CIS-2,4,5-TRIARYLIMIDAZOLINES AND USE THEREOF AS ANTICANCER MEDICINAL AGENTS Russian patent published in 2011 - IPC C07D233/22 C07D233/24 C07D233/26 C07D403/06 C07D401/06 C07D403/12 C07D413/12 C07D417/04 C07D417/14 A61K31/4164 A61K31/4178 A61K31/496 A61P35/00 

FIELD: chemistry.

SUBSTANCE: present invention relates to novel derivatives of cis-2,4,5-triarylimidazoline of general formula I and pharmaceutically acceptable salts thereof, where X₁ is selected from a group comprising lower alkoxy; X₂ and X₃ are independently selected from a group comprising hydrogen, halogen, cyano, lower alkyl, lower alkoxy, piperidinyl, -NX₄X₅, -SO₂NX₄X₅, -C(O)NX₄X₅, -C(O)X₆, -SOX₆, -SO₂X₆, -NC(O)-lower alkoxy, -C≡C-X₇, provided that both X₂ and X₃ do not denote hydrogen, lower alkyl or lower alkoxy, provided that when X₂ or X₃ denote hydrogen, the other does not denote lower alkyl, lower alkoxy or halogen, provided that when X₂ denotes -HX₄X₅, X₃ does not denote hydrogen, X₂ and X₃ together can form a ring selected from 5-7-member unsaturated rings which can contain three heteroatoms selected from S, N and O, X₄ and X₅ are independently selected from a group comprising hydrogen, lower alkyl, lower alkoxy, lower alkyl, substituted by a lower alkoxy, -SO₂-lower alkyl, -C(O)piperazinyl-3-one; X₆ is selected from a group comprising lower alkyl, morpholine, piperidine, pyrrolidine; X₇ is selected from a group comprising hydrogen, lower alkyl, trifluoromethyl; Y₁ and Y₂ are independently selected from a group comprising halogen; R is selected from a group comprising lower alkoxy, piperidinyl substituted with a five-member heterocyclic ring which contains one nitrogen heteroatom, piperidinyl substituted with a hydroxy, -CH₂OH or -C(O)NH₂, piperazinyl substituted with one or two R₁ [1,4]diazepanyl, substituted R₁, R₁ can denote one or two substitutes selected from a group comprising oxo, lower alkyl substituted with one R₂, -C(O)R₃, -SO₂-lower alkyl, -SO₂-five-memer heterocyclyl, which is selected from isoxazolyl, dimethylisoxazolyl, pyrrolidinyl, pyrrolyl, thiophenyl, imidazolyl, thiazolyl, thiazolidinyl, imidazolidinyl; R₂ is selected from a group comprising -SO₂-lower alkyl, hydroxy, lower alkoxy, -NH-SO₂-lower alkyl, -cyano, -C(O)R₄; R₃ is selected from a group comprising a five-member heterocyclyl which is selected from isoxazolyl, dimethylisoxazolyl, pyrrolidinyl, pyrrolyl, thiophenyl, imidazolyl, thiazolyl, thiazolidinyl, imidazolidinyl, lower alkyl, lower alkenyl, lower alkyl substituted with a six-member heterocyclyl selected from piperidinyl, piperazinyl, 3-oxopiperazinyl, morpholinyl, C₃-cycloalkyl; R₄ is selected from a group comprising hydroxy, morpholine, piperidine, 4-acetylpiperazinyl, -NR₅R₆; R₅ and R₆ are independently selected from a group comprising hydrogen, lower alkyl, lower alkyl substituted with lower alkoxy or cyano, lower alkoxy and C₃-cycloalkyl. The invention also relates to a pharmaceutical composition based on the formula I compound, use of the formula I compound in preparing a medicinal agent and a method for synthesis of the formula I compound.

EFFECT: novel derivatives of cis-2,4,5-triarylimidazoline of general formula I are obtained, which can be used to treat diseases, based on reaction of the MDM2 protein with p53-like protein, particularly as anticancer agent.

54 cl, 412 ex