Purine derivatives as a2a receptor agonists

FIELD: chemistry.

SUBSTANCE: invention relates to novel purine derivatives of general formula I in free form or in form of a pharmaceutically acceptable salt which have A2A agonist properties. In formula I , R1 denotes a N-bonded 5-6-member heterocyclic group containing 1-4 nitrogen atoms in the ring, which can be optionally substituted with oxo, phenyl or C1-8-alkyl, optionally substituted with hydroxy; R2 is hydrogen or C1-C8-alkyl, optionally substituted with hydroxy or 1-2 phenyls possibly substituted with hydroxy or C1-C8-alkoxy; R3 is C2-C8-alkynyl or C1-C8-alkoxycarbonyl, or R3 is amino substituted with C3-C8-cycloalkyl, optionally substituted with amino, hydroxy, benzyloxy or NH-C(=O)-NH-R6, or R3 is amino substituted with R4, -R4-benzyl or C5-C10-mono- or bicarbocyclic group, optionally substituted with hydroxy or C1-C8-alkoxycarbonyl, or R3 is aminocarbonyl optionally substituted with R5, or R3 is C1-C8-alkylamino optionally substituted with hydroxy, R5, NH-C(=O)-C1-C8-alkyl, -MH-SO2-C1-C8-alkyl, -NH-C(=O)-NH-R6 or phenyl, optionally substituted with phenyloxy, or R3 is a N-bonded 5-member heterocyclic group containing 1 nitrogen atom in the ring which may optionally be substituted with amino, C1-C8-alkylamino, di(C1-C8-alkyl)amino and other groups.

EFFECT: compounds can be useful in treating conditions mediated by activation of the adenosine A2A receptor, especially inflammatory or obstructive respiratory tract diseases.

9 cl, 5 tbl, 161 ex

 

The text descriptions are given in facsimile form.

1. The compound of formula I:

in free form or in the form of pharmaceutically acceptable salts, where
R1denotes the N-linked 5-6-membered heterocyclic group containing 1 to 4 nitrogen atoms in the cycle, which optionally may be substituted by oxo, phenyl or1-C8-alkyl, optionally substituted by hydroxy;
R2represents hydrogen or C1-C8-alkyl, optionally substituted by hydroxy or 1-2 fenelli, possibly substituted by hydroxy or C1-C8-alkoxy;
R3represents a C2-C8-quinil or C1-C8-alkoxycarbonyl,
or R3represents amino, substituted C2-C8-cycloalkyl, optionally substituted amino, hydroxy, benzyloxy, or-NH-C(=O)-NH-R6,
or R3represents amino, substituted R4, -R4the benzyl or5-C10-mono - or beerbottles group, optionally substituted by hydroxy or C1-C8-alkoxycarbonyl,
or R3is aminocarbonyl, optionally substituted R5,
or R3represents a C1-C8-alkylamino, optionally substituted hydroxy, R5, -NH-C(=O)-C1-C8-alkyl, -NH-SO2-C1-C8-alkyl, -NH-C(=O)-NH-R6or phenyl, optionally substituted, phenyloxy,
or R3pre is is a N-linked 5-membered heterocyclic group, containing 1 nitrogen atom in the cycle, which optionally may be substituted by amino, C1-C8-alkylamino, di(C1-C8-alkyl)amino, R4, -R4-C(=O)-benzyloxy, -NH-C(=O)-NH-R6, -NH-C(=O)-C1-C8-alkoxy, -NH-C(=O)-C3-C8-cycloalkyl, -NH-SO2-C1-C8-alkyl, -NH-C(=O)-NH-C1-C4-alkyl-R4, -NH-C(=O)-NH-C1-C4-alkyl-R4-phenyl, -NH-C(=O)-NH-C1-C4-alkyl-di(C1-C4-alkyl)amino, -NH-C(=O)-NH-phenyl-R4, -NH-C(=O)-NH-phenyl-SO2NH2or-NH-C(=O)-NH-phenyl-C1-C4-alkyl, optionally substituted by hydroxyl, carboxy, -C(=NH)NH2or1-C4-alkoxycarbonyl,
or R3represents a C1-C8-alkylaminocarbonyl or3-C8-cycloalkylcarbonyl, in each case optionally substituted amino, -NH-C(=O)-di(C1-C8-alkyl)amino, -NH-C(=O)-C1-C4-alkyl-di(C1-C4-alkyl)amino, -NH-C(=O)-NH-R6, -NH-C(=O)-NH-C1-C8-alkyl, -NH-C(=O)-NH-C1-C4-alkylphenyl, optionally substituted by hydroxyl, carboxy, -C(=NH)NH2or1-C4-alkoxycarbonyl,
R4and R5each independently represents a 5-6-membered heterocyclic group containing one or two heteroatoms in the cycle, selected from nitrogen and oxygen; and
R6 represents 5 - or 6-membered heterocyclic group containing one or two heteroatoms in the cycle selected from nitrogen, oxygen and sulfur, which optionally may be substituted 5 - or 6-membered heterocyclic group containing a nitrogen atom in the cycle.

