Benzazepine derivatives useful for treatment of 5ht2c receptor associated diseases

Abstract

The present invention relates to certain 1-substituted-2,3,4,5-tetrahydro-3-benzazepine derivatives of Formula (I), that are modulators of the 5HT2C receptor. Accordingly, compounds of the present invention are useful for the prophylaxis or treatment of 5HT2C receptor associated diseases, conditions or disorders, such as, obesity and related disorders.

1 .- 123 . (canceled) 
     
     
         124 . A method of treatment of: a disorder of the central nervous system;
 damage to the central nervous system; a cardiovascular disorder; a gastrointestinal disorder; diabetes insipidus; or sleep apnea comprising administering to an individual in need of such treatment a therapeutically effective amount of a compound of Formula (I):   
       
         
           
           
               
               
           
         
         wherein: 
         R 1  is H or C 1-8  alkyl; 
         R 2  is C 1-4  alkyl, —CH 2 —O—C 1-4  alkyl, C 1-4  haloalkyl or CH 2 OH; and 
         R 3 , R 4 , R 5  and R 6  are each independently H, C 1-4  alkyl, amino, cyano, halogen, C 1-4  haloalkyl, nitro or OH; or 
         a pharmaceutically acceptable salt or hydrate thereof; 
       
       provided that when R 2  is C 1-4  alkyl, —CH 2 —O—C 1-4  alkyl, and CH 2 OH then R 3  and R 6  are not both hydrogen. 
     
     
         125 . The method according to  claim 124 , wherein the disorder of the central nervous system is selected from: depression, atypical depression, bipolar disorders, anxiety disorders, obsessive-compulsive disorders, social phobias or panic states, sleep disorders, sexual dysfunction, psychoses, schizophrenia, migraine and other conditions associated with cephalic pain or other pain, raised intracranial pressure, epilepsy, personality disorders, Alzheimer disease, age-related behavioral disorders, behavioral disorders associated with dementia, organic mental disorders, mental disorders in childhood, aggressivity, age-related memory disorders, chronic fatigue syndrome, drug and alcohol addiction, obesity, bulimia, anorexia nervosa, and premenstrual tension. 
     
     
         126 . The method according to  claim 125 , wherein the disorder of the central nervous system is Alzheimer disease. 
     
     
         127 . The method according to  claim 125 , wherein the disorder of the central nervous system is male erectile dysfunction. 
     
     
         128 . The method according to  claim 124 , wherein the damage to the central nervous system is caused by trauma, stroke, a neurodegenerative disease, a toxic CNS disease, or an infective CNS disease. 
     
     
         129 . The method according to  claim 124 , wherein the damage to the central nervous system is caused by encephalitis or meningitis. 
     
     
         130 . The method according to  claim 124 , wherein the cardiovascular disorder is thrombosis. 
     
     
         131 . The method according to  claim 124 , wherein the gastrointestinal disorder is dysfunction of gastrointestinal motility. 
     
     
         132 . The method according to  claim 124 , wherein R 1  is H. 
     
     
         133 . The method according to  claim 124 , wherein R 1  is methyl. 
     
     
         134 . The method according to  claim 124 , wherein R 2  is C 1-4  alkyl. 
     
     
         135 . The method according to  claim 134 , wherein R 2  is methyl. 
     
     
         136 . The method according to  claim 124 , wherein R 3  is H. 
     
     
         137 . The method according to  claim 124 , wherein R 3  is halogen. 
     
     
         138 . The method according to  claim 124 , wherein R 4  is H. 
     
     
         139 . The method according to  claim 124 , wherein R 4  is halogen. 
     
     
         140 . The method according to  claim 124 , wherein R 5  is H. 
     
     
         141 . The method according to  claim 124 , wherein R 6  is H. 
     
     
         142 . The method according to  claim 124 , wherein R 6  is halogen. 
     
     
         143 . The method according to  claim 124 , wherein the compound is selected from:
 6,8-Dichloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine;   6-Chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine;   8-Chloro-9-fluoro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine; and   8,9-Dichloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine.   
     
     
         144 . The method according to  claim 124 , wherein the compound is 9-bromo-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine. 
     
     
         145 . The method according to  claim 124 , wherein the compound is selected from:
 N-methyl-8,9-dichloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine; and   N-methyl-9-bromo-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine.   
     
     
         146 . The method according to  claim 124 , wherein said compound is an R enantiomer. 
     
     
         147 . The method according to  claim 124 , wherein said compound is an S enantiomer.