IMIDAZOPYRIDAZINE DERIVATIVES AS MODULATORS OF TNF ACTIVITY Russian patent published in 2019 - IPC C07D487/04 A61K31/5025 A61P29/00 A61P25/00 A61P25/28 A61P9/00 A61P27/02 A61P35/00 A61P37/06 

FIELD: chemistry.

SUBSTANCE: object of the invention is substituted imidazo [1,2-b]pyridazine derivatives of formula IIB or pharmaceutically acceptable salts thereof. In formula IIB, E is -O-, -CH₂- or-C(O)-; Q is -CH₂-; Z is hydrogen or methyl; V is N; R¹² is hydrogen; R¹⁵ is a difluoromethoxy group; R¹⁶ is hydrogen or halogen; R²¹ is hydroxy(C₁-C₆)alkyl; or R²¹ is azetidinyl, piperidinyl, piperazinyl, morpholinyl or 3-azabicyclo[3.2.1]octanyl, any of these groups may optionally contain 1, 2 or 3 substituents independently selected from the group including trifluoromethyl, hydroxy group, C₁-C₆-alkylsulphonyl, oxo group, carboxy group and C₂-C₆alkoxycarbonyl; and R²³ is hydrogen. Invention also relates to a pharmaceutical composition comprising an effective amount of a compound of formula IIB or a pharmaceutically acceptable salt thereof, the use of a compound of formula IIB or a pharmaceutically acceptable salt thereof, and a method of treating and/or preventing rheumatoid arthritis or Crohn's disease.

(IIb).

EFFECT: compounds of formula IIB are active modulators of human TNFα activity and are therefore useful for the treatment and/or prevention of various human diseases, including autoimmune and inflammatory disorders; neurological and neurodegenerative disorders; pain and nociceptive disorders; cardiovascular disorders; metabolic disorders; eye disorders and oncological disorders; they are especially useful for the treatment and/or prevention of rheumatoid arthritis or Crohn's disease.

8 cl, 12 ex