Colipse-lipase inhibitors in the preparation of a pharmaceutical composition in order to prevent obesity

Abstract

The present invention relates to novel colipase-lipase inhibitors of the general formulae to be used in the treatment of prophylaxis of obesity, as well as pharmaceutical compositions containing the same, and method for treating obesity using said compounds.

1 . A use of a compound defined by the following general formulae 
       
         
           
           
               
               
           
         
       
       wherein
 R 1  and R 2  each independently is hydrogen, or lower alkyl, 
 R 3  and R 4  each independently is hydrogen, or lower alkyl 
 X is —O—, —C— or —S—, 
 Y is a covalent bound or is [—CH 2 —CH 2 —O—] x , wherein x is an integer from 0 to 8, preferably 0 to 5, 
 m is an integer from 0 to 30, preferably 4 to 16, more preferably 4 to 12, 
 R 5  is hydrogen, CH 3  or CF 3  in the preparation of a pharmaceutical composition, in order to prevent and/or reduce obesity. 
 
     
     
         2 . A use according to  claim 1 , wherein the pharmaceutical composition is used for the inhibition of colipase-pancreatic lipase controlled digestion of lipids in the intestine, in order to prevent and/or reduce obesity, 
     
     
         3 . A use according to  claim 1 , wherein X, Y, (CH 2 ) m  and R 5  together comprises at least 8 carbon atoms. 
     
     
         4 . A use according to  claim 1 , wherein (CH 2 ) m  comprises one or more double or triple bonds. 
     
     
         5 . A use according to  claim 1 , wherein the active compound is 
       2-(Dimethylamino)-ethyl-stearyl ether 
       2-(Dimethylamino)-ethyl-tetradecyl ether 
       2-(Dimethylamino)-ethyl-oleyl ether 
       2-(Dimethylamino)-ethyl-linolyl ether 
       2-(Dimethylamino)-ethyl-dodecyl ether 
       2-(Dimethylamino)-ethyl-octy-ether 
       2-(Diethylamino)-ethyl-stearyl ether 
       2-(Diethylamino)-ethyl-oleyl ether 
       2-(Diethylamino)-ethyl-linolyl ether 
       2-(Diethylamino)-ethyl-dodecyl ether 
       2-(Diethylamino)-ethyl-octyl ether 
       2-(Diisopropylamino)-ethyl-stearyl ether 
       2-(Diisopropylamino)-ethyl-oleyl ether 
       2-(Diisopropylamino)-ethyl-linolyl ether 
       2-(Diisopropylamino)-ethyl-dodecyl ether 
       2-(Diisopropylamino)-ethyl-octyl ether 
       2-(Dimethylamino)-ethyl-pentaethyleneglycol-stearyl ether 
       2-(Dimethylamino)-ethyl-pentaethyleneglycol-linolyl ether 
       2-(Dimethylamino)-ethyl-pentaethyleneglycol-oleyl ether 
       2-(Dimethylamino)-ethyl-pentaethyleneglycol-dodecyl ether 
       2-(Dimethylamino)-ethyl-pentaethyleneglycol-octyl ether 
       2-(Dimethylamino)-ethyl-pentaethyleneglycol butyl ether 
       2-(Dimethylamino)-ethyl-pentaethyleneglycol methyl ether 
       2-(Dimethylamino)-ethyl-pentaethyleneglycol ethyl ether 
       2-(Dimethylamino)-ethyl-triethyleneglycol-dodecyl ether 
       2-(Dimethylamino)-ethyl-triethyleneglycol-octyl ether 
       2-(Dimethylamino)-ethyl-triethyleneglycol butyl ether 
       2-(Dimethylamino)-ethyl-triethyleneglycol methyl ether 
       2-(Dimethylamino)-ethyl-triethyleneglycol ethyl ether 
       2-(Dipropylamino)-ethyl-octaethyleneglycol dodecyl ether 
       2-(Dimethylamino)-ethyl-octaethyleneglycol dodecyl ether 
       2-(Diethylamino)-ethyl-octaethyleneglycol dodecyl ether 
       N,N-dimethyl hexadecyl amine 
       N,N-dimethyl tetradecyl amine 
       N,N-dimethyl dodecyl amine 
     
     
         6 . A pharmaceutical composition comprising an inhibiting amount of a colipase-lipase inhibitor of the general formulae 
       
         
           
           
               
               
           
         
       
       wherein
 R 1  and R 2  each independently is hydrogen, or lower alkyl, 
 R 3  and R 4  each independently is hydrogen, or lower alkyl, 
 X is —O—, —C—, or —S—, 
 Y is a covalent bound or is [—CH 2 —CH 2 —O—] x , wherein x is an integer from 0 to 8, preferably 0 to 5, m is an integer from 0 to 30, preferably 4 to 16, more preferably 4 to 12, 
 R 5  is hydrogen, CH 3  or CF 3  for the inhibition of colipase-pancreatic lipase controlled digestion of lipids in the intestine, in order to prevent and/or reduce obesity together with any pharmaceutically inert excipients. 
 
       
         
           
           
               
               
           
         
       
     
     
         7 - 10 . (canceled) 
     
     
         11 . A use of a compound defined by the following general formulae 
       
         
           
           
               
               
           
         
       
       wherein
 R 1  and R 2  each independently is hydrogen, or lower alkyl, 
 R 3  and R 4  each independently is hydrogen, or lower alkyl, 
 X is —O—, —C— or —S—, 
 Y is a covalent bound or is [—CH 2 —CH 2 —O—] x , wherein x is an integer from 0 to 8, preferably 0 to 5, 
 m is an integer from 0 to 30, preferably 4 to 16, more preferably 4 to 12, 
 R 5  is hydrogen, CH 3  or CF 3  in the preparation of a pharmaceutical composition for reducing appetite, in order to prevent and/or reduce obesity. 
 
     
     
         12 . A use of a compound defined by the following general formulae 
       
         
           
           
               
               
           
         
       
       wherein
 R 1  and R 2  each independently is hydrogen, or lower alkyl, 
 R 3  and R 4  each independently is hydrogen, or lower alkyl, 
 X is —O—, —C— or —S—, 
 Y is a covalent bound or is [—CH 2 —CH 2 —O—] x , wherein x is an integer from 0 to 8, preferably 0 to 5, 
 m is an integer from 0 to 30, preferably 4 to 16, more preferably 4 to 12, 
 R 5  is hydrogen, CH 3  or CF 3  in the preparation of a pharmaceutical composition for reducing the expression of pancreatic lipase, in order to prevent and/or reduce obesity.