Pyrazole-amide compounds and pharmaceutical use thereof

Abstract

A compound represented by the following formula: wherein n is 1 or 2, or a pharmaceutically acceptable salt thereof, and a pharmaceutical use thereof.

1 .- 5 . (canceled) 
     
     
         6 . A method of inhibiting pyruvate dehydrogenase kinase (PDHK) in a mammal, comprising administering to the mammal in need thereof:
 (a) a compound selected from the group consisting of:
 i. a compound represented by formula [I]: 
   
       
         
           
           
               
               
           
         
         wherein n is 1 or 2, or a pharmaceutically acceptable salt thereof;
 ii. compound represented by formula [II]: 
 
       
       
         
           
           
               
               
           
         
         
            or a pharmaceutically acceptable salt thereof; 
           iii. a compound represented by formula [IIh]: 
         
       
       
         
           
           
               
               
           
         
         
            or a pharmaceutically acceptable salt thereof; and 
           iv. a compound represented by formula [III]: 
         
       
       
         
           
           
               
               
           
         
         
            or a pharmaceutically acceptable salt thereof; and 
         
         (b) at least one medicament for prophylaxis or treatment of diabetes, insulin resistance syndrome, metabolic syndrome, hyperglycemia, hyperlactacidemia, diabetic complications, cardiac failure, cardiomyopathy, myocardial ischemia, myocardial infarction, angina pectoris, dyslipidemia, atherosclerosis, peripheral arterial disease, intermittent claudication, chronic obstructive pulmonary disease, brain ischemia, cerebral apoplexy, mitochondrial disease, mitochondrial encephalomyopathy, cancer or pulmonary hypertension. 
       
     
     
         7 . The method of  claim 6 , wherein the compound and the at least one medicament are administered simultaneously. 
     
     
         8 . The method of  claim 6 , wherein the compound and the at least one medicament are administered separately. 
     
     
         9 . The method of  claim 6 , wherein the compound and the at least one medicament are administered continuously. 
     
     
         10 . The method of  claim 6 , wherein the diabetes is type 1 diabetes or type 2 diabetes. 
     
     
         11 . The method of  claim 6 , wherein the diabetic complications are selected from the group consisting of diabetic neuropathy, diabetic retinopathy, diabetic nephropathy, and cataract. 
     
     
         12 . The method composition of  claim 6 , wherein the cardiac failure is acute cardiac failure or chronic cardiac failure. 
     
     
         13 . A method for prophylaxis of diabetes, insulin resistance syndrome, metabolic syndrome, hyperglycemia, hyperlactacidemia, diabetic complications, cardiac failure, cardiomyopathy, myocardial ischemia, myocardial infarction, angina pectoris, dyslipidemia, atherosclerosis, peripheral arterial disease, intermittent claudication, chronic obstructive pulmonary disease, brain ischemia, cerebral apoplexy, mitochondrial disease, mitochondrial encephalomyopathy, cancer or pulmonary hypertension in a mammal, comprising administering to the mammal in need thereof:
 (a) a compound selected from the group consisting of:
 i) a compound represented by formula [I]: 
   
       
         
           
           
               
               
           
         
       
       wherein n is 1 or 2, or a pharmaceutically acceptable salt thereof;
   ii) a compound represented by formula [II]:   
 
       
         
           
           
               
               
           
         
         
            or a pharmaceutically acceptable salt thereof; 
           iii) a compound represented by formula [IIh]: 
         
       
       
         
           
           
               
               
           
         
         
            or a pharmaceutically acceptable salt thereof; and 
           iv) a compound represented by formula [III]: 
         
       
       
         
           
           
               
               
           
         
         
            or a pharmaceutically acceptable salt thereof; and 
         
         (b) at least one medicament for prophylaxis or treatment of diabetes, insulin resistance syndrome, metabolic syndrome, hyperglycemia, hyperlactacidemia, diabetic complications, cardiac failure, cardiomyopathy, myocardial ischemia, myocardial infarction, angina pectoris, dyslipidemia, atherosclerosis, peripheral arterial disease, intermittent claudication, chronic obstructive pulmonary disease, brain ischemia, cerebral apoplexy, mitochondrial disease, mitochondrial encephalomyopathy, cancer or pulmonary hypertension. 
       
     
     
         14 . The method of  claim 13 , wherein the diabetes is type 1 diabetes or type 2 diabetes. 
     
     
         15 . The method of  claim 13 , wherein the diabetic complications are selected from the group consisting of diabetic neuropathy, diabetic retinopathy, diabetic nephropathy, and cataract. 
     
     
         16 . The method of  claim 13 , wherein the cardiac failure is acute cardiac failure or chronic cardiac failure. 
     
     
         17 . A compound represented by formula: 
       
         
           
           
               
               
           
         
       
     
     
         18 . A compound represented by formula: 
       
         
           
           
               
               
           
         
       
     
     
         19 . A compound represented by formula: 
       
         
           
           
               
               
           
         
       
     
     
         20 . A compound represented by formula: 
       
         
           
           
               
               
           
         
       
     
     
         21 . A compound represented by formula: