| 摘要 |
FIELD: organic chemistry, heterocyclic compounds, pharmacy. SUBSTANCE: invention relates to new 2,6,9-trisubstituted derivatives of purine of the general formula (I) eliciting effect of selective inhibitors of kinases in cellular cycle (mitosis). In compounds of the general formula (I) R1 represents halogen atom or -X wherein X means NH, -O-; represents lower alkyl, substituted lower alkyl comprising from 1 to 3 substituents taken among the group including: group OR20 wherein R20 is hydrogen atom or lower alkyl, aryl, 5-6-membered monocyclic or 8-10-membered bicyclic heteroaryl comprising up to 2 nitrogen heteroatoms in cycle and, optionally, substituted with lower alkyl, mono-, di- or tricyclo--C3-15-cycloalkyl optionally substituted with group OR20 wherein R20 is hydrogen atom, 5-10-membered heterocyclyl comprising up to 2 heteroatoms in cycle, group NR20SO2R21 wherein R20 is hydrogen atom and R21 is phenyl and substituted phenyl comprising from 1 to 3 substituents taken among the group including halogen atom, nitro-group, lower alkyl, trifluoromethyl, lower alkoxy-group, 5-6-membered monocyclic heteroaryl comprising nitrogen or sulfur as heteroatom, group SO2NR20R23 wherein R20 and R23 are hydrogen atom, unsubstituted phenyl or phenyl substituted with halogen atom, lower alkyl, lower alkoxy- group, trifluoromethyl or group CN; cycloalyl comprising 3-10 carbon atoms; 5-10-membered heterocyclyl that can be substituted with benzyl; aryl; substituted phenyl comprising from 1 to 3 substituents taken among the group including halogen atom, nitro-group, lower alkyl, lower alkoxy-group, lower thioalkoxy-group, phenyl, phenoxy-group and phenyl substituted with nitro- -group; and 5-6-membered monocyclic heteroaryl comprising up to 2 heteroatoms taken among nitrogen and sulfur atoms that can be substituted with group OR20 wherein R20 is lower alkyl; R2 represents hydrogen atom or hydrocarbon comprising 1-20 carbon atoms and taken among the group including: lower alkyl, substituted lower alkyl comprising from 1 to 3 substituents taken among the group including halogen atom, cyano-group, group OR20 wherein R20 is hydrogen atom, group COR20 and group CO2R20 wherein R20 is lower alkyl or aryl; perfluoroisopropyl; C3-8-cycloalkyl; lower alkenyl; oleyl; cycloheteroalkyl wherein heterocyclic moiety is taken among epoxymethyl; aryl-lower alkyl and phenyl-lower alkyl substituted with 1-3 substituents in phenyl moiety taken among the group including lower alkyl, nitro-group, group COOR20 wherein R20 is lower alkyl, phenyl and 2-phenylethenyl; R3 represents hydrogen, halogen atom or group -NR4R5, wherein each among R4 and R5 is taken among the group including: hydrogen atom; lower alkyl; substituted lower alkyl comprising from 1 to 3 substituents taken among the group including groups: CN, OR20 wherein R20 is hydrogen atom or lower alkyl, COR20 wherein R20 is lower alkoxyalkyl, SR20 wherein R20 is benzyl and others. Invention relates also to pharmaceutically acceptable cationic salt, method for inhibition of cells proliferation and to pharmaceutical composition. Proposed compounds can be used for treatment, for example, autoimmune diseases, such as rheumatic arthritis, systemic lupus erythematosus, insulin-dependent diabetes mellitus (type I), disseminated sclerosis and also for treatment of cancer, cardiovascular diseases, such as restenosis and others. EFFECT: improved inhibition method, valuable medicinal properties of compounds. 52 cl, 10 tbl |
