2,6,9-triple-substituted purine derivative, pharmaceutically acceptable cationic salt, a method of inhibiting cell proliferation, pharmaceutical composition

 

The invention relates to novel 2,6,9-triple-substituted purine derivative of General formula I, having the effect of selective inhibitors of kinases of the cell cycle, which can be used, for example, for the treatment of, for example, autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus, diabetes type I, multiple sclerosis, and for the treatment of cancer, cardiovascular diseases such as restenosis, and other the Invention also relates to pharmaceutically acceptable cationic salts, the method of inhibiting the proliferation of cells and pharmaceutical compositions. In the compounds of General formula I1is halogen or R1'-X, where X=-NH, -O-; R1' is lower alkyl; substituted lower alkyl containing from 1 to 3 substituents selected from the group including a group OR20where R20is hydrogen or lower alkyl, aryl, 5-6 membered monocyclic or 8-10-membered bicyclic heteroaryl containing up to 2 heteroatoms of N in the cycle, and optionally substituted lower alkyl, mono-, di - or tricyclo-C3-15cycloalkyl, optionally substituted by a group OR20where R20is hydrogen, 5-10-membered heterocyclyl containing up to 2 heteroatoms is ewenny phenyl, containing from 1 to 3 substituents selected from the group comprising halogen, nitro, lower alkyl, trifluoromethyl, lower alkoxy, 5-6-membered monocyclic heteroaryl containing heteroatom is N or S, the group of SO2NR20R23where R20and R23are hydrogen, unsubstituted phenyl and phenyl substituted by halogen, lower alkyl, lower alkoxy, trifluoromethyl or a group of-CN; cycloalkyl containing 3-10 carbon atoms; 5-10-membered heterocyclyl, which can be substituted by benzyl; aryl; substituted phenyl containing from 1 to 3 substituents selected from the group comprising halogen, nitro, lower alkyl, lower alkoxy, lower dialkoxy, phenyl, phenoxy, and replaced by a nitro-group is phenyl; and a 5-6 membered monocyclic heteroaryl containing up to 2 heteroatoms selected from N and S atoms, and which may be substituted by a group OR20where R20is lower alkyl; R2represents hydrogen or a hydrocarbon containing 1 to 20 carbon atoms and selected from the group comprising lower alkyl; substituted lower alkyl containing from 1 to 3 substituents selected from the group comprising halogen, cyano, a group, OR20where R20is hydrogen, a group COR20and a group of CO2R20where R2020where R20is lower alkyl, phenyl and 2-phenylethenyl; R3represents hydrogen, halogen or the group-NR4R5where each of R4and R5independently selected from the group comprising hydrogen; lower alkyl; substituted lower alkyl containing from 1 to 3 substituents selected from the group comprising CN groups, OR20where R20is hydrogen or lower alkyl, COR20where R20is the lowest alkoxyalkyl, SR20where R20is benzyl, and other 5 C. and 47 C.p. f-crystals, 1 Il., 10 table.

Description text in facsimile form (see graphic material)

Claims

1. 2,6,9-triple-substituted purine derivative having the following formula I:

where R1is halogen or R1’-X, where X=-NH, -O-;

R1’ is lower alkyl; substituted lower alkyl containing from 1 to 3 substituents, selected monocyclic or 8-10-membered bicyclic heteroaryl, containing up to 2 heteroatoms of N in the cycle, and optionally substituted lower alkyl, mono-, di - or tricyclo-C3-15cycloalkyl, optionally substituted by a group OR20where R20is hydrogen, 5-10-membered heterocyclyl containing up to 2 heteroatoms in the cycle, the group NR20SO2R21where R20is hydrogen and R21is phenyl, and substituted phenyl containing from 1 to 3 substituents selected from the group comprising halogen, nitro, lower alkyl, trifluoromethyl, lower alkoxy, 5-6-membered monocyclic heteroaryl containing heteroatom N or S, the group of SO2NR20R23where R20and R23are hydrogen, unsubstituted phenyl and phenyl substituted by halogen, lower alkyl, lower alkoxy, trifluoromethyl or a group of-CN; cycloalkyl containing 3-10 carbon atoms; 5-10-membered heterocyclyl containing up to 2 heteroatoms in the cycle, which may be substituted by benzyl; aryl; substituted phenyl containing from 1 to 3 substituents selected from the group comprising halogen, nitro, lower alkyl, lower alkoxy, lower dialkoxy, phenyl, phenoxy, and replaced by a nitro-group is phenyl; and a 5-6 membered monocyclic heteroaryl containing up to 2 heteroatoms, selected from tomatored or hydrocarbon, containing 1-20 carbon atoms and selected from the group including: lower alkyl; substituted lower alkyl containing from 1 to 3 substituents selected from the group comprising halogen, cyano, a group, OR20where R20is hydrogen, a group COR20and a group of CO2R20where R20is lower alkyl or aryl; perforator; C3-8cycloalkyl; lower alkenyl; oleyl; cyclogeranyl, in which the heterocyclic part is selected from apoximately; aryl-lower alkyl; and phenyl-lower alkyl substituted in the phenyl part by 1-3 substituents selected from the group comprising lower alkyl, nitro, COOR group20where R20is lower alkyl, phenyl and 2-phenylethenyl;

