COMPOUNDS AND COMPOSITIONS AS INHIBITORS OF ENDOSOMAL TOLL-LIKE RECEPTORS Russian patent published in 2021 - IPC C07D471/04 C07D519/00 A61K31/437 A61P37/00 

FIELD: pharmaceutics.

SUBSTANCE: invention relates to a compound having a structure of the formula (A), or its pharmaceutically acceptable salt, which can be used to inhibit an endosomal Toll-like receptor. In the formula (A), R^A is

L is -CH₂- or -CH₂CH₂-; Y₁ is -CH₂- or -CH₂CH₂-; Y₂ is -CH₂- or -CH₂CH₂-; Y₃ is -CH₂-, -XCH₂- or -CH₂X-; X is -CH₂- or O; R¹ is -NHC(=O)R⁶, -NHC(=O)(CH₂)_nR⁶, -NH(CH₂)_nC(=O)R⁶, -NHC(=O)(CH₂)_mNHR⁵, -NHC(=O)(CH₂)_mN(R⁵)₂, -NHC(=O)(CHR⁹)_mNHR⁵, -NHC(=O)(CH₂)_mNH₂, -NHC(=O)(CH₂)nOR⁹, -NHC(=O)OR⁹, -NH(CH₂)_mC(=O)N(R⁵)₂, -NH(CHR⁹)_nC(=O)R⁶, NHC(=O)(CHR⁹)_nR⁶, -NH(CHR⁹)_mC(=O)R⁶, -NHR⁶, -NR⁵R⁶, -NH₂, -N(R⁵)₂, -NHR⁵, -NHR⁸, -NH(C(R⁹)₂)_nR¹⁰, -NR⁹C(=O)OR¹¹, -NH(CH₂)_nR⁶, -NH(CHR⁹)_nR⁶, -N(R⁶)₂, -NHC(=O)(CH₂)_nN(CD₃)₂, -NH(CHR⁹)_nCH₂OR⁹, -NHCH₂(CHR⁹)_nOR⁹, -NH(CHR⁹)_nOR⁹, -NR⁹(CH₂)_nOR⁹, -NHCH₂(C(R⁹)₂)_nOR⁹, -OR⁹, -NR⁹C(=O)R⁵, -NR⁹C(=O)(CH₂)_nR⁵, -NR⁹C(=O)OR⁵, -NHS(=O)₂R⁵, -NHC(=O)(CH₂)_nNR⁹C(=O)R⁵, -NHC(=O)(CH₂)_nNR⁹S(=O)2R⁵, , , 8-oxa-3-azabicyclo[3.2.1]octanyl or 4-6–element heterocycloalkyl having 1-2 ring elements independently selected from N, NH, NR¹⁶ and O, which is unsubstituted or substituted with 1-2 groups of R⁷; R² is H, C₁-C₆alkyl or C₁-C₆halogenalkyl; R³ is H, C₁-C₆alkyl, -CD₃ or benzyl substituted with 1-2 groups of R¹⁰; R⁴ is H, NH₂, C₁-C₆alkyl, halogen or phenyl substituted with 0-2 groups of R¹⁸; each R⁵ is independently selected from C₁-C₆alkyl, -CD₃ and -(CH₂)_nOR⁹; R⁶ is C₃-C₆cycloalkyl or 4-6-element heterocycloalkyl having 1-2 ring elements independently selected from N, NH, NR¹⁶ and O, which is unsubstituted or substituted with 1-2 groups of R¹²; each R⁷ is independently selected from C₁-C₆alkyl, hydroxyl and oxo; each R⁸ is independently selected from C₁-C₆halogenalkyl, -(C(R⁹)₂)_nOR⁹ and C₁-C₆alkyl substituted with 1-3 -OH; each R⁹ is independently selected from H and C₁-C₆alkyl; R¹⁰ is C₁-C₆alkoxy or C₃-C₆cycloalkyl; R¹¹ is C₃-C₆cycloalkyl that is unsubstituted or substituted with 1-3 C₁-C₆alkyl groups; each R¹² is independently selected from C₁-C₆alkyl, hydroxyl, halogen and C₁-C₆alkyl substituted with 1-3 -OH; R¹³ is H or C₁-C₆alkyl; R¹⁴ is H; each R¹⁶ is C₁-C₆alkyl; each R¹⁷ is independently selected from H and C₁-C₆alkyl; each R¹⁸ is independently selected from halogen, -CN, C₁-C₆alkoxy and C₁-C₆alkyl; m equals 1, 2, 3, 4, 5 or 6 and n equals 1, 2, 3, 4, 5 or 6. The invention also relates to a pharmaceutical composition for inhibiting an endosomal Toll-like receptor selected from TLR7, TLR8 or TLR9 and their combination containing therapeutically effective amount of the specified compound, and to a method for treating an autoimmune disease associated with the activity of an endosomal Toll-like receptor using a compound of the formula (A).

EFFECT: obtaining a compound for inhibiting Toll-like receptor.

22 cl, 7 tbl, 30 ex