BENZO[D]ISOXAZOLE DERIVATIVES AND THEIR APPLICATION Russian patent published in 2017 - IPC C07D261/20 C07D413/10 C07D413/06 C07D413/12 C07D413/14 C07D417/12 A61K31/42 A61K31/427 A61K31/428 A61K31/4427 A61P7/00 

FIELD: pharmacology.

SUBSTANCE: invention relates to a compound of the formula

(I), or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, wherein the linker L₁ is selected independently and represents -CH₂-, -NH-, -O- or -S-; R₁ is selected independently and is hydrogen, halogen, -C_1-3-alkyl, partially or fully halogenated -C_1-3-alkyl, -CN, -OH, -O-C_1-3-alkyl, -NH₂, -NHC_1-3-alkyl, -N (C_1-3-alkyl) C_1-3-alkyl, -C₁-₃-alkyl-NH₂, -C_1-3-alkyl-NH-C_1-3-alkyl, -C_1-3-alkyl-N(C_1-3-alkyl)C_1-3-alkyl or a 5-membered heteroaryl ring containing 1 to 4 N atoms and 0 to 1 S atom; R₁ group contains 0-2 R₄ substituents; R₂ is selected independently and is halogen, partially or fully halogenated -CH₃ or -OCH₃; R₃ is selected independently and is hydrogen or halogen; R₄ is selected independently and is halogen or C_1-3-alkyl; A cycle is selected independently and represents phenyl, a 5-6 membered heteroaryl ring containing 1 to 2 N atoms; A cycle contains 0-1 R₅ substituent and 0-2 R₆substituent; R₅ is selected independently and is phenyl; 5-9 membered heteroaryl containing 1 to 2 N atoms and 0 to 1 S or O atom, 5-6 membered cycloalkyl or 5-6 membered heterocycle containing 1 to 2 N atoms, 0 to 1 S or O atoms; R₅ contains 0-2 R'₆substituents; R₆ and R'₆ are selected independently and represent -OH, -C_1-3-alkyl, -C(O)OH, -C(O)NH₂, -NHC(O)H, -NHC(O)C_1-3-alkyl, -C_1-3-alkyl-NHC(O)H, -C_1-3-alkyl-NHC(O)C_1-3-alkyl, -NHC(O)OH, -C_1-3-alkyl-NHC(O)OH, -NH₂, -NHC_1-3-alkyl, -N(C_1-3-alkyl)C_1-3-alkyl, -C_1-3-alkyl-NH₂, -C_1-3-alkyl-NHC_1-3-alkyl, -C_1-3-alkyl-N(C_1-3-alkyl)C_1-3-alkyl, -CN, halogen, -S(O)₂NH₂, a 5-6 membered saturated, unsaturated or partially saturated heterocycle containing 1 to 4 N atoms, 0 to 1 atom S; R₆ and R'₆ contain 0-2 R₇ substituents; R₇ is selected independently and is = O, -C_1-3-alkyl, -NH₂, -NHC_1-3-alkyl, -N (C_1-3-alkyl) C_1-3-alkyl, -C_1-3-alkyl-NH₂, -C_1-3-alkyl-NHC_1-3-alkyl, -C_1-3-alkyl-N(C_1-3-alkyl)C_1-3-alkyl, -OH, -OC_1-3-alkyl, -C_1-3-alkyl-OH, -C_1-3-alkyl-O-C_1-3-alkyl or halogen. The compounds of the invention are intended to be used as inhibitors of the coagulation factor XIa in blood or plasma, as well as for preparation of a pharmaceutical composition for treatment and/or prevention of a condition of a mammal characterized by undesirable thrombosis. A pharmaceutical composition for treatment and/or prevention of a condition of a mammal characterized by undesired thrombosis comprises an effective amount of a compound of the invention and at least one pharmaceutically acceptable excipient.

EFFECT: increased efficiency of derivatives.

9 cl, 5 ex