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), RA 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
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Authors
Dates
2021-11-16—Published
2017-09-06—Filed