Aminocarbonylcarbamate compounds

Abstract

The present disclosure provides a compound represented by Formula (I) and a pharmaceutically acceptable salt which are effective as a dopamine reuptake inhibitor and a method of using the compound: wherein X is independently halo, alkyl, alkoxy or nitro; m is 0, 1, 2, 3 or 4; n is 1 or 2; R 1 and R 2 are independently H— or alkyl; R 3 is H—, alkyl or aralkyl; and R 4 is H— or aryl.

1 .- 15 . (canceled) 
     
     
         16 . A method for treating a dopamine reuptake-related disease comprising:
 administering to a mammal in need thereof an oral or parenteral formulation comprising (a) a therapeutically effective amount of a compound of Formula (I) or pharmaceutically acceptable salt thereof and (b) a therapeutically effective amount of an agent selected from the group consisting of adderall, concerta, dexedrine, focalin, metadate, methylin, ritalin, vyvanse, daytrana, and quillivant,   
       
         
           
           
               
               
           
         
         wherein 
         X is independently halo, alkyl, alkoxy or nitro; 
         m is 0, 1, 2, 3 or 4 
         n is 1 or 2; 
         R 1  and R 2  are independently H— or alkyl; 
         R 3  is H—, alkyl or aralkyl; and 
         R 4  is H— or aryl,
 wherein at least one of R 1 , R 2 , R 3  and R 4  is not H—, 
 or a compound selected from the group consisting of: 
 
         2-amino-3-(2-chlorophenyl)propyl (aminocarbonyl)carbamate; 
         2-amino-3-(2,4-dichlorophenyl)propyl (aminocarbonyl)carbamate; 
         2-amino-3-(3,4-dichlorophenyl)propyl (aminocarbonyl)carbamate; 
         2-amino-3-(4-chlorophenyl)propyl (aminocarbonyl)carbamate; 
         2-amino-3-(3-chlorophenyl)propyl (aminocarbonyl)carbamate; 
         2-amino-3-(4-nitrophenyl)propyl (aminocarbonyl)carbamate; 
         2-amino-3-(4-tert-butylphenyl)propyl (aminocarbonyl)carbamate; 
         2-amino-3-(2-fluorophenyl)propyl (aminocarbonyl)carbamate; 
         (2R)-2-amino-3-(2-chlorophenyl)propyl (aminocarbonyl)carbamate; 
         (2R)-2-amino-3-(2,4-dichlorophenyl)propyl (aminocarbonyl)carbamate; 
         (2R)-2-amino-3-(3,4-dichlorophenyl)propyl (aminocarbonyl)carbamate; 
         2-amino-3-phenylpropyl(aminocarbonyl)carbamate; 
         (2R)-2-amino-3-phenylpropyl(aminocarbonyl)carbamate; and 
         a pharmaceutically acceptable salt thereof. 
       
     
     
         17 . The method of  claim 16 , wherein the dopamine reuptake-related disease is selected from the group consisting of fatigue, obesity, narcolepsy, fibromyalgia, cataplexy, drug addiction, sexual dysfunction, restless legs syndrome, bipolar disorder, depression, excessive daytime sleepiness, obsessive-compulsive disorder, and binge eating disorder. 
     
     
         18 . The method of  claim 16 , wherein the oral or parenteral formulation further comprises at least one pharmaceutically-acceptable carrier. 
     
     
         19 . The method of  claim 18 , wherein the carrier is lactose, dibasic calcium phosphate, corn starch or a mixture thereof. 
     
     
         20 . The method of  claim 16 , wherein the compound is a compound of Formula (II): 
       
         
           
           
               
               
           
         
         wherein 
         X is independently halo, alkyl, alkoxy or nitro; 
         m is 0, 1, 2, 3 or 4; 
         n is 1 or 2; 
         R 1  and R 2  are independently H— or alkyl; and 
         R 4  is H— or aryl, and 
         wherein at least one of R 1 , R 2  and R 4  is not H—. 
       
     
     
         21 . The method according to  claim 20 , wherein the compound is selected from the group consisting of:
 2-(isopropylamino)-3-phenylpropyl (aminocarbonyl)carbamate;   2-(dimethylamino)-3-phenylpropyl (aminocarbonyl)carbamate;   2-(methylamino)-3-phenylpropyl (aminocarbonyl)carbamate; and   2-amino-3-phenylpropyl (anilinocarbonyl)carbamate.   
     
     
         22 . The method according to  claim 21 , wherein the compound is selected from the group consisting of:
 (2R)-2-(isopropylamino)-3-phenylpropyl (aminocarbonyl)carbamate;   (2R)-2-(dimethylamino)-3-phenylpropyl (aminocarbonyl)carbamate;   (2R)-2-(methylamino)-3-phenylpropyl (aminocarbonyl)carbamate; and   (2R)-2-amino-3-phenylpropyl (anilinocarbonyl)carbamate.   
     
     
         23 . The method according to  claim 22 , wherein the salt is hydrochloride. 
     
