Patent RU-2673079-C2 (RU)
Inventor: KHELDER Sven
IPC: C07D405/04
Filed: 2013-09-09
Granted: 2018-11-22
Abstract: FIELD: chemistry.SUBSTANCE: invention relates to organic chemistry, particularly to a heterocyclic compound of formula I or a pharmaceutically acceptable salt thereof, where W represents CR; X and Z are CH or N; Rselected from chlorine, phenyl, heteroaryl (selected from furan, pyridine, pyrimidine, isoxazole, imidazole and pyrazole), heterocyclyl (selected from pyrrolidine, piperidine, morpholine, piperazine, azetidine, 6-azaspiro[3.4]octane, 2-oxa-6-azaspiro[3.4]octane, 2-oxa-6-azaspiro[3.3]heptane, thiomorpholine-1,1-dioxide, 7-oxa-2-azaspiro[3.5]nonane, 6-oxa-2-azaspiro[3.4]octane, 2-oxa-7-azaspiro[4.4]nonane, 2-oxa-6-azaspiro[3.5]nonane and dihydropyran), (3-6C)cycloalkyl, NRR, OR, S(O)R(where p = 0), N(R)SORor N(R)SOR; and where Ris optionally substituted with 1–2 substituents selected from fluorine, cyano, hydroxy, (1-4C)alkyl, (1-4C)alkoxy, S(O)CH(where q = 2) and piperidine, and where any (1-4C)alkyl, (1-4C)alkoxy or heterocyclyl part present in the substituent group in R, is optionally further substituted with 1-2 substituents selected from fluorine, hydroxy, (1-4C)alkyl, NRR, ORand C(O)OR, where each of Rand Ris independently selected from H or (1-4C)alkyl; Rrepresents hydrogen, (1-4C)alkyl or (3-6C)cycloalkyl; Rrepresents hydrogen or (1-3C)alkyl; Ar has the formula,where (i) all of A, Aand Arepresent CH or (ii) one of Aand Arepresents N and others represent CH; Ris selected from hydrogen, cyano, (1-3C)alkyl, (1-3C)alkoxy, (1-3C)fluoroalkoxy and halogen and where any alkyl or alkoxy parts present in the substituent group R, are optionally further substituted with hydroxy or methoxy; Ris selected from halogen or cyano or Rrepresents a group of formula -L-L-R, where Lis absent, Lis absent or is selected from O, SO, C(O) or C(O)N(R), where each of Rand Ris independently selected from hydrogen or (1-2C)alkyl, and Ris (1-6C)alkyl, heteroaryl (selected from imidazole, pyrazole, isoxazole, triazole, tetrazole, pyrimidine, oxadiazole) or heterocyclyl (selected from morpholine, azetidine, piperidine, tetrahydropyran and piperazine), where Ris optionally further substituted with 1–2 substituents selected from (1-4C)alkoxy, (1-4C)alkyl, (1-5C)alkylsulfonyl, heterocyclyl (selected from morpholine), heterocyclyl-(1-2C)alkyl (where said heterocyclyl is piperazine); and when said substituent group contains an alkyl or heterocyclyl part, said part is optionally additionally substituted with hydroxy, (1-2C)alkyl, (1-2C)alkoxy or NRR(where each of Rand Ris independently selected from (1-3C) alkyl; each of Rand Ris independently selected from hydrogen, (1-6C)alkyl, (3-6C)cycloalkyl, (3-6C)cycloalkyl-(1-2C)alkyl or heterocyclyl (selected from tetrahydropyran, tetrahydrofuran, oxetane and piperidine), heterocyclyl-(1-2C)alkyl (where heterocyclyl is oxetane or tetrahydrofuran), and where Rand Rare optionally further substituted with 1–2 substituents selected from hydroxyl, fluorine, CF, (1-2C)alkyl or (1-2C)alkoxy; Rand Rare independently selected from hydrogen and (1-6C)alkyl; with the proviso that X represents only N when Z represents N; and Rdoes not represent methoxy when Rrepresents S(O)R, and Rrepresents heterocyclyl. Invention also relates to a pharmaceutical composition based on a compound of formula I, a method of treating a proliferative disorder, and methods for producing a compound of formula I..EFFECT: technical result is obtaining novel heterocyclic compounds useful for cancer treatment.21 cl, 209 ex