2. The compound according to claim 1, where
R1denotes the N-linked 5-6-membered heterocyclic group containing 1 to 4 nitrogen atoms in the cycle, which optionally may be substituted by oxo, phenyl or C1-C8-alkyl, optionally substituted by hydroxy;
R2represents hydrogen or C1-C8-alkyl, optionally substituted at one or two positions hydroxy or phenyl, optionally substituted at one or two positions hydroxy;
R3represents a C2-C8-quinil or C1-C8-alkoxycarbonyl,
or R3represents amino, substituted C3-C8-cycloalkyl, optionally substituted amino, hydroxy, benzyloxy, or-NH-C(=O)-NH-R6,
or R3represents amino, substituted R4, -R4the benzyl or5-C10-mono - or beerbottles group, optionally substituted by hydroxy or C1-C8-alkoxycarbonyl,
or R3is aminocarbonyl, optionally substituted R5,
or R3presented yet a C 1-C8-alkylamino, optionally substituted hydroxy, R5, -NH-C(=O)-C1-C8-alkyl, -NH-SO2-C1-C8-alkyl, -NH-C(=O)-NH-R6or phenyl, optionally substituted, phenyloxy,
or R3is a N-linked 5-membered heterocyclic group containing 1 nitrogen atom in the cycle, which optionally may be substituted by amino, di(C1-C8-alkyl)amino, R4, -R4-C(=O)-benzyloxy, -NH-C(=O)-NH-R6, -NH-C(=O)-C1-C8-alkoxy, -NH-C(=O)-C3-C8-cycloalkyl, -NH-SO2-C1-C8-alkyl, -NH-C(=O)-NH-C1-C4-alkyl-R4, -NH-C(=O)-NH-C1-C4-alkyl-R4-phenyl, -NH-C(=O)-NH-C1-C4-alkyl-di(C1-C4-alkyl)amino, -NH-C(=O)-NH-phenyl-R4, -NH-C(=O)-NH-phenyl-SO2NH2or-NH-C(=O)-NH-phenyl-C1-C4-alkyl, optionally substituted by hydroxyl, carboxy, -C(=NH)NH2or1-C4-alkoxycarbonyl,
or R3represents a C1-C8-alkylaminocarbonyl or3-C8-cycloalkylcarbonyl, in each case optionally substituted amino, -NH-C(=O)-di(C1-C8-alkyl)amino, -NH-C(=O)-C1-C4-alkyl-di(C1-C4-alkyl)amino, -NH-C(=O)-NH-R6, -NH-C(=O)-NH-C1-C8-alkyl or-NH-C(=O)-NH-C1-C4-alkylphenyl;
R4and R5is each independently represents a 5-6-membered heterocyclic group, containing one or two heteroatoms in the cycle, selected from nitrogen and oxygen; and
R6represents 5 - or 6-membered heterocyclic group containing one or two heteroatoms in the cycle selected from nitrogen, oxygen and sulfur, which optionally may be substituted 5 - or 6-membered heterocyclic group containing one nitrogen atom in the cycle.

