Compounds for Enhancing Arginase Activity and Methods of USe Thereof

Abstract

The present invention relates to a method for enhancing arginase activity in a damaged or injured cell. In other aspects, the invention provides a method for treating a disorder that can be treated by enhancing arginase activity in a human in need thereof, the method comprising administering to the human an effective amount of a compound that enhances arginase activity. Such disorders include ischemia, hypoxia, neurodegenerative disease or condition, stroke or trauma of the nervous system. In yet another aspect, the invention provides methods for promoting regeneration of a neural cell in a human in need thereof.

1 . A method for enhancing arginase activity in a damaged or injured cell in a human in need thereof, the method comprising administering to the human an effective amount of one of the following compounds: 2-hydroxyxanthone; 2-methoxyxanthone; 3-methylcholanthrene; 4,7-dimethoxyflavone; 4′-methoxychalcone; 4′-methoxyflavone; 5,4′-dimethoxyflavone; 5,7,4′-trimethoxyflavone; 5,7-dimethoxyisoflavone; 6,3′-dimethoxyflavone; Acacetin diacetate; Anisindione; Apigenin; Apigenin triacetate; Biochanin a; Biochanin a diacetate; Chlorpropham; Chrysophanol; Daidzein; Dehydrovariabilin; Derrubone; Derrusnin; Derrustone; Dibenzoylmethane; Fenbendazole; Formononetn; Genistein; Ginkgetin; Indoprofen; Ipraflavone; Liquiritigenin dimethyl ether; Methoxyvone; Methyl robustone; Phenazopyridine hydrochloride; Phenindione; Pinosylvin; Pinosylvin methyl ether; Piperine; Pramoxine hydrochloride; Resveratrol 4′-methyl ether, Retusin 7-methyl ether; Robustone; Spironolactone; Tilorone; Tranilast; or Xanthone; or a pharmaceutically acceptable salt of any such compound. 
   
   
       2 . A method according to  claim 1 , wherein the compound is Pinosylvin; Derrustone; Methoxyvone; Dehydrovariabilin; or Chrysophanol; or a pharmaceutically acceptable salt of any such compound. 
   
   
       3 . A method according to  claim 1 , wherein the compound comprises a 9H-xanthen-9-one selected from a group consisting of: 2-hydroxyxanthone, 2-methoxyxanthone, and xanthone; or a pharmaceutically acceptable salt of any such compound. 
   
   
       4 . A method according to  claim 1 , wherein the compound comprises a 4H-chromen-4-one selected from a group consisting of: 4,7-dimethoxyflavone; 4′-methoxyflavone; 5,4′-dimethoxyflavone; 5,7,4′-trimethoxyflavone; 5,7-dimethoxyisoflavone; 6,3′-dimethoxyflavone; Acacetin diacetate; Apigenin; Apigenin triacetate; Biochanin a; Biochanin a diacetate; Daidzein; Derrubone; Derrustone; Formononetn; Genistein; Ginkgetin; Ipraflavone; Liquiritigenin dimethyl ether, Methoxyvone; and Retusin 7-methyl ether, or a pharmaceutically acceptable salt of any such compound. 
   
   
       5 . A method according to  claim 4 , wherein the compound comprises a (4-methoxyphenyl)-4H-chromene-4-one selected from a group consisting of: 4,7-dimethoxyflavone; 4′-methoxyflavone; 5,4′-dimethoxyflavone; 5,7,4′-trimethoxyflavone; Acacetin diacetate; Biochanin a; Biochanin a diacetate; Formononetn; and Retusin 7-methyl ether; or a pharmaceutically acceptable salt of any such compound. 
   
   
       6 . A method according to  claim 1 , wherein the compound comprises a 1,3-benzodioxol selected from a group consisting of: Derrubone; Derrusnin; Derrustone; Methyl robustone; Piperine; and Robustone; or a pharmaceutically acceptable salt of any such compound. 
   
   
       7 . A method for enhancing arginase activity in a damaged or injured cell in a human in need thereof, the method comprising administering to the human an effective amount of Lansoprazole; or a pharmaceutically acceptable salt of such compound. 
   
   
       8 . A method for treating a disorder that can be treated by enhancing arginase activity in a human in need thereof, the method comprising administering to the human an effective amount of a compound that enhances arginase activity, wherein the compound is any one of the following: 2-hydroxyxanthone; 2-methoxyxanthone; 3-methylcholanthrene ; 4,7-dimethoxyflavone; 4′-methoxychalcone; 4′-methoxyflavone; 5,4′-dimethoxyflavone; 7,4′-trimethoxyflavone; 5,7-methoxyisoflavone; 6,3′-dimethoxyflavone; Acacetin diacetate; Anisindione; Apigenin; Apigenin triacetate; Biochanin a; Biochanin a diacetate; Chlorpropham; Chrysophanol; Daidzein; Dehydrovariabilin; Derrubone; Derrusnin; Derrustone; Dibenzoylmethane; Fenbendazole; Formononetn; Genistein; Ginkgetin; Indoprofen; Ipraflavone; Liquiritigenin dimethyl ether; Methoxyvone; Methyl robustone; Phenazopyridine hydrochloride; Phenindione; Pinosylvin; Pinosylvin methyl ether, Piperine; Pramoxine hydrochloride; Resveratrol 4′-methyl ether, Retusin 7-methyl ether, Robustone; Spironolactone; Tilorone; Tranilast; or Xanthone; or a pharmaceutically acceptable salt of any such compound. 
   