R3represents hydrogen, halogen or the group-NR4R5where each of R4and R5independently selected from the group comprising: hydrogen; lower alkyl; substituted lower alkyl containing from 1 to 3 substituents selected from the group comprising CN groups, OR20where R20is hydrogen or lower alkyl, COR20where R20is the lowest alkoxyalkyl, SR20where R20is benzyl, NR20R23where R20is hydrogen, and R23is the th phenyl, containing from 1 to 3 substituents selected from halogen and OR20where R20is hydrogen, lower alkyl or trifluoromethyl, and 5-6-membered heteroaryl containing heteroatom N; C2-4alkenyl; and (C3-8cycloalkyl, possibly substituted by a group of IT; provided that4and R5are not both simultaneously hydrogen, or R4and R5together with the nitrogen atom to which they are attached, form a 5-6-membered, saturated or unsaturated, heterocyclic ring which, in addition to the above nitrogen atom, optionally in the cycle contains another heteroatom selected from O and N, and which may be substituted by a group selected from the groups HE, phenyl, C1-4-alkyl, optionally substituted HE or phenylaminopropyl, and (R4’R5’ ) where (R4’R5’) refers to a group HE and phenyl simultaneously attached to the same atom in the cycle; provided that if R3is 2-hydroxyethylamino, a R2is methyl, R1’-X is not an amino, 3-methyl-2-butenylamine, benzylamino or m-hydroxyethylamino, if R3is 2-hydroxyethylamino, and R2is isopropyl, R1’-X is not benzylamino, m-hydroxine the oxyethyl, R1’-X is not benzylamino, and if R3selected from the group comprising 2-methyl-2-hydroxypropylamino and 2 diethylaminoethylamine and2is methyl, R1’-X is not benzylamino, or its pharmaceutically acceptable cationic salt, or its pharmaceutically acceptable acid additive salt.

2. 2,6,9-triple-substituted purine derivative under item 1, where R1’ is lower alkyl; substituted lower alkyl containing from 1 to 3 substituents selected from the group including a group OR20where R20is hydrogen or lower alkyl, aryl, 5-6 membered monocyclic or 8-10-membered bicyclic heteroaryl containing up to 2 heteroatoms of N in the cycle, and optionally substituted lower alkyl, mono-, di - or tricyclo-C3-15cycloalkyl, optionally substituted by a group OR20where R20is hydrogen, 5-10-membered heterocyclyl containing up to 2 heteroatoms in the cycle, the group NR20SO2R21where R20is hydrogen and R21is phenyl, and substituted phenyl containing from 1 to 3 substituents selected from the group comprising halogen, nitro, lower alkyl, trifluoromethyl, lower alkoxy, 5-6-membered monocyclic heteroaryl, with alseny phenyl and phenyl, substituted with halogen, lower alkyl, lower alkoxy, trifluoromethyl or a group of-CN; cycloalkyl containing 3-10 carbon atoms; 5-10-membered heterocyclyl containing up to 2 heteroatoms in the cycle, which may be substituted by benzyl; aryl; substituted phenyl containing from 1 to 3 substituents selected from the group comprising halogen, nitro, lower alkyl, lower alkoxy, lower dialkoxy, phenyl, phenoxy, and replaced by a nitro-group is phenyl; and a 5-6 membered monocyclic heteroaryl containing up to 2 heteroatoms selected from N and S atoms, and which may be substituted by a group OR20where R20is lower alkyl; R2represents hydrogen or a hydrocarbon containing 1 to 20 carbon atoms and selected from the group including: lower alkyl; substituted lower alkyl containing from 1 to 3 substituents selected from the group comprising halogen, cyano, a group, OR20where R20is hydrogen, a group COR20and a group of CO2R20where R20is lower alkyl or aryl; perforator; C3-8cycloalkyl; lower alkenyl; oleyl; cyclogeranyl, in which the heterocyclic part is selected from apoximately; aryl-lower alkyl; and phenyl-lower alkyl substituted in the phenyl part 1-3 zamestitetelem, phenyl and 2-phenylethenyl; R3represents a group-NR4R5where each of R4and R5independently selected from the group comprising: hydrogen; lower alkyl; substituted lower alkyl containing from 1 to 3 substituents selected from the group comprising CN groups, OR20where R20is hydrogen or lower alkyl, COR20where R20is the lowest alkoxyalkyl, SR20where R20is benzyl, NR20R23where R20is hydrogen, and R23is hydrogen, a CONH group2or lower alkyl, which is optionally substituted by a group HE, phenyl, substituted phenyl containing from 1 to 3 substituents selected from halogen and OR20where R20is hydrogen, lower alkyl or trifluoromethyl, and 5-6-membered heteroaryl containing heteroatom N; C2-4alkenyl; and (C3-8cycloalkyl, possibly substituted by a group of IT.

