FIELD: pharmaceuticals.
SUBSTANCE: invention relates to pladienolide derivatives or pharmaceutically acceptable salts thereof, represented by the general formula I, where R1 is selected from (a-m), and each of which may be optionally substituted by 1-3 groups independently selected from halogen atoms, hydroxyl groups, C1-C6 alkyl groups, C1-C6 alkoxy groups, C3-C8 cycloalkyl groups, and dimethylamino groups; R2, R3, R4, R5, R6 and R7 are each independently selected from hydrogen, hydroxyl groups and C1-C6 alkyl groups; R8, R9 and R13 are each independently selected from hydrogen and C1-C6 alkyl groups; R10, R11 and R12 are given in the claims; V represents -CH2-; W is selected from 3-8 membered carbocycles and 3-10 membered heterocycles containing 1-3 heteroatoms selected from nitrogen and oxygen, each of which may be optionally substituted by 1-2 groups independently selected from halogen atoms, groups of -NR8R9 and C1-C6 alkyl groups; X is independently selected from bond, 3-8 membered carbocycles and 3-8 membered heterocycles containing 1-2 heteroatoms selected from nitrogen, sulfur and oxygen, each of which may be optionally substituted by 1-2 groups independently selected from atoms halogen, hydroxyl groups, C1-C6 alkyl groups, hydroxy-C1-C6 alkyl groups, C1-C6 alkoxy groups, methoxy-C1-C6 alkyl groups, -SO2-C1-C6 alkyl groups and -NR14R15 groups, where each of R14 and R15 is independently selected from hydrogen and C1-C6 alkyl groups; Y is independently selected from hydrogen, 3-8 membered carbocycles and 3-8 membered heterocycles containing 1-2 heteroatoms selected from nitrogen, sulfur and oxygen, each of which may be optionally substituted by 1-2 groups independently selected from atoms halogen, hydroxyl groups, C1-C6 alkyl groups, hydroxy-C1-C6 alkyl groups, C1-C6 alkoxy groups, methoxy-C1-C6 alkyl groups, -SO2-C1-C6 alkyl groups and -NR14R15 groups, where each of R14 and R15 is independently selected from hydrogen and C1-C6 alkyl groups; each of L1 and L2 is independently selected from the relationship, -O-, -C(O)-, -C(O)O-, -N(R13)-C(O)-, -C(O)- N(R13)-, -N(R13)-S(O2)-, -S(O2)-N(R13)-, -S(O2)- and -N(R13)- ; and each n is independently selected from 0-4. The invention also relates to compounds represented by structural formulas IIa, IIb, IIc, IId, IIe, IIIa, IVa and specific compounds (shown in the claims).
EFFECT: compounds used as agents that have a targeted effect on the spliceosome for the treatment of cancer.
43 cl, 24 tbl, 268 ex
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