4H-quinolizin-4-one compounds exhibiting therapeutic activities
AssigneeKissei Pharmaceutical Co., Ltd.
InventorsYoshikazu Kurashina, Hiroshi Miyata, Den-ichi Momose
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Abstract
This invention provides novel 4H-quinolizin-4-one compounds which exhibit a selective inhibitory activity against IgE-antibody formation, and have utility for treatment of diseases associated with IgE formation in mammals, such as allergic bronchial asthma, allergic rhinitis, atopic dermatitis, hypersensitiveness, and the like.
Claims4
A method for the treatment of allergic bronchial asthma, allergic rhinitis, atopic dermatitis and hypersensitiveness diseases associated with immunoglobulin E-antibody formation in a mammal which comprises administering an effective dosage from about 0.1 mg to 10 mg per kg of mammal weight by oral administration of from about 0.02 mg to 5 mg per kg of mammal weight by parenteral administration per day of an immunoglobulin E-antibody formation-inhibiting 4H-quinolizin-4-one compound to the mammal;
- wherein the 4H-quinolizin-4-one compound corresponds to the formula:
- ##STR17## where R is an alkyl group or a phenylalkyl group;
- A is a substituted or unsubstituted phenyl group or a substituted or unsubstituted 5 or 6 membered heterocyclic group;
- with the proviso that the heterocyclic group is bonded to the quinolizine ring at a nitrogen atom of the heterocyclic ring;
- or a pharmaceutically acceptable salt thereof.
A method for the treatment of allergic bronchial asthma, allergic rhinitis, atopic dermatitis and hypersensitiveness diseases associated with immunoglobulin E-antibody formation in a mammal which comprises administering an effective dosage from about 0.1 mg to 10 mg per kg of mammal weight by oral administration or from about 0.02 mg to 5 per kg of mammal weight by parenteral administration per day of an immunoglobulin E-antibody formation-inhibiting 4H-quinolizin-4-one compound to the mammal;
- wherein the 4H-quinolizin-4-one compound corresponds to the formula:
- ##STR18## where R is an alkyl group or a phenylalkyl group;
- Ar is a substituted or unsubstituted phenyl group;
- or a pharmaceutically acceptable salt thereof.
A method for the treatment of allergic bronchial asthma, allergic rhinitis, atopic dermatitis and hypersensitiveness diseases associated with immunoglobulin E-antibody formation in a mammal which comprises administering an effective dosage from about 0.1 mg to 10 mg per kg of mammal weight by oral administration or from about 0.02 mg to 5 mg per kg mammal weight by parenteral administration per day of an immunoglobulin E-antibody formation-inhibiting 4H-quinolizin-4-one compound to the mammal;
- wherein the 4H-quinolizin-4-one compound corresponds to the formula:
- ##STR19## where R is an alkyl group or a phenylalkyl group;
- Het is a 5 or 6 membered heterocyclic group;
- with the proviso that the heterocyclic group is bonded to the quinolizine ring at a nitrogen atom of the heterocyclic ring;
- or a pharmaceutically acceptable salt thereof.
A method for the treatment of allergic bronchial asthma, allergic rhinitis, atopic dermatitis and hypersensitiveness diseases associated with immunoglobulin E-antibody formation in a mammal which comprises administering an effective dosage from about 0.1 mg to 10 mg per kg of mammal weight by oral administration or from about 0.02 mg to 5 mg per kg of mammal weight by parenteral administration per day of an immunoglobulin E-antibody formation-inhibiting 4H-quinolizin-4-one compound to the mammal;
- wherein the 4H-quinolizin-4-one compound is selected from the group consisting of 3-cyano-1-ethoxycarbonyl-2-phenyl-4H-quinolizin-4-one;
- 2-(4-biphenylyl)-3-cyano-1-ethoxycarbonyl-4H-quinolizin-4-one;
- 2-(4-Bromophenyl)-3-cyano-1-ethoxycarbonyl-4H-quinolizin-4-one;
- 3-cyano-1-ethoxycarbonyl-2-(4-tertbutylphenyl)-4H-quinolizin-4-one;
- 3-cyano-2-(3,4-dimethoxyphenyl)-1-ethoxycarbonyl-4H-quinolizin-4-one;
