US2020291059A1PendingUtilityA1

Compositions and methods for treating cns disorders

Assignee: SAGE THERAPEUTICS INCPriority: Dec 8, 2017Filed: Dec 7, 2018Published: Sep 17, 2020
Est. expiryDec 8, 2037(~11.4 yrs left)· nominal 20-yr term from priority
C07J 43/003C07J 7/0085C07J 7/002C07J 1/0059C07J 13/007C07J 7/007A61P 25/00A61K 31/58A61P 25/24C07B 2200/05
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Claims

Abstract

Provided herein is a deuterated compound of Formula (I) Formula (I) or a pharmaceutically acceptable salt thereof, wherein R 3a , R 5 , R 6a , R 6b , R 17 , R 21a , R 21 b, R m , R n , R 16a , R 16 b , R 7a , R 7b , R 12a , R 12b , R 11a , R 11b , R 2a , R2 b , R 19 , R 4a , and R 4b are defined herein. Also provided herein are pharmaceutical compositions comprising a compound of Formula (I) and methods of using the compounds, e.g., in the treatment of CNS-related disorders.

Claims

exact text as granted — not AI-modified
1 . A compound of Formula (I) 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof, wherein
 R 3a  is C 1 -C 6  alkyl optionally substituted with 1 or more independent occurrences of deuterium or X 2 —OX 3 , wherein each of X 2  and X 3  is independently a C 1 -C 6  alkylene optionally substituted with 1 more occurrences of deuterium; and 
 each of R 5 , R 6a , R 6b , R 17 , R 21a , R 21b , R m , R n , R 16a , R 16b , R 7a , R 7b , R 12a , R 12b , R 11a , R 11b , R 2a , R 2b , R 19 , R 4a , and R 4b  is independently selected from the group consisting of hydrogen and deuterium, 
 provided that 
 (a) if R 3a  is C 1 -C 6  alkyl with no occurrences of deuterium or X 2 —OX 3 , wherein each of X 2  and X 3  is independently an C 1 -C 6  alkylene with no occurrences of deuterium, then at least one of R 5 , R 6a , R 6b , R 17 , R 21a , R 21b , R m , and R n , R 16a , R 16b , R 7a , R 7b , R 12a , R 12b , R 11a , R 11b , R 2a , R 2b , R 19 , R 4a , and R 4b  is deuterium, or 
 (b) if all of R 5 , R 6a , R 6b , R 17 , R 21a , R 21b , R m , R n , R 16a , R 16b , R 7a , R 7b , R 12a , R 12b , R 11a , R 11b , R 2a , R 2b , R 19 , R 4a , and R 4b  are hydrogen, then R 3a  is C 1 -C 6  alkyl substituted with 1 or more independent occurrences of deuterium or X 2 —OX 3 , wherein X 2  and X 3  must be substituted with at least one occurrence of deuterium. 
 
     
     
         2 . The compound of  claim 1 , wherein R 3a  is C 1 -C 3  alkyl substituted with 0-7 independent occurrences of deuterium or X 2a —OX 3a , wherein X 2a  is C 1 -C 3  alkylene substituted with 0-7 independent occurrences of deuterium and X 3a  is C 1 -C 3  alkylene substituted with 0-7 independent occurrences of deuterium. 
     
     
         3 . The compound of  claim 1  or  2 , wherein if R 3a  is —CH 3 , then at least one of R 5 , R 6a , R 6b , R 17 , R 21a , R 21b , R m , and R n  is deuterium, or if all of R 5 , R 6a , R 6b , R 17 , R 21a , R 21b , R m , and R n  are hydrogen, then R 3a  is a methyl group substituted with 1-3 independent occurrences of deuterium. 
     
     
         4 . The compound of  claim 1 , wherein R 3a  is selected from the group consisting of —CH 3  and CD 3 . 
     
     
         5 . The compound of  claim 1  or  2 , wherein R 3a  is —CH 3 . 
     
     
         6 . The compound of  claim 1  or  2 , wherein R 3a  is —CD 3 . 
     
     
         7 . The compound any one of  claims 1 - 6 , wherein at least one of R 5 , R 6a , R 6b , R 17 , R 21a , R 21b , R m , R n , R 16a , R 16b , R 7a , R 7b , R 12a , R 12b , R 11a , R 11b , R 2a , R 2b , R 19 , R 4a , and R 4b  is deuterium. 
     
     
         8 . The compound of claim any one of  claims 1 - 7 , wherein at least one of R 5 , R 6a , R 6b , R 17 , R 21a , R 21b , R m , and R n  is deuterium. 
     
     
         9 . The compound of any one of  claims 1 - 6 , wherein R 3a  is —CH 3  and at least one of R 5 , R 6a , R 6b , R 17 , R 21a , R 21b , R m , R n , R 16a , R 16b , R 7a , R 7b , R 12a , R 12b , R 11a , R 11b , R 2a , R 2b , R 19 , R 4a , and R 4b  is deuterium. 
     
     
         10 . The compound of any one of  claims 1 - 9 , wherein R 3a  is —CH 3  and at least one of R 5 , R 6a , R 6b , R 17 , R 21a , R 21b , R m , and R n  is deuterium. 
     
