Pyrrolecarboxylic acid derivatives

Abstract

Novel pyrrolecarboxylic acid derivatives represented by the following formula: <IMAGE> where R1 is a hydrogen atom, an alkyl group of 5 to 25 carbon atoms or an alkenyl group of 5 to 25 carbon atoms, R2 is a hydrogen atom, a phenyl group or an optionally substituted alkyl group of 1 to 10 carbon atoms, and R3 is a hydrogen atom, an alkyl group of 5 to 25 carbon atoms or an alkenyl group of 5 to 25 carbon atoms, or pharmaceutically acceptable salts thereof are provided. The compounds are highly effective in reducing the level of triglyceride or cholesterol in serum, and useful as an active ingredient of a pharmaceutical composition for treating hyperlipemia and arteriosclerosis.

What is claimed is: 
     
       1. A pyrrolecarboxylic acid derivative represented by the following formula (I): ##STR19## wherein R 1  is a hydrogen atom, an alkyl group of 10 to 16 carbon atoms, ##STR20## or an alkenyl group of 8 to 16 carbon atoms, R 2  is a hydrogen atom, a phenyl group, or an alkyl group of 1 to 10 carbon atoms unsubstituted or substituted with a halogen atom, hydroxyl group, amino group, alkylamino group of 1 to 5 carbon atoms, carbamoyl group, C 1  -C 5  -alkylcarbonylamino group, alkylthio group of 1 to 5 carbon atoms, mercapto group, a C 1  -C 5  -alkylcarbonyloxy group of aminocarbonyloxy group, and R 3  is an alkyl group of 10 to 16 carbon atoms or an alkenyl group of 10 to 16 carbon atoms, provided that, when R 1  is a group other than a hydrogen atom, R 1  is not adjacent to CO 2  R 2 , or a pharmaceutically acceptable salt thereof. 
     
     
       2. The compound of claim 1, wherein R 2  is a hydrogen atom, a phenyl group or a linear or branched alkyl group of 1 to 4 carbon atoms unsubstituted or substituted with a halogen atom, hydroxyl group, amino group, alkylamino group of 1 to 5 carbon atoms, carbamoyl group, C 1  -C 5  -alkylcarbonylamino group, alkylthio group of 1 to 5 carbon atoms, mercapto group, C 1  -C 5  -alkylcarbonyloxy group or aminocarbonyloxy group. 
     
     
       3. A pharmaceutical composition for treating hyperlipemia and/or arteriosclerosis, comprising: a therapeutically effective amount of a pyrrolecarboxylic acid derivative represented by the formula (I): ##STR21## wherein R 1  is a hydrogen atom, an alkyl group of 10 to 16 carbon atoms, ##STR22## or an alkenyl group of 8 to 16 carbon atoms, R 2  is a hydrogen atom, a phenyl group, or an alkyl group of 1 to 10 carbon atoms unsubstituted or substituted with a halogen atom, hydroxyl group, amino group, alkylamino group of 1 to 5 carbon atoms, carbamoyl group, C 1  -C 5  -alkylcarbonylamino group, alkylthio group of 1 to 5 carbon atoms, mercapto group, a C 1  -C 5  -alkylcarbonyloxy group or aminocarbonyloxy group, and R 3  is an alkyl group of 10 to 16 carbon atoms or an alkenyl group of 10 to 16 carbon atoms, provided that, when R 1  is a group other than a hydrogen atom, R 1  is not adjacent to CO 2  R 2 , or a pharmaceutically acceptable salt thereof, in admixture with a pharmaceutically acceptable carrier or diluent. 
     
