Patent EP-1123936-A1 (EP)
Inventor: KAWANO YASUHIKO
IPC: C07D487/04
Filed: 1999-10-20
Abstract: A compound (I) represented by the formula:
 
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:
 
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:
 
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;
 
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.