SUBSTITUTED BENZOAZEPINES AS MODULATORS OF TOLL-LIKE RECEPTORS Russian patent published in 2016 - IPC C07D223/16 C07D401/04 C07D401/10 C07D401/14 C07D403/10 C07D403/14 C07D413/06 A61K31/55 A61P31/00 A61P35/00 

FIELD: chemistry.

SUBSTANCE: invention relates to a compound of formula I or tautomer, enantiomer or pharmaceutically acceptable salt thereof, where said formula Y represents -(O)_x(CH₂)_yR¹¹; x is selected from 0 and 1; y is selected from 0, 1, 2, and 3; R¹¹ is selected from phenyl, pyridyl, morpholinyl, 1-oxo-1,3-dihydroisobenzofuranyl and 2-oxo-tetrahydrofuranyl, when x equals 0, said phenyl or pyridinyl substituted -C(O)NR¹R² or T; R¹ and R² is selected independently from hydrogen and C_1-6alkyl, wherein said alkyl is optionally substituted -C(O)O(CH₂)_tR¹², or R¹ and R² together with a nitrogen atom to which they are bonded, form a saturated 5-member heterocycle containing 1-4 heteroatoms selected from nitrogen, oxygen and sulphur; t is selected from 0, 1, 2, and 3; R¹² is selected from C_3-6cycloalkyl and phenyl; T is selected from 2-oxo-1,3-dioxolane, 2-oxotetrahydrofuran -(CHR⁷)_zOR⁹, -(O)_u(CH₂)_sC(O)R⁸, -OSO₂R¹³ and -CH(OH)CH₂OH; R⁷ represents H; R⁸ is -OR¹⁰; R⁹ represents H; R¹⁰ is selected from C_1-6alkyl, -(CH(₂)R¹² and hydrogen, wherein said alkyl is optionally substituted with halogen or diC_1-6alkylamine; R¹³ represents CF₃; u is selected from 0 and 1; z is selected from 1, 2, and 3; s is selected from 1 and 2; R⁵ is selected from -NR³R⁴ and -OR¹⁰; R³ and R⁴ independently selected from H, C_1-12alkyl, -(O)_q(CH₂)_rP; said alkyl is optionally substituted with -OH; q is selected from 0 and 1; r is selected from 0, 1, 2, and 3; P is selected from phenyl, -SO₂R⁶, piperidinyl and pirrolidinyl; and R⁶ is -NH₂, provided that when R¹¹ is a phenyl or pyridyl, then a) x+y ≥ 1; or b) R¹¹ is substituted with T; or c) R₅ is NR³R⁴, and at least one of R³ or R⁴ is -(O)_q(CH₂)_rP-, and q+r ≥ 1; or d) at least one of R¹ or R² represents alkyl, substituted with -C(O)O(CH₂)R¹². Invention also relates to a pharmaceutical composition exhibiting TLR7- and/or TLR8 agonist activity, comprising an effective amount of a compound of formula I together with a pharmaceutically acceptable diluent or carrier.

EFFECT: substituted benzoazepine exhibiting TLR7- and/or TLR8 agonist activity.

17 cl, 3 tbl, 47 ex