3. 2,6,9-triple-substituted purine derivative under item 1, where R1’ is lower alkyl; substituted lower alkyl containing from 1 to 3 substituents selected from the group including: a group OR20where R20is hydrogen or lower alkyl, aryl, 5-6 membered monocyclic or 8-10-membered bicyclic, heteros3-15cycloalkyl, optionally substituted by a group OR20where R20is hydrogen, 5-10-membered heterocyclyl containing up to 2 heteroatoms in the cycle, the group NR20SO2R21where R20is hydrogen and R21is phenyl, and substituted phenyl containing from 1 to 3 substituents selected from the group comprising halogen, nitro, lower alkyl, trifluoromethyl, lower alkoxy, 5-6-membered monocyclic heteroaryl containing heteroatom N or S, the group of SO2NR20R23where R20and R23are hydrogen, unsubstituted phenyl and phenyl substituted by halogen, lower alkyl, lower alkoxy, trifluoromethyl or a group of-CN; cycloalkyl containing 3-10 carbon atoms; 5-10-membered heterocyclyl containing up to 2 heteroatoms in the cycle, which may be substituted by benzyl; aryl; substituted phenyl containing from 1 to 3 substituents selected from the group comprising halogen, nitro, lower alkyl, lower alkoxy, lower dialkoxy, phenyl, phenoxy, and replaced by a nitro-group is phenyl; and a 5-6 membered monocyclic heteroaryl containing up to 2 heteroatoms, selected from N and S atoms, and which may be substituted by a group OR20where R20is lower alkyl; R2represents Fodor lower alkyl, containing from 1 to 3 substituents selected from the group comprising halogen, cyano, a group, OR20where R20is hydrogen, the group COR20and CO2R20where R20is lower alkyl or aryl; perforator; C3-8cycloalkyl; cyclogeranyl, in which the heterocyclic part is selected from apoximately; aryl-lower alkyl; and phenyl-lower alkyl substituted in the phenyl part by 1-3 substituents selected from the group comprising lower alkyl and phenyl; R3represents a group-NR4R5where each of R4and R5independently selected from the group comprising: hydrogen; lower alkyl; substituted lower alkyl containing from 1 to 3 substituents selected from the group comprising CN groups, OR20where R20is hydrogen or lower alkyl, COR20where R20is the lowest alkoxyalkyl, SR20where R20is benzyl, NR20R23where R20is hydrogen, and R23is hydrogen, a CONH group2or lower alkyl, which is optionally substituted by a group HE, phenyl, substituted phenyl containing from 1 to 3 substituents selected from halogen and OR20where R20is hydrogen, lower alkyl or tripno, substituted by a group of IT.

4. 2,6,9-triple-substituted purine derivative under item 1, where R1’ is lower alkyl; substituted lower alkyl containing from 1 to 2 substituents selected from the group including: a group OR20where R20is hydrogen or lower alkyl, aryl, 5-6 membered monocyclic or 8-10-membered bicyclic heteroaryl containing up to 2 heteroatoms of N in the cycle, and optionally substituted lower alkyl, a group NR20SO2R21where R20is hydrogen and R21is phenyl, and substituted phenyl containing from 1 to 3 substituents selected from the group comprising halogen, lower alkyl, trifluoromethyl, lower alkoxy, 5-6-membered monocyclic heteroaryl containing heteroatom N or S, unsubstituted phenyl and phenyl substituted by halogen, lower alkyl, lower alkoxy, trifluoromethyl or a group of-CN; cycloalkyl containing 3-10 carbon atoms; 5-10-membered heterocyclyl containing up to 2 heteroatoms in the cycle, which may be substituted by benzyl; aryl; substituted phenyl, containing from 1 to 2 substituents selected from the group comprising halogen, lower alkyl, lower alkoxy, lower dialkoxy, phenyl, phenoxy; and a 5-6 membered monocyclic heteroaryl, soderjaschii alkyl; R2represents hydrogen or a hydrocarbon containing 1-10 carbon atoms and selected from the group including a substituted lower alkyl containing from 1 to 3 substituents selected from the group comprising halogen, cyano, a group, OR20where R20is hydrogen, a group COR20or CO2R20where R20is lower alkyl or aryl; With3-8cycloalkyl; cyclogeranyl, in which the heterocyclic part is selected from apoximately; aryl-lower alkyl; and phenyl-lower alkyl substituted in the phenyl part by 1-3 substituents selected from the group comprising lower alkyl and phenyl; R3represents a group-NR4R5where each of R4and R5independently selected from the group comprising: hydrogen; lower alkyl; substituted lower alkyl containing from 1 to 2 substituents selected from the group comprising CN groups, OR20where R20is hydrogen or lower alkyl, SR20where R20is benzyl, NR20R23where R20is hydrogen, and R23is hydrogen, a CONH group2or lower alkyl, which is optionally substituted by a group HE, phenyl, substituted phenyl containing from 1 to 3 substituents selected from halogen and OR2-4alkenyl; and (C3-8cycloalkyl, possibly substituted by a group of IT.

