FIELD: pharmacology.
SUBSTANCE: invention relates to a new compound of formula X or a pharmaceutically acceptable salt thereof which have the properties of a histone deacetylase (HDAC) inhibitor. The compounds can be used as active agents for pharmaceutical compositions suitable for use in the treatment of a tumour disease associated with impaired HDAC activity. Such a disease can be pancreatic carcinoma, hepatocellular carcinoma, colon tumours, mammary tumours, prostate tumours, lymphomas and skin tumours. In particular, tumour diseases can be melanoma and basal carcinomas, large-cell lung cancer, lung adenocarcinoma, small cell lung cancer, stomach cancer, ovarian adenocarcinoma, promyelocytic leukemia, chronic myelocytic leukemia or acute lymphocytic leukemia. In the formula
(I) R1 is hydrogen, (C1-C6)alkyl or (C3-C6)cycloalkyl; R2 is (C6)aryl, (C6)aryl(C1-C6)alkyl, heteroaryl(C1-C6)alkyl, wherein heteroaryl is a 5-membered monocyclic ring system containing one heteroatom in the ring selected from nitrogen, wherein the said system is fused to a benzene ring, halo(C6)aryl(C1-C6)alkyl or (C1-C6)alkoxy(C6)aryl(C1-C6)alkyl; R3 is N-hydroxyamino-oxo(C2-C6)alkenyl; R4 is hydrogen, N-hydroxyamino-oxo(C2-C6)alkenyl or N-hydroxyaminocarbonyl(C6)aryl(C1-C6)alkylene; R5 is hydrogen, halogen, N-hydroxyamino-oxo(C2-C6)alkenyl, N-hydroxyaminocarbonyl(C6)aryl(C1-C6)alkylene or (2E)-3-N-(2-aminophenyl)-3-oxo-propenyl; and R6 is hydrogen, N-hydroxyamino-oxo(C2-C6)alkenyl, N-hydroxyaminocarbonylphenyl or N-hydroxyaminocarbonyl(C6)aryl(C1-C6)alkylene; or (II) each of R1, R2, R5 and R6 is as defined in (I) above; R3 is hydrogen or N-hydroxyamino-oxo(C2-C6)alkenyl; and R4 is N-hydroxyamino-oxo(C2-C6)alkenyl or N-hydroxyaminocarbonyl(C6)aryl(C1-C6)alkylene; or (III) each of R1, R2, R4 and R6 is as defined in (I) above; R3 is as defined in (II) above; and R5 is N-hydroxyamino-oxo(C2-C6)alkenyl, N-hydroxyaminocarbonyl(C6)aryl(C1-C6)alkylene or (2E)-3-N-(2-aminophenyl)-3-oxo-propenyl; or (iv) each of R1, R2, R4, R5 is as defined in (I) above; R3 is as defined in (II) above; and R6 is N-hydroxyamino-oxo(C2-C6)alkenyl, N-hydroxyaminocarbonylphenyl or N-hydroxyaminocarbonyl(C6)aryl(C1-C6)alkylene; or (V) each of R1, R2, R5 and R6 is as defined in (III) above; R3 is hydrogen; and R4 is a halogen.
EFFECT: increased efficiency of treatment.
15 cl, 1 dwg, 1 tbl, 6 ex
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