US2015366870A1PendingUtilityA1

Novel compounds

Assignee: GLAXOSMITHKLINE LLCPriority: Dec 8, 2008Filed: Aug 31, 2015Published: Dec 24, 2015
Est. expiryDec 8, 2028(~2.3 yrs left)· nominal 20-yr term from priority
A61P 9/10A61P 9/14A61P 7/02A61P 9/00A61P 3/10A61P 3/06A61P 9/04A61P 3/04A61P 3/00A61P 1/14A61P 13/12C07D 473/06A61K 31/133C07D 473/04A61K 31/522
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Claims

Abstract

The present invention relates to a tris salt of 8-chloro-3-pentyl-3,7-dihydro-1H-purine-2,6-dione of Formula (A): corresponding manufacture processes, pharmaceutical formulations containing and uses of the aforementioned compound in therapy, particularly in treatment of diseases where under-activation of the HM74A receptor contributes to the disease or where activation of the receptor will be beneficial.

Claims

exact text as granted — not AI-modified
What is claimed is: 
     
         1 . A method for treating stroke in a human subject in need thereof, comprising administering to said subject a therapeutically effective amount of a compound which is 8-chloro-3-pentyl-3,7-dihydro-1H-purine-2,6-dione tris(hydroxymethyl)aminomethane (Formula (IA): 
       
         
           
           
               
               
           
         
       
     
     
         2 . The method according to  claim 1  wherein the compound is 8-chloro-3-pentyl-3,7-dihydro-1H-purine-2,6-dione tris(hydroxymethyl)aminomethane anhydrate 
     
     
         3 . The method according to  claim 2  wherein the compound is crystalline. 
     
     
         4 . The method according to  claim 3  wherein the crystalline form of the compound is characterised by an XRPD pattern comprising the following peaks: 
       
         
           
                 
                 
                 
               
                     
                     
                 
                     
                   Position 
                   d-spacing 
                 
                     
                   (±0.2° 2-theta) 
                   ((Å)) 
                 
                     
                     
                 
                     
                   10.1 
                   8.7 
                 
                     
                   10.5 
                   8.4 
                 
                     
                   12.2 
                   7.3 
                 
                     
                   13.0 
                   6.8 
                 
                     
                   13.5 
                   6.5 
                 
                     
                   17.3 
                   5.1 
                 
                     
                   17.5 
                   5.1 
                 
                     
                   17.9 
                   5.0 
                 
                     
                   18.3 
                   4.8 
                 
                     
                   19.2 
                   4.6 
                 
                     
                   19.8 
                   4.5 
                 
                     
                   20.2 
                   4.4 
                 
                     
                   20.6 
                   4.3 
                 
                     
                   20.9 
                   4.2 
                 
                     
                   21.7 
                   4.1 
                 
                     
                   22.1 
                   4.0 
                 
                     
                   23.3 
                   3.8 
                 
                     
                   23.9 
                   3.7 
                 
                     
                   24.6 
                   3.6 
                 
                     
                   26.3 
                   3.4 
                 
                     
                   27.1 
                   3.3 
                 
                     
                   27.9 
                   3.2 
                 
                     
                   28.2 
                   3.2 
                 
                     
                   28.6 
                   3.1 
                 
                     
                   29.6 
                    3.0. 
                 
                     
                     
                 
             
                
                
                
                
               
               
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
       
     
     
         5 . The method according to  claim 3  wherein the crystalline form of the compound is characterised by an XRPD pattern that is substantially as shown in  FIG. 2 . 
     
     
         6 . The method according to  claim 3  wherein the crystalline form of the compound is characterised by a melting endotherm with an onset melting temperature of 212±2° C. in a DSC thermogram. 
     
     
         7 . The method according to  claim 3  wherein the crystalline form of the compound is characterised by the following absorption peaks in an ATR-IR spectrum of the solid product: 3370, 3041, 2946, 2858, 1680, 1656, 1528, 1266, 1243, 1078, 1068, 1049±1 cm-1. 
     
     
         8 . The method according to  claim 3  wherein the crystalline form of the compound is characterised in that it has an ATR infra red spectrum that is substantially as shown in  FIG. 6 . 
     
     
         9 . A method for treating multiple sclerosis in a human subject in need thereof, comprising administering to said subject a therapeutically effective amount of a compound which is 8-chloro-3-pentyl-3,7-dihydro-1H-purine-2,6-dione tris(hydroxymethyl)aminomethane (Formula (IA): 
       
         
           
           
               
               
           
         
       
     
     
         10 . The method according to  claim 9  wherein the compound is 8-chloro-3-pentyl-3,7-dihydro-1H-purine-2,6-dione tris(hydroxymethyl)aminomethane anhydrate. 
     
     
         11 . The method according to  claim 10  wherein the compound is crystalline. 
     
