Cyclic bioisosteres of purine system derivatives and use thereof in therapy

FIELD: chemistry.

SUBSTANCE: invention relates to a cyclic bioisostere of purine system derivatives, with general structural formula given below , where R = , Li, Na or K, R1 = -H, -NH2, -Br, -Cl, -OH, -COOH; A = -N- for B=-N=, Z = -CH-; A = -CH= for B = -N=, Z = -CH-; A = -CH= for B = -N=, Z = -N=; A = -CH= for B = -CH=, Z - -CH=; A = -CH= for B = -CH=, Z = -N=, except compounds in which A = -CH= for B = -CH=, Z = -CH=, R= Li, Na or K and R1= -NH2 in the 5th position of the benzo[d]-3H-pyridazine-1,4-dione nucleus, and its pharmacologically acceptable salts, with normalising effect on intracellular processes.

EFFECT: obtaining compounds which can be used for normalising intracellular processes in therapy of disorders, caused by intracellular acidosis and/or oxygen deficiency and/or excess formation of free radicals and/or excess formation of free radical forms of oxygen and/or high thrombocyte aggregation and/or erythrocytes and/or adverse effects and/or nitrergic cell mechanism disorder.

17 cl, 14 tbl, 15 dwg

 

The text descriptions are given in facsimile form.

1. Cyclic bioisostere purine derivatives of the system having the General structural formula
,
where R=the atom of Li, Na or K,
R1=-N, -NH2, -Br, -Cl, -OH, -COOH,
In=-N=, -CH=, Z=-CH=, -N=,
A=-N==-N=, Z=-CH-,
A=-CH= at=-N=, Z=-CH-,
A=-CH= at=-N=, Z=, N=,
A=-CH==CH=, Z=-CH=,
A=-CH==CH=, Z=, N=,
with the exception of compounds in which A=-CH==CH=, Z=-CH=, R=Li, Na or K and R1=-NH2in the 5th position of the benzo[d]-3H-pyridazine-1,4-dinonogo kernel
and its pharmacologically acceptable salts, has a normalizing effect on intracellular processes.

2. The compound according to claim 1, characterized in that it is derived pyrido[2,3-d]-6N-pyridazine-5,8-dione, having the General formula
,
where R=the atom of Li, Na or K,
R1=-N, -NH2, -Br, -OH, -COOH.

3. The compound according to claim 1, wherein selected from the group including:
7-(β-D-ribofuranosyl)pyrido[2,3-d]-6N-pyridazine-5,8-dione sodium salt (1),
4-amino-7-(β-D-ribofuranosyl)pyrido[2,3-d]-6N-pyridazine-5,8-dione sodium salt (2),
3-bromo-7-(β-D-ribofuranosyl)pyrido[2,3-d]-6N-pyridazine-5,8-dione sodium salt (3),
4-hydroxy-7-(β-D-ribofuranosyl)pyrido[2,3-d]-6N-pyridazine-5,8-dione disodium salt (4),
3-carboxy-7-(β-D-ribofuranosyl)pyrido[2,3-d]-6N-pyridazine-5,8-dione disodium salt (5),
pyrido [2,3-d]-6N-pyridazine-5,8-dione lithium salt (6),
pyrido [2,3-d]-6N-pyridazine-5,8-dione sodium salt (7),
pyrido [2,3-d]-6N-pyridazine-5,8-dione potassium salt (8).

4. The compound according to claim 1, characterized in that it is derived from benzo[d]-3H-pyridazine-1,4-dione, having the General formula
,
where R=the atom of Li, Na or K,
R1=-H, -Cl, -OH, -COOH.

5. The compound according to claim 1, wherein selected from the group including:
2-(β-D-ribofuranosyl)benzo[d]-3H-pyridazine-1,4-dione sodium salt (9),
5-amino-2-(β-D-ribofuranosyl)benzo[d]-3H-pyridazine-1,4-dione sodium salt (10),
6-amino-2-(β-D-ribofuranosyl)benzo[d]-3H-pyridazine-1,4-dione sodium salt (11),
5-chloro-2-(β-D-ribofuranosyl)benzo[d]-3H-pyridazine-1,4-dione sodium salt(12),
5-hydroxy-2-(β-D-ribofuranosyl)benzo[d]-3H-pyridazine-1,4-dione disodium salt (13),
6-amino-benzo[d]-3H-pyridazine-1,4-dione potassium salt (16),
5-hydroxy-benzo[d]-3H-pyridazine-1,4-dione disodium salt (17),
6-carboxy-benzo[d]-3H-pyridazine-1,4-dione disodium salt (18).

6. The compound according to claim 1, characterized in that it is derived pyrazino[2,3-d]-6N-pyridazine-5,8-dione, having the General formula
,
where R=the atom of Li, Na or K,
R1=-N, -NH2, -Br, -OH, -COOH.

