Lipid derivatives

Abstract

The present invention relates to lipid compounds of the general formula (I): wherein —R 1 and R 2 are the same or different and may be selected from a group of substituents consisting of a hydrogen atom, an alkyl group, a halogen atom, and an alkoxy group; —X is COR 3 or CH 2 OR 4 , wherein —R 3 is selected from the group consisting of hydrogen, hydroxy, alkoxy, and amino, —wherein X further comprises carboxylic acid derivatives when R 3 is hydroxyl; and —R 4 is selected from the group consisting of hydrogen, alkyl or acyl, —Y is a C 9 to C 21 alkene with one or more double bonds with E or Z configuration; or any pharmaceutically acceptable complex, solvate or pro-drug thereof. The present invention also relates to pharmaceutical compositions comprising such lipid compounds, and to such lipid compounds for use as medicaments or for diagnostic purposes.

1 - 127 . (canceled) 
     
     
         128 . A method for the treatment of a condition related to elevated functions of at least one of the human peroxisome proliferator-activated receptor (PPAR) isoforms α, γ, or δ, comprising administering to a mammal in need thereof a pharmaceutically effective amount of a lipid compound of formula (I): 
       
         
           
           
               
               
           
         
         wherein 
         n=0, 1, or 2; 
         R 1  and R 2  are the same or different and are chosen from a hydrogen atom, an alkyl group, a halogen atom, or an alkoxy group; 
         X is chosen from COR 3  or CH 2 OR 4 , wherein R 3  is chosen from a hydrogen atom, a hydroxy group, an alkoxy group, or an amino group, wherein when R 3  is hydroxy, X is optionally a carboxylic acid derivative; and R 4  is chosen from a hydrogen atom, an alkyl group, or an acyl group; and 
         Y is an unsubstituted C 9  to C 21  alkene with at least one double bond having either E or Z configuration, wherein R 1  and R 2  are not both a hydrogen atom. 
       
     
     
         129 . The method according to  claim 128 , wherein R 3  is a hydroxy group, and X is a carboxylic derivative. 
     
     
         130 . The method according to  claim 129 , wherein the carboxylic derivative is a phospholipid, mono-, di-, or triglyceride. 
     
     
         131 . A method for the treatment of a condition related to elevated functions of RXR comprising administering to a mammal in need thereof a pharmaceutically effective amount of a lipid compound of formula (I): 
       
         
           
           
               
               
           
         
         wherein 
         n=0, 1, or 2; 
         R 1  and R 2  are the same or different and are chosen from a hydrogen atom, an alkyl group, a halogen atom, or an alkoxy group; 
         X is chosen from COR 3  or CH 2 OR 4 , wherein R 3  is chosen from a hydrogen atom, a hydroxy group, an alkoxy group, or an amino group, wherein when R 3  is hydroxy, X is optionally a carboxylic acid derivative; and R 4  is chosen from a hydrogen atom, an alkyl group, or an acyl group; and 
         Y is an unsubstituted C 9  to C 21  alkene with at least one double bond having either E or Z configuration, wherein R 1  and R 2  are not both a hydrogen atom. 
       
     
     
         132 . The method according to  claim 131 , wherein R 3  is a hydroxy group, and X is a carboxylic derivative. 
     
     
         133 . The method according to  claim 132 , wherein the carboxylic derivative is a phospholipid, mono-, di-, or triglyceride. 
     
     
         134 . A method for the treatment of a condition related to elevated functions of NFkB comprising administering to a mammal in need thereof a pharmaceutically effective amount of a lipid compound of formula (I): 
       
         
           
           
               
               
           
         
         wherein 
         n=0, 1, or 2; 
         R 1  and R 2  are the same or different and are chosen from a hydrogen atom, an alkyl group, a halogen atom, or an alkoxy group; 
         X is chosen from COR 3  and CH 2 OR 4 , wherein R 3  is chosen from a hydrogen atom, a hydroxy group, an alkoxy group, or an amino group, wherein when R 3  is hydroxy, X is optionally a carboxylic acid derivative; and R 4  is chosen from a hydrogen atom, an alkyl group, or an acyl group; and 
         Y is an unsubstituted C 9  to C 21  alkene with at least one double bond having either E or Z configuration, wherein R 1  and R 2  are not both a hydrogen atom. 
       
