US2023250128A1PendingUtilityA1

Neuroactive steroids and compositions thereof

Assignee: SAGE THERAPEUTICS INCPriority: May 31, 2019Filed: Sep 2, 2022Published: Aug 10, 2023
Est. expiryMay 31, 2039(~12.8 yrs left)· nominal 20-yr term from priority
C07J 43/003C07J 1/0011C07J 9/00C07J 41/0055C07J 51/00C07J 11/00C07J 7/007C07J 1/0022C07J 21/008C07J 41/0094C07J 7/002C07J 9/005C07J 7/0085C07J 31/006C07J 5/0015C07J 71/001C07J 13/007C07J 17/00C07J 31/003C07J 21/00C07J 41/0088C07J 7/0095A61P 25/00A61P 25/18A61P 25/20A61P 25/28A61P 25/14A61P 25/24A61P 25/30A61P 25/08A61P 27/16A61P 9/00A61P 7/00A61P 29/00A61P 25/04A61K 31/58
78
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Claims

Abstract

Provided herein is a compound of Formula (I):or a pharmaceutically acceptable salt thereof, wherein R1a, R1b, R2a, R2b, R3, R4a, R4b, R5, R6a, R6b, R7a, R7a, R11a, R11b, R12a, R12b, R16a, R16b, R19, R11a, R22, RX, RY and n 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 - 104 . (canceled) 
     
     
         105 . A method of treating a CNS-related disorder in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a compound of Formula (I-e6): 
       
         
           
           
               
               
           
         
       
       a pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising a compound of Formula (I-e6) or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient; 
       wherein:
 each of R 2a , R 2b , R 15a , and R 15b  is hydrogen; 
 R 3  is unsubstituted C 1-3  alkyl, —CH 2 OCH 3 , or —CH 2 OCH 2 CH 3 ; 
 R 19  is hydrogen, methyl, or ethyl; 
 R X  is —OH; 
 R Y  is methyl; and 
 R 22  is —CN. 
 
     
     
         106 . The method of  claim 105 , wherein R 3  is methyl, ethyl, or propyl. 
     
     
         107 . The method of  claim 106 , wherein R 3  is methyl. 
     
     
         108 . The method of  claim 106 , wherein R 3  is ethyl. 
     
     
         109 . The method of  claim 106 , wherein R 3  is propyl. 
     
     
         110 . The method of  claim 105 , wherein R 3  is —CH 2 OCH 3 . 
     
     
         111 . The method of  claim 105 , wherein R 3  is —CH 2 OCH 2 CH 3 . 
     
     
         112 . The method of  claim 105 , wherein R 19  is hydrogen. 
     
     
         113 . The method of  claim 105 , wherein R 19  is methyl. 
     
     
         114 . The method of  claim 105 , wherein R 19  is ethyl. 
     
     
         115 . The method of  claim 105 , 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. 
     
     
         116 . The method of  claim 105 , wherein the CNS-related disorder is depression. 
     
     
         117 . The method of  claim 116 , wherein the depression is postpartum depression. 
     
     
         118 . The method of  claim 116 , wherein the depression is major depressive disorder. 
     
     
         119 . The method of  claim 118 , wherein the major depressive disorder is moderate major depressive disorder. 
     
     
         120 . The method of  claim 118 , wherein the major depressive disorder is severe major depressive disorder. 
     
     
         121 . The method of  claim 105 , wherein the CNS-related disorder is tremor. 
     
     
         122 . The method of  claim 121 , wherein the tremor is essential tremor. 
     
     
         123 . The method of  claim 105 , wherein the CNS-related disorder is seizure. 
     
     
         124 . The method of  claim 105 , wherein the CNS-related disorder is epilepsy or status epilepticus. 
     
     
         125 . The method of  claim 124 , wherein the CNS-related disorder is status epilepticus, and wherein the status epilepticus is convulsive status epilepticus or non-convulsive status epilepticus. 
     
     
         126 . The method of  claim 105 , wherein the CNS-related disorder is Tourette's syndrome. 
     
     
         127 . The method of  claim 105 , wherein the CNS-related disorder is obsessive compulsive disorder (OCD). 
     
