SPIRO CONDENSED PYRROLIDINE DERIVATIVES AS INHIBITORS OF DEUBIQUITINATING ENZYMES (DUB) Russian patent published in 2020 - IPC C07D471/10 C07D471/20 C07D498/20 A61K31/4353 A61K31/537 

FIELD: organic chemistry.

SUBSTANCE: invention relates to a compound of formula I:

a tautomer thereof or a pharmaceutically acceptable salt thereof. In formula (I), each of R^1a, R^1b, R^1c and R^1d is hydrogen; each of R^1e and R^1f is hydrogen; ring A is 5–11 member monocyclic or bicyclic heterocyclyl ring which in addition to amide nitrogen can contain 1, 2 or 3 heteroatoms, each of which is independently selected from N, O and S, and which can optionally be substituted with one or two -Q¹-(R²)_n, which can be identical or different, where n is 0 or 1, Q¹ is halogen, oxo, -CONR³R⁴, -C₁-C₆alkyl, -C₁-C₆alkoxy, covalent bond, -CO-, -CONR³- or C₁-C₆alkylene; wherein said alkyl is optionally substituted with 1–4 halogen substituents, R² represents 3–10 membered heterocyclyl, heteroaryl or aryl ring, which is optionally substituted with one or two substitutes independently selected from halogen, cyano, oxo, -CONR⁶R⁷, -NR⁶COR⁷, -C₁-C₆alkyl, -C₁-C₆alkoxy, -Q^2a-R⁸, -Q^2b-CONR⁶-Q^2c-R⁸ and -Q²-NR⁶SO₂-Q^2c-R⁸; wherein said heterocyclyl and heteroaryl rings contain 1, 2 or 3 heteroatoms, each of which is independently selected from N, O and S; wherein said aryl ring is selected from phenyl and naphthyl; wherein said alkyl is optionally substituted with hydroxyl; and wherein said alkoxy is optionally substituted with one or more halogen; Q^2a is a covalent bond, an oxygen atom, -SO₂-, -CO- or C₁-C₆alkylene; each of Q^2b and Q^2c is a covalent bond; each of R³ and R⁴ independently represents hydrogen or C₁-C₆alkyl; each of R⁶ and R⁷ independently represents hydrogen or C₁-C₆alkyl; R⁸ denotes 6-member heterocyclyl which is optionally substituted with methyl; phenyl, which is optionally substituted with chlorine; or cyclopropyl; where said heterocyclyl ring contains 1 or 2 heteroatoms, each of which is independently selected from N and O. Also disclosed is a pharmaceutical composition.

EFFECT: disclosed are novel compounds for use as Cezanne 1 inhibitors.

16 cl, 7 tbl, 39 ex