Substituted Phenethylamines With Serotoninergic And/Or Norepinephrinergic Activity

Abstract

Chemical syntheses and medical uses of novel inhibitors of the uptake of monoamine neurotransmitters and pharmaceutically acceptable salts and prodrugs thereof, for the treatment and/or management of psychotropic disorders, anxiety disorder, generalized anxiety disorder, depression, post-traumatic stress disorder, obsessive-compulsive disorder, panic disorder, hot flashes, senile dementia, migraine, hepatopulmonary syndrome, chronic pain, nociceptive pain, neuropathic pain, painful diabetic retinopathy, bipolar depression, obstructive sleep apnea, psychiatric disorders, premenstrual dysphoric disorder, social phobia, social anxiety disorder, urinary incontinence, anorexia, bulimia nervosa, obesity, ischemia, head injury, calcium overload in brain cells, drug dependence, and/or premature ejaculation are described.

What is claimed is: 
     
         1 . A compound of Formula 1: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt, solvate, or prodrug thereof, wherein: 
         R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , R 12 , R 13 , R 14 , R 15 , R 16 , R 17 , and R 18  are independently hydrogen or deuterium; 
         R 19 , R 20 , and R 21  are independently —CH 3  or —CD 3 ; 
         wherein the compound contains at least one deuterium atom; and has deuterium enrichment that is at least about 1%. 
       
     
     
         2 . The compound as recited in  claim 1 , which is: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt, solvate, or prodrug thereof. 
       
     
     
         3 . The compound of  claim 1 , wherein said compound is a mixture of enantiomers. 
     
     
         4 . The compound of  claim 1 , wherein sites designated as D contain deuterium enrichment of greater than 10%. 
     
     
         5 . The compound of  claim 1 , wherein sites designated as D contain deuterium enrichment of greater than 20%. 
     
     
         6 . The compound of  claim 1 , wherein sites designated as D contain deuterium enrichment of greater than 50%. 
     
     
         7 . The compound of  claim 1 , wherein sites designated as D contain deuterium enrichment of greater than 70%. 
     
     
         8 . The compound of  claim 1 , wherein sites designated as D contain deuterium enrichment of greater than 90%. 
     
     
         9 . A pharmaceutical composition comprising a compound of  claim 1  and a pharmaceutically acceptable carrier. 
     
     
         10 . A method of treating a disease or condition involving monoamine reuptake, comprising administering to a mammalian subject in need thereof a therapeutically effective amount of a compound of  claim 1 . 
     
     
         11 . The method of  claim 10 , wherein the disease or condition is an anxiety disorder, generalized anxiety disorder, depression, post-traumatic stress disorder, obsessive-compulsive disorder, panic disorder, hot flashes, senile dementia, migraine, hepatopulmonary syndrome, chronic pain, nociceptive pain, neuropathic pain, painful diabetic retinopathy, bipolar depression, obstructive sleep apnea, psychiatric disorders, premenstrual dysphoric disorder, social phobia, social anxiety disorder, urinary incontinence, anorexia, bulimia nervosa, obesity, ischemia, head injury, calcium overload in brain cells, drug dependence, or premature ejaculation. 
     
     
         12 . The method of  claim 10 , wherein the disease or condition is a drug addition. 
     
     
         13 . The method of  claim 12 , wherein the drug addiction is an addiction to tobacco, alcohol, marijuana, or cocaine.