     
         128 . A method of treating a CNS-related disorder in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a compound selected from 
       
         
           
                 
                 
               
                     
                 
                   Com- 
                     
                 
                   pound  
                     
                 
                   No. 
                   Structure 
                 
                     
                 
                     
                 
                 
                 
               
                   2 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                 
                   3 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                 
                   7 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                 
                   11 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                 
                   15 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                 
                   24 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                 
                   26 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                 
             
                
                
                
                
                
               
               
                
               
            
             
                
                
                
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
       
       a pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising the compound or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient. 
     
     
         129 . The method of  claim 128 , wherein the compound is a compound of the formula 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof. 
     
     
         130 . The method of  claim 128 , wherein the compound is a compound of the formula 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof. 
     
     
         131 . The method of  claim 128 , wherein the compound is a compound of the formula 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof. 
     
     
         132 . The method of  claim 128 , wherein the compound is a compound of the formula 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof. 
     
     
         133 . The method of  claim 128 , wherein the compound is a compound of the formula 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof. 
     
     
         134 . The method of  claim 128 , wherein the compound is a compound of the formula 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof. 
     
     
         135 . The method of  claim 128 , wherein the compound is a compound of the formula 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof. 
     
     
         136 . The method of  claim 128 , 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. 
     
     
         137 . The method of  claim 128 , wherein the CNS-related disorder is depression. 
     
     
         138 . The method of  claim 137 , wherein the depression is postpartum depression. 
     
     
         139 . The method of  claim 137 , wherein the depression is major depressive disorder. 
     
     
         140 . The method of  claim 139 , wherein the major depressive disorder is moderate major depressive disorder. 
     
     
         141 . The method of  claim 139 , wherein the major depressive disorder is severe major depressive disorder. 
     
     
         142 . The method of  claim 128 , wherein the CNS-related disorder is tremor. 
     
     
         143 . The method of  claim 142 , wherein the tremor is essential tremor. 
     
     
         144 . The method of  claim 128 , wherein the CNS-related disorder is seizure. 
     
     
         145 . The method of  claim 128 , wherein the CNS-related disorder is epilepsy or status epilepticus. 
     
     
         146 . The method of  claim 145 , wherein the CNS-related disorder is status epilepticus, and wherein the status epilepticus is convulsive status epilepticus or non-convulsive status epilepticus. 
     
     
         147 . The method of  claim 128 , wherein the CNS-related disorder is Tourette's syndrome. 
     
     
         148 . The method of  claim 128 , wherein the CNS-related disorder is obsessive compulsive disorder (OCD). 
     
     
         149 . A method of treating a CNS-related disorder in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a compound selected from 
       
         
           
                 
                 
               
                     
                 
                   Com- 
                     
                 
                   pound No. 
                   Structure 
                 
                     
                 
                   29 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                 
                   42 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                 
                   44 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                 
             
                
                
                
                
               
               
                
                
                
                
                
                
               
            
           
         
       
       a pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising the compound or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient. 
     
     
         150 . The method of  claim 149 , wherein the compound is a compound of the formula 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof. 
     
     
         151 . The method of  claim 149 , wherein the compound is a compound of the formula 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof. 
     
     
         152 . The method of  claim 149 , wherein the compound is a compound of the formula 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof. 
     
     
         153 . The method of  claim 149 , 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. 
     
     
         154 . The method of  claim 149 , wherein the CNS-related disorder is depression. 
     
     
         155 . The method of  claim 154 , wherein the depression is postpartum depression. 
     
     
         156 . The method of  claim 154 , wherein the depression is major depressive disorder. 
     
     
         157 . The method of  claim 156 , wherein the major depressive disorder is moderate major depressive disorder. 
     
     
         158 . The method of  claim 156 , wherein the major depressive disorder is severe major depressive disorder. 
     
     
         159 . The method of  claim 149 , wherein the CNS-related disorder is tremor. 
     
     
         160 . The method of  claim 159 , wherein the tremor is essential tremor. 
     
     
         161 . The method of  claim 149 , wherein the CNS-related disorder is seizure. 
     
     
         162 . The method of  claim 149 , wherein the CNS-related disorder is epilepsy or status epilepticus. 
     
     
         163 . The method of  claim 162 , wherein the CNS-related disorder is status epilepticus, and wherein the status epilepticus is convulsive status epilepticus or non-convulsive status epilepticus. 
     
     
         164 . The method of  claim 149 , wherein the CNS-related disorder is Tourette's syndrome. 
     
     
         165 . The method of  claim 149 , wherein the CNS-related disorder is obsessive compulsive disorder (OCD).

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