(HETERO)ARYL CYCLOPROPYLAMINE COMPOUNDS AS LSD1 INHIBITORS Russian patent published in 2018 - IPC C07C211/35 C07D213/74 C07D295/18 C07D231/12 C07D207/14 C07D333/36 C07D277/38 A61K31/135 A61K31/12 A61K31/381 A61K31/415 A61K31/44 A61P35/02 A61P35/00 A61P31/12 A61P25/28 

FIELD: pharmaceuticals.

SUBSTANCE: invention relates to a novel (hetero)aryl cyclopropylamine compound of formula (I) or a pharmaceutically acceptable salt thereof, wherein the substituents of the cyclopropyl moiety -A-B and -NH-D can be in the trans-configuration or a compound can be an optically active stereoisomer. In the compound of formula I

A is phenyl, naphthyl, pyridyl, thiophenyl, pyrrolyl, furanyl, or thiazolyl, wherein said phenyl, said naphthyl, said pyridyl, said thiophenyl, said pyrrolyl, said furanyl, or said thiazolyl is optionally substituted with one or more R¹; B is hydrogen, R¹ or -L-E; E is phenyl, pyridinyl, pyrazolyl or indazolyl, wherein said phenyl, said pyridinyl, said pyrazolyl or said indazolyl is optionally substituted with one or more R²; L is a bond, -O-, -NH-, -CH₂-NH- or -CH₂-O-, where said groups -CH₂-NH- and -CH₂-O- are linked to ring A via the N or O atom, respectively and are linked to ring E via the -CH₂- group contained in said groups -CH₂-NH- and -CH₂-O-; D is selected from D1, D2, D3 and D4:

,

where a cyclobutyl ring contained in D1, cyclopentyl ring contained in D2, cyclohexyl ring contained in D3, and cycloheptyl ring contained in D4, is optionally substituted with one or more R⁴; each R¹ is independently selected from the group consisting of halogen, C₁-C₄-alkyl, halogen-C₁-C₄-alkyl, C₁-C₄-alkoxy group and C₃-C₆-cycloalkyl; each R² is independently selected from the group, including C₁-C₈-alkyl, a hydroxy group, halogen, halogen-C₁-C₈-alkyl, halogen-C₁-C₈-alkoxy group, cyano group, N-sulfonamide group and C₁-C₈-alkoxy group; R³ is selected from a group comprising -NR⁷R⁸ and –C₁-C₄-alkylene-NR⁷R⁸; each R⁴ is independently selected from the group consisting of C₁-C₈-alkyl, halogen, halogen-C₁-C₈-alkyl, halogen-C₁-C₈-alkoxy group and C₁-C₈-alkoxy group; each R⁷ and each R⁸ is independently selected from the group consisting of hydrogen, C₁-C₈-alkyl, R¹²R¹³N-C₁-C₈-alkyl and hydroxy-C₁-C₈-alkyl, or R⁷ and R⁸ are linked to each other and together with the N atom to which they are bouned form a saturated 3-7 membered heterocyclic ring, which optionally contains one additional heteroatom selected from the group consisting of N, O and S, wherein one or more C atoms of said heterocyclic ring are optionally oxidized to form CO groups, wherein one or more of the S atoms of said heterocyclic ring, if present, are optionally oxidized to form independently SO groups or SO₂ groups, and wherein said heterocyclic ring is optionally substituted with one or more R¹¹; each R¹¹ is independently selected from the group consisting of C₁-C₈-alkyl, halogen, C₁-C₈-alkoxy group, hydroxy group and -NR¹²R¹³; each R¹² and each R¹³ is independently selected from the group consisting of hydrogen and C₁-C₈-alkyl; each R^w, R^x, R^y and R^z is independently selected from the group consisting of hydrogen, halogen and C₁-C₄-alkyl.

EFFECT: compounds possess the properties of a lysine-specific demethylase-1 inhibitor (LSD1) and can be used to treat cancer selected from a group consisting of breast cancer, lung cancer, prostate cancer, colorectal cancer, brain cancer, skin cancer, blood cancer, leukemia, lymphoma and myeloma (wherein leukemia can be acute myelogenous leukemia (AML), chronic myeloid leukemia (CML), chronic neutrophilic leukemia, chronic eosinophilic leukemia, chronic lymphocytic leukemia (CLL), acute lymphoblastic leukemia (ALL) and hairy cell leukemia); compounds can also be used to treat or prevent a viral infection, including to treat or prevent the reactivation of the virus after latency associated with LSD1.

88 cl, 3 tbl, 111 ex