention and/or delay of progression of cancer. |
