Method for preventing and treating visceral pain and gastrointestinal disorders

Abstract

The compounds of formula I-IV: wherein n is an integer of from 1 to 4, or pharmaceutically acceptable salts thereof are useful to prevent and treat visceral pain and gastrointestinal disorders.

1 . A method for the prevention or treatment of visceral pain comprising administering to a patient in need of treatment an effective amount of a compound of formula I-IV:  
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof, wherein n is an integer of from 1 to 4.  
     
     
         2 . (Cancelled)  
     
     
         3 . The method of  claim 1 , wherein the compound is selected from: 
 (1α,6α,8β)(2-Aminomethyl-octahydro-inden-2-yl)-acetic acid,    (2-Aminomethyl-octahydro-inden-2-yl)-acetic acid,    (2-Aminomethyl-octahydro-pentalen-2-yl)-acetic acid,    (3-Aminomethyl-bicyclo[3.2.0]hept-3-yl)-acetic acid,    (1α,3α,5α)-3-aminomethyl-bicyclo[3.2.0]heptane-3-acetic acid,    (1α,5β)(3-Aminomethyl-bicyclo[3.1.0]hex-3-yl)-acetic acid,    (1α,5β)(3-Aminomethyl-bicyclo[3.2.0]hept-3-yl)-acetic acid,    (1α,5β)(2-Aminomethyl-octahydro-pentalen-2-yl)-acetic acid,    (1α,6β)(2-Aminomethyl-octahydro-inden-2-yl)-acetic acid,    (1α,7β)(2-Aminomethyl-decahydro-azulen-2-yl)-acetic acid,    (1α,5β)(3-Aminomethyl-bicyclo[3.1.0]hex-3-yl)-acetic acid,    (1α,5β)(3-Aminomethyl-bicyclo[3.2.0]hept-3-yl)-acetic acid,    (1α,5β)(2-Aminomethyl-octahydro-pentalen-2-yl)-acetic acid,    (1α,6β)(2-Aminomethyl-octahydro-inden-2-yl)-acetic acid,    (1α,7β)(2-Aminomethyl-decahydro-azulen-2-yl)-acetic acid,    (1α,3α,5α)(3-Aminomethyl-bicyclo[3.1.0]hex-3-yl)-acetic acid,    (1α,3α,5α)(2-Aminomethyl-octahydro-pentalen-2-yl)-acetic acid,    (1α,6α,8α)(2-Aminomethyl-octahydro-inden-2-yl)-acetic acid,    (1α,7α,9α)(2-Aminomethyl-decahydro-azulen-2-yl)-acetic acid,    (1α,3β,5α)(3-Aminomethyl-bicyclo[3.1.0]hex-3-yl)-acetic acid,    (1α,3β,5α)(3-Aminomethyl-bicyclo[3.2.0]hept-3-yl)-acetic acid,    (1α,3β,5α)(2-Aminomethyl-octahydro-pentalen-2-yl)-acetic acid,    (1α,6α,8β)(2-Aminomethyl-octahydro-inden-2-yl)-acetic acid,    (1α,7α,9β)(2-Aminomethyl-decahydro-azulen-2-yl)-acetic acid,    ((1R,3R,6R)-3-Aminomethyl-bicyclo[4.1.0]hept-3-yl)-acetic acid,    ((1R,3S,6R)-3-Aminomethyl-bicyclo[4.1.0]hept-3-yl)-acetic acid,    ((1S,3S,6S)-3-Aminomethyl-bicyclo[4.1.0]hept-3-yl)-acetic acid,    ((1S,3R,6S)-3-Aminomethyl-bicyclo[4.1.0]hept-3-yl)-acetic acid,    ((1R,3R,6S)-3-Aminomethyl-bicyclo[4.2.0]oct-3-yl)-acetic acid,    ((1R,3S,6S)-3-Aminomethyl-bicyclo[4.2.0]oct-3-yl)-acetic acid,    ((1S,3S,6R)-3-Aminomethyl-bicyclo[4.2.0]oct-3-yl)-acetic acid,    ((1S,3R,6R)-3-Aminomethyl-bicyclo[4.2.0]oct-3-yl)-acetic acid,    ((3αR,5R,7αS)-5-Aminomethyl-octahydro-inden-5-yl)-acetic acid,    ((3αR,5S,7αS)-5-Aminomethyl-octahydro-inden-5-yl)-acetic acid,    ((3αS,5S,7αR)-5-Aminomethyl-octahydro-inden-5-yl)-acetic acid,    ((3αS,5R,7αR)-5-Aminomethyl-octahydro-inden-5-yl)-acetic acid,    ((2R,4αS,8αR)-2-Aminomethyl-decahydro-naphthalen-2-yl)-acetic acid,    ((2S,4αS,8αR)-2-Aminomethyl-decahydro-naphthalen-2-yl)-acetic acid,    ((2S,4αR,8αS)-2-Aminomethyl-decahydro-naphthalen-2-yl)-acetic acid,    ((2R,4αR,8αS)-2-Aminomethyl-decahydro-naphthalen-2-yl)-acetic acid,    ((2R,4αS,9αR)-2-Aminomethyl-decahydro-benzocyclophepten-2-yl)-acetic acid,    ((2S,4αS,9αR)-2-Aminomethyl-decahydro-benzocyclophepten-2-yl)-acetic acid,    ((2S,4αR,9αS)-2-Aminomethyl-decahydro-benzocyclophepten-2-yl)-acetic acid,    ((2R,4αR,9αS)-2-Aminomethyl-decahydro-benzocyclophepten-2-yl)-acetic acid,    ((1R,3R,6S)-3-Aminomethyl-bicyclo[4.1.0]hept-3-yl)-acetic acid,    ((1R,3S,6S)-3-Aminomethyl-bicyclo[4.1.0]hept-3-yl)-acetic acid,    ((1S,3S,6R)-3-Aminomethyl-bicyclo[4.1.0]hept-3-yl)-acetic acid,    ((1S,3R,6R)-3-Aminomethyl-bicyclo[4.1.0]hept-3-yl)-acetic acid,    ((1R,3R,6R)-3-Aminomethyl-bicyclo[4.2.0]oct-3-yl)-acetic acid,    ((1R,3S,6R)-3-Aminomethyl-bicyclo[4.2.0]oct-3-yl)-acetic acid,    ((1S,3S,6S)-3-Aminomethyl-bicyclo[4.2.0]oct-3-yl)-acetic acid,    ((1S,3R,6S)-3-Aminomethyl-bicyclo[4.2.0]oct-3-yl)-acetic acid,    ((3αR,5R,7αR)-5-Aminomethyl-octahydro-inden-5-yl)-acetic acid,    ((3αR,5S,7αR)-5-Aminomethyl-octahydro-inden-5-yl)-acetic acid,    ((3αS,5S,7αS)-5-Aminomethyl-octahydro-inden-5-yl)-acetic acid,    ((3αS,5R,7αS)-5-Aminomethyl-octahydro-inden-5-yl)-acetic acid,    ((2R,4αR,8αR)-2-Aminomethyl-decahydro-naphthalen-2-yl)-acetic acid,    ((2S,4αS,8αR)-2-Aminomethyl-decahydro-naphthalen-2-yl)-acetic acid,    ((2S,4αR,8αS)-2-Aminomethyl-decahydro-naphthalen-2-yl)-acetic acid,    ((2R,4αS,8αS)-2-Aminomethyl-decahydro-naphthalen-2-yl)-acetic acid,    ((2R,4αR,9αR)-2-Aminomethyl-decahydro-benzocyclophepten-2-yl)-acetic acid,    ((2S,4αR,9αR)-2-Aminomethyl-decahydro-benzocyclophepten-2-yl)-acetic acid,    ((2S,4αS,9αS)-2-Aminomethyl-decahydro-benzocyclophepten-2-yl)-acetic acid, and    ((2R,4αS,9αS)-2-Aminomethyl-decahydro-benzocyclophepten-2-yl)-acetic acid, or a pharmaceutically acceptable salt thereof.    
     
