US2022112491A1PendingUtilityA1

Processes for preparing phosphorodiamidate morpholino oligomers

61
Assignee: SAREPTA THERAPEUTICS INCPriority: May 24, 2016Filed: Dec 23, 2020Published: Apr 14, 2022
Est. expiryMay 24, 2036(~9.9 yrs left)· nominal 20-yr term from priority
C07F 9/65616C12N 2310/334C12N 2310/314C12N 2310/3233A61K 48/00C12N 2310/351C12N 2310/336C12N 2310/11C12N 15/113C07F 9/65583C12N 2310/333C08G 81/024A61P 21/00
61
PatentIndex Score
0
Cited by
0
References
0
Claims

Abstract

Provided herein are processes for preparing an oligomer (e.g., a morpholino oligomer). The synthetic processes described herein may be advantageous to scaling up oligomer synthesis while maintaining overall yield and purity of a synthesized oligomer.

Claims

exact text as granted — not AI-modified
1 .- 22 . (canceled) 
     
     
         23 . A compound of Formula (A5): 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof, wherein R 1  is a support-medium, R 3  is selected from the group consisting of trityl, monomethoxytrityl, dimethoxytrityl and trimethoxytrityl, and 
         R 4  is 
       
       
         
           
           
               
               
           
         
       
     
     
         24 . The compound of  claim 23 , wherein the support-medium comprises a material selected from the group consisting of glass, modified or functionalized glass, plastics (including acrylics, polystyrene (e.g., polystyrene with 1% crosslinked divinylbenzene), copolymers of styrene and other materials, polypropylene, polyethylene, polybutylene, polyurethanes, and TEFLON), polysaccharides, nylon or nitrocellulose, ceramics, resins, silica or silica-based materials (including silicon and modified silicon), carbon, metals, and optical fiber bundles. 
     
     
         25 . The compound of  claim 23 , wherein the compound of Formula (A5) is of Formula (A5a): 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof, wherein: 
         R 1  is a support-medium, 
         R 3  is selected from the group consisting of trityl, monomethoxytrityl, dimethoxytrityl and trimethoxytrityl, and 
         R 4  is 
       
       
         
           
           
               
               
           
         
       
     
     
         26 . The compound of  claim 26 , wherein the support-medium comprises a material selected from the group consisting of glass, modified or functionalized glass, plastics (including acrylics, polystyrene (e.g., polystyrene with 1% crosslinked divinylbenzene), copolymers of styrene and other materials, polypropylene, polyethylene, polybutylene, polyurethanes, and TEFLON), polysaccharides, nylon or nitrocellulose, ceramics, resins, silica or silica-based materials (including silicon and modified silicon), carbon, metals, and optical fiber bundles. 
     
     
         27 . A compound of Formula (A9): 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof, wherein n 22, R 1  is a support-medium, R 3  is selected from the group consisting of trityl, monomethoxytrityl, dimethoxytrityl and trimethoxytrityl, and R 2  is, per the oligomeric compound of Formula (C), wherein R 2  is at each position from 1 to 22 and 5′ to 3′: 
       
       
         
           
                 
                 
                 
               
                     
                     
                 
                     
                   Position No. 
                     
                 
                     
                   5′ to 3′ 
                   R 2   
                 
                     
                     
                 
                     
                 
                 
                 
                 
               
                     
                   1 
                   PC 
                 
                     
                   2 
                   PA 
                 
                     
                   3 
                   PA 
                 
                     
                   4 
                   T 
                 
                     
                   5 
                   DPG 
                 
                     
                   6 
                   PC 
                 
                     
                   7 
                   PC 
                 
                     
                   8 
                   PA 
                 
                     
                   9 
                   T 
                 
                     
                   10 
                   PC 
                 
                     
                   11 
                   PC 
                 
                     
                   12 
                   T 
                 
                     
                   13 
                   DPG 
                 
                     
                   14 
                   DPG 
                 
                     
                   15 
                   PA 
                 
                     
                   16 
                   DPG 
                 
                     
                   17 
                   T 
                 
                     
                   18 
                   T 
                 
                     
                   19 
                   PC 
                 
                     
                   20 
                   PC 
                 
                     
                   21 
                   T 
                 
                     
                   22 
                   DPG 
                 
                     
                     
                 
             
                
                
                
                
               
               
                
               
            
             
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
       
       wherein: 
       PC is 
       
         
           
           
               
               
           
         
       
       DPG is 
       
         
           
           
               
               
           
         
       
       T is 
       
         
           
           
               
               
           
         
       
       and PA is 
       
         
           
           
               
               
           
         
       
     
     
         28 . The compound of  claim 27 , wherein the support-medium comprises a material selected from the group consisting of glass, modified or functionalized glass, plastics (including acrylics, polystyrene (e.g., polystyrene with 1% crosslinked divinylbenzene), copolymers of styrene and other materials, polypropylene, polyethylene, polybutylene, polyurethanes, and TEFLON), polysaccharides, nylon or nitrocellulose, ceramics, resins, silica or silica-based materials (including silicon and modified silicon), carbon, metals, and optical fiber bundles. 
     
     
         29 . The compound of  claim 27 , wherein the compound of Formula (A9) is of Formula (A9a): 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof, wherein n 22, R 1  is a support-medium, R 3  is selected from the group consisting of trityl, monomethoxytrityl, dimethoxytrityl and trimethoxytrityl, and R 2  is, per the oligomeric compound of Formula (C), wherein R 2  is at each position from 1 to 22 and 5′ to 3′: 
       
       
         
           
                 
                 
                 
               
                     
                     
                 
                     
                   Position No. 
                     
                 
                     
                   5′ to 3′ 
                   R 2   
                 
                     
                     
                 
                     
                 
                 
                 
                 
               
                     
                   1 
                   PC 
                 
                     
                   2 
                   PA 
                 
                     
                   3 
                   PA 
                 
                     
                   4 
                   T 
                 
                     
                   5 
                   DPG 
                 
                     
                   6 
                   PC 
                 
                     
                   7 
                   PC 
                 
                     
                   8 
                   PA 
                 
                     
                   9 
                   T 
                 
                     
                   10 
                   PC 
                 
                     
                   11 
                   PC 
                 
                     
                   12 
                   T 
                 
                     
                   13 
                   DPG 
                 
                     
                   14 
                   DPG 
                 
                     
                   15 
                   PA 
                 
                     
                   16 
                   DPG 
                 
                     
                   17 
                   T 
                 
                     
                   18 
                   T 
                 
                     
                   19 
                   PC 
                 
                     
                   20 
                   PC 
                 
                     
                   21 
                   T 
                 
                     
                   22 
                   DPG 
                 
                     
                     
                 
             
                
                
                
                
               
               
                
               
            
             
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
       
       wherein: 
       PC is 
       
         
           
           
               
               
           
         
       
       DPG is 
       
         
           
           
               
               
           
         
       
       T is 
       
         
           
           
               
               
           
         
       
       and PA is 
       
         
           
           
               
               
           
         
       
     
     
         30 . The compound of  claim 29 , wherein the support-medium comprises a material selected from the group consisting of glass, modified or functionalized glass, plastics (including acrylics, polystyrene (e.g., polystyrene with 1% crosslinked divinylbenzene), copolymers of styrene and other materials, polypropylene, polyethylene, polybutylene, polyurethanes, and TEFLON), polysaccharides, nylon or nitrocellulose, ceramics, resins, silica or silica-based materials (including silicon and modified silicon), carbon, metals, and optical fiber bundles.

Cited by (0)

No later patents cite this yet.

References (0)

No backward citations on record.