3. The compound according to claim 2, where
R1denotes the N-linked 5-6-membered heterocyclic group containing 1 to 4 nitrogen atoms in the cycle, which optionally may be substituted by oxo, phenyl, stands, ethyl or stands, substituted hydroxy;
R2represents hydrogen or C1-C8-alkyl, optionally substituted at one or two positions hydroxy or phenyl, optionally substituted at one or two positions hydroxy;
R3represents a C2-C6-quinil or1-C4-alkoxycarbonyl,
or R3represents amino, substituted C3-C6-cycloalkyl, optionally substituted amino, hydroxy, benzyloxy, or-NH-C(=O)-NH-R6,
or R3represents amino, substituted R4, -R4the benzyl or5-C10-mono - or beerbottles group, optionally substituted by hydroxy or C1-C4-alkoxycarbonyl,
or R3is Soboh aminocarbonyl, optionally substituted R5,
or R3represents a C1-C4-alkylamino, optionally substituted hydroxy, R5, -NH-C(=O)-C1-C4-alkyl, -NH-SO2-C1-C4-alkyl, -NH-C(=O)-NH-R6or phenyl, optionally substituted, phenoxy,
or R3is a N-linked 5-membered heterocyclic group containing 1 nitrogen atom in the cycle, which optionally may be substituted by amino, di(C1-C4-alkyl)amino, R4, -R4-C(=O)-benzyloxy, -NH-C(=O)-NH-R6, -NH-C(=O)-C1-C4-alkoxy, -NH-C(=O)-C3-C6-cycloalkyl, -NH-SO2-C1-C4-alkyl, -NH-C(=O)-NH-C1-C4-alkyl-R4, -NH-C(=O)-NH-C1-C4-alkyl-R4-phenyl, -NH-C(=O)-NH-C1-C4-alkyl-di(C1-C4-alkyl)amino, -NH-C(=O)-NH-phenyl-R4, -NH-C(=O)-NH-phenyl-SO2NH2or-NH-C(=O)-NH-phenyl-C1-C4-alkyl, optionally substituted by hydroxyl, carboxy, -C(=NH)NH2or1-C4-alkoxycarbonyl,
or R3represents a C1-C4-alkylaminocarbonyl or3-C6-cycloalkylcarbonyl, in each case optionally substituted amino, -NH-C(=O)-di(C1-C4-alkyl)amino, -NH-C(=O)-C1-C4-alkyl-di(C1-C4-alkyl)amino, -NH-C(=O)-NH-R6, -NH-C(=O)-NH-C1-C4-what Kilom or-NH-C(=O)-NH-benzyl;
R4and R5each independently represents a 5-6-membered heterocyclic group containing one or two heteroatoms in the cycle, selected from nitrogen and oxygen; and
R6represents 5 - or 6-membered heterocyclic group containing one or two heteroatoms in the cycle selected from nitrogen, oxygen and sulfur, which optionally may be substituted 5 - or 6-membered heterocyclic group containing a nitrogen atom in the cycle.

