CONDENSED DERIVATIVES OF IMIDAZOLE AND PYRAZOLE AS MODULATORS OF ACTIVITY TNF Russian patent published in 2019 - IPC C07D471/04 A61K31/437 C07D519/00 A61P37/00 A61P43/00 

FIELD: chemistry.

SUBSTANCE: present invention relates to a compound of formula (IIB-A) and a pharmaceutically acceptable salt thereof, which can be used in medicine: (IIB-A), where A denotes C-R² or N; D denotes C-R⁴ or N; E denotes -CH₂- or -CH(CH₃)-; Y denotes a group of formula:

, where sign (*) denotes position of attachment to the rest of the molecule; R^1g denotes hydrogen, fluorine, chlorine, bromine, cyano group, trifluoromethyl, hydroxyisopropyl, methylthio group, methylsulphinyl, methylsulphonyl, carboxy group, methoxycarbonyl, aminocarbonyl, methylaminocarbonyl, ethylaminocarbonyl, isopropylaminocarbonyl, dimethylaminocarbonyl, hydroxyethylaminocarbonyl, hydroxyisopropylaminocarbonyl, 1-hydroxy-2-methylprop-2-ylaminocarbonyl, methoxyethylaminocarbonyl, cyclopropylaminocarbonyl, oxazolylmethylaminocarbonyl, hydroxyoxetanyl, methoxy oxetanyl, piperazinylcarbonyl, hydroxypyrrolidinylcarbonyl, oxopiperazinylcarbonyl, methylsulphonylazetidinylcarbonyl or tert-butoxycarbonylpiperazinylcarbonyl; R^2g and R^3g are hydrogen or halogen; R^7a and R^7b denote hydrogen or C₁-C₆-alkyl; R^8a and R^8b denote hydrogen, halogen or C₁-C₆-alkyl; or R^8a and R^8b together with the carbon atom to which they are both bonded, denote cyclopropyl; R^9a and R^9b independently denote hydrogen or C₁-C₆-alkyl; R² is hydrogen or halogen; R⁴ denotes hydrogen; R⁵ denotes C₁-C₆-alkyl, optionally substituted with halogen, hydroxy group or C₁-C₆-alkoxy group; V denotes C-R²² or N; R²¹ denotes hydroxy(C₁-C₆)alkyl, methylsulphonyl, methylsulphoxyminyl, ethylsulphoxyminyl or (methyl)(N-methyl)sulfoxyminyl; or R²¹ denotes cyclopropyl, cyclobutyl, cyclohexyl, oxetanyl, azetidinyl, tetrahydropyranyl, piperidinyl, piperazinyl, morpholinyl, diazepanyl, 6-oxa-3-azabicyclo[3.1.1]heptanyl, 3-azabicyclo-[3.2.1]octanyl, 3,7-dioxa-9-azabicyclo[3.3.1]nonanyl, 3-oxa-6-azaspiro[3.3]heptanyl or 6-thia-2-azaspiro[3.3]heptanyl, any of these groups may optionally contain 1, 2 or 3 substitutes independently selected from a group comprising halogen, C₁-C₆-alkyl, trifluoromethyl, hydroxy group, oxo group, amino group, carboxy group and C₂-C₆-alkoxycarbonyl; R²² denotes hydrogen, halogen or C₁-C₆-alkyl; and R²³ denotes hydrogen, C₁-C₆-alkyl, trifluoromethyl or C₁-C₆-alkoxy group.

EFFECT: novel effective inhibitors of TNFα activity are disclosed and pharmaceutical compositions based thereon for treating rheumatoid arthritis or Crohn's disease.

7 cl, 256 ex