Derivatives pyridazine, drugs based on them and the way to treat arthritis

 

The invention relates to the derivatives of pyridazine General formula I, in which R1represents phenyl or pyridyloxy group which may be substituted by 1-3 substituents selected from halogen and lower alkoxygroup; R2represents a phenyl group which may be substituted at the 4th position of the lower alkoxygroup, lower alkylthiol, lower alkylsulfonyl or lower alkylsulfonyl group and in other positions 1 or 2 substituents selected from halogen atoms, lower CNS groups, lower alkylthio, lower alkylsulfonyl groups and lower alkylsulfonyl groups;3represents a hydrogen atom; a lower CNS group; halogenated lower alkyl group; a lower cycloalkyl group; phenyl, pyridyloxy or fenoxaprop, which may be substituted by 1-3 substituents selected from halogen atoms, lower alkyl groups, lower CNS groups, carboxyl groups, lower alkoxycarbonyl groups, nitro, amino, lower alkylamino and lower alkylthio; unsubstituted or substituted lower alkyl group piperidino, piperidinyl, piperazine derivatives or morpholinopropan; unsubstituted and the Yu or substituted lower alkylamino group piperazinylcarbonyl group; A represents a linear or branched lower alkylenes or lower alkynylamino group having 1-6 carbon atoms; or And can mean single bond when R3represents the lower cycloalkyl or halogenated lower alkyl group; X represents an oxygen atom or a sulfur atom; provided that the following combinations are excluded: R1and R2represent 4 metoksifenilny, X represents an oxygen atom, a represents a single bond, and R3represents a hydrogen atom or 2-chloraniline group; or their salts. These compounds are inhibitors of the production of interleukin-1-. In addition, the objects of the invention are medicinal product, which is an inhibitor of the production of interleukin-1-, a drug for the prevention and treatment of arthritis and the treatment of arthritis. 4 C. and 4 h.p. f-crystals, 4 PL.

Table T T TV

Claims

1. Derivatives pyridazine General formula Iin which R1represents phenyl or pyridyloxy group, which may be the optimum group, which may be substituted at the 4th position of the lower alkoxygroup, lower alkylthiol, lower alkylsulfonyl group or lower alkylsulfonyl group and in other positions 1 or 2 substituents selected from halogen atoms, lower CNS groups, lower alkylthio, lower alkylsulfonyl groups and lower alkylsulfonyl group; R3represents a hydrogen atom; a lower CNS group; halogenated lower alkyl group; a lower cycloalkyl group; phenyl, pyridyloxy or fenoxaprop, which may be substituted by 1-3 substituents selected from halogen atoms, lower alkyl groups, lower CNS groups, carboxyl groups, lower alkoxycarbonyl groups, nitro, amino, lower alkylamino and lower alkylthio; unsubstituted or substituted lower alkyl group piperidino, piperidinyl, piperazine derivatives or morpholinopropan; unsubstituted or substituted benzyl group aminocarbonyl group; lower alkylcarboxylic group or unsubstituted or substituted lower alkyl group piperazinylcarbonyl group; A represents a linear or branched lower alkylenes group having from 1 is kind; or maybe also mean a single bond when R3represents the lower cycloalkyl group or halogenated lower alkyl group; X is an oxygen atom or a sulfur atom; provided that the following combinations are excluded: R1and R2represent 4 metoksifenilny group, X represents an oxygen atom, a represents a single bond, and R3represents a hydrogen atom or 2-chloraniline group, or their salts.

2. Derivatives pyridazine under item 1, which are compounds represented by the following formula (IA)

where R4represents a linear or branched lower alkyl or lower alkenylphenol group, lower cycloalkyl group or lower cycloalkenyl group;
X is an oxygen atom or a sulfur atom,
or their salts.

3. Derived pyridazine or its salt under item 1, which is a 5,6-bis(4-methoxyphenyl)-2-ethyl-2H-pyridazin-3-one, 5,6-bis(4-methoxyphenyl)-2-methyl-2H-pyridazin-3-one, 5,b-bis(4-methoxyphenyl)-2-isopropyl-2H-pyridazin-3-one, 5,6-bis(4-methoxyphenyl)-2-isobutyl-2H-pyridazin-3-one, 2-allyl-5,6-bis(4-methoxyphenyl)-2H-pyridazin-3-one, 5,6-bis(4-methoxyphenyl)-2-cyclopropyl-2H-pyridazin-3-one, 5,6-bis(4-methoxyphenyl)-2-cyclopropyl-mental-2H-pyridazin-3-one, 5,6-bis(4-methoxyphenyl)-2-cyclopentylmethyl-2H-pyridazin-3-one, 5,6 - bis(4-methoxyphenyl)-2-(4-chlorocinnamoyl)-2H-pyridazin-3-one, 5-(4-chlorophenyl)-6-(4-methylthiophenyl)-2-benzyl-2H-pyridazin-3-one, 5,6-bis(4-methoxyphenyl)-2-benzyl-2H-pyridazin-3-tion or 5,6-bis(3-fluoro-4-methoxyphenyl)-2-ethyl-2H-pyridazin-3-one or its salt.

4. The drug, which is an inhibitor of the production of interleukin-1-containing as an active ingredient derived pyridazine or its salt according to any one of paragraphs.1-3.

5. Drug for prevention or treatment of arthritis, containing as an active ingredient derived pyridazine or its salt according to any one of paragraphs.1-3.

6. Derived pyridazine or its salt according to any one of paragraphs.1-3, intended for the manufacture of a medicinal product, representing an inhibitor of the production of interleukin-1.

7. Derived pyridazine or its salt according to any one of paragraphs.1-3, intended for the manufacture of a medicinal product for the prevention or treatment of arthritis.

8. A method of treating arthritis which comprises the administration to a patient in need of such treatment, derived pyridazine or its salt according to any one of paragraphs. 1-3.

 

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