     
     
         135 . The method according to  claim 134 , wherein R 3  is a hydroxy group, and X is a carboxylic derivative. 
     
     
         136 . The method according to  claim 135 , wherein the carboxylic derivative is a phospholipid, mono-, di-, or triglyceride. 
     
     
         137 . A method for the treatment of an inflammatory disease or condition comprising administering to a mammal in need thereof a pharmaceutically effective amount of a lipid compound of formula (I): 
       
         
           
           
               
               
           
         
         wherein 
         n=0, 1, or 2; 
         R 1  and R 2  are the same or different and are chosen from a hydrogen atom, an alkyl group, a halogen atom, or an alkoxy group; 
         X is chosen from COR 3  or CH 2 OR 4 , wherein R 3  is chosen from a hydrogen atom, a hydroxy group, an alkoxy group, or an amino group, wherein when R 3  is hydroxy, X is optionally a carboxylic acid derivative; and R 4  is chosen from a hydrogen atom, an alkyl group, or an acyl group; and 
         Y is an unsubstituted C 9  to C 21  alkene with at least one double bond having either E or Z configuration, wherein R 1  and R 2  are not both a hydrogen atom. 
       
     
     
         138 . The method according to  claim 137 , wherein R 3  is a hydroxy group, and X is a carboxylic derivative. 
     
     
         139 . The method according to  claim 138 , wherein the carboxylic derivative is a phospholipid, mono-, di-, or triglyceride. 
     
     
         140 . A method for reduction of plasma insulin, blood glucose, and/or serum triglycerides comprising administering to a mammal in need thereof a pharmaceutically effective amount of a lipid compound of formula (I): 
       
         
           
           
               
               
           
         
         wherein 
         n=0, 1, or 2; 
         R 1  and R 2  are the same or different and are chosen from a hydrogen atom, an alkyl group, a halogen atom, or an alkoxy group; 
         X is chosen from COR 3  or CH 2 OR 4 , wherein R 3  is chosen from a hydrogen atom, a hydroxy group, an alkoxy group, or an amino group, wherein when R 3  is hydroxy, X is optionally a carboxylic acid derivative; and R 4  is chosen from a hydrogen atom, an alkyl group, or an acyl group; and 
         Y is an unsubstituted C 9  to C 21  alkene with at least one double bond having either E or Z configuration, wherein R 1  and R 2  are not both a hydrogen atom. 
       
     
     
         141 . The method according to  claim 140 , wherein R 3  is a hydroxy group, and X is a carboxylic derivative. 
     
     
         142 . The method according to  claim 141 , wherein the carboxylic derivative is a phospholipid, mono-, di-, or triglyceride. 
     
     
         143 . A method for the treatment of elevated triglyceride levels, LDL cholesterol levels, and/or VLDL cholesterol levels comprising administering to a mammal in need thereof a pharmaceutically effective amount of a lipid compound of formula (I): 
       
         
           
           
               
               
           
         
         wherein 
         n=0, 1, or 2; 
         R 1  and R 2  are the same or different and are chosen from a hydrogen atom, an alkyl group, a halogen atom, or an alkoxy group; 
         X is chosen from COR 3  or CH 2 OR 4 , wherein R 3  is chosen from a hydrogen atom, a hydroxy group, an alkoxy group, or an amino group, wherein when R 3  is hydroxy, X is optionally a carboxylic acid derivative; and R 4  is chosen from a hydrogen atom, an alkyl group, or an acyl group; and 
         Y is an unsubstituted C 9  to C 21  alkene with at least one double bond having either E or Z configuration, wherein R 1  and R 2  are not both a hydrogen atom. 
       
