Methods of treatment of sepsis and inflammation using oxypurine nucleosides

 

The invention relates to certain oxipurinol the nucleosides, compounds related data oxipurinol the nucleosides, acyl derivatives and compositions that contain at least one of these compounds. The invention also relates to methods of treatment or prevention of disorders of the blood-forming organs and changes in hematopoiesis, as well as for treatment and prevention of inflammatory diseases by introducing a composition or compound of animals. The method provides a more effective treatment. 5 C. and 4 h.p. f-crystals, 22 tab., 69 Il.

Description text in facsimile form (see graphic part). T T T

Claims

1. A method of reducing toxicity of bacterial endotoxin in animals, which consists in the introduction of specified animal down-toxicity the number of compounds or compositions containing one or more compounds of the formulawhere RA- H or the acyl radical of carboxylic, alkylphosphonic or alkylsulfonic acid acyl radical of alkylphosphate or alkylsulfate or alkyl radical with carbon atoms of 2 to 30; RB- H or the acyl radical of carboxylic the initial radical with carbon atoms of 2 to 30; Z is H, HE, = O or otherCwhere RC- H or acyl radicals of carboxylic acids with the number of carbon atoms from 2 to 30 or an alkyl radical containing 2 to 30 carbon atoms; L Is N or orDwhere RD- H or the acyl radical of carboxylic, alkylphosphonic or alkylsulfonates acid acyl radical of alkylphosphate or alkylsulfate or alkyl radical with carbon atoms of 2 to 30; M Is N or orEwhere RE- H or the acyl radical of carboxylic, alkylphosphonic or alkylsulfonic acid acyl radical of alkylphosphate or alkylsulfate or alkyl radical with carbon atoms of 2 to 30, provided that at least one of L or M is N; Q is H, halogen, otherFwhere RF- H or acyl or alkyl radical containing from 1 to 10 carbon atoms; S two links connected to the carbon, in this case, the adjacent double bond in the carbon - nitrogen represents a single bond and N, therefore, is connected with the nitrogen SRGwhere RG- H or acyl or alkyl radical containing from 1 to 10 carbon atoms; a double bond is connected to the carbon, in this case, the adjacent double bond in the carbon - nitrogen represents a single bond and N is then connected to this C-C bond between positions 2' and 3' Almaznogo residue may but not necessarily, present
or

where Z is otherCwhere RC- H, or acyl radicals of carboxylic acids with the number of carbon atoms from 2 to 30, alkyl radical containing 2 to 30 carbon atoms;
Q is H, halogen, otherFwhere RF- H or acyl or alkyl radical containing from 1 to 10 carbon atoms; S double bond is connected to the carbon, in this case, the adjacent double bond in the carbon - nitrogen represents a single bond and N is then connected to a nitrogen SRGwhere RG- H or acyl or alkyl radical containing from 1 to 10 carbon atoms; a double bond is connected to the carbon, in this case, the adjacent double bond in the carbon - nitrogen represents a single bond and N is then connected with the nitrogen or orHwhere RH- H or acyl or alkyl radical containing from 1 to 10 carbon atoms,
or their pharmaceutically acceptable salt.

2. Method for the treatment or prevention of sepsis, which consists in the introduction of specified animal an effective amount of the compounds or compositions containing one or more compounds of the formula

where RA- H or the acyl radical of carboxylic, and the radical with the number of carbon atoms from 2 to 30;
RB- H or the acyl radical of carboxylic, alkylphosphonic or alkylsulfonic acid acyl radical of alkylphosphate or alkylsulfate or alkyl radical with carbon atoms of 2 to 30;
Z is H, HE, = O or otherCwhere RC- H, or acyl radicals of carboxylic acids with the number of carbon atoms from 2 to 30, alkyl radical containing 2 to 30 carbon atoms;
L - N or orDwhere RD- H or the acyl radical of carboxylic, alkylphosphonic or alkylsulfonic acid acyl radical of alkylphosphate or alkylsulfate or alkyl radical with carbon atoms of 2 to 30;
M - N or orEwhere RE- H or the acyl radical of carboxylic, alkylphosphonic or alkylsulfonic acid acyl radical of alkylphosphate or alkylsulfate or alkyl radical with carbon atoms of 2 to 30, provided that at least one of L or M means N;
Q is H, halogen, otherFwhere RF- H or acyl or alkyl radical containing from 1 to 10 carbon atoms, 's two links connected to the carbon, in this case, the adjacent double bond in the carbon - nitrogen represents a single bond and N, therefore, is connected with the nitrogen SRGwhere RG- H or acyl AE adjacent double bond carbon - nitrogen is a single bond and N is then connected with the nitrogen or orHwhere RH- H or acyl or alkyl radical containing from 1 to 10 carbon atoms;
C-C bond between positions 2' and 3' Almaznogo balance is possible, but not necessarily, present
or