5. 2,6,9-triple-substituted purine derivative under item 1, where X=-NH-.

6. 2,6,9-triple-substituted purine derivative under item 1, where R3represents a group-NR4R5where R4and R5together with the nitrogen atom to which they are attached, form a 5-6-membered, saturated or unsaturated, heterocyclic ring which, in addition to the above nitrogen atom, optionally in the cycle contains another heteroatom selected from O and N, and which may be substituted by a group selected from the groups HE, phenyl, C1-4-alkyl, optionally substituted HE or phenylaminopropyl, and (R4’R5’ ) where (R4’R5’) refers to a group HE and phenyl simultaneously attached to the same atom in the cycle.

7. 2,6,9-triple-substituted purine derivative under item 3, where R1’ is chosen from the group comprising lower alkyl, substituted aryl, substituted phenyl or 5-6 membered monocyclic or 8-10-membered bicyclic-heteroaryl containing up to 2 heteroatoms of N in the cycle, and optionally substituted lower alkyl.

8. 2,6,9-triple-substituted purine derivative under item 7, where R1’ is chosen from the group comprising lower alkyl, samisen the e R2selected from the group comprising lower alkyl and substituted lower alkyl.

9. 2,6,9-triple-substituted purine derivative under item 3, where R1’ represents lower alkyl, which is substituted by aryl, a 5-6 membered monocyclic or 8-10-membered bicyclic-heteroaryl containing up to 2 heteroatoms of N in the cycle, or substituted phenyl containing from 1 to 2 substituents selected from the group comprising halogen, nitro, C1-3alkyl, trifluoromethyl, lower alkoxy, a group of SO2NR20R23where R20and R23are hydrogen, unsubstituted phenyl and phenyl substituted by halogen, lower alkyl, lower alkoxy, trifluoromethyl or a group of-CN; 5-10-membered heterocyclyl containing up to 2 heteroatoms in the cycle; aryl; substituted phenyl containing from 1 to 2 substituents selected from the group comprising halogen, C1-3alkyl, lower alkoxy, lower dialkoxy, phenyl, phenoxy; and a 5-6 membered monocyclic heteroaryl containing up to 2 heteroatoms selected from N and S atoms, and which may be substituted by a group OR20where R20is lower alkyl; R2represents hydrogen or a hydrocarbon containing 1-10 carbon atoms and selected from the group including: lower alkyl; substituted lower alkyl, zodergasse hydrogen; and C3-8cycloalkyl; each of R4and R5independently selected from the group including: lower alkyl; substituted lower alkyl containing from 1 to 2 substituents selected from the group comprising CN groups, OR20where R20is hydrogen or lower alkyl, SR20where R20is benzyl, NR20R23where R20is hydrogen, and R23is hydrogen, a CONH group2or lower alkyl, which is optionally substituted by a group HE, phenyl, substituted phenyl containing from 1 to 3 substituents selected from halogen and OR20where R20is hydrogen, lower alkyl or trifluoromethyl, and 5-6-membered heteroaryl containing a heteroatom of N; and (C3-8cycloalkyl, possibly substituted by a group of IT.

10. 2,6,9-triple-substituted purine derivative under item 3, where R1’ is chosen from the group comprising 5-10-membered heterocyclyl containing up to 2 heteroatoms in the cycle; aryl; substituted phenyl containing from 1 to 3 substituents selected from the group comprising halogen, nitro, lower alkyl, lower alkoxy, lower dialkoxy, phenyl, phenoxy, and replaced by a nitro-group is phenyl; and a 5-6 membered monocyclic heteroaryl containing up to 2 heteroatoms selected from N and S atoms, and E. purine on p. 3, where R1’ are selected from the group including aryl, unsubstituted pyridyl, pyridyl substituted by a group OR20where R20- lower alkyl, and substituted phenyl containing from 1 to 3 substituents selected from the group comprising halogen, nitro, lower alkyl, lower alkoxy, lower dialkoxy, phenyl, phenoxy, and replaced by a nitro-group is phenyl; R2selected from the group comprising lower alkyl and substituted lower alkyl containing from 1 to 3 substituents selected from the group comprising halogen, cyano, a group, OR20where R20is hydrogen, the group COR20and CO2R20where R20is lower alkyl or aryl.

12. 2,6,9-triple-substituted purine derivative under item 2, where R3is-NR4R5where each of R4and R5, independently, selected from the group comprising hydrogen; lower alkyl; substituted lower alkyl; With3-8cycloalkyl and C3-8cycloalkyl substituted by a group of IT.

