Hydantoin derivatives

Abstract

The present invention relates to novel hydantoin derivatives, processes for producing said hydantoin derivatives, pharmaceutical compositions containing at least one of said hydantoin derivatives as aldose reductase inhibitors and novel intermediate compounds in the synthesis of said hydantoin derivatives. The present invention is based on the selection of a hydantoin which is bonded by a sulfonyl group to various substituents at the 1-position of the hydantoin skeleton. The compounds of the present invention have a strong inhibitory activity against aldose reductase. These compounds are extremely useful for the treatment and/or prevention of various forms of diabetic complications based on the accumulation of polyol metabolites.

What is claimed is: 
     
       1. A sulfonylglycine derivative represented by the formula (IV):   Q--SO.sub.7 NHCH.sub.7 CO--R                               (IV)     wherein R represents a hydroxy group, an alkoxy group or an amino group which may be substituted with an alkoxycarbonyl group, Q represents a benzo[b]furan-2-yl group which may be substituted by one or more substituents which are the same or different and selected from the group consisting of a halogen atom, a lower alkyl group, a nitro group, a cyano group, an optionally protected carboxy group, an optionally protected carboxymethyl group, a halogenated lower alkyl group, a lower alkylthio group, a lower alkylcarbonyl group, a lower alkoxy group, a lower alkylsulfinyl group, a lower alkylsulfonyl group, an optionally protected hydroxy group other than a lower alkoxy group, an optionally protected amino group, a carbamoyl group and a phenyl group.   
     
     
       2. A sulfonylglycine derivative as claimed in claim 1, wherein said substituents are 1 to 3 halogen atoms. .[.3. A sulfonylglycine derivative represented by the formula (IV):   Q--SO.sub.2 NHCH.sub.2 CO--R                               (IV)     where R represents a hydroxy group, an alkoxy group or an amino group which may be substituted with an alkoxycarbonyl group, Q represents a thiazolyl group which may be substituted by one or more substituents which are the same or different and selected from the group consisting of a halogen atom, a lower alkyl group, a nitro group, a cyano group, an optionally protected carboxy group, an optionally protected carboxymethyl group, a halogenated lower alkyl group, a lower alkylthio group, a lower alkylcarbonyl group, a lower alkoxy group, a lower alkylsulfinyl group, a lower alkylsufonyl group, an optionally protected hydroxy group other than a lower alkoxy group, an optionally protected amino group, and a carbamoyl group..]. .[.4. A sulfonylglycine derivative as claimed in claim 1 wherein   
     
     
        Q represents a pyridyl group which may be substituted..]. 5. A sulfonylglycine derivative as claimed in claim .[.1.]. .Iadd.18 .Iaddend.wherein Q represents an indolyl group which may be substituted. 
     
     
           A sulfonylglycine derivative as claimed in claim .[.1.]. .Iadd.18 .Iaddend.wherein Q represents a benzothiazolyl group which may be 
     
     
        substituted. 7. A sulfonylglycine derivative as claimed in claim .[.1.]. .Iadd.18 .Iaddend.wherein Q represents a benzisothiazolyl group which may 
     
     
        be substituted. 8. A sulfonylglycine derivative as claimed in claim .[.1.]. .Iadd.18 .Iaddend.wherein Q represents a coumarinyl group which 
     
     
        may be substituted. 9. A sulfonylglycine derivative as claimed in claim .[.1.]. .Iadd.18 .Iaddend.wherein Q represents a chromonyl group which may 
     
     
        be substituted. 10. A sulfonylglycine derivative as claimed in claim .[.1.]. .Iadd.18 .Iaddend.wherein Q represents a benzimidazolyl group 
     
     
        which may be substituted. 11. A sulfonylglycine derivative as claimed in claim .[.1.]. .Iadd.18 .Iaddend.wherein Q represents a benzotriazolyl 
     
     
        group which may be substituted. 12. A sulfonylglycine derivative as claimed in claim .[.1.]. .Iadd.18 .Iaddend.wherein Q represents a 
     
     
        benzisoxazolyl group which may be substituted. .[.13.  A sulfonylglycine derivative represented by the formula (IV):   Q--SO.sub.2 NHCH.sub.2 CO--R                               (IV)     wherein   R represents a hydroxy group, an alkoxy group or an amino group which may be substituted with an alkoxycarbonyl group, Q represents a furyl group, a pyridyl group, an indolyl group, a benzothiazolyl group, a benzisothiazolyl group, a benzothienyl group, a coumarinyl group, a chromonyl group, a benzimidazolyl group, a benzotriazolyl group or a benzisoxazolyl group any one of which may be substituted by one or more substituents which are the same or different and selected from a group consisting of a halogen atom, a lower alkyl group, a nitro group, a cyano group, an optionally protected carboxy group, an optionally protected carboxymethyl group, a halogenated lower alkyl group, a lower alkylthio group, a lower alkylcarbonyl group, a lower alkoxy group, a lower alkylsulfinyl group, a lower alkylsulfonyl group, an optionally protected hydroxy group other than a lower alkoxy group, an optionally protected amino group, a carbamoyl group and a phenyl group,   or Q represents a benzo[b]furan-2-yl group which may be substituted by one or more substituents which are the same or different and are selected from the group consisting of a halogen atom, a cyano group, an optionally protected carboxymethyl group, a halogenated lower alkyl group, a lower alkylthio group, a lower alkylsulfinyl group, a lower alkylsulfonyl group,   
     
     
        a carbamoyl group and a phenyl group..]. 14. A sulfonylglycine derivative as claimed in claim .[.13.]. .Iadd.18.Iaddend., wherein Q represents a 
     
     
        furyl group, a benzothienyl group or a benzo[b]furan-2-yl group. 15. A sulfonylglycine derivative as claimed in claim 14, wherein Q represents a 
     
     
        benzo[b]thien-2-yl group which may b substituted. 16. A sulfonylglycine derivative as claimed in claim 14, wherein Q represents a 
     
     
        benzo[b]furan-2-yl group which may b substituted. 17. A sulfonylglycine derivative as claimed in claim 16, wherein the said substituents are 1 to 
     
     
        3 halogen atoms. .Iadd.18.  A sulfonylglycine derivative represented by the formula (IV):   Q--SO.sub.2 NHCH.sub.2 CO--R                               (IV)     where R represents a hydroxy group, an alkoxy group or an amino group which may be substituted with an alkoxycarbonyl group, Q represents a furyl group, an indolyl group, a benzothiazolyl group, a benzisothiazolyl group, a benzothienyl group, a coumarinyl group, a chromonyl group, a benzimidazolyl group, a benzotriazolyl group or a benzisoxazolyl group any one of which may be substituted by one or more substituents which are the same or different and are selected from the group consisting of a halogen atom, a lower alkyl group, a nitro group, a cyano group, an optionally protected carboxymethyl group, a halogenated lower alkyl group, a lower alkylthio group, a lower alkylcarbonyl group, a lower alkoxy group, a lower alkylsulfinyl group, a lower alkylsulfonyl group, an optionally protected hydroxy group other than a lower alkoxy group, an optionally protected amino group, a carbamoyl group, and a phenyl group, or Q represents a benzo[b]furan-2-yl group which may be substituted by one or more substituents which are the same or different and are selected from the group consisting of a halogen atom, a cyano group, an optionally protected carboxymethyl group, a halogenated lower alkyl group, a lower alkylthio group, a lower alkylsulfinyl group, a lower alkylsulfonyl group, a carbamoyl group and a phenyl group. .Iaddend.