Pharmaceutical compositions containing fluorinated or perfluorinated carboxylic acids

Abstract

The molecules of formula (I) are useful in treating diabetes, obesity, hypercholesterolaemia, hyperlipidaemia, cancer, inflammation or other conditions in which modulation of lipis of eicosanoid status or functions may be desirable. Formula (I): Z 1 —Z 1 —Z 2 wherein a) Z 1 represents CO 2 H or a derivative thereof; b) Z 2 represents F, H, —CO 2 H or a derivative thereof; and c) X represents fluorinated alkylene; or a solvate thereof, for example a perfluorinated fatty acid or derivative thereof.

1 . A method of treatment of a patient comprising:
 administering to the patient an effective amount of a compound of formula I,
   z 1 -x-z 2    
   wherein
 Z 1  represents —CO 2 H or a derivative thereof; 
 Z 2  represents F, H, —C0 2 H or a derivative thereof; and 
 X represents fluorinated alkylene; 
 or a solvate thereof; and 
   treating the patient to address a need of the patient.   
     
     
         2 . The method of  claim 1  wherein the need is selected from:
 modulation of body mass or modulation of increase in body mass, and/or in need of modulation of plasma insulin, plasma glucose, plasma triglycerides, plasma cholesterol and/or leptin. 
 
     
     
         3 . The method of  claim 1  wherein the need consists of:
 delivery of an antitumour agent or an antiinflammatory agent, or modulation in lipid or eicosanoid status. 
 
     
     
         4 . The method of  claim 1  wherein the addressed need is selected from:
 treating a person who is overweight or obese and/or has diabetes, hyperlipidaemia, atherosclerosis, coronary heart disease, stroke, obstructive sleep apnoea, arthritis and/or reduced fertility, or is at risk of developing such a condition. 
 
     
     
         5 . The method of  claim 1  wherein the need is selected from modulation of PPAR activity or PPARc activity. 
     
     
         6 . The method of  claim 5  wherein the need is an increase in PPAR activity; and
 wherein said compound is a PPAR agonist. 
 
     
     
         7 . The method of  claim 6  wherein the wherein the PPAR agonist is either PPARα or PPARy. 
     
     
         8 . The method of  claim 1  wherein the need is modulation of lipid or eicosanoid status or function. 
     
     
         9 . The method of  claim 1  wherein the need is selected from:
 reduction of body mass or prevention of increase in body mass, and/or in need of reduction of plasma insulin, plasma glucose, plasma triglycerides, plasma cholesterol and/or leptin. 
 
     
     
         10 . The method of  claim 1  wherein the need is selected from:
 reduction of body mass or prevention of increase in body mass, and/or in need of reduction of plasma insulin, plasma glucose, plasma triglycerides, plasma cholesterol and/or leptin. 
 
     
     
         11 . The method of  claim 1 , wherein said patient is a human. 
     
     
         12 . A medicament for the treatment of a patient, said medicament comprising:
 a compound of formula I,
   z 1 -x-Z 2    
   wherein
 Z 1  represents —CO 2 H or a derivative thereof; 
 Z 2  represents F, H, —CO 2 H or a derivative thereof; and 
 X represents fluorinated alkylene; 
 or a solvate thereof; 
   wherein said medicament is directed towards a specific treatment of said patient.   
     
     
         13 . The medicament of  claim 12 , wherein said specific treatment is selected from the group consisting of:
 reduction of body mass or prevention of increase in body mass, and/or in need of reduction of plasma insulin, plasma glucose, plasma triglycerides, plasma cholesterol and/or leptin.   
     
     
         14 . The medicament of  claim 12  wherein said specific treatment of said patient is selected from:
 overweight or obese and/or has diabetes, hyperlipidaemia, atherosclerosis, coronary heart disease, stroke, obstructive sleep apnoea, arthritis and/or reduced fertility, or is at risk of developing such a condition. 
 
     
     
         15 . The medicament of  claim 12  wherein said specific treatment of said patient is selected from:
 the need of an antitumour agent or an antiinflammatory agent or of modulation of lipid or eicosanoid status or function, or of modulation of a lipid metabolising or binding entity activity. 
 
     
     
         16 . The medicament of  claim 12 , wherein said compound comprises a perfluorinated fatty acid or derivative thereof. 
     
     
         17 . The medicament of  claim 12 , wherein said medicament further comprises a compound selected from:
 a fluorinated carboxylic acid or perfluorinated carboxylic acid or pharmaceutically acceptable salt, ester or halide thereof.   
     
     
         18 . The medicament of  claim 12 , wherein said medicament further comprises a compound selected from:
 perfluorooctanoic acid (PFOA) or a pharmaceutically acceptable salt, ester or halide thereof, including ammonium perfluorooctanoate (APFO).   
     
     
         19 . A screening method for identifying a drug-like compound or lead compound for the development of a drug-like compound comprising the steps of:
 exposing a mammal to a compound of formula I as defined in  claim 1  or derivative thereof;   measuring the plasma insulin, glucose, cholesterol, triglyceride and/or leptin level of the mammal is measured, and/or bodyweight of the mammal and/or lipid or eicosanoid status or function of the mammal.   
     
