Substituted furochromenes, preparation thereof and their antiinflammatory action

A process for the preparation of a compound of the formula (I),

• wherein
• A and B taken together with the carbon atoms to which the are attached, each independently represent an aromatic moiety or a heteroaromatic moiety, which is
• (a) unsubstituted or substituted by one or more substituents which are each independently selected from the group consisting of halogen, C1-C4-alkyl, C2-C4-alkenyl, C2-C4-alkynyl, halo-C1-C4-alkyl, hydroxy, C1-C4-alkoxy, trifluoromethoxy, C1-C4-alkanoyl, amino, amino-C1-C4-alkyl, N—(C1-C4-alkyl)amino, N,N-di(C1-C4-alkyl)amino, sulfanyl, C1-C4-alkylsulfanyl, sulfo, C1-C4-alkylsulfo, sulfino, C1-C4-alkylsulfino, carboxy, C1-C4-alkoxycarbonyl, cyano, and nitro;
• or
• (b) condensed with an unsubstituted or substituted heteroaromatic moiety or heterocycle, and
• tautomers, pharamaceutically acceptable salts and solvates thereof, comprising reacting a compound of the formula (II)
• wherein R1 is hydrogen, methyl or ethyl, and A and B are the same as in the compound of formula (I)
• in an acidic medium at a reaction temperature of from about room temperature to about 150° C.

A process for the preparation of a compound of formula (II)

• wherein
• A and B taken together with the carbon atoms to which the are attached, each independently represent an aromatic moiety or a heteroaromatic moiety, which is
• (a) unsubstituted or substituted by one or more substituents which are each independently selected from the group consisting of halogen, C1-C4-alkyl, C2-C4-alkenyl, C2-C4-alkynyl, halo-C1-C4-alkyl, hydroxy, C1-C4-alkoxy, trifluoromethoxy, C1-C4-alkanoyl, amino, amino-C1-C4-alkyl, N—(C1-C4-alkyl)amino, N,N-di(C1-C4-alkyl)amino, sulfanyl, C1-C4-alkylsulfanyl, sulfo, C1-C4-alkylsulfo, sulfino, C1-C4-alkylsulfino, carboxy, C1-C4-alkoxycarbonyl, cyano, and nitro;
• or
• (b) condensed with an unsubstituted or substituted heteroaromatic moiety or heterocycle, and
• tautomers, pharamaceutically acceptable salts and solvates thereof
• comprising condensing a compound of formula (III) or a salt thereof
• with dimethoxyacetaldehyde of the formula (IV)
• in an aqueous-organic medium at a temperature that is the boiling temperature of the aqueous-organic medium.

A pharmaceutical composition comprising a compound of formula (I)

• or a compound of formula (II)
• wherein
• A and B taken together with the carbon atoms to which the are attached, each independently represent an aromatic moiety or a heteroaromatic moiety, which is
• (a) unsubstituted or substituted by one or more substituents which are each independently selected from the group consisting of halogen, C1-C4-alkyl, C2-C4-alkenyl, C2-C4-alkynyl, halo-C1-C4-alkyl, hydroxy, C1-C4-alkoxy, trifluoromethoxy, C1-C4-alkanoyl, amino, amino-C1-C4-alkyl, N—(C1-C4-alkyl)amino, N,N-di(C1-C4-alkyl)amino, sulfanyl, C1-C4-alkylsulfanyl, sulfo, C1-C4-alkylsulfo, sulfino, C1-C4-alkylsulfino, carboxy, C1-C4-alkoxycarbonyl, cyano, and nitro;
• or
• (b) condensed with an unsubstituted or substituted heteroaromatic moiety or heterocycle, and
• tautomers, pharamaceutically acceptable salts and solvates thereof, and a pharmaceutically acceptable diluent or carrier.

A method of treating or preventing an inflammatory disease or condition associated with an undesirable inflammatory immune response, which comprises administering to a subject an amount of a compound of formula (I)

• or a compound of formula (II)
• wherein
• A and B taken together with the carbon atoms to which the are attached, each independently represent an aromatic moiety or a heteroaromatic moiety, which is
• (a) unsubstituted or substituted by one or more substituents which are each independently selected from the group consisting of halogen, C1-C4-alkyl, C2-C4-alkenyl, C2-C4-alkynyl, halo-C1-C4-alkyl, hydroxy, C1-C4-alkoxy, trifluoromethoxy, C1-C4-alkanoyl, amino, amino-C1-C4-alkyl, N—(C1-C4-alkyl)amino, N,N-di(C1-C4-alkyl)amino, sulfanyl, C1-C4-alkylsulfanyl, sulfo, C1-C4-alkylsulfo, sulfino, C1-C4-alkylsulfino, carboxy, C1-C4-alkoxycarbonyl, cyano, and nitro;
• or
• (b) condensed with an unsubstituted or substituted heteroaromatic moiety or heterocycle, and
• tautomers, pharamaceutically acceptable salts and solvates thereof, effective to reduce or inhibit said inflammatory response.

A method of inhibiting one or more inflammatory processes selected from the group consisting of granulocyte degranulation and eosinophil infiltration, comprising exposing an organ or tissue afflicted with inflammation to an amount of a compound of formula (I)

• or a compound of formula (II)
• wherein
• A and B taken together with the carbon atoms to which the are attached, each independently represent an aromatic moiety or a heteroaromatic moiety, which is
• (a) unsubstituted or substituted by one or more substituents which are each independently selected from the group consisting of halogen, C1-C4-alkyl, C2-C4-alkenyl, C2-C4-alkynyl, halo-C1-C4-alkyl, hydroxy, C1-C4-alkoxy, trifluoromethoxy, C1-C4-alkanoyl, amino, amino-C1-C4-alkyl, N—(C1-C4-alkyl)amino, N,N-di(C1-C4-alkyl)amino, sulfanyl, C1-C4-alkylsulfanyl, sulfo, C1-C4-alkylsulfo, sulfino, C1-C4-alkylsulfino, carboxy, C1-C4-alkoxycarbonyl, cyano, and nitro;
• or
• (b) condensed with an unsubstituted or substituted heteroaromatic moiety or heterocycle, and
• tautomers, pharamaceutically acceptable salts and solvates thereof, effective to inhibit said inflammatory process.