Abstract: A novel prophylactic/remedy for immunopathy is provided which is not neutralized by a neutralizing antibody to Staphylococcal enterotoxin B (SEB), known as one of superantigens, and may effectively act as a superantigen. A modified SEB having a reduced reactivity with a neutralizing antibody to SEB (anti-SEB antibody) and a prophylactic/remedy for immunopathy comprising as an active ingredient said modified SEB. The modified SEB of the present invention may be prepared with the evolutionary molecular engineering technique by introducing amino acid substitution in the amino acid sequence of SEB, especially at an epitope recognition site of the anti-SEB antibody in the amino acid sequence of SEB.

Abstract: A modified Staphylococcal enterotoxin B (SEB) having resistance to a protease and a reduced toxicity and a vaccine comprising said modified SEB are provided. A modified SEB which has an amino acid sequence as set forth in SEQ ID NO: 1 wherein each of the lysine at 97-position and the lysine at 98-position are substituted with any other amino acid, or a derivative thereof and a vaccine comprising said modified SEB or a derivative thereof.

Abstract: A modified Staphylococcal enterotoxin B (SEB) having resistance to a protease and a reduced toxicity and a vaccine comprising said modified SEB are provided. A modified SEB which has an amino acid sequence as set forth in SEQ ID NO: 1 wherein each of the lysine at 97-position and the lysine at 98-position are substituted with any other amino acid, or a derivative thereof and a vaccine comprising said modified SEB or a derivative thereof.

Abstract: The present invention provides a prophylactic and/or therapeutic agent for rheumatoid arthritis comprising 2-benzyl-5-(4-chlorophenyl)-6-[4-(methylthio)phenyl]-2H-pyridazin-3-one and leflunomide in combination. The prophylactic and/or therapeutic agent of the present invention can be administered orally, exhibits an excellent arthritis suppressive effect with fewer side effects, and is therefore useful for the prophylaxis and/or treatment of rheumatoid arthritis.

Abstract: This invention relates to pyridazine derivatives represented by the formula (1): wherein R1 represents a (substituted) aryl group, R2 represents a phenyl group substituted at 4-position by a lower alkoxyl, group or a lower alkylthio group, R3 represents a lower alkoxyl group, a halogenated lower alkyl group, a lower cycloalkyl group, a (substituted) aryl group, a (substituted) aryloxy group, a (substituted) nitrogen-containing heterocyclic ring residue, a (substituted) aminocarbonyl group or a lower alkylcarbonyl group, A represents a single bond, a lower alkylene group or a lower alkenylene group, X represents O or S, and the dashed line indicates that the carbon-carbon bond between the 4-position and the 5-position is a single bond or a double bond, or salts thereof; and also to medicines containing them as effective ingredients.

Abstract: The invention provides a method for the prevention and/or treatment of rheumatoid arthritis, characterized in that the method comprises administering an IL-1? inhibitor and a calcineurin inhibitor, and a preventive and/or therapeutic medicine for rheumatoid arthritis including an IL-1? inhibitor and a calcineurin inhibitor in combination. According to the invention, there can be provided a medicine and method for treating rheumatoid arthritis which exhibits suppressed side effects and excellent potency for suppression of arthritis.

Abstract: This invention relates to pyridazine derivatives represented by the formula (1): wherein R1 represents a (substituted) aryl group, R2 represents a phenyl group substituted at 4-position by a lower alkoxyl, group or a lower alkylthio group, R3 represents a lower alkoxyl group, a halogenated lower alkyl group, a lower cycloalkyl group, a (substituted) aryl group, a (substituted) aryloxy group, a (substituted) nitrogen-containing heterocyclic ring residue, a (substituted) aminocarbonyl group or a lower alkylcarbonyl group, A represents a single bond, a lower alkylene group or a lower alkenylene group, X represents O or S, and the dashed line indicates that the carbon-carbon bond between the 4-position and the 5-position is a single bond or a double bond, or salts thereof; and also to medicines containing them as effective ingredients.

