Patent RU-2220968-C2 (RU)
Title: 2,6,9-trisubstituted purine derivative, pharmaceutically acceptable cationic salt, method for inhibition of cell proliferation, pharmaceutical composition
Inventor: LUM ROBERT T
IPC: C07D473/36
Filed: 1997-08-01
Granted: 2004-01-10
Abstract: 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) R 1  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 OR 20  wherein R 20  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--C 3-15 -cycloalkyl optionally substituted with group OR 20  wherein R 20  is hydrogen atom, 5-10-membered heterocyclyl comprising up to 2 heteroatoms in cycle, group NR 20 SO 2 R 21  wherein R 20  is hydrogen atom and R 21  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 SO 2 NR 20 R 23  wherein R 20  and R 23  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 OR 20  wherein R 20  is lower alkyl; R 2  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 OR 20  wherein R 20  is hydrogen atom, group COR 20  and group CO 2 R 20  wherein R 20  is lower alkyl or aryl; perfluoroisopropyl; C 3-8 -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 COOR 20  wherein R 20  is lower alkyl, phenyl and 2-phenylethenyl; R 3  represents hydrogen, halogen atom or group -NR 4 R 5 , wherein each among R 4  and R 5  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, OR 20  wherein R 20  is hydrogen atom or lower alkyl, COR 20  wherein R 20  is lower alkoxyalkyl, SR 20  wherein R 20  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