METHODS AND COMPOSITIONS FOR TARGETED PROTEIN DEGRADATION Russian patent published in 2024 - IPC C07D495/14 A61K31/551 A61K47/55 A61P35/00 

FIELD: chemistry; medicine.

SUBSTANCE: invention relates to organic and medical chemistry, specifically to a compound of formula I or a pharmaceutically acceptable salt thereof, where X is C(O) or (C₁-C₄) alkylene; A is ; W is 5- or 6-member heteroaryl containing 2 or 3 ring heteroatoms selected from nitrogen and oxygen, optionally substituted with 1–3 groups selected from R²; V is phenyl, optionally substituted with 1–3 groups selected from R³; R¹ is (C₁-C₄) alkyl or halogen (C₁-C₄)alkyl; R² is -OR^a, -SR^a, -C(O)NR^aR^b, or -C(O)NR^a(C_1-4alkylene)NR^aR^b; each of R^a and R^b is independently selected from hydrogen and (C₁-C₄) alkyl, where said (C₁-C₄) alkyl is optionally substituted with one or more halogen or 3–7-membered heterocyclyl containing 1 ring heteroatom, selected from nitrogen; R³ is halogen; and L is a linker as specified in the claims. Invention also relates to a group of individual compounds, as well as to a pharmaceutical composition for BRD4 protein degradation and to the use of a compound of formula I for treating cancer susceptible to BRD4 degradation.

EFFECT: creation of chimeras for tumor-directed protein degradation (T-PEACH), containing the first fragment, which is capable of binding to the target protein (for example, BRD4) or proteins, and a second fragment which is capable of binding the protein-chaperone or protein component of the chaperone complex.

21 cl, 6 dwg, 9 tbl, 5 ex