where Z is otherCwhere RC- H, or acyl radicals of carboxylic acids with the number of carbon atoms from 2 to 30, alkyl radical containing 2 to 30 carbon atoms;
Q is H, halogen, otherFwhere RF- H or acyl or alkyl radical containing from 1 to 10 carbon atoms; S double bond is connected to the carbon, in this case, the adjacent double bond in the carbon - nitrogen represents a single bond and N is then connected with the nitrogen; SRGwhere RG- H or acyl or alkyl radical containing from 1 to 10 carbon atoms; a double bond is connected to the carbon, in this case, the adjacent double bond in the carbon-nitrogen represents a single bond and N is then connected with the nitrogen or orHwhere RH- H or acyl or alkyl radical containing from 1 to 10 carbon atoms,
or their pharmaceutically acceptable salt.

3. Method of reducing inflammation in impositio, containing one or more compounds of the formula

where RA- H or the acyl radical of carboxylic, alkylphosphonic or alkylsulfonic acid acyl radical of alkylphosphate or alkylsulfate or alkyl radical with carbon atoms of 2 to 30;
RB- H or the acyl radical of carboxylic, alkylphosphonic or alkylsulfonic acid acyl radical of alkylphosphate or alkylsulfate or alkyl radical with carbon atoms of 2 to 30;
Z is H, HE, = O or otherCwhere RC- H or acyl radicals of carboxylic acids with the number of carbon atoms from 2 to 30 or an alkyl radical containing 2 to 30 carbon atoms;
L - N or orDwhere RD- H or the acyl radical of carboxylic, alkylphosphonic or alkylsulfonic acid acyl radical of alkylphosphate or alkylsulfate or alkyl radical with carbon atoms of 2 to 30;
M - N or orEwhere RE- H or the acyl radical of carboxylic, alkylphosphonic or alkylsulfonic acid acyl radical of alkylphosphate or alkylsulfate or alkyl radical with carbon atoms of 2 to 30, provided that at least one of L or M means N;
Q is H, halogen, otherFwhere RFGwhere RG- H or acyl or alkyl radical containing from 1 to 10 carbon atoms; a double bond is connected to the carbon, in this case, the adjacent double bond in the carbon - nitrogen represents a single bond and N is then connected with the nitrogen or orHwhere RH- H or acyl or alkyl radical containing from 1 to 10 carbon atoms;
C-C bond between positions 2' and 3' Almaznogo balance is possible, but not necessarily, present
or

where Z is otherCwhere RC- H, or acyl radicals of carboxylic acids with the number of carbon atoms from 2 to 30, alkyl radical containing 2 to 30 carbon atoms;
Q is H, halogen, otherFwhere RF- H or acyl or alkyl radical containing from 1 to 10 carbon atoms; S double bond is connected to the carbon, in this case, the adjacent double bond in the carbon - nitrogen represents a single bond and N is then connected to a nitrogen; SRGwhere RG- H or acyl or alkyl radical containing from 1 to 10 carbon atoms; a double bond is connected with coal is United with the nitrogen or orHwhere RH- H or acyl or alkyl radical containing from 1 to 10 carbon atoms,
or their pharmaceutically acceptable salt.

4. The method according to p. 3, characterized in that the inflammation induced by endotoxin, bacteria, viral or fungal infection.

5. The method according to p. 3, characterized in that the inflammation caused by an autoimmune disease.

6. Method for the mobilization of stem cells from bone marrow into peripheral circulation, which consists in contacting these stem cells with the compound or composition containing one or more compounds of the formula

where RA- H or the acyl radical of carboxylic, alkylphosphonic or alkylsulfonic acid acyl radical of alkylphosphate or alkylsulfate or alkyl radical with carbon atoms of 2 to 30;
RB- H or the acyl radical of carboxylic, alkylphosphonic or alkylsulfonic acid acyl radical of alkylphosphate or alkylsulfate or alkyl radical with carbon atoms of 2 to 30;
Z is H, HE, = O or otherCwhere RC- H, or acyl radicals of carboxylic acids with the number of carbon atoms from 2 to 30, alkyl radical, containing the or alkylsulfonic acid, acyl radical of alkylphosphate or alkylsulfate or alkyl radical with carbon atoms of 2 to 30;
M - N or orEwhere RE- H or the acyl radical of carboxylic, alkylphosphonic or alkylsulfonic acid acyl radical of alkylphosphate or alkylsulfate or alkyl radical with carbon atoms of 2 to 30, provided that at least one of L or M means N;
Q is H, halogen, otherFwhere RF- H or acyl or alkyl radical containing from 1 to 10 carbon atoms; S two links connected to the carbon, in this case, the adjacent double bond in the carbon - nitrogen represents a single bond and N, therefore, is connected with the nitrogen; SRGwhere RG- H or acyl or alkyl radical containing from 1 to 10 carbon atoms; a double bond is connected to the carbon, in this case, the adjacent double bond in the carbon - nitrogen represents a single bond and N is then connected with the nitrogen or orHwhere RH- H or acyl or alkyl radical containing from 1 to 10 carbon atoms;
C-C bond between positions 2' and 3' Almaznogo balance is possible, but not necessarily, present
or

