SPIROINDOLINONE DERIVATIVES Russian patent published in 2011 - IPC C07D471/10 C07D471/20 A61K31/4545 A61K31/496 A61K31/5377 A61P35/00 A61P35/04 

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula: where X is selected from a group consisting of hydrogen, halogen, cyano, nitro, ethenyl, cyclopropyl, methyl, ethyl, isopropyl, methoxy and vinyl; Y denotes hydrogen or fluorine; R₄ and R₅ denote hydrogen or lower alkyl; one of R₁ and R₈ is selected from a group consisting of lower alkyl, substituted lower alkyl, lower alkenyl, substituted lower alkenyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocycle, substituted heterocycle, cycloalkyl, substituted cycloalkyl, cycloalkenyl and substituted cycloalkenyl, and the other denotes hydrogen; one of R₆ and R₇ is selected from a group consisting of lower alkyl, substituted lower alkyl, lower alkenyl, substituted lower alkenyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocycle, substituted heterocycle, cycloalkyl, substituted cycloalkyl, cycloalkenyl and substituted cycloalkenyl, and the other denotes hydrogen, cyano group or lower alkyl; R₂ is selected from a group consisting of hydrogen, lower alkyl and substituted lower alkyl; R₃ is selected from a group consisting of oxygen, sulphur and NNH(C=O)OR₉; R₉ denotes lower alkyl or substituted lower alkyl; where the term "substituted" denotes substitution with 1-5 substitutes independently selected from a group consisting of lower alkyl, lower alkenyl, lower alkynyl, dioxo-lower alkenyl, halogen, hydroxy, -CN, -CF₃, -NH₂, -N(H, lower alkyl), N(lower alkyl)₂, aminocarbonyl, carboxy, -NO₂, lower alkoxy, thio-lower alkoxy, lower alkylsulphonyl, aminosulphonyl, lower alkylcarbonyl, lower alkylcarbonyloxy, lower alkoxycarbonyl, lower alkylcarbonyl-NH, fluoro-lower alkyl, fluoro-lower alkoxy, lower alkoxy-carbonyl-lower alkoxy, carboxy-lower alkoxy, carbamoyl-lower alkoxy, hydroxy-lower alkoxy, -NH₂-lower alkoxy, -N(H, lower alkyl)-lower alkoxy, -N(lower alkyl)₂-lower alkoxy, benzyloxy-lower alkoxy, mono or di-lower alkyl, substituted with aminosulphonyl or lower alkyl, which can optionally be substituted with a halogen, hydroxy, -NH₂, -N(H, lower alkyl) or -N(lower alkyl)₂; the term "heteroaryl" denotes an aromatic heterocyclic ring system containing up to two rings; and the term "heterocycle" denotes a substituted or unsubstituted 5-8-member mono- or bicyclic, aromatic or non-aromatic hydrocarbon, where 1-3 carbon atoms are replaced with a heteroatom selected from a nitrogen, oxygen or sulphur atom; and pharmaceutically acceptable salts thereof or esters. The invention also relates to a pharmaceutical composition, use of compounds in claims 1-31, as well as to methods of producing compounds of formulae II and III.

EFFECT: obtaining novel biologically active compounds which inhibit interaction of MDM2 protein with a p53-like peptide.

38 cl, 186 ex