Patent RU-2689305-C2 (RU)
Inventor: DEJVIDSON Dzhejms Eduard Pol
IPC: A61P35/00
Filed: 2014-07-22
Granted: 2019-05-27
Abstract: FIELD: chemistry.SUBSTANCE: invention relates to organic chemistry and specifically to a heterocyclic compound of general formula (I) or an enantiomer thereof, a diastereomer, an addition salt thereof with a pharmaceutically acceptable acid, where Het is 5,6,7,8-tetrahydroindolysin, indolysin, 1,2-dimethyl-1H-pyrrole; T is a hydrogen atom, linear or branched (C-C)alkyl group or alkyl(C-C)-NRRgroup, Rand Rare a hydrogen atom or a linear or branched (C-C)alkyl group, or Rand Rtogether with the nitrogen atom carrying them, form a heterocycloalkyl group which is morpholine or piperazine, Ris a linear or branched (C-C)alkyl group, an aryl group or a heteroaryl group which is a pyrrol group or pyrrolo[2,3-b]pyridinyl group, Ris an aryl or linear or branched (C-C)alkyl group, Ris a hydrogen atom, Ris a group R', R'-CO-, R'-O-CO-, NR'R''-CO-, R'-SO-, where R'and R''represent a hydrogen atom, linear or branched (C-C)alkyl group which is optionally substituted with 1–2 groups selected from: (i) a heteroaryl group optionally substituted with a pyrazine-2-yl group, (ii) an aryl group, aryloxy group, arylamino group or arylthio group, where aryl and aryloxy groups are optionally substituted with one or two halogen atoms, or a group selected from: a methyl group, [2-(morpholin-4-yl)ethyl]amino group, [2-(dimethylamino)ethyl]amino group, [2-(dimethylamino)ethoxy] groups, dimethylaminomethyl groups, morpholinyl-CHgroup, (4-methylpiperazin-1-yl)-CHtrifluoromethoxy group; methoxy groups; cyano group or (4-methylpiperazin-1-yl) group; (iii) a phenylcarbamoyl group, (iv) cycloalkyl, (v) heterocycloalkyl, (vi) benzyloxy groups, (vii) -NHor hydroxy; linear or branched (C-C)alkenyl group which is substituted with an aryl group, where the aryl group is optionally substituted with one or two halogen atoms or a methoxy group, a trifluoromethyl group, cycloalkyl, heterocycloalkyl; an aryl group; (4-methylpiperazin-1-yl)phenyl group, or heteroaryl, p = p'= 0, q = 1 or 2 and q'= 1, wherein it is also assumed that: "aryl" denotes a phenyl or naphthyl group, "heteroaryl" denotes any mono- or bicyclic group consisting of 5–10 ring members containing at least one aromatic moiety and containing from 1 to 4 heteroatoms selected from oxygen, sulfur and nitrogen, "cycloalkyl" denotes any mono- or bicyclic, non-aromatic, carbocyclic group containing from 3 to 10 ring members, which can include condensed or bridged ring systems, "heterocycloalkyl" denotes any mono- or bicyclic, non-aromatic, carbocyclic group consisting of 4–10 ring members and containing from 1 to 2 heteroatoms selected from oxygen, sulfur, SO, SOand nitrogen, wherein aryl, heteroaryl, cycloalkyl and heterocycloalkyl groups, defined in such a way, and alkyl, alkenyl groups can be substituted with 1-3 groups selected from: linear or branched (C-C) alkyl group; linear or branched (C-C) alkynyl group; linear or branched (C-C) alkoxy; hydroxyl; oxo; cyano; -COOR'; -NR'R''; R'CONR''-; NR'R''CO-; trifluoromethyl; trifluoromethoxy; halogen; aryl; heteroaryl; wherein it is assumed that R' and R'' independently of each other represent a hydrogen atom or a linear or branched (C-C)alkyl group. Invention also relates to specific compounds, a method of producing a compound of formula (I), a pharmaceutical composition based on the compound of formula (I), use of the composition and a compound of formula (I)..EFFECT: technical result is obtaining novel heterocyclic compounds which inhibit apoptotic activity of Bcl-2 family proteins useful in treating malignant growths, autoimmune diseases and immune system diseases.28 cl, 1 tbl, 817 ex