4. The compound according to claim 1, where
R1denotes the N-linked 5-6-membered heterocyclic group containing 1 to 4 nitrogen atoms in the cycle, which optionally may be substituted by oxo, phenyl or C1-C8-alkyl, optionally substituted by hydroxy;
R2represents hydrogen or C1-C8-alkyl, optionally substituted by hydroxy or phenyl;
R3represents a C2-C8-quinil or C1-C8-alkoxycarbonyl,
or R3represents amino, substituted C3-C8-cycloalkyl, optionally substituted amino, hydroxy, benzyloxy, or-NH-C(=O)-NH-R6,
or R3represents amino, substituted C5-C10-mono - or beerbottles group, optionally substituted by hydroxy or C1-C8-alkoxycarbonyl,
or R3is aminocarbonyl, obazatelno substituted R 5,
or R3represents a C1-C8-alkylamino, optionally substituted hydroxy, R5, -NH-C(=O)-C1-C8-alkyl, -NH-SO2-C1-C8-alkyl, -NH-C(=O)-NH-R6or phenyl, optionally substituted, phenyloxy,
or R3is a N-linked 5-membered heterocyclic group containing 1 nitrogen atom in the cycle, which optionally may be substituted by amino, C1-C8-alkylamino, di(C1-C8-alkyl)amino, -NH-C(=O)-NH-R6, -NH-C(=O)-NH-phenyl-C1-C4-alkyl,
or R3represents a C1-C8-alkylaminocarbonyl or3-C8-cycloalkylcarbonyl, in each case optionally substituted amino, -NH-C(=O)-NH-R6, -NH-C(=O)-NH-C1-C4-alkylphenyl,
R4and R5each independently represents a 5-6-membered heterocyclic group containing at least one heteroatom in the cycle selected from the group consisting of nitrogen and oxygen; and
R6represents 5 - or 6-membered heterocyclic group containing one or two heteroatoms in the cycle selected from nitrogen, oxygen and sulfur, which optionally may be substituted 5 - or 6-membered heterocyclic group containing a nitrogen atom in the cycle.

5. The compound according to claim 4, where
R1denotes the N-linked 5-6-membered hetero is clichesque group, containing 1 to 4 nitrogen atoms in the cycle, which optionally may be substituted by oxo, phenyl or1-C8-alkyl, optionally substituted by hydroxy;
R2represents hydrogen or C1-C8-alkyl, optionally substituted by hydroxy or phenyl;
R3represents a C2-C8-quinil or C1-C8-alkoxycarbonyl,
or R3represents amino, substituted C3-C8-cycloalkyl, optionally substituted amino, hydroxy, benzyloxy, or-NH-C(=O)-NH-R6,
or R3represents amino, substituted C5-C10-mono - or beerbottles group, optionally substituted by hydroxy or C1-C8-alkoxycarbonyl,
or R3is aminocarbonyl, optionally substituted R5,
or R3represents a C1-C8-alkylamino, optionally substituted hydroxy, R5, -NH-C(=O)-C1-C8-alkyl, -NH-SO2-C1-C8-alkyl, -NH-C(=O)-NH-R6or phenyl, optionally substituted, phenyloxy,
or R3is a N-linked 5-membered heterocyclic group containing 1 nitrogen atom in the cycle, which optionally may be substituted by amino or-NH-C(=O)-NH-R6,
or R3represents a C1-C8-alkylaminocarbonyl optionally substituted amino, -NH-C(=O)-NH-R6or-NH-C(=O)-NH-C1-C4-alkylphenyl;
R5is a 5-6-membered heterocyclic group containing one or two heteroatoms in the cycle, selected from nitrogen and oxygen; and
R6represents 5 - or 6-membered heterocyclic group containing one or two heteroatoms in the cycle selected from nitrogen, oxygen and sulfur, which optionally may be substituted 5 - or 6-membered heterocyclic group containing a nitrogen atom in the cycle.