     
         4 . The method according to  claim 1 , wherein the compound is the compound of formula I or a pharmaceutically acceptable salt thereof.  
     
     
         5 . A method for the prevention or treatment of visceral pain comprising administering to a patient in need of treatment an effective amount of (1α,3α,5α)-3-aminomethyl-bicyclo[3.2.0]heptane-3-acetic acid or a pharmaceutically acceptable salt thereof.  
     
     
         6 . (Cancelled)  
     
     
         7 . (Cancelled)  
     
     
         8 . (Cancelled)  
     
     
         9 . (Cancelled)  
     
     
         10 . A method according to any one of claims  1 ,  3 ,  4  or  5 , wherein the disorder is associated with dysmenorrhea pain, pelvic pain, cystitis pain and pancreatitis.  
     
     
         11 . A pharmaceutical composition for the treatment or prevention of visceral pain and GI disorders comprising a compound of formula I-IV.  
     
     
         12 . The pharmaceutical composition according to  claim 11  comprising (1(1α,3α,5α)-3-aminomethyl-bicyclo[3.2.0]heptane-3-acetic acid.  
     
     
         13 . The pharmaceutical composition according to  claim 11  or  12  for treating or preventing disorders selected from the group consisting of functional bowel disorders such as gastro-esophageal reflux, dyspepsia, irritable bowel syndrome, functional abdominal pain syndrome, or inflammatory bowel diseases such as Crohn's disease, ileitis or ulcerative colitis, or disorders associated with dysmenorrhea pain, pelvic pain, cystitis pain and pancreatitis.  
     
     
         14 . The pharmaceutical composition according to  claim 11 , which is in a form suitable for oral administration.