Nicotinic acetylcholine receptor agonists

Abstract

The invention provides novel nicotinic acetylcholine receptor agonists, for example, phantasmidine and derivatives thereof, for example a compound of formula I. Also disclosed are methods of treating disorders responsive to nicotinic acetylcholine receptor agonists such as Alzheimer's disease, schizophrenia, Myasthenia Gravis, Tourette's syndrome, Parkinson's disease, epilepsy, pain, and cognitive dysfunction by treatment with the nicotinic acetylcholine receptor agonists.

1 - 45 . (canceled) 
     
     
         46 . A method for treating or preventing a disorder responsive to a nicotinic acetylcholine receptor agonist, comprising administering to a mammal in need of treatment a therapeutically effective amount of a compound of formula (I): 
       
         
           
           
               
               
           
         
         wherein R 1  is H, CH 3  or CH 3 CO; 
         or a compound of formula (II): 
       
       
         
           
           
               
               
           
         
         wherein R 1  is selected from the group consisting of C 1 -C 12  alkyl and R 2 CO, wherein R 2  is hydrogen or C 1 -C 12  alkyl; 
         W is O or S; 
         Z is a bond; 
         p=1-3; m=0; n=1; 
         Y is hydrogen; and 
         X is halogen; 
         an enantiomer thereof, stereoisomer thereof, racemic mixtures thereof, or a pharmaceutically acceptable salt thereof; 
         provided that the compound is not phantasmidine of the formula: 
       
       
         
           
           
               
               
           
         
       
     
     
         47 . The method of  claim 46 , wherein the compound is of formula (I) and R 1  is H. 
     
     
         48 . The method of  claim 46 , wherein the compound is of formula (I) and R 1  is CH 3 . 
     
     
         49 . The method of  claim 46 , wherein the compound is of formula (I) and R 1  is CH 3 CO. 
     
     
         50 . The method of  claim 46 , wherein the compound is of formula (II) and W is O. 
     
     
         51 . The method of  claim 50 , wherein R 1  is C 1 -C 6  alkyl. 
     
     
         52 . The method of  claim 51 , wherein R 1  is methyl. 
     
     
         53 . The method of  claim 51 , wherein X is chloro. 
     
     
         54 . The method of  claim 46 , wherein the compound, enantiomer thereof, stereoisomer thereof, racemic mixture thereof, or a pharmaceutically acceptable salt thereof is administered in combination with one or more pharmaceutically acceptable carriers. 
     
     
         55 . The method of  claim 54 , wherein the one or more pharmaceutically acceptable carriers are selected from the group consisting of anti-oxidants, buffers, bacteriostats, tonicity agents, suspending agents, solubilizers, thickening agents, stabilizers, preservatives, sugars, alcohols, glycols, saline, fatty acids, fatty acid esters, phospholipids, surfactants, soaps, oils, phosphoglycerides, collagen, gelatin, silicone materials, lubricants, fillers, colorants, diluents, cyclodextrin, buffering agents, disintegrating agents, moistening agents, preservatives, flavoring agents, and propellants. 
     
     
         56 . The method of  claim 46 , wherein the disorder is a disorder of the central nervous system. 
     
     
         57 . The method of  claim 56 , wherein the disorder of the central nervous system is selected from the group consisting of Alzheimer's disease, schizophrenia, Myasthenia Gravis, Tourette's syndrome, Parkinson's disease, epilepsy, and cognitive dysfunction. 
     
     
         58 . The method of  claim 46 , wherein the disorder is tobacco dependence. 
     
     
         59 . The method of  claim 46 , wherein the disorder is glaucoma. 
     
     
         60 . The method of  claim 46 , wherein treatment of the disorder comprises relaxation of muscle tissue. 
     
     
         61 . The method of  claim 46 , wherein the disorder is a cardiovascular disorder. 
     
     
         62 . The method of  claim 61 , wherein the disorder is hypertension. 
     
     
         63 . The method of  claim 46 , wherein the disorder is pain.