Therapeutic drug for lipid-peroxidation-induced diseases and screening method for therapeutic drugs for lipid-peroxidation-induced diseases

Abstract

The present invention provides: an assay method that uses a compound represented by formula (I) as a fluorescent probe molecule and that is for detecting the lipid peroxidation suppression activity of a test compound; an assay kit that uses the assay method; a screening method that uses the assay method; and a pharmaceutical composition that is for the treatment, etc. of diseases (such as age-related macular degeneration) that are induced by lipid peroxidation reactions.

1 . A pharmaceutical composition for preventing or treating a lipid peroxidation reaction-induced disease or inhibiting progression of the lipid peroxidation reaction-induced disease in a subject, comprising an effective amount of at least one compound selected from the group consisting of a group: methyldopa (methyldopa sesquihydrate), apomorphine ((R)-(−)-apomorphine hydrochloride), eseroline ((−)-eseroline fumarate), ethoxyquine (6-ethoxy-2,2,4-trimethyl-1,2-dihydroquinoline), olanzapine (2-methyl-4-(4-methyl-1-piperazinyl)-10H-thieno[2,3-b][1,5]benzodiazepine, methyl 3-amino-4-(phenylamino)benzoate, methyl 3-amino-4-((4-methoxyphenyl)amino)benzoate, methyl 3-amino-4-((3-methoxyphenyl)amino)benzoate, methyl 3-amino-4-(benzylamino)benzoate, methyl 3-amino-4-((1-phenylethyl)amino)benzoate, 1-(4-(trifluoromethoxy)phenyl)indolin-5-amine, 1-(3,5-dimethylphenyl)-1H-indol-6-amine, 1-(3,5-dimethylphenyl)indolin-6-amine, 1-(4-methoxyphenyl)-1H-indol-6-amine, 1-(4-(methylthio)phenyl)-1H-indol-6-amine, 1-(4-(trifluoromethoxy)phenyl)-1H-indol-5-amine. 
     
     
         2 . The pharmaceutical composition according to  claim 1 , wherein the disease is selected from the group consisting of Alzheimer' type dementia, chronic kidney diseases, diabetic neuropathy, liver disorder, age-related macular degeneration, postischemic brain disorder, vascular dementia, arteriosclerosis, Parkinson's disease, multiple sclerosis, cancer, asthma, hypertension, cardiovascular diseases, and age-related eye disease. 
     
     
         3 . The pharmaceutical composition according to  claim 1 , wherein the disease is age-related macular degenerative disease. 
     
     
         4 . The pharmaceutical composition according to  claim 1 , wherein the compound is methyldopa (methyldopa sesquihydrate). 
     
     
         5 . The pharmaceutical composition according to  claim 1 , wherein the lipid peroxidation reaction-induced disease is a lipid peroxidation reaction-induced retinal disease in outer nuclear layer (ONL). 
     
     
         6 . The pharmaceutical composition according to  claim 3 , wherein the age-related macular degenerative disease is an atrophic age-related macular degenerative disease. 
     
     
         7 . The pharmaceutical composition according to  claim 3 , wherein the age-related macular degenerative disease is an exudative age-related macular degenerative disease. 
     
     
         8 . A method for preventing or treating a lipid peroxidation reaction-induced disease or inhibiting progression of the lipid peroxidation reaction-induced disease in a subject, which comprises applying an effective amount of at least one compound to the subject,
 wherein the compound is selected from the group consisting of a group: methyldopa (methyldopa sesquihydrate), apomorphine ((R)-(−)-apomorphine hydrochloride), eseroline ((−)-eseroline fumarate), ethoxyquine (6-ethoxy-2,2,4-trimethyl-1,2-dihydroquinoline), olanzapine (2-methyl-4-(4-methyl-1-piperazinyl)-10H-thieno[2,3-b][1,5]benzodiazepine, methyl 3-amino-4-(phenylamino)benzoate, methyl 3-amino-4-((4-methoxyphenyl)amino)benzoate, methyl 3-amino-4-((3-methoxyphenyl)amino)benzoate, methyl 3-amino-4-(benzylamino)benzoate, methyl 3-amino-4-((1-phenylethyl)amino)benzoate, 1-(4-(trifluoromethoxy)phenyl)indolin-5-amine, 1-(3,5-dimethylphenyl)-1H-indol-6-amine, 1-(3,5-dimethylphenyl)indolin-6-amine, 1-(4-methoxyphenyl)-1H-indol-6-amine, 1-(4-(methylthio)phenyl)-1H-indol-6-amine, 1-(4-(trifluoromethoxy)phenyl)-1H-indol-5-amine.   
     
     
         9 . The method according to  claim 8 , wherein the disease is selected from the group consisting of Alzheimer' type dementia, chronic kidney diseases, diabetic neuropathy, liver disorder, age-related macular degeneration, postischemic brain disorder, vascular dementia, arteriosclerosis, Parkinson's disease, multiple sclerosis, cancer, asthma, hypertension, cardiovascular diseases, and age-related eye disease. 
     
     
         10 . The method according to  claim 8 , wherein the disease is age-related macular degenerative disease. 
     
     
         11 . The method according to  claim 8 , wherein the compound is methyldopa (methyldopa sesquihydrate). 
     
     
         12 . The method according to  claim 8 , wherein the lipid peroxidation reaction-induced disease is a lipid peroxidation reaction-induced retinal disease in outer nuclear layer (ONL). 
     
     
         13 . The method according to  claim 10 , wherein the age-related macular degenerative disease is an atrophic age-related macular degenerative disease. 
     
     
         14 . The method according to  claim 10 , wherein the age-related macular degenerative disease is an exudative age-related macular degenerative disease.