INHIBITOR COMPOUNDS Russian patent published in 2018 - IPC C07D401/14 C07D413/14 C07D401/04 C07D405/04 C07D471/04 A61K31/4725 A61K31/4375 A61K31/519 A61P35/00 

FIELD: chemistry.

SUBSTANCE: invention relates to organic chemistry, particularly to a heterocyclic compound of formula I or a pharmaceutically acceptable salt thereof, where W represents CR₃; X and Z are CH or N; R₁ selected from chlorine, phenyl, heteroaryl (selected from furan, pyridine, pyrimidine, isoxazole, imidazole and pyrazole), heterocyclyl (selected from pyrrolidine, piperidine, morpholine, piperazine, azetidine, 6-azaspiro[3.4]octane, 2-oxa-6-azaspiro[3.4]octane, 2-oxa-6-azaspiro[3.3]heptane, thiomorpholine-1,1-dioxide, 7-oxa-2-azaspiro[3.5]nonane, 6-oxa-2-azaspiro[3.4]octane, 2-oxa-7-azaspiro[4.4]nonane, 2-oxa-6-azaspiro[3.5]nonane and dihydropyran), (3-6C)cycloalkyl, NR₇R₈, OR₉, S(O)_pR₉ (where p = 0), N(R₁₀)SO₂R₉ or N(R₁₀)SOR₉; and where R₁ is optionally substituted with 1–2 substituents selected from fluorine, cyano, hydroxy, (1-4C)alkyl, (1-4C)alkoxy, S(O)_qCH₃ (where q = 2) and piperidine, and where any (1-4C)alkyl, (1-4C)alkoxy or heterocyclyl part present in the substituent group in R₁, is optionally further substituted with 1-2 substituents selected from fluorine, hydroxy, (1-4C)alkyl, NR_aR_b, OR_a and C(O)OR_a, where each of R_a and R_b is independently selected from H or (1-4C)alkyl; R₃ represents hydrogen, (1-4C)alkyl or (3-6C)cycloalkyl; R₄ represents hydrogen or (1-3C)alkyl; Ar has the formula

,

where (i) all of A₁, A₂ and A₃ represent CH or (ii) one of A₁ and A₂ represents N and others represent CH; R₅ is selected from hydrogen, cyano, (1-3C)alkyl, (1-3C)alkoxy, (1-3C)fluoroalkoxy and halogen and where any alkyl or alkoxy parts present in the substituent group R₅, are optionally further substituted with hydroxy or methoxy; R₆ is selected from halogen or cyano or R₆ represents a group of formula -L¹-L²-R₁₇, where L¹ is absent, L² is absent or is selected from O, SO₂, C(O) or C(O)N(R₂₀), where each of R₂₀ and R₂₁ is independently selected from hydrogen or (1-2C)alkyl, and R₁₇ is (1-6C)alkyl, heteroaryl (selected from imidazole, pyrazole, isoxazole, triazole, tetrazole, pyrimidine, oxadiazole) or heterocyclyl (selected from morpholine, azetidine, piperidine, tetrahydropyran and piperazine), where R₁₇ is optionally further substituted with 1–2 substituents selected from (1-4C)alkoxy, (1-4C)alkyl, (1-5C)alkylsulfonyl, heterocyclyl (selected from morpholine), heterocyclyl-(1-2C)alkyl (where said heterocyclyl is piperazine); and when said substituent group contains an alkyl or heterocyclyl part, said part is optionally additionally substituted with hydroxy, (1-2C)alkyl, (1-2C)alkoxy or NR_eR_f (where each of R_e and R_f is independently selected from (1-3C) alkyl; each of R₈ and R₉ is independently selected from hydrogen, (1-6C)alkyl, (3-6C)cycloalkyl, (3-6C)cycloalkyl-(1-2C)alkyl or heterocyclyl (selected from tetrahydropyran, tetrahydrofuran, oxetane and piperidine), heterocyclyl-(1-2C)alkyl (where heterocyclyl is oxetane or tetrahydrofuran), and where R₈ and R₉ are optionally further substituted with 1–2 substituents selected from hydroxyl, fluorine, CF₃, (1-2C)alkyl or (1-2C)alkoxy; R₇ and R₁₀ are independently selected from hydrogen and (1-6C)alkyl; with the proviso that X represents only N when Z represents N; and R₆ does not represent methoxy when R₁ represents S(O)₂R₉, and R₉ represents heterocyclyl. Invention also relates to a pharmaceutical composition based on a compound of formula I, a method of treating a proliferative disorder, and methods for producing a compound of formula I.

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EFFECT: technical result is obtaining novel heterocyclic compounds useful for cancer treatment.

21 cl, 209 ex