13. 2,6,9-triple-substituted purine derivative under item 8, where R1’ is-CH2-aryl or-CH2-(substituted phenyl); R2represents lower alkyl, R4=N, a R5is CH2-CH2NH2, chr'CH2NH2, -CH2chr'NH2where R’ n the defaults isopropyl.

15. 2,6, 9-triple-substituted purine derivative under item 8, where R1’ is-CH2-aryl or-CH2- (substituted phenyl), R2represents lower alkyl, R4=-CH2CH2HE, and R5=-CH2CH2NH2or chr'CH2NH2or CH2chr'NH2where R’ represents hydrogen or C1-6alkyl.

16. 2,6,9-triple-substituted purine derivative under item 3, where R2represents isopropyl.

17. 2,6,9-triple-substituted purine derivative on PP 12, where R1’ is aryl containing 6 carbon atoms, or substituted phenyl containing from 1 to 2 substituents selected from the group comprising halogen, lower alkyl, lower alkoxy, phenyl and substituted by a nitro-group is phenyl; R2represents hydrogen or a hydrocarbon containing 1-6 carbon atoms and selected from the group including a substituted lower alkyl containing one Deputy, selected from the group comprising halogen and group OR20where R20is hydrogen; and (C3-8cycloalkyl; each of R4and R5, independently, selected from the group comprising hydrogen; lower alkyl; substituted lower alkyl containing from 1 to 2 substituents selected from the group comprising CN groups, OR20where R20the camping hydrogen, the CONH group2or lower alkyl, which is optionally substituted by a group HE, phenyl, substituted phenyl containing from 1 to 3 substituents selected from halogen and OR20where R20is lower alkyl or trifluoromethyl; With3-8cycloalkyl and C3-8cycloalkyl substituted by a group of IT, each of the hydrocarbon contains from 1 to 12 carbon atoms.

18. 2,6,9-triple-substituted purine derivative under item 12, where R1’ is aryl containing 6 carbon atoms, or substituted phenyl containing from 1 to 2 substituents selected from the group comprising halogen, C1-3alkyl, C1-2alkoxy, phenyl; R2is isopropyl; each of R4and R5, independently, selected from the group comprising hydrogen; lower alkyl; substituted lower alkyl containing one Deputy, selected from the group comprising group OR20where R20is hydrogen or C1-2the alkyl, NR20R23where R20is hydrogen, and R23is hydrogen or C1-3by alkyl; C3-8cycloalkyl and C3-8cycloalkyl substituted by a group of IT; and each of the hydrocarbon contains from 1 to 12 carbon atoms.

19. 2,6,9-triple-substituted purine derivative under item 12, where R11’ represents substituted phenyl-(lower alkyl) specified substituted phenyl containing from 1 to 2 substituents selected from the group comprising halogen, lower alkyl, trifluoromethyl, lower alkoxy, 5-6-membered monocyclic heteroaryl containing heteroatom N or S, unsubstituted phenyl and phenyl substituted by halogen, lower alkyl, lower alkoxy, trifluoromethyl or a group of-CN; R2represents hydrogen or a hydrocarbon containing 1-6 carbon atoms and selected from the group including: lower alkyl; substituted lower alkyl containing one Deputy, selected from the group comprising halogen and group OR20where R20is hydrogen; and (C3-8cycloalkyl; each of R4and R5, independently, selected from the group comprising hydrogen; lower alkyl; substituted lower alkyl containing from 1 to 2 substituents selected from the group comprising CN groups, OR20where R20is hydrogen or lower alkyl, NR20R23where R20is hydrogen, and R23is hydrogen, a CONH group2or lower alkyl, which is optionally substituted by a group HE, phenyl, substituted phenyl containing from 1 to 3 substituents selected from halogen and OR20, config group HE; each of the hydrocarbon contains from 1 to 12 carbon atoms.

20. 2,6,9-triple-substituted purine derivative under item 12, where R1’ is-CH2-phenyl, where the phenyl ring is optionally substituted with 1-2 substituents selected from the group comprising halogen, C1-3alkyl, trifluoromethyl, lower alkoxy, unsubstituted phenyl and phenyl substituted by halogen, lower alkyl, trifluoromethyl or a group of-CN; R2is isopropyl; each of R4and R5independently selected from the group comprising hydrogen; lower alkyl; substituted lower alkyl containing one Deputy, selected from the group comprising group OR20where R20is hydrogen or C1-2the alkyl, NR20R23where R20is hydrogen, and R23is hydrogen or C1-3by alkyl; C3-8cycloalkyl and C3-8cycloalkyl substituted by a group of IT, each of the hydrocarbon contains from 1 to 12 carbon atoms.