     
       4. A pyrrolecarboxylic acid derivative represented by the following formula: ##STR23## wherein R 1  is an alkyl group of 10 to 16 carbon atoms, ##STR24## or an alkenyl group of 10 to 16 carbon atoms and R 2  is a hydrogen atom, a phenyl group, or an alkyl group of 1 to 10 carbon atoms unsubstituted or substituted with a halogen atom, hydroxyl group, amino group, alkylamino group of 1 to 5 carbon atoms, carbamoyl group, C 1  -C 5  -alkylcarbonylamino group, alkylthio group of 1 to 5 carbon atoms, mercapto group, a C 1  -C 5  -alkylcarbonyloxy group or aminocarbonyloxy group, provided that R 1  is not adjacent to CO 2  R 2 , or a pharmaceutically acceptable salt thereof. 
     
     
       5. A pyrrolecarboxylic acid derivative or a pharmaceutically acceptable salt thereof as defined in claim 4, wherein R 2  is a hydrogen atom, a phenyl group or an alkyl group of 1 to 5 carbon atoms unsubstituted or substituted with a halogen atom, hydroxyl group, alkylamino group of 1 to 5 carbon atoms or alkylthio group of 1 to 5 carbon atoms. 
     
     
       6. A pyrrolecarboxylic acid derivative or a pharmaceutically acceptable salt thereof as defined in claim 4, wherein R 2  is a hydrogen atom, a phenyl group or an alkyl group of 1 to 5 carbon atoms. 
     
     
       7. A pyrrolecarboxylic acid derivative or a pharmaceutically acceptable salt thereof as defined in claim 4, wherein R 2  is a hydrogen atom or an alkyl group of 1 to 5 carbon atoms. 
     
     
       8. A pyrrolecarboxylic acid derivative or a pharmaceutically acceptable salt thereof as defined in claim 4, wherein R 1  is an alkyl group of 10 to 16 carbon atoms. 
     
     
       9. A pyrrolecarboxylic acid derivative or a pharmaceutically acceptable salt thereof as defined in claim 4, wherein R 2  is hydrogen atom. 
     
     
       10. A pharmaceutical composition for treating hyperlipemia and/or arteriosclerosis comprising a therapeutically effective amount of pyrrolecarboxylic acid derivative represented by the following formula (I'): ##STR25## wherein R 1  is an alkyl group of 10 to 16 carbon atoms, ##STR26## or an alkenyl group of 10 to 16 carbon atoms and R 2  is a hydrogen atom, a phenyl group, or an alkyl group of 1 to 5 carbon atoms unsubstituted or substituted with a halogen atom, hydroxyl group, amino group, alkylamino group of 1 to 5 carbon atoms, carbamoyl group, C 1  -C 5  -alkylcarbonylamino group, alkylthio group of 1 to 5 carbon atoms, mercapto group, a C 1  -C 5  -alkylcarbonyloxy group or aminocarbonyloxy group, provided that R 1  is not adjacent to CO 2  R 2 , or a pharmaceutically acceptable salt thereof, in admixture with a pharmaceutically acceptable carrier of diluent. 
     
     
       11. The derivative of claim 1, wherein R 1  is alkenyl of 10 to 16 carbon atoms. 
     
     
       12. The composition of claim 3, wherein R 1  is alkenyl of 10 to 16 carbon atoms. .Iadd.13. 4-tridecylpyrrole-2-carboxylic acid. .Iaddend. .Iadd.14. A pharmaceutical composition for treating hyperlipemia, comprising a therapeutically effective amount of 4-tridecylpyrrole-2-carboxylic acid or a pharmaceutically acceptable salt thereof in admixture with a pharmaceutically acceptable carrier or diluent. .Iaddend. .Iadd.15. A pharmaceutical composition for treating arteriosclerosis, comprising a therapeutically effective amount of 4-tridecylpyrrole-2-carboxylic acid or a pharmaceutically acceptable salt thereof in admixture with a pharmaceutically acceptable carrier or 
     
     
        diluent. .Iaddend. .Iadd.16.  A method of reducing the level of triglyceride or cholesterol in serum, which comprises administering a therapeutically effective amount of 4-tridecylpyrrole-2-carboxylic acid or a pharmaceutically acceptable salt thereof to a patient suffering from high level of triglyceride or cholesterol in serum. .Iaddend.