Abstract: The present invention relates to an agent for the prevention/therapy of a disease caused by keratinocyte growth, which comprises, as an active ingredient, a compound represented by General Formula (1): wherein A represents a group selected from groups of the following formulas: X represents CH or N; Y represents CH2 or C?O; Z represents CH or N; R1 represents an alkoxy group; R2 and R3 each independently represent an alkyl group; R4 represents an alkyl group, and a group of the following formula: R5 each independently represent an alkoxy group or an alkylthio group; m represents an integer from 1 to 3; n represents an integer of 1 or 2; and o represents an integer of 1 or 2, or a salt thereof, or a solvate of the compound or the salt.

Abstract: The present invention relates to a preventive and/or therapeutic agent for rheumatoid arthritis. The present invention provides a preventive and/or therapeutic agent for rheumatoid arthritis containing 2-benzyl-5-(4-chlorophenyl)-6-[4-(methylthio)phenyl]-2H-pyridazin-3-one and a COX2 inhibitor.

Abstract: This invention relates to pyridazine derivatives represented by the formula (1): wherein R1 represents a (substituted) aryl group, R2 represents a phenyl group substituted at 4-position by a lower alkoxyl group or a lower alkylthio group, R3 represents a lower alkoxyl group, a halogenated lower alkyl group, a lower cycloalkyl group, a (substituted) aryl group, a (substituted) aryloxy group, a (substituted) nitrogen-containing heterocyclic ring residue, a (substituted) aminocarbonyl group or a lower alkylcarbonyl group, A represents a single bond, a lower alkylene group or a lower alkenylene group, X represents O or S, and the dashed line indicates that the carbon-carbon bond between the 4-position and the 5-position is a single bond or a double bond, or salts thereof; and also to medicines containing them as effective ingredients.

Abstract: The present invention is directed to a compound represented by formula (1): (wherein R1 represents an alkyl group which may have a substituent or an alkenyl group which may have a substituent; and each of R2 and R3 represents a hydrogen atom, an alkyl group, a hydroxyalkyl group, a dihydroxyalkyl group, or an alkynyl group, or R2 and R3 form, together with the nitrogen atom adjacent thereto, a nitrogen-containing saturated heterocyclic group which may have a substituent) and a drug composition containing the compound. The compound exhibits tumor necrosis factor (TNF-?) production inhibitory effect and improved absorption upon oral administration.

Abstract: The present invention relates to a preventive and/or therapeutic medicine for rheumatoid arthritis containing 2-benzyl-5-(4-chlorophenyl-6-[4-(methylthio)phenyl]-2H-pyridazin-3-one and methotrexate. The medicine of the present invention can be administered orally and exhibits suppressed side effects and excellent potency for suppression of arthritis.

Abstract: This invention relates to pyridazine derivatives represented by the formula (1): wherein R1 represents a (substituted) aryl group, R2 represents a phenyl group substituted at 4-position by a lower alkoxyl group or a lower alkylthio group, R3 represents a lower alkoxyl group, a halogenated lower alkyl group, a lower cycloalkyl group, a (substituted) aryl group, a (substituted) aryloxy group, a (substituted) nitrogen-containing heterocyclic ring residue, a (substituted) aminocarbonyl group or a lower alkylcarbonyl group, A represents a single bond, a lower alkylene group or a lower alkenylene group, X represents O or S, and the dashed line indicates that the carbon-carbon bond between the 4-position and the 5-position is a single bond or a double bond, or salts thereof; and also to medicines containing them as effective ingredients.

Abstract: A novel prophylactic/remedy for immunopathy is provided which is not neutralized by a neutralizing antibody to Staphylococcal enterotoxin B (SEB), known as one of superantigens, and may effectively act as a superantigen. A modified SEB having a reduced reactivity with a neutralizing antibody to SEB (anti-SEB antibody) and a prophylactic/remedy for immunopathy comprising as an active ingredient said modified SEB. The modified SEB of the present invention may be prepared with the evolutionary molecular engineering technique by introducing amino acid substitution in the amino acid sequence of SEB, especially at an epitope recognition site of the anti-SEB antibody in the amino acid sequence of SEB.

