Selective subtype alpha 2 adrenergic agents and methods for use thereof

Abstract

The invention provides well-defined heterocyclic compounds that are useful as subtype selective alpha 2 adrenergic agonists. As such, the compounds described herein are useful in treating a wide variety of disorders associated with selective subtype modulation of alpha 2 adrenergic receptor.

What is claimed is: 
     
         1 . A compound represented by the structure: 
       
         
           
           
               
               
           
         
         wherein:
 X is S; 
 Z 1 -Z 6  are each independently C, N, O, or S, with the proviso that at least one of Z 1 -Z 6  is N; 
 n and m are each independently 1 to 5; 
 p is 0 or 1; 
 each R 1  and R 2  is independently H, lower alkyl, lower alkenyl, lower alkynyl, halide, hydroxy, alkoxy, trifluoromethyl, 
 
         —N(R 6 ) 2 , —CN, —CO 2 R 6 , or —CH 2 OH; or
 when n is 2, each R 1  taken together with the carbon atoms to which they are attached forms a fused aryl, substituted aryl, heteroaryl, substituted heteroaryl, cycloalkyl, substituted cycloalkyl, heterocyclic, or substituted heterocyclic ring; 
 R 3 , R 4 , R 5 , and R 6  are each independently H or lower alkyl; 
 
       
       or pharmaceutically acceptable salts thereof. 
     
     
         2 . The compound of  claim 1 , wherein p is 1. 
     
     
         3 . The compound of  claim 1 , wherein R 1  is H, lower alkyl, chloro, fluoro, trifluoromethyl, or methoxy. 
     
     
         4 . A compound having the structure 
       
         
           
           
               
               
           
         
         wherein:
 Z 1 -Z 5  are each independently C, N, O, or S, with the proviso that at least one of Z 1 -Z 5  is N;
 n and m are each independently 1 to 5; 
 p is 0 or 1; 
 each R 1  and R 2  is independently H, lower alkyl, halide, hydroxy, alkoxy, or trifluoromethyl; 
 
 
       
       or pharmaceutically acceptable salts thereof. 
     
     
         5 . The compound of  claim 4 , having any one of the following structures: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
     
     
         6 . The compound of  claim 4  having the structure: 
       
         
           
           
               
               
           
         
       
     
     
         7 . A method for treating a disorder wherein the disorder is pain, visceral pain, corneal pain, headache pain, migraine, neuropathic pain, chronic pain, associated with selective subtype modulation of alpha 2B and alpha 2C adrenergic receptors, comprising administering to a subject in need thereof a pharmaceutical composition comprising a therapeutically effective amount of at least one compound of  claim 1 , or any combination thereof, or pharmaceutically acceptable salts, tautomers, enantiomers, and diastereomers thereof. 
     
     
         8 . The method, according to  claim 7 , wherein the subject is a human. 
     
     
         9 . The method of  claim 7 , wherein the disorder is chronic pain. 
     
     
         10 . The method of  claim 7 , wherein the disorder is neuropathic pain. 
     
     
         11 . The method of  claim 7 , wherein the disorder is visceral pain. 
     
     
         12 . The method of  claim 7 , wherein the disorder is glaucoma. 
     
     
         13 . The method of  claim 7 , wherein the disorder is elevated intraocular pressure. 
     
     
         14 . The method of  claim 7 , wherein the pharmaceutical composition is administered orally.