FURIN INHIBITORS Russian patent published in 2023 - IPC C07D211/26 C07D213/76 C07D401/04 C07D401/14 C07D413/12 C07D487/08 A61K31/44 A61K31/4427 A61K31/496 A61P11/00 A61P43/00 

FIELD: organic chemistry.

SUBSTANCE: invention relates to the compound of formula (I), or its pharmaceutically acceptable salt, where A¹, A², A³, A⁴, A⁵ and A⁶ each independently represents N, CH or CR⁶ where 0–3 of A¹, A², A³, A⁴, A⁵ and A⁶ are N; X is O or NR⁸; R¹ and R² each represents hydrogen, (C₁-C₄)alkyl or H₂N(C₁-C₄)alkyl-; or R¹ and R² taken together with the nitrogen atom to which they are attached are a 4–11 membered monocyclic or fused, bridged or spirobicyclic saturated ring, optionally containing 1–2 additional heteroatoms independently selected from oxygen, nitrogen and sulfur, said ring being optionally substituted with 1–3 substituents independently selected from halogen, hydroxyl, oxo, -OCONR⁸R⁹, -CO2R⁸, -C(O)CO₂R⁸, R⁷, -OR⁷, -NHR⁸, -NR⁷R⁸, -C(O)R⁷, -CONHR⁸, -CONR⁷R⁸ and -SO₂R⁷; R³ is selected from the group consisting of halogen, methyl, fluoromethyl, difluoromethyl and trifluoromethyl; R⁴ and R⁵ each represents hydrogen, (C₁-C₄)alkyl or (C₁-C₄)alkoxy(C₂-C₄)alkyl-; or R⁴ and R⁵ taken together with the nitrogen atom to which they are attached are a 4–11 membered monocyclic or fused, bridged or spirobicyclic saturated ring, optionally containing 1–2 additional heteroatoms independently selected from oxygen, nitrogen and sulfur, said ring being optionally substituted with 1–3 substituents independently selected from halogen, hydroxyl, oxo, -OCONR⁸R⁹, -CO₂R⁸, -C(O)CO₂R⁸, -SO₂(C₁-C₄)alkyl, R⁷, -OR⁷, -NHR⁸, -NR⁷R⁸, -N(R⁸)C(O)R⁹, -N(R⁸)SO₂R⁹, - N(R⁸)CONR⁸R⁹, -N(R⁸)CON(R⁸)SO₂R⁹, -C(O)R⁷, -CONHR⁸, -CONR⁷R⁸ and -P(O)R^8R9, R⁶ is independently selected from halogen, (C₁-C₄)alkyl, halo(C₁-C₄)alkyl, hydroxyl and (C₁-C₄)alkoxy; R⁷ is independently selected from (C₁-C₆)alkyl, (C₂-C₆)alkenyl, halo(C₁-C₆)alkyl, (C₃-C₆)cycloalkyl, and (C₃-C₆)cycloalkyl (C₁-C₄)alkyl-, each optionally substituted with 1–2 substituents independently selected from triazolyl, tetrazolyl, -CO₂R⁸, -CONR⁸R⁹, -CON(R⁸)CO₂(C₁-C₄)alkyl, hydroxyl, oxo, (C₁-C₄)alkoxy, -OCONR⁸R⁹, -OCON(R⁸)C(O)R⁹, (C₁-C₄)alkyl, HO(C₁-C₄)alkyl-, -NR⁸R⁹, -N(O)R⁸R⁹, -N(R⁸)C(O)R⁹, -N(R⁸)CO₂(C₁-C₄)alkyl, -N(R⁸)CH₂CO₂R⁹, -N(R⁸)CONR⁸R, -N(R⁸)CON(R⁸)C(O)R⁹, -N(R⁸)CON(R⁸)CO₂(С₁-С₄)alkyl, -N(R⁸)SO₂R⁹, -N(R⁸)CON(R⁸)SO₂R⁹, -SO(С₁-С₄)alkyl, -SO₂(С₁-С₄)alkyl, -SO₃R⁸, -SO₂NR⁸R⁹, -B(OH)₂, -P(O)R⁸R⁹ and -P(O)(OR⁸)(OR⁹); each R⁸ and R⁹ are either hydrogen (С₁-С₄)alkyl or (С₃-С₆)cycloalkyl; and n is either 1, 2, 3 or 4. The invention also relates to specific compounds, a pharmaceutical composition, a method for the treatment of pulmonary fibrosis and cystic fibrosis, and the use of a compound of formula (I).

EFFECT: inhibition of furin by the compound of formula (I), useful for the treatment of furin-mediated diseases, including fibrotic diseases.

25 cl, 16 dwg, 26 tbl, 399 ex