BICYCLIC COMPOUNDS AS PD1/PD-L1 INTERACTION/ACTIVATION INHIBITORS Russian patent published in 2022 - IPC C07C217/58 C07C229/14 C07C229/48 C07C233/36 C07C255/54 C07C255/59 C07D207/16 C07D209/54 C07D211/40 C07D211/56 C07D211/60 C07D213/30 C07D213/85 C07D221/04 C07D265/30 C07D295/96 C07D401/12 C07D401/14 C07D403/12 C07D405/12 C07D471/04 C07D491/107 A61K31/165 A61K31/397 A61K31/40 A61K31/445 A61K31/454 A61K31/4545 A61K45/06 A61P31/00 A61P35/00 

FIELD: medicine.

SUBSTANCE: invention relates to compounds of the formula I, their stereoisomers and pharmaceutically acceptable salts, which are inhibitors of PD-1/PD-L1 activation. In the formula (I), X₁ is selected from -CH₂O-; R₄ is selected from hydrogen; X is selected from CR₃ or N; R₁, R₂, R₃, R₆, and R₇ are independently selected from hydrogen, halogen, C_1-6 alkyl, (4-10-element heterocycloalkyl)-C_1-4 alkyl-, OR^a or C(O)OR^a, where C_1-6 alkyl and (4-10-element heterocycloalkyl)-C_1-4 alkyl- are optionally substituted with 1, 2, or 3 R^b substitutes, and 4-10-element heterocycloalkyl has 1-3 heteroatoms selected from nitrogen and oxygen, and is mono- or bicyclic; R^a is selected from C_1-6 alkyl, C_1-4 haloalkyl, C_6-10 aryl-C_1-4 alkyl-, C_3-10 cycloalkyl-C_1-4 alkyl-, (5-10-element heteroaryl)-C_1-4 alkyl-, or (4-10-element heterocycloalkyl)-C_1-4 alkyl-, where C_1-6 alkyl, C_6-10 aryl-C_1-4 alkyl-, C_3-10 cycloalkyl-C_1-4 alkyl-, (5-10-element heteroaryl)-C_1-4 alkyl-, and (4-10-element heterocycloalkyl)-C_1-4 alkyl- are independently optionally substituted with 1, 2, 3, 4, or 5 R^d substitutes, and 4-10-element heterocycloalkyl and 5-10-element heteroaryl have 1-3 heteroatoms selected from nitrogen; R^b is selected from hydroxy, amino, C_1-4 alkyl, 4-10-element heterocycloalkyl, OR^c, C(O)NR^cR^c, C(O)OR^c, NHR^c, NR^cR^c, or NR^cC(O)R^c, where C_1-4 alkyl and 4-10-element heterocycloalkyl are optionally substituted with 1, 2, or 3 R^d substitutes, and 4-10-element heterocycloalkyl has 1-3 heteroatoms selected from nitrogen and oxygen, and is mono- or bicyclic; R^c is selected from hydrogen, C_1-6 alkyl, or C_3-10 cycloalkyl, where C_1-6 alkyl and C_3-10 cycloalkyl are optionally substituted with 1, 2, or 3 R^f substitutes; R^d is selected from cyano, halogen, C_6-10 aryl, 5-10-element heteroaryl, C_3-10 cycloalkyl, 4-10-element heterocycloalkyl, C(O)NR^eR^e, or C(O)OR^e, where C_6-10 aryl, 5-10-element heteroaryl, C_3-10 cycloalkyl, and 4-10-element heterocycloalkyl are optionally substituted with 1, 2, or 3 R^f substitutes, and 4-10-element heterocycloalkyl and 5-10-element heteroaryl have 1-3 heteroatoms selected from nitrogen; R^f is selected from C_1-4 alkyl, halogen, CN, OR^g, C(O)NR^gR^g, C(O)OR^g, or NR^gC(O)R^g; R^g is selected from hydrogen or C_1-6 alkyl; R^e is selected from hydrogen; m is 1 or 2; ring A is selected from C_6-10 aryl substituted with C_1-4 alkyl, cyano, or C_1-4 haloalkyl, and ring B is selected from C_6-10 aryl. The invention also relates to options of compounds of the formula (I), a method for their production, a pharmaceutical composition, use for the treatment and methods for the treatment of various diseases associated with the activation of PD-1/PD-L1, including cancer.

EFFECT: obtaining compounds for the treatment of PD-1/PD-L1-associated diseases.

13 cl, 5 tbl, 99 ex