FUSED 1,4-DIHYDRODIOXIN DERIVATIVES AS INHIBITORS OF HEAT SHOCK TRANSCRIPTION FACTOR 1 Russian patent published in 2018 - IPC C07D405/14 C07D319/08 C07D405/12 C07D407/12 C07D409/12 C07D417/12 C07D417/14 C07D471/04 C07D487/08 C07D491/56 A61K31/357 A61K31/404 A61K31/428 A61K31/436 A61P35/00 

FIELD: chemistry.

SUBSTANCE: invention relates to a compound of the formula I in which A₁ is selected from N or CR₁, A₂ is selected from N or CR₂ provided that only one of A₁ or A₂ can be N; R₁ and R₂ each is independently selected from hydrogen, fluorine, chlorine; R₄ is selected from fluorine, chlorine, bromine, iodine, CF₃, cyano, (1-4C)alkyl, or a group of the formula: WXYZ, wherein W is (1-3C)alkylene; X is O-; Y is absent; Z is hydrogen; Q is selected from the group of formula II, wherein A_4a and A_4b each is independently selected from N or CR₉, where each present R₉ is independently selected from hydrogen, halogen, (1-3C)alkyl or (1-3C)alkoxy; A_4c is N or CR₁₀; R₁₀ is selected from halogen, hydroxy or group W¹-X¹-Y¹-X⁴-Z¹, where W¹ is absent; X¹ is absent or is N(R^j) -, where R^j is hydrogen; Y¹ is absent or represents a linking group of the formula - [CR^kR^l]_q-, in which q is an integer selected from 1, 2, 3 or 4, and R^k and R^l each is independently selected from hydrogen or (1-2C)alkyl; X⁴ is absent or is O-, -N(R^j)-, where R^j is hydrogen; and Z¹ is (1-6C)alkyl, phenyl, 5- or 6-membered heteroaryl or 4-7 membered heterocyclyl containing 1, 2 or 3 heteroatoms selected from nitrogen or sulfur; and where Z¹ optionally further substituted with one or more substituent groups independently selected from halogen and (1-4C)alkyl, pyrrolidinyl, morpholinyl; and wherein any alkyl or heterocyclyl group present in the substituent group on Z¹, optionally further substituted with NR^oR^p or (1-2C)alkyl; where R^o and R^p is selected from (1-2C)alkyl; provided that R₁₀ is only hydrogen, halogen or t-butyl when at least one of A_4a and A_4b is N or CR₉, in which R₉ is a substituent as defined above, but not hydrogen; or Q is a group of formula III, wherein A₅ is selected from N or CR₅, where R₅ is selected from hydrogen; ring A is: a condensed phenyl ring; a fused 5- or 6-membered carbocyclic ring; a fused 5- or 6-membered heteroaryl ring, comprising one or two heteroatoms independently selected from N, S or O; or a fused 5-, 6- or 7-membered heterocyclic ring containing one or two heteroatoms independently selected from N, S or O; A₆ is selected from N, O, S, CR₆, C(R₆)₂, NR₆₀, where R₆ is selected from hydrogen and R₆₀ is hydrogen, O^- or (1-6C)alkyl; A₇ is selected from N, CR₇, S, S(O)₂ or C(R₇)₂; m is 0, 1 or 2; R₇ and R₁₁ each independently is halogen, cyano, oxo or W²-X²-Y²-X³-Z², where W² is absent or represents a linking group of the formula -[CR^xR^y]_r-, in which r is an integer selected from 1, 2, 3 or 4, and R^x and R^y each is independently selected from hydrogen or (1-2C)alkyl; X² is absent, is -O-, -N(R^z)- or -N(R^z)-C(O)O, where R^z is selected from hydrogen or methyl; Y² is absent or represents a linking group of the formula - [CR^aaR^bb]_s-, in which s is an integer selected from 1, 2, 3 or 4, and R^aa and R^bb each is independently selected from hydrogen or (1-2C)alkyl; X³ is absent, is -O-, -C(O)O-, -N (R^cc) - or -N (R^cc) -C(O)O-, where R^cc is selected from hydrogen or methyl; and Z² is hydrogen, (1-6C)alkyl, (2-6C)alkenyl, 4-7 membered heterocyclyl containing 1, 2 or 3 heteroatoms selected from nitrogen, oxygen or sulfur; and where Z² is optionally further substituted with one or more substituent groups independently selected from halogen, (1-4C)-alkoxy, (1-4C)alkyl, (3-8C)cycloalkyl, provided that when R₇ is hydrogen (that is, when W², X², Y² and X³ there are no Z² is hydrogen), then ring A is an uncondensed dioxane ring, or a pharmaceutically acceptable salt thereof. Also, the invention relates to a pharmaceutical composition for the treatment of an HSF-1-mediated condition based on said compounds.

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EFFECT: technical result - new compounds have been obtained that can be used in medicine in the treatment of proliferative diseases, such as cancer, autoimmune or viral diseases.

25 cl, 218 ex