- 3-cyano-1-ethoxycarbonyl-2-(4-methoxyphenyl)-4H-quinolizin-4-one;
- 3-cyano-1-ethoxycarbonyl-2-(4-methylphenyl)-4H-quinolizin-4-one;
- 3-cyano-1-ethoxycarbonyl-2-(3,4-methylenedioxyphenyl)-4H-quinolizin-4-one;
- 3-cyano-2-(2,4-dichlorophenyl)-1-ethoxycarbonyl-4H-quinolizin-4-one;
- 3-cyano-2-phenyl-1-propoxycarbonyl-4H-quinolizin-4-one;
- 3-cyano-1-methoxycarbonyl-2-phenyl-4H-quinolizin-4-one;
- 3-cyano-1-ethoxycarbonyl-2-(4-fluorophenyl)-4H-quinolizin-4-one;
- 3-cyano-1-ethoxycarbonyl-2-(3-fluoro-4-methylphenyl)-4H-quinolizin-4-one;
- 3-cyano-2-(3,4-dimethylphenyl)-1-ethoxycarbonyl-4H-quinolizin-4-one;
- 3-cyano-1-ethoxycarbonyl-2-(4-ethoxyphenyl)-4H-quinolizin-4-one;
- 3-cyano-1-ethoxycarbonyl-2-(4-isopropoxyphenyl)-4H-quinolizin-4-one;
- 3-cyano-1-ethoxycarbonyl-2-(3-methoxyphenyl)-4H-quinolizin-4-one;
- 2-(4-benzyloxyphenyl)-3-cyano-1-ethoxycarbonyl-4H-quinolizin-4-one;
- 3-cyano-1-ethoxycarbonyl-2-(3,4,5-trimethoxyphenyl)-4H-quinolizin-4-one;
- 3-cyano-1-ethoxycarbonyl-2-(4-nitrophenyl)-4H-quinolizin-4-one;
- 3-cyano-1-ethoxycarbonyl-2-(2-methoxyphenyl)-4H-quinolizin-4-one;
- 2-(3-bromophenyl)-3-cyano-1-ethoxycarbonyl-4H-quinolizin4-one;
- 2-(3-benzyloxy-4-methoxyphenyl)-3-cyano-1-ethoxycarbonyl-4H-quinolizin-4-o ne;
- 2-(4-benzyloxy-3-methoxyphenyl)-3-cyano-1-ethoxycarbonyl-4H-quinolizin-4-o ne;
- 3-cyano-1-ethoxycarbonyl-2-(4-methylthiophenyl)-4H-quinolizin-4-one;
- 2(4-acetylaminophenyl)-3-cyano-1-ethoxycarbonyl-4H-quinolizin-4-one;
- 2-(4-benzoylphenyl)-3-cyano-1-ethoxycarbonyl-4H-quinolizin-4-one;
- 3-cyano-2-(2,3-dimethoxyphenyl)-1-ethoxycarbonyl-4H-quinolizin-4-one;
- 3-cyano-2-(3,5-dimethoxyphenyl)-1-ethoxycarbonyl-4H-quinolizin-4-one;
- 3-cyano-1-ethoxycarbonyl-2-(4-hydroxyphenyl)-4H-quinolizin-4-one;
- 3-cyano-2-(3,4-dihydroxyphenyl)-1-ethoxycarbonyl-4H-quinolizin-4-one;
- 3-cyano-1-ethoxycarbonyl-2-(4-hydroxy-3-methoxyphenyl)-4H-quinolizin-4-one ;
- 3-cyano-1-ethoxycarbonyl-2-(3-hydroxy-4-methoxyphenyl)-4H-quinolizin-4-on e;
- 2-(4-aminophenyl)-3-cyano-1-ethoxycarbonyl-4H-quinolizin-4-one;
- 3-cyano-1-ethoxycarbonyl-2-methylthio-4H-quinolizin-4-one;
- 3-cyano-2-methylthio-1-(3-phenylpropoxycarbonyl)-4H-quinolizin-4-one;
- 3-cyano-1-ethoxycarbonyl-2-piperidino-4H-quinolizin-4-one;
- 3-cyano-1-(3-phenylpropoxycarbonyl)-2-piperidino-4H-quinolizin-4-one;
- 3-cyano-1-ethoxycarbonyl-2-(1-pyrrolidinyl)-4H-quinolizin-4-one;
- 3-cyano-1-(3-phenylpropoxycarbonyl)-2-(1-pyrrolidinyl)-4Hquinolizin-4-one;
- 3-cyano-1-ethoxycarbonyl-2-[4-(2-hydroxyethyl)piperazin-1-yl-4H-quinolizin -4-one;
- 3-cyano-1-ethoxycarbonyl-2-(4-formylpiperazin-1-yl)-4H-quinolizin-4-one;
- 3-cyano-2-(4-formylpiperazin-1-yl)-1-(3-phenylpropoxycarbonyl)-4H-quinoliz in-4-one;
- 3-cyano-1-ethoxycarbonyl-2-(4-methylpiperazin-1-yl)-4H-quinolizin-4one;
- 3-cyano-2-(4-methylpiperazin-1-yl)-1-(3-phenylpropoxycarbonyl)-4H-quinoliz in-4-one;
- 2-(4-benzylpiperidino)-3-cyano-1-ethoxycarbonyl-4H-quinolizin-4-one;
- 2-(4-benzylpiperidino)-3-cyano-1-(3-phenylpropoxycarbonyl)-4H-quinolizin-4 -one;
- 3-cyano-1-ethoxycarbonyl-2-(4-phenylpiperidino)-4H-quinolizin-4-one;
- 3-cyano-2-(4-phenylpiperidino)-1-(3-phenylpropoxycarbonyl)-4H-quinolizin-4 -one;
- 3-cyano-1-ethoxycarbonyl-2-morpholino-4H-quinolizin-4-one;
- 3-cyano-2-morpholino-1-(3-phenylpropoxycarbonyl)-4H-quinolizin-4-one;
- 3-cyano-1-ethoxycarbonyl-2-(imidazol-1-yl)-4H-quinolizin-4-one;
- 3-cyano-2-(imidazol-1-yl)-1-(3-phenylpropoxycarbonyl)-4H-quinolizin-4-one;
- 3-cyano-1-ethoxycarbonyl-2-(1,3,4-triazol-1-yl)-4H-quinolizin-4-one;
- 3-cyano-1-(3-phenylpropoxycarbonyl)-2-(1,3,4-triazol-1-yl)-4H-quinolizin-4 -one;
- 3-cyano-2-[4-(2-hydroxyethyl)piperazin-1-yl]-1-(3-phenylpropoxycarbonyl)-4 H-quinolizin-4-one;
- 3-cyano-1-ethoxycarbonyl-2-(4-morpholinocarbonylmethylpiperazin-1-yl)-4H-q uinolizin-4-one;
- 3-cyano-2-4-morpholinocarbonylmethylpiperazin-1-yl)-1-(3-phenylpropoxycarb onyl)-4H-quinolizin-4-one;
- and 3-cyano-1-(2-hydroxyethyloxycarbonyl)-2-piperidino-4H-quinolizin-4-one;or a pharmaceutically acceptable salt thereof.
Dependencies are inferred from the claim text.