5-[(PIPERAZIN-1-YL)-3-OXO-PROPYL]-IMIDAZOLIDINE-2,4-DIONE DERIVATIVES AS ADAMTS INHIBITORS FOR TREATING OSTEOARTHRITIS Russian patent published in 2019 - IPC C07D403/06 C07D403/14 A61K31/496 A61P19/02 A61P19/04 

FIELD: chemistry.

SUBSTANCE: in general formula I R¹ is H, C_1-4 alkyl, optionally substituted with one group R⁴; C_3-7 monocyclic cycloalkyl optionally substituted with one group R⁴; 4-7 membered monocyclic heterocycloalkyl containing 1 to 2 heteroatoms N, optionally substituted with one -C(=O)C_1-4 alkyl or -C(=O)OC_1-4 alkyl; phenyl, optionally substituted with one or two independently selected groups R⁵; phenyl condensed with 5-membered monocyclic heterocycloalkyl containing 1 heteroatom N, wherein said heterocycloalkyl is optionally substituted with one =O; 5-6 membered monocyclic heteroaryl containing 1 or 2 heteroatoms independently selected from N and O, optionally substituted with one or two independently selected groups R⁵; R² is independently selected from H, C_1-4 alkoxy and C_1-4 alkyl, optionally substituted with one group of OH, CN, C_1-4 alkoxy optionally substituted with one phenyl group, or 5-6 membered monocyclic heteroaryl, including 2 heteroatoms independently selected from N, optionally substituted with one or two independently selected C_1-4 alkyl groups; each R^3a and R^3b is independently selected from H and C_1-4 alkyl; Cy is 6-10-member monocyclic or condensed bicyclic aryl, optionally substituted with one to three independently selected groups R⁶; 5-10-member monocyclic or condensed bicyclic heteroaryl, including 1, 2 or 3 heteroatoms independently selected from N, O and S, optionally substituted with one or two independently selected groups R⁶; R⁴ is OH, C_1-4 alkoxy, optionally substituted C_1-4 alkoxy or phenyl; C_1-4 thioalkoxy, 4-6-membered monocyclic heterocycloalkyl, including one or more heteroatoms independently selected from N and O, optionally substituted with one or two independently selected halogen groups or -C(=O)OC_1-4 alkyl; -C(=O)OR^7a, -C(=O)NR^7bR^7c, -NHC(=O)OR^7d, -NHC(=O)R^7e or -NR^8aR^8b; each R⁵ is halogen, CN, C_1-4 alkyl optionally substituted with one or three independently selected halogen groups or -NR^9aR^9b; C_1-4 alkoxy optionally substituted with -NR^9eR^9f, or -S(=O)₂C_1-4 alkyl; each R⁶ is a halogen, -CN, -NO₂, -CH₃, 5-6 membered monocyclic heteroaryl containing 1 or 2 heteroatoms of N, optionally substituted with one independently selected group of halogen or C_1-4 alkyl, or -NR^9gR^9h; each R^7a, R^7b, R^7c, R^7d or R^7e is H or C_1-4 alkyl, optionally substituted with OH or C_1-4 alkoxy group; each R^8a or R^8b is independently selected from H and C_1-4 alkyl, optionally substituted with phenyl; each R^9a, R^9b, R^9c, R^9d, R^9e, R^9f, R^9g and R^9h is independently selected from H and C_1-4 alkyl.

EFFECT: disclosed is a compound of formula I, having the properties of an ADAMTS inhibitor, and a pharmaceutical composition based thereon for preventing and / or treating inflammatory conditions and / or diseases associated with cartilage degradation and / or cartilage tissue homeostasis associated with ADAMTS activity.

16 cl, 14 tbl, 5 ex