     
         12 . The method according to  claim 10  wherein the crystalline form of the compound is characterised by an XRPD pattern comprising the following peaks: 
       
         
           
                 
                 
                 
               
                     
                     
                 
                     
                   Position 
                   d-spacing 
                 
                     
                   (±0.2° 2-theta) 
                   ((Å)) 
                 
                     
                     
                 
                     
                   10.1 
                   8.7 
                 
                     
                   10.5 
                   8.4 
                 
                     
                   12.2 
                   7.3 
                 
                     
                   13.0 
                   6.8 
                 
                     
                   13.5 
                   6.5 
                 
                     
                   17.3 
                   5.1 
                 
                     
                   17.5 
                   5.1 
                 
                     
                   17.9 
                   5.0 
                 
                     
                   18.3 
                   4.8 
                 
                     
                   19.2 
                   4.6 
                 
                     
                   19.8 
                   4.5 
                 
                     
                   20.2 
                   4.4 
                 
                     
                   20.6 
                   4.3 
                 
                     
                   20.9 
                   4.2 
                 
                     
                   21.7 
                   4.1 
                 
                     
                   22.1 
                   4.0 
                 
                     
                   23.3 
                   3.8 
                 
                     
                   23.9 
                   3.7 
                 
                     
                   24.6 
                   3.6 
                 
                     
                   26.3 
                   3.4 
                 
                     
                   27.1 
                   3.3 
                 
                     
                   27.9 
                   3.2 
                 
                     
                   28.2 
                   3.2 
                 
                     
                   28.6 
                   3.1 
                 
                     
                   29.6 
                    3.0. 
                 
                     
                     
                 
             
                
                
                
                
               
               
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
       
     
     
         13 . The method according to  claim 10  wherein the crystalline form of the compound is characterised by an XRPD pattern that is substantially as shown in  FIG. 2 . 
     
     
         14 . The method according to  claim 10  wherein the crystalline form of the compound is characterised by a melting endotherm with an onset melting temperature of 212±2° C. in a DSC thermogram. 
     
     
         15 . The method according to  claim 10  wherein the crystalline form of the compound is characterised by the following absorption peaks in an ATR-IR spectrum of the solid product: 3370, 3041, 2946, 2858, 1680, 1656, 1528, 1266, 1243, 1078, 1068, 1049±1 cm-1. 
     
     
         16 . The method according to  claim 10  wherein the crystalline form of the compound is characterised in that it has an ATR infra red spectrum that is substantially as shown in  FIG. 6 . 
     
     
         17 . A method for treating inflammatory sequelae of viral or bacterial infection in a human subject in need thereof, comprising administering to said subject a therapeutically effective amount of a compound which is 8-chloro-3-pentyl-3,7-dihydro-1H-purine-2,6-dione tris(hydroxymethyl)aminomethane anyhydrate (Formula (IA): 
       
         
           
           
               
               
           
         
       
     
     
         18 . The method according to  claim 17  wherein the compound is 8-chloro-3-pentyl-3,7-dihydro-1H-purine-2,6-dione tris(hydroxymethyl)aminomethane anhydrate. 
     
     
         19 . The method according to  claim 18  wherein the compound is crystalline. 
     
     
         20 . The method according to  claim 18  wherein the crystalline form of the compound is characterised by an XRPD pattern comprising the following peaks: 
       
         
           
                 
                 
                 
               
                     
                     
                 
                     
                   Position 
                   d-spacing 
                 
                     
                   (±0.2° 2-theta) 
                   ((Å)) 
                 
                     
                     
                 
                     
                   10.1 
                   8.7 
                 
                     
                   10.5 
                   8.4 
                 
                     
                   12.2 
                   7.3 
                 
                     
                   13.0 
                   6.8 
                 
                     
                   13.5 
                   6.5 
                 
                     
                   17.3 
                   5.1 
                 
                     
                   17.5 
                   5.1 
                 
                     
                   17.9 
                   5.0 
                 
                     
                   18.3 
                   4.8 
                 
                     
                   19.2 
                   4.6 
                 
                     
                   19.8 
                   4.5 
                 
                     
                   20.2 
                   4.4 
                 
                     
                   20.6 
                   4.3 
                 
                     
                   20.9 
                   4.2 
                 
                     
                   21.7 
                   4.1 
                 
                     
                   22.1 
                   4.0 
                 
                     
                   23.3 
                   3.8 
                 
                     
                   23.9 
                   3.7 
                 
                     
                   24.6 
                   3.6 
                 
                     
                   26.3 
                   3.4 
                 
                     
                   27.1 
                   3.3 
                 
                     
                   27.9 
                   3.2 
                 
                     
                   28.2 
                   3.2 
                 
                     
                   28.6 
                   3.1 
                 
                     
                   29.6 
                    3.0. 
                 
                     
                     
                 
             
                
                
                
                
               
               
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
       
     
     
         21 . The method according to  claim 18  wherein the crystalline form of the compound is characterised by an XRPD pattern that is substantially as shown in  FIG. 2 . 
     
     
         22 . The method according to  claim 18  wherein the crystalline form of the compound is characterised by a melting endotherm with an onset melting temperature of 212±2° C. in a DSC thermogram. 
     
     
         23 . The method according to  claim 18  wherein the crystalline form of the compound is characterised by the following absorption peaks in an ATR-IR spectrum of the solid product: 3370, 3041, 2946, 2858, 1680, 1656, 1528, 1266, 1243, 1078, 1068, 1049±1 cm-1. 
     
     
         24 . The method according to  claim 18  wherein the crystalline form of the compound is characterised in that it has an ATR infra red spectrum that is substantially as shown in  FIG. 6 .

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