21. 2,6,9-triple-substituted purine derivative under item 12, where R1’ is chosen from the group comprising lower alkyl, substituted aryl or substituted by phenyl, unsubstituted pyridyl-(lower alkyl) and substituted pyridyl-(lower alkyl); R2selected from the group including bottom cyano, group OR20where R20is hydrogen, a group COR20and a group of CO2R20where R20is lower alkyl or aryl; and (C3-8cycloalkyl; R4selected from the group comprising substituted C2-6alkyl; R5selected from the group comprising hydrogen; lower alkyl; substituted lower alkyl; With3-8cycloalkyl and C3-8cycloalkyl substituted by a group of IT.

22. 2,6,9-triple-substituted purine derivative under item 8, where R1’ is benzyl, substituted with halogen, alkoxy, phenyl, peredelnoj or nitro-group; R2is isopropyl; R4=H; R5=CH2-CH2NH2.

23. 2,6,9-triple-substituted purine derivative under item 8, where R1’ is benzyl, substituted with halogen, alkoxy, phenyl, peredelnoj or nitrogroup, R2is isopropyl, R4=H, R5=CH2chr'NH2where R’ represents hydrogen or C1-6alkyl.

24. 2,6,9-triple-substituted purine derivative under item 8, where R1’ is benzyl, substituted with halogen, alkoxy, phenyl, peredelnoj or nitrogroup, R2is isopropyl; R4=H and R5=CH2CR'R NH2where R’ represents hydrogen or C1-6alkyl.

25. 2(trifluoromethyl)-phenyl]methyl}amino)purine-2-yl]amino}ethane-1-ol;

{[(2S)oxolan-2-yl)methyl](6-[{(4-forfinal)methyl}amino]-9-(methylethyl)purine-2-yl)amine;

[((2R)oxolan-2-yl)methyl](6-{[(4-forfinal)methyl]amino}-9-(methylethyl)purine-2-yl)amine;

(2-amino-ethyl)(6-{[3,5-dichlorophenyl)methyl]amino}-9-(methylethyl) purine-2-yl)amine;

(2-amino-ethyl)[6-({[4-chloro-3-(trifluoromethyl)phenyl]methyl}-amino)-9-(methylethyl)purine-2-yl]amine;

[[(6-{[(4-chlorophenyl)methyl]amino}-9-(methylethyl)purine-2-yl]amino]-3-methylbutanoic;

(2-amino-2-methylpropyl)(6-{[(4-chlorophenyl)methyl]amino}-9-(methylethyl)purine-2-yl)amine;

3-(2-[bis(2-hydroxyethyl)amino]-6-{[4-chlorophenyl)methyl]-amino} - purine-9-yl)butane-2-he;

2-[(6-{[(4-chlorophenyl)methyl]amino]-9-(methylethyl)purine-2-yl)amino]-3-methylbutane-1-ol;

4-[({2-[(2-aminoethyl)amino]-9-(methylethyl)purine-6-yl}-amino)methyl] benzosulfimide;

2-[(2-hydroxyethyl)(6-{[(4-methoxyphenyl)methyl]amino}-9-(methylethyl)purine-2-yl)amino]Ethan-1-ol;

2-((2-hydroxyethyl){9-(methylethyl)-6-[(4-phenylphenyl)amino]-purine-2-yl}amino)ethane-1-ol;

{2-[(2-amino-2-propyl)amino]-9-(methylethyl)purine-6-yl}-[(4-chlorophenyl)methyl]amine;

{2-[(2-amino-ethyl)amino]-9-(methylethyl)purine-6-yl}[(4-chlorophenyl)methyl]amine,

{2-[(2-aminopropyl)amino]-9-(methylethyl)purine-6-yl}[(4 - chlorophenyl)methyl]amine;

2-[(2-amino-ethyl)(6-{[(4-chlorophenyl)methyl]amino}-9-(methylethyl)purine-2-yl)amino]Ethan-1-ol.

26. 2,6, who, containing from 1 to 3 substituents selected from the group comprising halogen, nitro, lower alkyl, lower alkoxy, lower dialkoxy, phenyl, phenoxy, and replaced by a nitro-group is phenyl; unsubstituted pyridyl; pyridyl substituted by a group OR20where R20is lower alkyl; R2selected from the group comprising lower alkyl; substituted lower alkyl containing from 1 to 3 substituents selected from the group comprising halogen, cyano, a group, OR20where R20is hydrogen, a group COR20and a group of CO2R20where R20is lower alkyl or aryl; and (C3-8cycloalkyl; R4selected from the group comprising substituted C2-6alkyl; and R5selected from the group comprising hydrogen; lower alkyl; substituted lower alkyl; With3-8cycloalkyl and C3-8cycloalkyl substituted by a group of IT.

27. 2,6,9-triple-substituted purine derivative under item 12, where R1’ is chosen from the group comprising lower alkyl, substituted aryl or substituted by phenyl, unsubstituted pyridyl-(lower alkyl) and substituted pyridyl-(lower alkyl); R2selected from the group comprising lower alkyl; substituted lower alkyl containing from 1 to 3 substituents selected from the group comprising halogen, tzia is p> is lower alkyl or aryl; and (C3-8cycloalkyl, and each of R4and R5represents substituted C2-6alkyl.

