Carbamoyl Phenylalaninol Compounds and Uses Thereof

Abstract

The present invention relates to carbamoyl phenylalaninol compounds and methods of using the same to treat disorders.

What is claimed is: 
     
         1 . A compound of Formula I: 
       
         
           
           
               
               
           
         
         wherein 
         R is optionally substituted lower alkyl of 1 to 8 carbon atoms, halogen, optionally substituted alkoxy containing 1 to 3 carbon atoms, nitro, hydroxy, cyano, trifluoromethyl, or optionally substituted thioalkoxy containing 1 to 3 carbon atoms; 
         x is an integer of 0 to 3, with the proviso that R may be the same or different when x is 2 or 3; 
         R 1 , R 2 , and R 3  are independently hydrogen, optionally substituted lower alkyl of 1 to 8 carbon atoms, optionally substituted aryl, optionally substituted arylalkyl, or optionally substituted cycloalkyl of 3 to 7 carbon atoms; or 
         R 2  and R 3  can be joined to form a 5 to 7-membered heterocycle optionally substituted with a member selected from the group consisting of alkyl and aryl groups, wherein the heterocycle can comprise 1 to 2 nitrogen atoms and 0 to 1 oxygen atom, wherein the nitrogen atoms are not directly connected with each other or with the oxygen atom; 
         or a pharmaceutically acceptable salt thereof; 
         wherein the compound is not compound 1: 
       
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof. 
       
     
     
         2 . The compound of  claim 1 , which is a compound of Formula II: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof. 
       
     
     
         3 . A composition comprising the compound of  claim 1  or  2 . 
     
     
         4 . A pharmaceutical composition comprising the compound of  claim 1  or  2  and a pharmaceutically acceptable carrier. 
     
     
         5 . The composition of  claim 3  or  4 , wherein the composition is a dosage form. 
     
     
         6 . The composition of  claim 5 , wherein the composition is an immediate release oral dosage form. 
     
     
         7 . The composition of  claim 6 , wherein the composition is a tablet or a capsule. 
     
     
         8 . A method of treating narcolepsy, cataplexy, excessive daytime sleepiness, drug addiction, sexual dysfunction, fatigue, fibromyalgia, attention deficit/hyperactivity disorder, restless legs syndrome, depression, bipolar disorder, or obesity in a subject in need thereof, or promoting smoking cessation in a subject in need thereof, comprising administering to the subject the a compound of Formula I: 
       
         
           
           
               
               
           
         
         wherein 
         R is optionally substituted lower alkyl of 1 to 8 carbon atoms, halogen, optionally substituted alkoxy containing 1 to 3 carbon atoms, nitro, hydroxy, cyano, trifluoromethyl, or optionally substituted thioalkoxy containing 1 to 3 carbon atoms; 
         x is an integer of 0 to 3, with the proviso that R may be the same or different when x is 2 or 3; 
         R 1 , R 2 , and R 3  are independently hydrogen, optionally substituted lower alkyl of 1 to 8 carbon atoms, optionally substituted aryl, optionally substituted arylalkyl, or optionally substituted cycloalkyl of 3 to 7 carbon atoms; or 
         R 2  and R 3  can be joined to form a 5 to 7-membered heterocycle optionally substituted with a member selected from the group consisting of alkyl and aryl groups, wherein the heterocycle can comprise 1 to 2 nitrogen atoms and 0 to 1 oxygen atom, wherein the nitrogen atoms are not directly connected with each other or with the oxygen atom; 
         or a pharmaceutically acceptable salt thereof. 
       
     
     
         9 . A method of inducing a pro-cognitive effect in a subject in need thereof, comprising administering to the subject the a compound of Formula I: 
       
         
           
           
               
               
           
         
         wherein 
         R is optionally substituted lower alkyl of 1 to 8 carbon atoms, halogen, optionally substituted alkoxy containing 1 to 3 carbon atoms, nitro, hydroxy, cyano, trifluoromethyl, or optionally substituted thioalkoxy containing 1 to 3 carbon atoms; 
         x is an integer of 0 to 3, with the proviso that R may be the same or different when x is 2 or 3; 
         R 1 , R 2 , and R 3  are independently hydrogen, optionally substituted lower alkyl of 1 to 8 carbon atoms, optionally substituted aryl, optionally substituted arylalkyl, or optionally substituted cycloalkyl of 3 to 7 carbon atoms; or 
         R 2  and R 3  can be joined to form a 5 to 7-membered heterocycle optionally substituted with a member selected from the group consisting of alkyl and aryl groups, wherein the heterocycle can comprise 1 to 2 nitrogen atoms and 0 to 1 oxygen atom, wherein the nitrogen atoms are not directly connected with each other or with the oxygen atom; 
         or a pharmaceutically acceptable salt thereof. 
       
     
     
         10 . The method of  claim 9 , wherein the subject has ADHD, bipolar depression, major depressive disorder, schizoaffective disorders, PTSD, Alzheimer's Disease, Parkinson's Disease, dementia, or multiple sclerosis. 
     
     
         11 . A method of treating nightmares and/or sleep-related disturbances associated with PTSD in a subject in need thereof, comprising administering to the subject the a compound of Formula I: 
       
         
           
           
               
               
           
         
         wherein 
         R is optionally substituted lower alkyl of 1 to 8 carbon atoms, halogen, optionally substituted alkoxy containing 1 to 3 carbon atoms, nitro, hydroxy, cyano, trifluoromethyl, or optionally substituted thioalkoxy containing 1 to 3 carbon atoms; 
         x is an integer of 0 to 3, with the proviso that R may be the same or different when x is 2 or 3; 
         R 1 , R 2 , and R 3  are independently hydrogen, optionally substituted lower alkyl of 1 to 8 carbon atoms, optionally substituted aryl, optionally substituted arylalkyl, or optionally substituted cycloalkyl of 3 to 7 carbon atoms; or 
         R 2  and R 3  can be joined to form a 5 to 7-membered heterocycle optionally substituted with a member selected from the group consisting of alkyl and aryl groups, wherein the heterocycle can comprise 1 to 2 nitrogen atoms and 0 to 1 oxygen atom, wherein the nitrogen atoms are not directly connected with each other or with the oxygen atom; 
         or a pharmaceutically acceptable salt thereof. 
       
     
     
         12 . The method of any one of  claims 8 - 11 , wherein the compound is a compound of Formula II: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof. 
       
     
     
         13 . The method of any one of  claims 8 - 11 , wherein the compound is compound 1: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof. 
       
     
     
         14 . The method of any one of  claims 8 - 11 , wherein the compound is compound 2: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof. 
       
     
     
         15 . The method of any one of  claims 8 - 14 , comprising administering a composition comprising the compound. 
     
     
         16 . The method of any one of  claims 8 - 14 , comprising administering a pharmaceutical composition comprising the compound and a pharmaceutically acceptable carrier. 
     
     
         17 . The method of  claim 15  or  16 , wherein the composition is a dosage form. 
     
     
         18 . The method of  claim 17 , wherein the composition is an immediate release oral dosage form. 
     
     
         19 . The method of  claim 18 , wherein the composition is a tablet or a capsule.