COMPOUNDS TARGETING BRM AND RELATED USES THEREOF Russian patent published in 2023 - IPC C07D413/14 C07D417/14 A61K31/427 A61K31/4439 A61K31/422 A61P35/00 

FIELD: chemistry.

SUBSTANCE: invention relates to bifunctional compounds PTM-L-ULM, where ULM has the chemical structure:

, , , or ,

L is a ligand and PTM has a chemical structure represented by formula I, III, IVb or VI:

(I),

III

(IVb) or (VI)

where W_PTM1 is phenyl optionally substituted with 1 hydroxy; W_PTM2 is imidazolyl or pyridazinyl, the pyridazinyl being optionally substituted with 1 amino; W_PTM3 is absent or is 3,8-diazabicyclo[3.2.1]octanyl, 3,6-diazabicyclo[3.1.1]heptanyl, or pyrimidinyl, the pyrimidinyl being optionally substituted with 1 amino; W_PTM4 is 3,8-diazabicyclo[3.2.1]octanyl; W_PTM5 is absent or is phenyl, pyridinyl, pyrazinyl, pyrimidinyl, pyridazinyl or pyrazolyl; W_PTM6 and W_PTM7 are a spirocyclic ring system with a structure selected from:

, , , and ,

as well as the use of the compound in the manufacture of a medicament for the treatment of a disease or disorder associated with accumulation and aggregation of SMARCA4, BRAHMA or BRM.

EFFECT: new bifunctional compounds that have a targeted effect through proteolysis (PROTAC) have been obtained, which are used as modulators of targeted ubiquitination of various polypeptides and other proteins that can be useful in diseases or disorders associated with the accumulation and aggregation of SMARCA4, BRAHMA or BRM such as lung cancer.

24 cl, 2 tbl, 533 ex, 2 dwg