   
       9 . A method according to  claim 8 , wherein the disorder is ischemia. 
   
   
       10 . A method according to  claim 8 , wherein the disorder is hypoxia 
   
   
       11 . A method according to  claim 8 , wherein the disorder is a neurodegenerative disease or condition. 
   
   
       12 . A method according to  claim 11 , wherein the neurodegenerative disease or condition is any one of the following: Alexander disease, Alper's disease, Alzheimer's disease, Amyotrophic lateral sclerosis, Ataxia telangiectasia, Batten disease (also known as Spielmeyer-Vogt-Sjogren-Batten disease), Bovine spongiform encephalopathy (BSE), Canavan disease, Cockayne syndrome, Corticobasal degeneration, Creutzfeldt-Jakob disease, Huntington disease, HIV-associated dementia, Kennedy's disease, Krabbe disease, Lewy body dementia, Machado-Joseph disease (Spinocerebellar ataxia type 3), Multiple sclerosis, Multiple System Atrophy, Neuroborreliosis, Parkinson disease, Pelizaeus-Merzbacher Disease, Pick's disease, Primary lateral sclerosis, Prion diseases, Refsum's disease, Sandhoff disease, Schilder's disease, Schizophrenia, Spielmeyer-Vogt-Sjogren-Batten disease (also known as Batten disease), Spinocerebellar ataxia (multiple types with varying characteristics), Spinal muscular atrophy, Steele-Richardson-Olszewski disease, Tabes dorsalis, or other dimentias. 
   
   
       13 . A method according to  claim 8 , wherein the disorder is stroke. 
   
   
       14 . A method according to  claim 8 , wherein the disorder is trauma to the central nervous system or peripheral nervous system. 
   
   
       15 . A method according to  claim 8 , wherein the compound is Pinosylvin; Derrustone; Methoxyvone; Dehydrovariabilin; or Chrysophanol, or a pharmaceutically acceptable salt of any such compound. 
   
   
       16 . A method for treating a disorder that can be treated by enhancing arginase activity in a human in need thereof, the method comprising administering to the human an effective amount of Lansoprazole; or a pharmaceutically acceptable salt of such compound. 
   
   
       17 . A method for promoting regeneration of a neural cell in a human in need thereof, the method comprising administering to the human an effective amount of a compound that enhances arginase activity, wherein the compound is any one of the following: 2-hydroxyxanthone; 2-methoxyxanthone; 3-methylcholanthrene ; 4,7-dimethoxyflavone; 4′-methoxychalcone; 4′-methoxyflavone; 5,4′-dimethoxyflavone; 5,7,4′-trimethoxyflavone; 5,7-dimethoxyisoflavone; 6,3′-dimethoxyflavone; Acacetin diacetate; Anisindione; Apigenin; Apigenin triacetate; Biochanin a; Biochanin a diacetate; Chlorpropham; Chrysophanol; Daidzein; Dehydrovariabilin; Derrubone; Derrusnin; Derrustone; Dibenzoylmethane; Fenbendazole; Formononetn; Genistein; Ginkgetin; Indoprofen; Ipraflavone; Liquiritigenin dimethyl ether; Methoxyvone; Methyl robustone; Phenazopyridine hydrochloride; Phenindione; Pinosylvin; Pinosylvin methyl ether, Piperine; Pramoxine hydrochloride; Resveratrol 4′-methyl ether; Retusin 7-methyl ether; Robustone; Spironolactone; Tilorone; Tranilast; or Xanthone; or a pharmaceutically acceptable salt of any such compound. 
   
   
       18 . A method according to  claim 17 , wherein the compound is Pinosylvin; Derrustone; Methoxyvone; Dehydrovariabilin; or Chrysophanol; or a pharmaceutically acceptable salt of any such compound. 
   
   
       19 . A method for promoting regeneration of a neural cell in a human in need thereof, the method comprising administering to the human an effective amount of Lansoprazole; or a pharmaceutically acceptable salt of such compound. 
   
   
       20 . A method according to  claim 19 , wherein the neural cell is a neuron. 
   
   
       21 . A method according to  claim 19 , wherein the neural cell is a glial cell.