7. The compound according to claim 1, wherein selected from the group including:
7-(β-D-ribofuranosyl)pyrazino[2,3-d]-6N-pyridazine-5,8-dione sodium salt (19),
2-amino-7-(β-D-ribofuranosyl)pyrazino[2,3-d]-6N-pyridazine-5,8-dione sodium salt (20),
3-amino-7-(β-D-ribofuranosyl)pyrazino[2,3-d]-6N-pyridazine-5,8-dione sodium salt (21),
3-bromo-7-(β-D-ribofuranosyl)pyrazino[2,3-d]-6N-pyridazine-5,8-dione sodium salt (22),
2-hydroxy-7-(β-D-ribofuranosyl)pyrazino[2,3-d]-6N-pyridazine-5,8-dione disodium salt (23),
2-carboxy-7-(β-D-ribofuranosyl)pyrazino[2,3-d]-6N-pyridazine-5,8-dione disodium salt (24),
pyrazino[2,3-d]-6N-pyridazine-5,8-dione lithium salt (25),
pyrazino[2,3-d]-6N-pyridazine-5,8-dione sodium salt (26),
3-bromo-pyrazino[2,3-d]-6N-pyridazine-5,8-dione potassium salt (27),
2-amino-pyrazino[2,3-d]-6N-pyridazine-5,8-dione sodium salt (28).

8. Connect the Addendum according to claim 1, characterized in that derives pyrimido[4,5-d]-6N-pyridazine-5,8-dione, having the General formula
,
where R=the atom of Li, Na or K,
R1=-N, -NH2, -Br, -OH, -COOH.

9. The compound according to claim 1, wherein selected from the group including:
7-(β-D-ribofuranosyl)pyrimido[4,5-d]-6N-pyridazine-5,8-dione sodium salt (29),
2-amino-7-(β-D-ribofuranosyl)pyrimido[4,5-d]-6N-pyridazine-5,8-dione sodium salt (30),
4-amino-7-(β-D-ribofuranosyl)pyrimido[4,5-d]-6N-pyridazine-5,8-dione sodium salt (31),
2-bromo-7-(β-D-ribofuranosyl)pyrimido[4,5-d]-6N-pyridazine-5,8-dione sodium salt (32),
4-hydroxy-7-(β-D-ribofuranosyl)pyrimido[4,5-d]-6N-pyridazine-5,8-dione sodium salt (33),
4-carboxy-7-(β-D-ribofuranosyl)pyrimido[4,5-d]-6N-pyridazine-5,8-dione sodium salt (34),
pyrimido[4,5-d]-6N-pyridazine-5,8-dione lithium salt (35),
2-amino-pyrimido[4,5-d]-6N-pyridazine-5,8-dione sodium salt (36),
4-bromo-pyrimido[4,5-d]-6N-pyridazine-5,8-dione potassium salt (37).

10. The compound according to claim 1, characterized in that it has the ability to eliminate intracellular metabolic acidosis, associate excessively formed in the cell free radicals, associate excessively formed in the cell free radical forms of oxygen, to normalize netservices mechanisms of cells, reduce platelet aggregation and Erythro itov.

11. The compound according to claim 1, characterized in that it has the ability interact with adenosylcobalamin receptors.

12. The compound according to claim 1, characterized in that it has the ability interact with adenosylcobalamin receptors on the nuclear membrane of cells and inside nucleated cells.

13. The compound according to claim 1, characterized in that it has hepatoprotective action.

14. The use of cyclic bioisosteres purine derivatives of the system having the structural formula

where R=the atom of Li, Na or K,
R1=-N, -NH2, -Br, -Cl, -OH, -COOH,
In=-N=, -CH=, Z = CH - N=
A=-N==-N=, Z=-CH-,
A=-CH= at=-N=, Z=-CH-,
A=-CH= at=-N-, Z=-N=,
A=-CH==CH-, Z=-CH=,
A=-CH==CH=, Z=-N,
and its pharmacologically acceptable salts for the normalization of intracellular processes in the treatment of disorders caused by intracellular acidosis and/or oxygen deficiency and/or excess production of free radicals and/or excessive formation of free radical forms of oxygen and/or increased aggregation of platelets and/or red blood cells and/or harmful effects and/or disorder netservices mechanisms of cells.

15. The application 14, characterized in that the aforementioned compounds are used as hepatoprotectors d the I prevention of disorders caused by harmful influences.

16. The application 14, characterized in that the active ingredient is placed in a pharmaceutically acceptable liquid carrier or solvent.

17. The application 14, characterized in that the active ingredient is placed in a pharmaceutically acceptable liquid carrier selected from the group comprising water, a physiological fluid, buffer solutions.



 

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