6. The compound according to claim 5, in which:
R1denotes the N-linked 5-6-membered heterocyclic group containing 1 to 4 nitrogen atoms in the cycle, which optionally may be substituted by oxo, phenyl or1-C4-alkyl, optionally substituted by hydroxy;
R2represents hydrogen or C1-C4-alkyl, optionally substituted by hydroxy or phenyl; and
R3represents a C2-C6-quinil or1-C4-alkoxycarbonyl, or R3represents amino, substituted C3-C6-cycloalkyl, optionally substituted amino, hydroxy, benzyloxy, or-NH-C(=O)-NH-R6,
or R3represents amino, substituted C5-C10-mono - or beerbottles group, optionally substituted by hydroxy or C1-C4-alkoxycarbonyl,
or R is aminocarbonyl, optionally substituted R5,
or R3represents a C1-C4-alkylamino, optionally substituted hydroxy, R5, -NH-C(=O)-C1-C4-alkyl, -NH-SO2-C1-C4-alkyl, -NH-C(=O)-NH-R6or phenyl, optionally substituted, phenyloxy,
or R3is pyrrolidinyl, optionally substituted amino,
or R3is a N-linked 5-membered heterocyclic group containing 1 nitrogen atom in the cycle, which is optionally substituted amino or-NH-C(=O)-NH-R6,
or R3represents a C1-C4-alkylaminocarbonyl, optionally substituted amino, -NH-C(=O)-NH-R6or-NH-C(=O)-NH-C1-C4-alkylphenyl;
R5is a 5-6-membered heterocyclic group containing one or two heteroatoms in the cycle, selected from nitrogen and oxygen; and
R6represents 5 - or 6-membered heterocyclic group containing one or two heteroatoms in the cycle selected from nitrogen, oxygen and sulfur, which optionally may be substituted 5 - or 6-membered heterocyclic group containing a nitrogen atom in the cycle.

7. The compound according to any one of the preceding paragraphs, with agonistic action on adenosine receptor (A2Aintended for the Holocene medicines.

8. Pharmaceutical composition having agonistic action on the adenosine receptor And2Acomprising as active ingredient a compound according to any one of claims 1 to 6 in an effective amount together with a pharmaceutically acceptable diluent or carrier.

9. The use of compounds according to any one of claims 1 to 6 to obtain a medicinal product intended for the treatment of condition mediated by activation of the receptor adenosine A2A.



 

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18 cl, 13 ex

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16 cl, 8 dwg, 4 tbl, 525 ex

Comt inhibitors // 2354655

FIELD: chemistry.

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17 cl, 19 ex, 1 tbl

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10 cl, 10 dwg, 9 tbl, 14 ex

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18 cl, 138 tbl, 527 ex

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The invention relates to new compounds of General formulas I, II, III

< / BR>
or their pharmaceutically acceptable salts, in which the dotted lines indicate optional double bonds; A is-CR7or N; - - NR1R2, -CR1R2R11, -C(= CR2R12R1, -NHCHR1R2, -ОСHR1R2, -SCHR1R2, -CHR2OR12,