     
         20 . The method of  claim 17  further comprising the step of:
 selecting a compound on exposure to which the plasma insulin, glucose, cholesterol, triglyceride and/or leptin level of the mammal is changed or reduced, and/or bodyweight or bodyweight increase of the mammal is changed or reduced. 
 
     
     
         21 . A screening method for identifying a drug-like compound or lead compound for the development of a drug-like compound comprising the steps:
 selecting a compound of formula I as defined in  claim 1  or derivative thereof;   exposing said compound to a PPAR polypeptide;   binding the compound to the PPAR polypeptide; and   measuring the change in the activity of the PPAR polypeptide.   
     
     
         22 . A screening method for identifying a drug-like compound or lead compound for the development of a drug-like compound comprising the steps:
 selecting a compound of formula I as defined in  claim 1  or derivative thereof;   exposing said compound to a lipid metabolising or binding entity, for example cycloxygenase (for example cyclooxygenase I or cyclooxygenase II) or phospholipase A (for example phospholipase A2);   binding the compound to the lipid metabolising or binding entity; and   measuring the change in the activity of the lipid metabolising or binding entity.   
     
     
         23 . A screening method for identifying a drug-like compound or lead compound for the development of a drug-like compound comprising the steps:
 selecting a cell;   selecting a compound of formula I as defined in  claim 1  or derivative thereof;   exposing said cell to said compound; and   measuring the phenotype, differentiation, and/or eicosanoid biosynthesis of the cell.   
     
     
         24 . The method of  claim 21  wherein said selected compound changes the phenotype, differentiation, and/or eicosanoid biosynthesis of the cell. 
     
     
         25 . The method of  claim 24  wherein in said change of the phenotype, differentiation, and/or eicosanoid biosynthesis of the cell is reduced. 
     
     
         26 . The screening method of  claim 19  further comprising the step of identifying a compound. 
     
     
         27 . The method of  claim 26 , where said identified compound is for use in medicine. 
     
     
         28 . The method of  claim 27 , wherein the use in medicine is selected from:
 the treatment of a patient in need of modulation of body mass or modulation of increase in body mass, and/or in need of modulation of plasma insulin, plasma glucose, plasma triglycerides, plasma cholesterol and/or leptin.   
     
     
         29 . The method of  claim 27 , wherein the use in medicine is selected from:
 the treatment of a patient who is overweight or obese and/or has diabetes, hyperlipidaemia, atherosclerosis, coronary heart disease, stroke, obstructive sleep apnoea, arthritis and/or reduced fertility, or is at risk of developing such a condition.   
     
     
         30 . The method of  claim 27 , wherein the use in medicine is selected from:
 treating a patient in need of modulation of PPAR (for example PPARα) activity, or in need of an antitumour agent or an antiinflammatory agent, or in need of modulation of lipid or eicosanoid status or function, or in need of modulation of lipid metabolising or binding entity activity.   
     
     
         31 . The method of  claim 30  wherein said use in medicine is a patient in need of an increase in PPAR activity; and
 the compound is a PPAR or PPARα agonist. 
 
     
     
         32 . The method of  claim 27 , wherein the use in medicine is selected from: a patient in need of modulation of body mass or modulation of increase in body mass, and/or in need of modulation of plasma insulin, plasma glucose, plasma triglycerides, plasma cholesterol and/or leptin;
 said method further comprising:   administering to the patient an effective amount of said identified compound.   
     
     
         33 . The method of  claim 27 , wherein the use is selected from:
 treatment of a patient who is overweight or obese and/or has diabetes, hyperlipidaemia, atherosclerosis, coronary heart disease, stroke, obstructive sleep apnoea, arthritis and/or reduced fertility, or is at risk of developing such a condition,   said method further comprising:   administering to the patient an effective amount of said identified compound.   
     
     
         34 . The method of  claim 27 , wherein the use in medicine is selected from:
 treatment of a patient in need of modulation of PPAR (for example PPARα) activity, or in need of an antitumour agent or an antiinflammatory agent, or in need of modulation of lipid or eicosanoid status or function, or of a lipid metabolising or binding entity activity;   said method further comprising:   administering to the patient an effective amount of said identified compound identified.   
     
     
         35 . The method of  claim 34 , wherein said identified compound is for use in the manufacture of a composition for use as a food supplement or a food additive. 
     
     
         36 . A food product comprising a foodstuff and a compound of formula I as defined in  claim 1 , wherein the food is not laboratory rodent feed. 
     
     
         37 . A kit of parts of a screening system comprising:
 (1) a library of compounds each of formula I as defined in  claim 1  or a derivative thereof,   and (2) a PPAR polypeptide or polynucleotide encoding a PPAR polypeptide, and/or a test mammal.   
     
     
         38 . A kit of parts of a screening system comprising:
 (1) a library of compounds each of formula I as herein defined or a derivative thereof; and   (2) a lipid metabolising or binding entity (for example COXI or COXII or phospholipase A2 or lipoxygenase) or polynucleotide encoding a lipid metabolising or binding entity.