     
     
         144 . The method according to  claim 143 , wherein R 3  is a hydroxy group, and X is a carboxylic derivative. 
     
     
         145 . The method according to  claim 144 , wherein the carboxylic derivative is a phospholipid, mono-, di-, or triglyceride. 
     
     
         146 . A method for the treatment of a hyperlipidemic condition, comprising administering to a mammal in need thereof a pharmaceutically effective amount of a lipid compound of formula (I): 
       
         
           
           
               
               
           
         
         wherein 
         n=0, 1, or 2; 
         R 1  and R 2  are the same or different and are chosen from a hydrogen atom, an alkyl group, a halogen atom, or an alkoxy group; 
         X is chosen from COR 3  or CH 2 OR 4 , wherein R 3  is chosen from a hydrogen atom, a hydroxy group, an alkoxy group, or an amino group, wherein when R 3  is hydroxy, X is optionally a carboxylic acid derivative; and R 4  is chosen from a hydrogen atom, an alkyl group, or an acyl group; and 
         Y is an unsubstituted C 9  to C 21  alkene with at least one double bond having either E or Z configuration, wherein R 1  and R 2  are not both a hydrogen atom. 
       
     
     
         147 . The method of  claim 146 , wherein the hyperlipidemic condition is hypertriglyceridemia. 
     
     
         148 . The method according to  claim 146 , wherein R 3  is a hydroxy group, and X is a carboxylic derivative. 
     
     
         149 . The method according to  claim 148 , wherein the carboxylic derivative is a phospholipid, mono-, di-, or triglyceride. 
     
     
         150 . A method for treatment obesity or an overweight condition comprising administering to a mammal in need thereof a pharmaceutically effective amount of a lipid compound of formula (I): 
       
         
           
           
               
               
           
         
         wherein 
         n=0, 1, or 2; 
         R 1  and R 2  are the same or different and are chosen from a hydrogen atom, an alkyl group, a halogen atom, or an alkoxy group; 
         X is chosen from COR 3  or CH 2 OR 4 , wherein R 3  is chosen from a hydrogen atom, a hydroxy group, an alkoxy group, or an amino group, wherein when R 3  is hydroxy, X is optionally a carboxylic acid derivative; and R 4  is chosen from a hydrogen atom, an alkyl group, or an acyl group; and 
         Y is an unsubstituted C 9  to C 21  alkene with at least one double bond having either E or Z configuration, wherein R 1  and R 2  are not both a hydrogen atom. 
       
     
     
         151 . The method according to  claim 150 , wherein R 3  is a hydroxy group, and X is a carboxylic derivative. 
     
     
         152 . The method according to  claim 151 , wherein the carboxylic derivative is a phospholipid, mono-, di-, or triglyceride. 
     
     
         153 . A method for the treatment of peripheral insulin resistance and/or a diabetic condition comprising administering to a mammal in need thereof a pharmaceutically effective amount of a lipid compound of formula (I): 
       
         
           
           
               
               
           
         
         wherein 
         n=0, 1, or 2; 
         R 1  and R 2  are the same or different and are chosen from a hydrogen atom, an alkyl group, a halogen atom, or an alkoxy group; 
         X is chosen from COR 3  or CH 2 OR 4 , wherein R 3  is chosen from a hydrogen atom, a hydroxy group, an alkoxy group, or an amino group, wherein when R 3  is hydroxy, X is optionally a carboxylic acid derivative; and R 4  is chosen from a hydrogen atom, an alkyl group, or an acyl group; and 
         Y is an unsubstituted C 9  to C 21  alkene with at least one double bond having either E or Z configuration, wherein R 1  and R 2  are not both a hydrogen atom. 
       
     
     
         154 . The method according to  claim 153 , wherein R 3  is a hydroxy group, and X is a carboxylic derivative. 
     
     
         155 . The method according to  claim 154 , wherein the carboxylic derivative is a phospholipid, mono-, di-, or triglyceride.