TRICYCLIC COMPOUNDS PROVIDING DESTRUCTION OF IKAROS PROTEIN AND AIOLOS PROTEIN Russian patent published in 2025 - IPC C07D209/92 A61K31/403 A61K31/4545 A61K31/5377 A61P35/00 A61P35/02 

FIELD: chemistry; pharmaceutics.

SUBSTANCE: invention relates to organic chemistry and pharmaceutics, specifically a compound of formula I or formula II, or a pharmaceutically acceptable salt thereof, compound 218, its enantiomers, pharmaceutically acceptable salts which bind Cereblon for breaking down the Ikaros protein or the Aiolos protein via the ubiquitin-proteasome pathway, a pharmaceutical composition based thereon, their use for the preparation of a therapeutic agent and a method of treating a disorder which is cancer or a tumour mediated by cerebellum in a human being. In general formula I or formula II, X¹ and X² are independently selected from CH and N; X³ is selected from communication, NR², C(R³R^3’), O, C(O), C(S), S, S(O) and S(O)₂; R¹ is selected from hydrogen, halogen, cyano, nitro, NH₂, -OH, -NR²R⁴, -OR⁴, -(CR³R^3’)-R⁴, -C(O)R⁴, -SR⁴, -S(O)R⁴ and -S(O)₂R⁴; R²⁰, R²¹, R²², R²³ and R²⁴ independently in each case are selected from a group consisting of a bond, C₁-C₄ alkyl, -C(O)-, -C(O)O-, -OC(O)-, -SO₂-, -S(O)-, -C(S)-, -C(O)NR²-, -NR²C(O)-, -O-, -S-, -NR²-, -P(O)(R²⁸)-, -P(O)-, C₂-C₄ alkenyl, C₂-C₄ alkynyl, C₁-C₄ haloalkyl, C₆-C₁₄ aryl, 3–14-membered heterocycle with 1–3 heteroatoms selected from nitrogen, sulphur and oxygen, 5–10-member heteroaryl with 1–3 heteroatoms selected from nitrogen, sulphur and oxygen, bicyclic and C₃-C₈ cycloalkyl; each of them is optionally substituted with 1, 2, 3 or 4 substituents independently selected from R⁴⁰; and where R²⁰, R²¹, R²², R²³ and R²⁴ cannot be selected so that -C(O)-, -C(O)O-, -OC(O)-, -SO₂-, -S(O)-, -P(O)(R²⁸)-, -P(O)- and -C(S)- fragments are adjacent to each other; or -O-, -S- or -NR²- fragments are adjacent to each other; R²⁵ is selected from hydrogen, C₁-C₄ alkyl, C₂-C₄ alkenyl, C₂-C₄ alkynyl, halogen, hydroxyl, C₁-C₄ alkoxy, azide, amino, cyano, -OR², -NR²R^2’, -NR²SO₂R²⁸, -OSO₂R²⁸, -SO₂R²⁸, C₁-C₄ haloalkyl, C₆-C₁₄ aryl, 5–10-membered heteroaryl with 1–3 heteroatoms selected from nitrogen, sulphur and oxygen, 3–14-membered heterocycle with 1–3 heteroatoms selected from nitrogen, sulphur and oxygen, bicycle and C₃-C₈ cycloalkyl; each of such R²⁵ groups is optionally substituted with 1, 2, 3 or 4 groups independently selected from R¹². Other values of radicals are given in the claim.

EFFECT: disclosed are tricyclic compounds which provide for the destruction of the Ikaros protein and the Aiolos protein.

233 cl, 2 tbl, 295 ex