-CHR2SR12, -C(S)R2or-C(O)R2N-ethyl-2,2,2-triptorelin; G is oxygen, sulfur, NH, NH3hydrogen, methoxy, ethoxy, triptoreline, methyl, ethyl, dimethoxy, NH2, NHCH3N(CH3)2or trifluoromethyl; Y Is N; Z is NH, O, S, -N(C1-C2alkyl) or-C(R13R14), where R13and R14independently of one another represent hydrogen, trifluoromethyl or methyl, or one of the elements of R13and R14is cyano and the other is hydrogen or stands; R1- C1-C6alkyl which may be optionally substituted by one or two substituents R8independently from each other selected from the group comprising hydroxy, fluorine, chlorine, bromine, iodine, CF3C1-C4alkoxy, -O-CO-(C1-C4alkyl), where (C1-C2- C1-C12alkyl, aryl or -(C1-C4alkylene)aryl, where aryl is phenyl, naphthyl; R3is methyl, ethyl, fluorine, chlorine, bromine, iodine, cyano, methoxy, OCF3, methylthio, methylsulphonyl, CH2HE or CH2OCH3; R4is hydrogen, C1-C4alkyl, fluorine, chlorine, bromine, iodine, C1-C4alkoxy, triptoreline, -CH2OCH3, -CH2OCH2CH3, -CH2CH2OCH3, -CF3, amino, nitro, -NH(C1-C4alkyl), -N(CH3)2, -NHCOCH3, -NHCONHCH3, hydroxy, -CO(C1-C4alkyl), -Cho, COOH, cyano, or-COO(C1-C4alkyl), where C1-C4the alkyl may be substituted by one Deputy chosen from the group comprising hydroxy, amino, -NHCOCH3, -NH(C1-C2alkyl), -N(C1-C2alkyl)2, fluorine, chlorine, cyano, nitro; R5is phenyl, naphthyl, pyridyl, pyrimidyl, where each of the above groups R5substituted with one to three substituents that are independently from each other selected from fluorine, chlorine, C1-C6the alkyl or C1-C6alkoxyl, or one Deputy chosen from the group comprising hydroxy, iodine, bromine, formyl, cyano, nitro, trifluoromethyl, amino, -(C1-C6these groups of R5may be optionally substituted with one hydroxy-group; R6is hydrogen or C1-C6alkyl; R7is hydrogen, methyl; R11is hydrogen, hydroxy, fluorine or methoxy; R12is hydrogen or C1-C4alkyl, and R16and R17independently of one another represent hydrogen, hydroxy, methyl, ethyl, methoxy or ethoxy, except that both R16and R17cannot both be methoxy or ethoxy; or R16and R17together form oxo (=O) group; provided that if G is an atom of oxygen, sulfur, NH or NCH3he is joined by a double bond to a five-membered ring of the formula III, and further provided that R6is absent when the nitrogen atom to which it is linked, is attached by a double bond to an adjacent carbon atom in the ring

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, etc

FIELD: organic chemistry, heterocyclic compounds, biochemistry.

SUBSTANCE: invention relates to new compounds - purine derivatives of the general formula (I): in free form or salt wherein X means oxygen or sulfur atom or group NR5; R1 means alkyl, alkenyl, cycloalkyl, benzocycloalkyl, cycloalkylalkyl or aralkyl group that can be substituted optionally with hydroxy-, carboxy-group or alkoxycarbonyl; or if X means NR5 then R1 can mean alternatively heterocyclic group taken among benzylpiperidyl or the formula: ; or group of the formula (II): ; R2 means hydrogen atom, alkyl or alkoxy-group; R3 means hydrogen atom, alkoxy-, carboxy-group, carboxyalkyl, alkoxycarbonyl, -N(R9)R10, (C1-C4)-alkylene-SO2N(R11)R12 or -CON(R13)R14; or if two substitutes R2 and R3 are joined to adjacent carbon atoms in indicated benzene ring then in common with carbon atoms to which they are joined they mean heterocyclic group comprising 5-10 ring atoms among them one or two atoms mean heteroatoms taken among nitrogen, oxygen and sulfur atom; R4 means hydrogen atom, alkoxy-, carboxy-group, carboxyalkyl, -SO2N(R11)R12, -N(R9)R10 or -CON(R13)R14; or if two substitutes R3 and R4 are joined to adjacent carbon atoms in indicated benzene ring then in common with carbon atoms to which they are joined they mean heterocyclic group comprising 5-6 ring atoms among them one or two atoms mean heteroatoms taken among nitrogen, oxygen or sulfur atom; R5 means hydrogen atom or alkyl; R6, R7 and R8 mean hydrogen atom, or one of these radicals means -SO2NH2, -N(CH3)COCH3, -CONH2 and two others mean hydrogen atom; R9 means hydrogen atom or alkyl; R10 means hydrogen atom, -COR15 wherein R15 means alkyl, alkoxy-group; or R9 and R10 in common with nitrogen atom to which they are joined mean heterocyclic group comprising 5 or 6 ring atoms among them one or two atoms mean heteroatoms taken among nitrogen and oxygen atom; R11 means hydrogen atom or alkyl; R12 means hydrogen atom, alkyl, hydroxyalkyl, carboxyalkyl or alkoxycarbonylalkyl; or R11 and R12 in common with nitrogen atom to which they are joined mean heterocyclic group comprising 5 or 6 ring atoms among them one or two atoms mean heteroatoms taken among nitrogen and oxygen atom; R13 and R14 each and independently of one another means hydrogen atom or alkyl with exception of 2-(para-n-butylanilino)-6-methoxypurine, 2-(para-n-butylanilino)-6-(methylthio)purine, 2,6-di-(phenylamino)-purine, 2,6-di-(para-tolylamino)-purine and 2-(para-tolylamino)-6-(phenylamino)-purine.