Abstract: A phenylpyridazine derivative represented by the formula (1): Wherein, R1, R2, R3, X, Y, Z and n have the same meaning as defined in the specification; or a salt thereof, or a medicine containing the compound. The present invention provides water-soluble phenylpyridazine derivatives and medicines containing them, which have excellent inhibitory activity against interleukin-? production, high water solubility and high oral absorbability.

Abstract: This invention relates to pyridazine derivatives represented by the formula (1): wherein R1 represents a (substituted) aryl group, R2 represents a phenyl group substituted at 4-position by a lower alkoxyl group or a lower alkylthio group, R3 represents a lower alkoxyl group, a halogenated lower alkyl group, a lower cycloalkyl group, a (subsituted) aryl group, a (substituted) aryloxy group, a (substituted) nitrogen-containing heterocyclic ring residue, a (substituted) aminocarbonyl group or a lower alkylcarbonyl group, A represents a single bond, a lower alkylene group or a lower alkenylene group, X represents O or S, and the dashed line indicates that the carbon-carbon bond between the 4-position and the 5-position is a single bond or a double bond, or salts thereof; and also to medicines containing them as effective ingredients.

Abstract: This invention relates to a method of inhibiting OPN production, which comprises administering an effective amount of a pyridazine derivative represented by the following formula (I) or a salt thereof: wherein: R1 means a substituted or unsubstituted phenyl or pyridyl group; R2 means a substituted phenyl group; R3 means a hydrogen atom or a substituted or unsubstituted phenyl or pyridyl group; A means a single bond, a C1-6 linear or branched alkylene group, or a C2-9 linear or branched alkenylene group; and X means an oxygen atom or a sulfur atom.

Abstract: The present invention is directed to a compound represented by formula (1): (wherein R1 represents an alkyl group which may have a substituent or an alkenyl group which may have a substituent; and each of R2 and R3 represents a hydrogen atom, an alkyl group, a hydroxyalkyl group, a dihydroxyalkyl group, or an alkynyl group, or R2 and R3 form, together with the nitrogen atom adjacent thereto, a nitrogen-containing saturated heterocyclic group which may have a substituent) and a drug composition containing the compound. The compound exhibits tumor necrosis factor (TNF-?) production inhibitory effect and improved absorption upon oral administration.

Abstract: Compounds having the formula (1): wherein R1 represents an alkyl or alkenyl group, R2 and R3 each independently represent a hydrogen atom or an alkyl, hydroxyalkyl, dihydroxyalkyl or alkynyl group, or R2 and R3 may be fused together with the adjacent nitrogen atom to form a substituted or unsubstituted, nitrogen-containing, saturated heterocyclic group, X, Y and Z each independently represent a hydrogen atom, an alkyl group, a halogen atom or the like, and n stands for an integer of from 1 to 5; and also to medicinal compositions containing them. These compounds have inhibitory activity against IL-1? production, high water solubility and good oral absorbability.

Abstract: This invention relates to pyridazine derivatives represented by the formula (1): wherein R1 represents a (substituted) aryl group, R2 represents a phenyl group substituted at 4-position by a lower alkoxyl group or a lower alkylthio group, R3 represents a lower alkoxyl group, a halogenated lower alkyl group, a lower cycloalkyl group, a (subsituted) aryl group, a (substituted) aryloxy group, a (substituted) nitrogen-containing heterocyclic ring residue, a (substituted) aminocarbonyl group or a lower alkylcarbonyl group, A represents a single bond, a lower alkylene group or a lower alkenylene group, X represents O or S, and the dashed line indicates that the carbon-carbon bond between the 4-position and the 5-position is a single bond or a double bond, or salts thereof; and also to medicines containing them as effective ingredients.