     
         24 . The method according to  claim 16 , wherein the compound is a compound of Formula (III): 
       
         
           
           
               
               
           
         
         wherein 
         X is independently halo, alkyl, alkoxy or nitro; 
         m is 0, 1, 2, 3 or 4; 
         n is 1 or 2; 
         R 1  and R 2  are independently H— or alkyl; and 
         R 3  is H—, alkyl or aralkyl, and 
         wherein at least one of R 1 , R 2  and R 3  is not H—. 
       
     
     
         25 . The method according to  claim 24 , wherein the compound is selected from the group consisting of:
 2-amino-3-phenylpropyl (aminocarbonyl)methylcarbamate;   2-(dimethylamino)-3-phenylpropyl (aminocarbonyl)methylcarbamate;   2-amino-3-phenylpropyl (aminocarbonyl)benzylcarbamate;   2-amino-3-phenylpropyl (aminocarbonyl)ethylcarbamate;   2-amino-3-(2-chlorophenyl)propyl (aminocarbonyl)methylcarbamate;   2-amino-3-(4-fluorophenyl)propyl (aminocarbonyl)methylcarbamate;   2-amino-3-(4-chlorophenyl)propyl (aminocarbonyl)methylcarbamate;   2-amino-3-(2,4-dichlorophenyl)propyl (aminocarbonyl)methylcarbamate;   2-amino-3-(3,4-dichlorophenyl)propyl (aminocarbonyl)methylcarbamate;   2-amino-3-(4-nitrophenyl)propyl (aminocarbonyl)methylcarbamate;   2-amino-3-(4-methylphenyl)propyl (aminocarbonyl)methylcarbamate;   2-amino-3-(4-ethoxyphenyl)propyl (aminocarbonyl)methylcarbamate; and   2-amino-4-phenylbutyl (aminocarbonyl)methylcarbamate.   
     
     
         26 . The method according to  claim 25 , wherein the compound is selected from the group consisting of:
 (2R)-2-amino-3-phenylpropyl (aminocarbonyl)methylcarbamate;   (2R)-2-(dimethylamino)-3-phenylpropyl (aminocarbonyl)methylcarbamate;   (2R)-2-amino-3-phenylpropyl (aminocarbonyl)benzylcarbamate;   (2R)-2-amino-3-phenylpropyl (aminocarbonyl)ethylcarbamate;   (2R)-2-amino-3-(2-chlorophenyl)propyl (aminocarbonyl)methylcarbamate;   (2R)-2-amino-3-(4-chlorophenyl)propyl (aminocarbonyl)methylcarbamate;   (2R)-2-amino-3-(2,4-dichlorophenyl)propyl (aminocarbonyl)methylcarbamate;   (2R)-2-amino-3-(3,4-dichlorophenyl)propyl (aminocarbonyl)methylcarbamate;   (2S)-2-amino-3-phenylpropyl (aminocarbonyl)methylcarbamate;   (2R)-2-amino-3-(4-nitrophenyl)propyl (aminocarbonyl)methylcarbamate;   (2R)-2-amino-3-(4-methylphenyl)propyl (aminocarbonyl)methylcarbamate;   (2R)-2-amino-3-(4-ethoxyphenyl)propyl (aminocarbonyl)methylcarbamate; and   (2R)-2-amino-4-phenylbutyl (aminocarbonyl)methylcarbamate.   
     
     
         27 . The method according to  claim 26 , wherein the salt is hydrochloride. 
     
     
         28 . A compound or hydrochloride salt thereof, wherein the compound is selected from the group consisting of:
 (2R)-2-amino-3-phenylpropyl (aminocarbonyl)methylcarbamate;   (2R)-2-(dimethylamino)-3-phenylpropyl (aminocarbonyl)methylcarbamate;   (2R)-2-amino-3-phenylpropyl (aminocarbonyl)benzylcarbamate;   (2R)-2-amino-3-phenylpropyl (aminocarbonyl)ethylcarbamate;   (2R)-2-amino-3-(2-chlorophenyl)propyl (aminocarbonyl)methylcarbamate;   (2R)-2-amino-3-(4-chlorophenyl)propyl (aminocarbonyl)methylcarbamate;   (2R)-2-amino-3-(2,4-dichlorophenyl)propyl (aminocarbonyl)methylcarbamate;   (2R)-2-amino-3-(3,4-dichlorophenyl)propyl (aminocarbonyl)methylcarbamate;   (2S)-2-amino-3-phenylpropyl (aminocarbonyl)methylcarbamate;   (2R)-2-amino-3-(4-nitrophenyl)propyl (aminocarbonyl)methylcarbamate;   (2R)-2-amino-3-(4-methylphenyl)propyl (aminocarbonyl)methylcarbamate;   (2R)-2-amino-3-(4-ethoxyphenyl)propyl (aminocarbonyl)methylcarbamate; and   (2R)-2-amino-4-phenylbutyl (aminocarbonyl)methylcarbamate.