EFFECT: valuable biochemical properties of compounds.

11 cl, 4 tbl, 221 ex

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, etc

The invention relates to new compounds of General formula I

< / BR>
where R is chosen from the group comprising R2, R2NH - or R3R4N-R5-, where R2selected from the group including9-C12-alkyl,

< / BR>
and

< / BR>
where each R6independently selected from the group including hydrogen, C3-C8-cycloalkyl,1-C4-alkyl and (CH2)m-phenyl, where m = integer 0-8; x = 1-8 integer; n = 0-8 integer; z is chosen from the group comprising phenyl, heterocycle, cycloalkyl and naphthalene, and M is chosen from the group comprising hydrogen, C1-C4-alkyl,

< / BR>
and

< / BR>
where each R6' are independently selected from the group including hydrogen, C3-C8-cycloalkyl,1-C4-alkyl and (CH2)m-phenyl, where m' = integer 0-8; n' = integer 0-8; x' = 1-8 integer; Q is hydrogen or C1-C4-alkyl, and Z' is chosen from the group comprising phenyl, heterozygote selected from the group including D, E,

< / BR>
and

< / BR>
where each D is independently selected from the group comprising trifluoromethyl, triptoreline and C1-C4-alkoxy; each E is independently selected from the group including Hal, HE and1-C8-alkyl; Z is chosen from the group comprising phenyl, cycloalkyl and naphthalene; each R6"is hydrogen, n = integer 0-8; x" = 1-8 integer, and M' is hydrogen, Z' may be optionally substituted by groups D', E', each D' is independently selected from the group comprising trifluoromethyl, triptoreline and C1-C4-alkoxy; each E' is independently selected from the group including Hal, HE and1-C8-alkyl; R3and R4selected from the group including hydrogen, C1-C4-alkyl and (CH2)y-phenyl, where y = 0-8 integer, provided that R3and R4both denote hydrogen; R5- C1-C8-alkylene and R1selected from the group including cyclopentyl, cyclopentenyl and isopropyl, and their pharmaceutically acceptable salts, optical isomers and hydrates, provided that when R2refers to a group

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

< / BR>
where D, b, R6", x", n", M' and Z" accept above values

the method of treatment of a patient with proliferative disorders by assigning the compounds I, the method of preventing apoptosis of nerve cells, ways of protecting nerve cells from apoptosis and destruction caused by antitumor agents, and pharmaceutical composition

The invention relates to new derivatives of purine of formula I, II, III and IV, pharmaceutical compositions and method of treatment of a pathological state characterized by thrombotic activity

The invention relates to new compounds of General formula I, in which R is selected from the group consisting of R2, R2NH or H2N-R3 where R2 is selected from the group consisting of C1-C8the alkyl and formula (II), where Z is selected from the group consisting of phenyl, heterocycle and cycloalkyl, each R4 independently represents hydrogen or C1-C4alkyl, and n is an integer equal to 1 to 8; where each1-C8alkyl, and Z optionally substituted by 1-3 substituents, which may be the same or different, selected from the group consisting of Hal, HE and1-C4of alkyl; R3 represents C1-C8alkylene; and R1 is selected from the group consisting of cyclopentyl and isopropyl, and their pharmaceutically acceptable salts, optical isomers and hydrates

The invention relates to a method for producing analogues of nucleosides dimethoxyaniline
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