FUSED PYRIDAZINE DERIVATIVES, PROCESS FOR THE PREPARATION OF THE SAME AND USES THEREOF

摘要

A compound (I) represented by the formula: <CHEM> wherein Ar<1> and Ar<2> are Independently an aromatic group optionally having a substituent, and Ar<1> and Ar<2> may form a condensed cyclic group with an adjacent carbon atom; ring B is a nitrogen-containing heterocycle optionally having a substituent; X and Y are the same or different and are independently a band, an oxygen atom, S(O)p (p is an integer of 0 to 2), NR<4> wherein R<4> is a hydrogen atom or a lower alkyl group, or a bivalent linear lower hydrocarbon group which may contain 1 to 3 hetero atoms and the bivalent linear lower hydrocarbon group may be substituted; A is a nitrogen atom or CR<7> wherein R<7> is a hydrogen atom, a halogen atom, a hydrocarbon optionally having a substituent, an acyl group or a hydroxy group optionally having a substituent; R<1>, R<2> and R<3> are the same or different and are independently a hydrogen atom, ahalogen atom, ahydrocarbon group optionally having a substituent, an acyl group or a hydroxy group optionally having a substituent; R<8> is a hydrogen atom, a hydroxy group which may be substituted by lower alkyl or a carboxyl group, provided that the nitrogen-containing heterocycle represented by ring B is not a heterocycle represented by the formula: <CHEM> wherein n is 0 or 1, or a salt thereof, exhibits excellent anti-allergic, anti-histaminic, anti-inflammatory and eosinophil chemotaxis inhibiting activity and is useful as a pharmaceutical composition for preventing or treating allergic skin diseases such as contact dermatitis, pruritus, dried dermatitis, acute urticaria and prurigo. According to the method for producing of the present invention, the compound (I') represented by the formula: <CHEM> wherein Ar<1'> and Ar<2'> are independently an aromatic group optionally having a substituent, and Ar<1'> and Ar<2'> may form a condensed cyclic group with an adjacent carbon atom; ring B' is a nitrogen-containing heterocycle optionally having a substituent; X and Y are the same or different and are independently a bond, an oxygen atom, S(O)p (p is an integer of 0 to 2), NR<4> wherein R<4> is a hydrogen atom or a lower alkyl group, or a bivalent linear lower hydrocarbon group which may contain 1 to 3 hetero atoms and the bivalent linear lower hydrocarbon group may be substituted; A is a nitrogen atom or CR<7> wherein R<7> is a hydrogen atom, a halogen atom, a hydrocarbon optionally having a substituent, an acyl group or a hydroxy group optionally having a substituent; R<1> is a hydrocarbon group substituted with an optionally esterified carboxyl group, R<2> and R<3> are the same or different and are independently a hydrogen atom, a halogen atom, a hydrocarbon group optionally having a substituent, an acyl group or a hydroxy group optionally having a substituent; R<8> is a hydrogen atom, a hydroxy group which may be substituted by lower alkyl or a carboxyl group, or a salt thereof, exhibiting excellent anti-allergic, anti-histaminic, anti-inflammatory and eosinophil chemotaxis inhibiting activity and is useful as a pharmaceutical composition for preventing or treating adthma, allergic rhinitis, atopic dermatitis, allergic conjunctivitis, chronic urticaria, can be produced in good efficiency and in a high yield. The hydrate of a compound represented by the formula; <CHEM> wherein R is a hydrogen atom or an ethyl group, or a succinate or citrate of the compound (I") exhibits excellent anti-allergic, anti-histaminic, anti-inflammatory and eosinophil chemotaxis inhibiting activity and is useful as a pharmaceutical composition for preventing or treating adthma, allergic rhinitis, atopic dermatitis, allergic conjunctivitis, chronic urticaria, and has excellent stability.