Nitrogen-containing heterocyclic amide compound and pharmaceutical use thereof

Abstract

The present invention provides a compound having a PDHK inhibitory activity and useful for the treatment or prophylaxis of diabetes (type 1 diabetes, type 2 diabetes etc.), insulin resistance syndrome, metabolic syndrome, hyperglycemia, hyperlactacidemia, diabetic complications (diabetic neuropathy, diabetic retinopathy, diabetic nephropathy, cataract etc.), cardiac failure (acute cardiac failure, chronic 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, pulmonary hypertension or Alzheimer disease. The present invention relates to a compound of the formula [I-a] or the formula [II], or a pharmaceutically acceptable salt thereof:wherein each symbol means the same as that described in the specification.

1 .- 35 . (canceled) 
     
     
         36 . A method for producing a compound represented by formula [I-a]: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof, wherein the method comprises a step of performing an amidation reaction of a compound presented by formula [2]: 
       
         
           
           
               
               
           
         
       
       and a compound represented by formula [17]: 
       
         
           
           
               
               
           
         
       
       wherein
 a bond in a dotted line is a single bond or a double bond, 
 X 1  is a carbon atom, a nitrogen atom or an oxygen atom, 
 X 2  is a carbon atom or a nitrogen atom, 
 R 1a  is C 1-4  alkyl or C 1-4  alkylcarbonyl, 
 R 2  is halogen, cyano or C 1-4  alkyl, 
 m is 0 or 1, 
 n is 0, 1 or 2, when n is 2, each R 2  is the same or different, 
 A 1 , A 2 , A 3 , A 4 , A 5 , A 6  and A 7  are each independently selected from a carbon atom, a nitrogen atom and an oxygen atom, A 8  is selected from a carbon atom and a nitrogen atom, and a total number of nitrogen and oxygen atoms contained in a partial structural formula: 
 
       
         
           
           
               
               
           
         
         is 0, 1, 2 or 3, 
         t is 0 or 1, 
         r is 0, 1 or 2, and a total of t and r is 1 or 2, and 
         w is 0 or 1. 
       
     
     
         37 . A compound represented by formula (17):