where Z is otherCwhere R Q is H, halogen, otherFwhere RF- H or acyl or alkyl radical containing from 1 to 10 carbon atoms; S double bond is connected to the carbon, in this case, the adjacent double bond in the carbon - nitrogen represents a single bond and N is then connected with the nitrogen; SRGwhere RG- H or acyl or alkyl radical containing from 1 to 10 carbon atoms; a double bond is connected to the carbon, in this case, the adjacent double bond in the carbon - nitrogen represents a single bond and N is then connected with the nitrogen or orHwhere RH- H or acyl or alkyl radical containing from 1 to 10 carbon atoms,
or their pharmaceutically acceptable salt.

7. The way to reduce levels of gamma interferon, factor that causes necrosis of tumor cells-alpha, interleukin-1 and/or interleukin-6, which consists in the introduction of specified animal number, effective to reduce these levels, compounds containing one or more compounds of the formula

where RA- H or the acyl radical of carboxylic, alkylphosphonic or alkylsulfonic acid acyl radical of alkylphosphate or alkylsulfate or alkyl radical with the number at the acid, acyl radical of alkylphosphate or alkylsulfate or alkyl radical with carbon atoms of 2 to 30;
Z is H, HE, = O or otherCwhere RC- H, or acyl radicals of carboxylic acids with the number of carbon atoms from 2 to 30 or an alkyl radical containing 2 to 30 carbon atoms;
L - N or orDwhere RD- H or the acyl radical of carboxylic, alkylphosphonic or alkylsulfonic acid acyl radical of alkylphosphate or alkylsulfate or alkyl radical with carbon atoms of 2 to 30;
M - N or orEwhere RE- H or the acyl radical of carboxylic, alkylphosphonic or alkylsulfonic acid acyl radical of alkylphosphate or alkylsulfate or alkyl radical with carbon atoms of 2 to 30, provided that at least one of L or M means N;
Q is H, halogen, otherFwhere RF- H or acyl or alkyl radical containing from 1 to 10 carbon atoms; S two links connected to the carbon, in this case, the adjacent double bond in the carbon - nitrogen represents a single bond and N, therefore, is connected with the nitrogen; SRGwhere RG- H or acyl or alkyl radical containing from 1 to 10 carbon atoms; a double bond is connected to the carbon is replaced with the nitrogen or orHwhere RH- H or acyl or alkyl radical containing from 1 to 10 carbon atoms;
C-C bond between positions 2' and 3' Almaznogo balance is possible, but not necessarily, present
or

where Z is otherCwhere RC- H or acyl radicals of carboxylic acids with the number of carbon atoms from 2 to 30 or an alkyl radical containing 2 to 30 carbon atoms;
Q is H, halogen, otherFwhere RF- H or acyl or alkyl radical containing from 1 to 10 carbon atoms; S double bond is connected to the carbon, in this case, the adjacent double bond in the carbon - nitrogen represents a single bond and N is then connected with the nitrogen; SRGwhere RG- H or acyl or alkyl radical containing from 1 to 10 carbon atoms; a double bond is connected to the carbon, in this case, the adjacent double bond in the carbon - nitrogen represents a single bond and N is then connected with the nitrogen or orHwhere RH- H or acyl or alkyl radical containing from 1 to 10 carbon atoms,
or their pharmaceutically acceptable salt.

8. The method according to any of paragraphs. 1-7, characterized in that the said connection means acyl derivative Repoliticization.

 

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< / BR>
where arabinofuranosyl residue substituted for 2'-, 3'- or 5'-positions, and esters formed by carboxylic acids, in which decarbonising part selected from n-propyl, tert-butyl, n-butyl, methoxymethyl, benzyl, phenoxymethyl, phenyl, methanesulfonyl and succinyl

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< / BR>
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< / BR>
a benzyl, robotjam, 2-deoxyribosyl or (CH2)n-OR1where n is 1 or 2, and R1is CH2CH2OH or< / BR>
or their salts

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(l) where R is a C1-C4-alkyl, optionally substituted by one or more hydroxyl groups, or R is

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