Nicotinic receptor non-competitive antagonists

Abstract

The present invention relates to compounds that modulate nicotinic receptors as non-competitive antagonists, methods for their synthesis, methods for use, and their pharmaceutical compositions.

What is claimed is: 
     
         1 . A method for the treatment or prevention of a disease or condition mediated by a neuronal nicotinic receptor comprising the administration of a compound of Formula I: 
       
         
           
           
               
               
           
         
       
       wherein
 each of R 1  and R 2  individually is H, C 1-6  alkyl, or aryl-substituted C 1-6  alkyl, or R 1  and R 2  combine with the nitrogen atom to which they are attached to form a 3- to 8-membered ring, which ring may be optionally substituted with C 1-6  alkyl, aryl, C 1-6  alkoxy, or aryloxy substituents; 
 R 3  is H, C 1-6  alkyl, or C 1-6  alkoxy-substituted C 1-6  alkyl; 
 each of R 4 , R 5 , R 6 , and R 7  individually is H, C 1-6  alkyl, or C 1-6  alkoxy; 
 L 1  is a linker species selected from the group consisting of CR 8 R 9 , CR 8 R 9 CR 10 R 11 , and O; 
 L 2  is a linker species selected from the group consisting of CH 2 , CH 2 CH 2 , CH 2 CH 2 CH 2 , and CH 2 CH 2 CH 2 CH 2 ; 
 each of R 8 , R 9 , R 10 , and R 11  individually is hydrogen or C 1-6  alkyl; and 
 the dashed line indicates an optional double bond; 
 or a pharmaceutically acceptable salt thereof. 
 
     
     
         2 . The method of  claim 1 , wherein the disease or condition is IBS-D, OAB, nicotine addiction, smoking cessation, depression, major depressive disorder, or hypertension. 
     
     
         3 . A method for the treatment or prevention of a disease or condition mediated by a neuronal nicotinic receptor comprising the administration of a compound 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof. 
     
     
         4 . The method of  claim 3 , wherein the disease or condition is IBS-D, OAB, nicotine addiction, smoking cessation, depression, major depressive disorder, or hypertension.