FIELD: chemistry; pharmaceutics.
SUBSTANCE: invention relates to a novel compound of formula (I), a stereoisomer thereof or a pharmaceutically acceptable salt thereof. In formula (I)
X is selected from a group consisting of hydrogen, benzofuranyl, dihydrobenzofuranyl, chromanyl, dihydroindenyl, tetrahydronaphthalenyl, -CH(R1)NH-R2 and -CH(R1)OR2, where R1 is hydrogen or C1-8alkyl; where benzofuranyl can optionally be substituted with one R3, where R3 is C(=O)-O(R4), where R4 is C1-6alkyl, or -C(=O)-N(R4)(R5), where R4 is hydrogen and R5 is C1-6alkyl, substituted with 5-6-member heterocyclyl, having 1 N heteroatom; Y is H or -CH2NH-AZ; A is selected from a group consisting of a single bond, C1-8alkylene, C3-10cycloalkylene, 5-6-member heterocyclylene having 1 heteroatom N, -C(=O)- and -CH2C(=O)-, where alkylene, cycloalkylene and heterocyclylene can optionally be substituted with one to three R4, where R4 is C1-6alkyl, benzyl or amino; Z is selected from a group consisting of hydrogen, -N(R4)(R5), C1-8alkyl, C3-10cycloalkyl, 4-6-member heterocyclyl, having 1 or 2 heteroatoms selected from a group consisting of N and O, 5-member heterocyclyl, having 1 heteroatom N and substituted with two adjacent substitutes R3, which form 6-member heteroaryl ring having 1 N heteroatom; phenyl, benzyl and 5-6-member heteroaryl, having 1 or 2 heteroatoms selected from a group consisting of N, O and S, where alkyl, cycloalkyl, heterocyclyl, phenyl, benzyl and heteroaryl may optionally be substituted with one or two R3, where R3 is selected from a group consisting of halogen, C1-8alkyl, C1-4aminoalkyl, C1-4hydroxyalkyl, C1-4alkoxyalkyl, C3-10cycloalkyl, benzyl, oxo, C(=O)-O(R4), -C(=O)-N(R4)(R5), -O(R4), -N(R4)(R5), methylpiperidine and 5-6-member heterocyclyl, having 1 or 2 heteroatoms selected from a group consisting of N and O; R2 selected from a group consisting of phenyl, benzyl, biphenyl, tetrahydronaphthalenyl, dihydroindenyl, 5-6-member heterocyclyl, having 1 heteroatom, selected from a group consisting of N and O, and 5-9 membered heteroaryl, having one or two heteroatoms selected from a group consisting of N or O, where each of said values R2 can optionally be substituted with one to three substitutes selected from halogen, C1-8alkyl, C3-10cycloalkyl, -CF3, -CN, -NO2, -C(=O)-O(R4), -C(=O)-N(R4)(R5), -O(R4), -OCF3, -N(R4)(R5), C1-8alkoxyS1-8alkyl, -C1-8alkyl-C(=O)R4, -C(=O)R4, -C1-8alkyl-R4, -NH-C(=O)R4, -C1-8alkyl-NR4R5 and pyridinyl; R4 or R5 is independently selected from a group consisting of hydrogen, C1-6alkyl, C1-4aminoalkyl, dimethylaminopropyl, dimethylaminoethyl, C1-4fluoroalkyl, C1-4hydroxyalkyl, C3-10cycloalkyl group(C3-8cycloalkyl)C1-6alkyl, 5-6-member heterocyclyl, having 1 heteroatom O or N, phenyl, a group (5-6 membered heterocyclyl having 1 or 2 heteroatoms selected from N or CO)-C1-8alkyl, (5-6-member heteroaryl, having 1 heteroatom N)-C1-6alkyl and benzyl, where cycloalkyl, heterocyclyl, phenyl, cycloalkylalkyl, heterocyclylalkyl, heteroarylalkyl and benzyl can optionally be substituted with one or more substituents independently selected from R1, where R1 is selected from a group consisting of amino, C1-8alkyl, C1-8alkoxy, C1-8alkoxyalkyl, C1-4aminoalkyl, C1-4fluoroalkyl, C1-4hydroxyalkyl, C3-10cycloalkyl, acetyl, benzyl, 5-6-member heterocyclyl, having one N heteroatom; or, alternatively, adjacent R4 and R5 form 5-6-member N-containing heterocyclyl which can additionally contain 1 heteroatom selected from N and O, and which is optionally substituted with R1, where R1 is selected from C1-8alkyl, benzyl, C1-8alkoxy, with the proviso that X is not hydrogen when Y is hydrogen; and when Y is H, X is -CH(R1)OR2, R1 is H, and R2 is phenyl, then such phenyl is substituted with one to three substitutes selected from C1-8alkyl, C3-10cycloalkyl, -CF3, -CN, -NO2, -C(=O)-O(R4), -C(=O)-N(R4)(R5), -O(R4), -OCF3, -N(R4)(R5), C1-8alkoxyS1-8alkyl, -C1-8alkyl-C(=O)R4, -C(=O)R4, -C1-8alkyl-R4, -NH-C(=O)R4, pyridinyl and -C1-8alkyl-NR4R5, and this substituted phenyl can additionally be substituted with halogen.
EFFECT: compounds have histoneLysine demethylase (KDM) inhibitor activity and can be used for treating cancer or KDM dysregulated disease, in particular for treating cancer, selected from a group consisting of prostate cancer, lung cancer, breast cancer, stomach cancer, cervical cancer, melanoma, renal cell carcinoma and leukemia.
9 cl, 2 dwg, 3 tbl, 241 ex
формула - formula
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Authors
Dates
2019-04-09—Published
2015-10-27—Filed