Patent RU-2411238-C2 (RU)
Inventor: FOTUKHI NADER
IPC: C07D233/26
Filed: 2006-03-13
Granted: 2011-02-10
Abstract: 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 X 1  is selected from a group comprising lower alkoxy; X 2  and X 3  are independently selected from a group comprising hydrogen, halogen, cyano, lower alkyl, lower alkoxy, piperidinyl, -NX 4 X 5 , -SO 2 NX 4 X 5 , -C(O)NX 4 X 5 , -C(O)X 6 , -SOX 6 , -SO 2 X 6 , -NC(O)-lower alkoxy, -C≡C-X 7 , provided that both X 2  and X 3  do not denote hydrogen, lower alkyl or lower alkoxy, provided that when X 2  or X 3  denote hydrogen, the other does not denote lower alkyl, lower alkoxy or halogen, provided that when X 2  denotes -HX 4 X 5 , X 3  does not denote hydrogen, X 2  and X 3  together can form a ring selected from 5-7-member unsaturated rings which can contain three heteroatoms selected from S, N and O, X 4  and X 5  are independently selected from a group comprising hydrogen, lower alkyl, lower alkoxy, lower alkyl, substituted by a lower alkoxy, -SO 2 -lower alkyl, -C(O)piperazinyl-3-one; X 6  is selected from a group comprising lower alkyl, morpholine, piperidine, pyrrolidine; X 7  is selected from a group comprising hydrogen, lower alkyl, trifluoromethyl; Y 1  and Y 2  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, -CH 2 OH or -C(O)NH 2 , piperazinyl substituted with one or two R 1  [1,4]diazepanyl, substituted R 1 , R 1  can denote one or two substitutes selected from a group comprising oxo, lower alkyl substituted with one R 2 , -C(O)R 3 , -SO 2 -lower alkyl, -SO 2 -five-memer heterocyclyl, which is selected from isoxazolyl, dimethylisoxazolyl, pyrrolidinyl, pyrrolyl, thiophenyl, imidazolyl, thiazolyl, thiazolidinyl, imidazolidinyl; R 2  is selected from a group comprising -SO 2 -lower alkyl, hydroxy, lower alkoxy, -NH-SO 2 -lower alkyl, -cyano, -C(O)R 4 ; R 3  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, C 3 -cycloalkyl; R 4  is selected from a group comprising hydroxy, morpholine, piperidine, 4-acetylpiperazinyl, -NR 5 R 6 ; R 5  and R 6  are independently selected from a group comprising hydrogen, lower alkyl, lower alkyl substituted with lower alkoxy or cyano, lower alkoxy and C 3 -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