     
         11 . The compound of any one of  claims 1 - 10 , wherein R 5  and R 6a  are hydrogen. 
     
     
         12 . The compound of any one of  claims 1 - 10 , wherein R 5  and R 6a  are deuterium. 
     
     
         13 . The compound of any one of  claims 1 - 12 , wherein R 17  is hydrogen. 
     
     
         14 . The compound of any one of  claims 1 - 12 , wherein R 17  is deuterium. 
     
     
         15 . The compound of any one of  claims 1 - 14 , wherein each of R 21a  and R 21b  is independently selected from the group consisting of hydrogen and deuterium. 
     
     
         16 . The compound of any one of  claims 1 - 15 , wherein R 21a  and R 21b  are hydrogen. 
     
     
         17 . The compound of any one of  claims 1 - 15 , wherein R 21a  and R 21b  are deuterium. 
     
     
         18 . The compound of any one of  claims 1 - 17 , wherein R m  and R n  are hydrogen. 
     
     
         19 . The compound of any one of  claims 1 - 17 , wherein R m  and R n  are deuterium. 
     
     
         20 . The compound of any one of  claims 1 - 13 , wherein R 21a , R 21b , R m , and R n  are deuterium. 
     
     
         21 . The compound of any one of  claims 1 - 10 , wherein R 17  and R 16a  are deuterium and R 16b  is hydrogen. 
     
     
         22 . The compound of any one of  claims 1 - 21 , wherein R 19  is hydrogen. 
     
     
         23 . The compound of any one of  claims 1 - 23 , wherein the compound of Formula (I) is the compound of Formula (I-A) 
       
         
           
           
               
               
           
         
       
     
     
         24 . The compound of any one of  claims 1 - 10 , wherein the compound of Formula (I) is the compound of Formula (I-B) 
       
         
           
           
               
               
           
         
       
     
     
         25 . The compound of  claim 1 , wherein the compound of Formula (I) is the compound of Formula (I-C) 
       
         
           
           
               
               
           
         
       
     
     
         26 . The compound of  claim 23 , wherein the compound of Formula (I-C) is selected from the group consisting of the compounds identified in the table below: 
       
         
           
                 
                 
                 
                 
                 
                 
                 
                 
                 
                 
               
                     
                 
                   Compound 
                     
                     
                     
                     
                     
                     
                     
                     
                     
                 
                   Number 
                   R 3a   
                   R 5   
                   R 6a   
                   R 6b   
                   R 17   
                   R 21a   
                   R 21b   
                   R m   
                   R n   
                 
                     
                 
                   1 
                   —CD 3   
                   H 
                   H 
                   H 
                   H 
                   H 
                   H 
                   H 
                   H 
                 
                   2 
                   —CH 3   
                   D 
                   D 
                   H 
                   H 
                   H 
                   H 
                   H 
                   H 
                 
                   3 
                   —CH 3   
                   H 
                   H 
                   H 
                   D 
                   H 
                   H 
                   H 
                   H 
                 
                   4 
                   —CH 3   
                   H 
                   H 
                   H 
                   H 
                   D 
                   D 
                   H 
                   H 
                 
                   5 
                   —CH 3   
                   H 
                   H 
                   H 
                   H 
                   H 
                   H 
                   D 
                   D 
                 
                   6 
                   —CD 3   
                   H 
                   H 
                   H 
                   H 
                   D 
                   D 
                   D 
                   D 
                 
                   7 
                   —CH 3   
                   H 
                   H 
                   H 
                   H 
                   D 
                   D 
                   D 
                   D 
                 
                   8 
                   —CD 3   
                   H 
                   H 
                   H 
                   H 
                   H 
                   H 
                   D 
                   D 
                 
                     
                 
             
                
                
                
                
               
               
                
                
                
                
                
                
                
                
                
               
            
           
         
       
       wherein any atom not labeled as deuterium is present at its natural isotopic abundance. 
     
     
         27 . A pharmaceutically acceptable salt of a compound of any one of the preceding claims. 
     
     
         28 . A pharmaceutical composition comprising a compound of any one of  claims 1 - 24  or pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient. 
     
     
         29 . A method of treating a CNS-related disorder in a subject in need thereof, comprising administering to the subject an effective amount of a compound of any one of  claims 1 - 24  or a pharmaceutically acceptable salt thereof. 
     
     
         30 . The method of  claim 29 , wherein the CNS-related disorder is a sleep disorder, a mood disorder, a schizophrenia spectrum disorder, a convulsive disorder, a disorder of memory and/or cognition, a movement disorder, a personality disorder, autism spectrum disorder, pain, traumatic brain injury, a vascular disease, a substance abuse disorder and/or withdrawal syndrome, tinnitus, or status epilepticus. 
     
     
         31 . The method of  claim 29 , wherein the CNS-related disorder is depression. 
     
     
         32 . The method of  claim 29 , wherein the CNS-related disorder is postpartum depression. 
     
     
         33 . The method of  claim 29 , wherein the CNS-related disorder is major depressive disorder. 
     
     
         34 . The method of  claim 31 , wherein the major depressive disorder is moderate major depressive disorder. 
     
     
         35 . The method of  claim 31 , wherein the major depressive disorder is severe major depressive disorder.

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