28. 2,6,9-triple-substituted purine derivative under item 12, where R1’ is-CH2-aryl or-CH2-substituted phenyl, where substituted phenyl has 1 to 3 substituents selected from the group comprising halogen, nitro, lower alkyl, trifluoromethyl, lower alkoxy, 5-6-membered monocyclic heteroaryl containing heteroatom N or S, the group of SO2NR20R23where R20and R23are hydrogen, unsubstituted phenyl and phenyl substituted by halogen, lower alkyl, lower alkoxy, trifluoromethyl or a group of-CN; R2represents lower alkyl or substituted lower alkyl containing from 1 to 3 substituents selected from the group comprising halogen, cyano, a group, OR20where R20is hydrogen, a group COR20and a group of CO2R20where R20is lower alkyl or aryl; and each of R4and R5represents-CH2CH2OH, -chr'CH2OH or-CH2chr'OH, where R’ represents hydrogen or C1-6alkyl.

29. 2,6,9-triple-substituted purine derivative under item 12, where R1’ is-CH2-aryl or-CHLogin, nitro, lower alkyl, trifluoromethyl, lower alkoxy, 5-6-membered monocyclic heteroaryl containing heteroatom N or S, the group of SO2NR20R23where R20and R23are hydrogen, unsubstituted phenyl and phenyl substituted by halogen, lower alkyl, lower alkoxy, trifluoromethyl or a group of-CN; R2is lower alkyl; R4=H, a R5=-CH2CH2NH2, chr'CH2NH2or-CH2chr'NH2where R’ represents hydrogen or C1-6alkyl.

30. 2,6,9-triple-substituted purine derivative according to p. 29, where R2represents isopropyl.

31. 2,6,9-triple-substituted purine derivative under item 12, where R1’ is-CH2-aryl or-CH2-substituted phenyl, where substituted phenyl has 1 to 3 substituents selected from the group comprising halogen, nitro, lower alkyl, trifluoromethyl, lower alkoxy, 5-6-membered monocyclic heteroaryl containing heteroatom N or S, the group of SO2NR20R23where R20and R23are hydrogen, unsubstituted phenyl and phenyl substituted by halogen, lower alkyl, lower alkoxy, trifluoromethyl or a group of-CN; R2is lower alkyl; R4=-CH2CH2OH, a R5=-CH2CH2p>

32. 2,6,9-triple-substituted purine derivative on p. 31, where R2represents isopropyl.

33. 2,6,9-triple-substituted purine derivative on p. 28, where R2represents isopropyl.

34. 2,6,9-triple-substituted purine derivative under item 12, where R1’ are selected from the group including aryl, substituted phenyl containing from 1 to 3 substituents selected from the group comprising halogen, nitro, lower alkyl, lower alkoxy, lower dialkoxy, phenyl, phenoxy, and replaced by a nitro-group is phenyl; unsubstituted pyridyl; pyridyl substituted by a group OR20where R20is lower alkyl; R2selected from the group comprising lower alkyl; substituted lower alkyl containing from 1 to 3 substituents selected from the group comprising halogen, cyano, a group, OR20where R20is hydrogen, a group COR20and a group of CO2R20where R20is lower alkyl or aryl; and each of R4and R5is substituted With2-6alkyl.

35. 2,6,9-triple-substituted purine derivative under item 12, where R1’ is aryl or substituted phenyl containing from 1 to 3 substituents selected from the group comprising halogen, nitro, lower alkyl, lower alkoxy, lower dialkoxy, phenyl, phenoxy, and someseni is stitely, selected from the group comprising halogen, cyano, a group, OR20where R20is hydrogen, a group COR20and a group of CO2R20where R20is lower alkyl or aryl;

and each of R4and R5is CH2CH2HE HR'CH2OH or-CH2chr'OH, where R’ represents hydrogen or C1-6alkyl.

36. 2,6,9-triple-substituted purine derivative on p. 35, where R2represents isopropyl.

37. 2,6,9-triple-substituted purine derivative under item 12, where R1’ is benzyl, substituted with halogen, lower alkoxy, phenyl, pyridium or nitro-group; R2represents isopropyl, and each of R4and R5represents-CH2CH2HE.

38. 2,6,9-triple-substituted purine derivative under item 12, where R1’ is benzyl, substituted with halogen, lower alkoxy, phenyl, pyridium or nitrogroup, R2is isopropyl, R4=H, a R5=CH2CH2NH2.

39. 2,6,9-triple-substituted purine derivative under item 12, where R1’ is benzyl, substituted with halogen, lower alkoxy, C1-3the alkyl, CF3, phenyl, pyridium or nitrogroup, R2is isopropyl, R4=H, a R5=CH2chr'NH2, g ’ represents benzyl, substituted with halogen, lower alkoxy, C1-3the alkyl, CF3, phenyl, pyridium or nitrogroup, R2is isopropyl, R4=H, a R5=CH2CR'R NH2where R’ represents hydrogen or C1-6alkyl.

