8-azabicyclo[3.2.1]octane compounds as mu opioid receptor antagonists

Abstract

The invention provides novel 8-azabicyclo[3.2.1]octane compounds of formula (I):wherein R1, R2, R3, A, and G are defined in the specification, or a pharmaceutically-acceptable salt or solvate thereof, that are antagonists at the mu opioid receptor. The invention also provides pharmaceutical compositions comprising such compounds, methods of using such compounds to treat conditions associated with mu opioid receptor activity, and processes and intermediates useful for preparing such compounds.

1 - 2 . (canceled) 
     
     
         3 . A method of inhibiting mu opioid receptor in a mammal in need thereof, the method comprising administering to the mammal a pharmaceutical composition comprising a compound of formula: 
       
         
           
           
               
               
           
         
       
        or a pharmaceutically acceptable salt thereof, and a pharmaceutically-acceptable carrier. 
     
     
         4 . The method of  claim 3 , wherein the pharmaceutical composition is administered orally. 
     
     
         5 . The method of  claim 3 , wherein the pharmaceutical composition is a tablet. 
     
     
         6 . The method of  claim 3 , wherein the pharmaceutical composition is a capsule. 
     
     
         7 . The method of  claim 3 , wherein the pharmaceutical composition is a gelatin capsule. 
     
     
         8 . The method of  claim 3 , wherein the pharmaceutical composition is a pill. 
     
     
         9 . The method of  claim 3 , wherein the mammal has opioid-induced bowel dysfunction or post-operative ileus. 
     
     
         10 . The method of  claim 3 , wherein the mammal has chronic constipation, constipation-predominant irritable bowel syndrome (C-IBS), diabetic and idiopathic gastroparesis, and functional dyspepsia.