Pyrrolopyrimidine and pyrrolopyridine derivatives

Abstract

The present invention relates to pyrrolopyrimidine compounds according to Formula I and their use in the prophylaxis and/or treatment of pain, inflammatory conditions, cardiovascular diseases, neurodegenerative diseases, neurological diseases, complications of type I diabetes, cancer and/or fibrotic diseases. In a particular aspect, the present compounds are ASK inhibitors, particularly ASK1 inhibitors. The present invention also provides methods for the production of a compound of the invention, pharmaceutical compositions comprising a compound of the invention, the use of the compounds in the prophylaxis and/or treatment of pain, inflammatory conditions, cardiovascular diseases, neurodegenerative diseases, neurological diseases, complications of type I diabetes, cancer and/or fibrotic diseases.

1 - 11 . (canceled) 
     
     
         12 . A method for prophylaxis and/or treatment of chronic obstructive pulmonary disease (COPD), inflammatory bowel disease (IBD), idiopathic pulmonary fibrosis (IPF) and/or diabetic kidney disease (DKD), comprising administering an effective amount of a compound according to Formula I: 
       
         
           
           
               
               
           
         
       
       wherein
 R 1  is H, CH 3 , F or Cl; 
 X is N, CH or C—CN; and 
 R 2  is CH 3  or halogen;
 or a pharmaceutically acceptable salt thereof, to an individual in need thereof. 
 
 
     
     
         13 . The method of  claim 12 , wherein R 1  is F. 
     
     
         14 . The method of  claim 12 , wherein R 2  is CH 3 . 
     
     
         15 . The method of  claim 12 , wherein X is CH. 
     
     
         16 . The method of  claim 12 , wherein X is C—CN. 
     
     
         17 . The method of  claim 12 , wherein X is N. 
     
     
         18 . The method of  claim 12 , wherein the compound is:
 2-amino-5-fluoro-N-[1-(5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-4-piperidyl]pyridine-4-carboxamide,   2-amino-5-methyl-N-[1-(5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-4-piperidyl]pyridine-4-carboxamide,   2-amino-5-chloro-N-[1-(5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-4-piperidyl]-pyridine-4-carboxamide,   2-amino-N-[1-(5-chloro-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-4-piperidyl]pyridine-4-carboxamide,   2-amino-N-[1-(5-chloro-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-4-piperidyl]-5-fluoro-pyridine-4-carboxamide,   2-amino-N-[1-(5-cyano-3-methyl-1H-pyrrolo[2,3-b]pyridin-4-yl)-4-piperidyl]-5-fluoro-pyridine-4-carboxamide, or   2-amino-N-[1-(3-chloro-1H-pyrrolo[2,3-b]pyridin-4-yl)-4-piperidyl]-5-fluoro-pyridine-4-carboxamide.   
     
     
         19 . A method for prophylaxis and/or treatment of chronic obstructive pulmonary disease (COPD), inflammatory bowel disease (IBD), idiopathic pulmonary fibrosis (IPF) and/or diabetic kidney disease (DKD), comprising administering a pharmaceutical composition comprising a compound according to Formula I: 
       
         
           
           
               
               
           
         
       
       wherein
 R 1  is H, CH 3 , F or Cl; 
 X is N, CH or C—CN; and 
 R 2  is CH 3  or halogen;
 or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier, to an individual in need thereof. 
 
 
     
     
         20 . The method of  claim 19 , wherein R′ is F. 
     
     
         21 . The method of  claim 19 , wherein R 2  is CH 3 . 
     
     
         22 . The method of  claim 19 , wherein X is CH. 
     
     
         23 . The method of  claim 19 , wherein X is C—CN. 
     
     
         24 . The method of  claim 19 , wherein X is N. 
     
     
         25 . The method of  claim 19 , wherein the compound is:
 2-amino-5-fluoro-N-[1-(5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-4-piperidyl]pyridine-4-carboxamide,   2-amino-5-methyl-N-[1-(5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-4-piperidyl]pyridine-4-carboxamide,   2-amino-5-chloro-N-[1-(5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-4-piperidyl]-pyridine-4-carboxamide,   2-amino-N-[1-(5-chloro-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-4-piperidyl]pyridine-4-carboxamide,   2-amino-N-[1-(5-chloro-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-4-piperidyl]-5-fluoro-pyridine-4-carboxamide,   2-amino-N-[1-(5-cyano-3-methyl-1H-pyrrolo[2,3-b]pyridin-4-yl)-4-piperidyl]-5-fluoro-pyridine-4-carboxamide, or   2-amino-N-[1-(3-chloro-1H-pyrrolo[2,3-b]pyridin-4-yl)-4-piperidyl]-5-fluoro-pyridine-4-carboxamide.