41. 2,6,9-triple-substituted purine derivative under item 1, selected from the group comprising 2-{(2-hydroxyethyl)[9-(methylethyl)-6-({[4-(trifluoromethyl)-phenyl]methyl}amino)purine-2-yl]amino}ethane-1-ol,

[((2S)oxolan-2-yl)methyl](6-[{(4-forfinal)methyl}amino]-9-(methylethyl)purine-2-yl)amine;

[((2R)oxolan-2-yl)methyl](6-{[(4-forfinal)methyl]amino}-9-(methylethyl)purine-2-yl)amine;

(2-amino-ethyl)(6-{[3,5-dichlorophenyl)methyl]amino}-9-(methylethyl)purine-2-yl)amine;

(2-amino-ethyl)[6-({[4-chloro-3-(trifluoromethyl)phenyl]methyl}-amino)-9-(methylethyl)purine-2-yl]amine;

[(6-{[(4-chlorophenyl)methyl]amino}-9-(methylethyl)purine-2-yl)amino]-3-methylbutanoic;

(2-amino-2-methylpropyl)(6-{[(4-chlorophenyl)methyl]amino}-9-(methylethyl)purine-2-yl)amine;

3-(2-[bis(2-hydroxyethyl)amino]-6-{[(4-chlorophenyl)methyl]-amino} - purine-9-yl}butane-2-he;

2-[(6-{[(4-chlorophenyl)methyl]amino}-9-(methylethyl)purine-2-yl)amino]-3-methylbutane-1-ol;

4-[({2-[(2-aminoethyl)amino]-9-(methylethyl)purine-6-yl}-amino)methyl] benzosulfimide;

2-[(2-hydroxyethyl)(6-{[(4-methoxyphenyl)methyl]amino}-9-(methylethyl)purine-2-yl)Amin who drank)amino]-9-(methylethyl)purine-6-yl}-[(4-chlorophenyl)methyl]amine;

{2-[(2-amino-ethyl)amino]-9-(methylethyl)purine-6-yl}[(4-chlorophenyl)methyl]amine;

{2-[(2-aminopropyl)amino]-9-(methylethyl)purine-6-yl}[(4-chlorophenyl)methyl]amine and

2-[(2-amino-ethyl)(6-{[(4-chlorophenyl)methyl]amino}-9-(methylethyl)purine-2-yl)amino]Ethan-1-ol.

42. 2,6,9-triple-substituted purine derivative under item 12, where R1’ is phenyl, substituted by halogen, lower alkoxy, phenyl or nitro-group; R2represents isopropyl, and each of R4and R5represents-CH2CH2HE.

43. 2,6,9-triple-substituted purine derivative under item 12, where R1’ is biphenylyl; R2represents isopropyl, and each of R4and R5represents-CH2CH2HE.

44. 2,6,9-triple-substituted purine derivative under item 12, where R1’ is chosen from the group comprising 3-dimethoxyphenyl, 4-dimethoxyphenyl, 4-bromophenyl, 4-phenylbenzyl, 4-methoxybenzyl, 4-biphenyl, 3-methoxybenzyl, 4-(2-thienyl)benzyl, 4-(4-methyl)phenylbenzyl, 4-(4-trifluoromethyl)phenylbenzyl, 4-(4-nitrilo)phenylbenzyl, 4-(2-pyridinyl)benzyl, piperonyl, 3-methoxybenzyl, 4-Chlorobenzyl and 4-nitrobenzyl; R2is isopropyl, a R4and R5both represent-CH2CH2HE.

45. 2,6,9-triple-substituted purine derivative according to p. 44, where R1’ viil)phenylbenzyl, 4-(4-trifluoromethyl)-phenylbenzyl, 4-(4-nitrilo)phenylbenzyl, 4-(2-pyridinyl)benzyl, piperonyl, 3-dimethoxyphenyl, 4-dimethoxyphenyl and 4-bromophenyl.

46. Pharmaceutically acceptable cationic salt of the compound under item 1.

47. Pharmaceutically acceptable acid additive salt of the compound under item 1.

48. Method of inhibiting cell proliferation in mammals comprising the administration to a mammal a therapeutically effective amount of one or more compounds on p. 1.

49. The method according to p. 48, where therapeutically effective amount is from about 0.001 to 100 mg/kg weight of the mammal.

50. The method according to p. 48, where the compound is administered to a mammal suffering from a disorder that is associated with cell proliferation and which is a cancer.

51. The method according to p. 50, where the mammal is man.

52. The pharmaceutical composition inhibiting the proliferation of cells containing one or more compounds on p. 1 and one or more pharmaceutical carriers.

 

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< / BR>
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< / BR>
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< / BR>
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< / BR>
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< / BR>
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< / BR>
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< / BR>
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< / BR>
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< / BR>
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< / BR>
< / BR>
< / BR>
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< / BR>
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