Highly selective sigma receptor ligands

Abstract

A compound useful for treating subjects in need of therapy involving sigma receptors or for alleviation of affects resulting from drug abuse having the general formula I in which R 1 can be a radical of an optionally substituted C-4 to C-7 N-containing heterocycle such as, for example, radicals of optionally substituted piperidines, optionally substituted piperazines, optionally substituted tetrahydropyridines, optionally substituted azepanes, tertiary amines (cyclic or acyclic), isoindoline-1,3-dione, or optionally substituted tetrahydroisoquinolones (aromatically substituted): R 2,3,4,5,6 can each independently be any one or combinations of the following moieties, cyano, nitro, acyl, alkyl, amido, azido, isothiocyanate, isocyanate optionally substituted anilino, halogens, ethers, sulfonamides, thioacyl, nitro, aromatic, heterocyclic, olefinic, acetylene, deuterium, or tritium; Y can be either CH, CH 2 , O, S, OCH 2 , N—R, N—Ar, C—R, C—Ar; Z can be either H, O, S, S—R or NR. R groups can be either H, aryls, alkyls, or cycloalkyls; “n” can be 1 to 5 carbons in length and stereoisomers, functional analogs, and pharmaceutically acceptable salts thereof and wherein the moiety bridging R 1 and N can be optionally substituted alkylene, optionally substituted alkenylene or optionally substituted alkynylene and where the alkylene group can include an inserted C 3 -C 5 cycloalkyl group, aromatic and heterocyclic group.

1 - 34 . (canceled) 
     
     
         35 . A method of treating a subject for alleviation of effects in the subject resulting from drug intake or drug abuse by the subject comprising administering to the subject a therapeutically effective amount of at least one compound having the general formula I 
       
         
           
           
               
               
           
         
       
       wherein R 1  can be an optionally substituted piperidine, an optionally substituted piperazine, an optionally substituted tetrahydropyridine, an optionally substituted azepane or an optionally substituted tetrahydroisoquinoline in which the optional substituents are on the aromatic moiety or an optionally substituted tetrahydropiperidine, or a radical of an optionally substituted cyclic or acyclic tertiary amine or isoindoline-1,3-dione: R 2,3,4,5  can each independently be any one or combinations of the following moieties, hydrogen, cyano, nitro, acyl, alkyl, amido, azido, isothiocyanate, isocyanate, optionally substituted anilino, halogens, ethers, sulfonamides, thioacyl, nitro, aromatic, heterocyclic, olefinic, acetylene, deuterium, or tritium; wherein when R 2,3,4,5  is a halogen, the halogen is fluorine, bromine or iodine “n” can be 1 to 5 carbons in length and wherein the moiety bridging R 1  and N can be optionally substituted alkylene, optionally substituted alkenylene or optionally substituted alkynylene with the exclusion of the following compounds: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
       and stereoisomers, or pharmaceutically acceptable salts thereof. 
     
     
         36 . A method according to  claim 35  wherein the drug abuse or drug intake results from methamphetamine intake or methamphetamine abuse by the subject. 
     
     
         37 . A method according to  claim 35  wherein the drug intake or drug intake results from cocaine abuse or cocaine intake by the subject. 
     
     
         38 . A method of treating a subject having a need for therapy involving sigma receptors comprising administering to the subject an effective amount of at least one compound of  claim 35 . 
     
     
         39 . A method of treating a subject to prevent neurotoxic effects resulting from drug abuse or drug intake by the subject comprising administering to the subject a therapeutically effective amount of at least one compound having the general formula I 
       
         
           
           
               
               
           
         
       
       wherein R 1  can be an optionally substituted piperidine, an optionally substituted piperazine, an optionally substituted tetrahydropyridine, an optionally substituted azepane or an optionally substituted tetrahydroisoquinoline in which the optional substituents are on the aromatic moiety or an optionally substituted tetrahydropiperidine, or a radical of an optionally substituted cyclic or acyclic tertiary amine or isoindoline-1,3-dione: R 2,3,4,5  can each independently be any one or combinations of the following moieties, hydrogen, cyano, nitro, acyl, alkyl, amido, azido, isothiocyanate, isocyanate, optionally substituted anilino, halogens, ethers, sulfonamides, thioacyl, nitro, aromatic, heterocyclic, olefinic, acetylene, deuterium, or tritium; wherein when R 2,3,4,5  is a halogen, the halogen is fluorine, bromine or iodine “n” can be 1 to 5 carbons in length and wherein the moiety bridging R 1  and N can be optionally substituted alkylene, optionally substituted alkenylene or optionally substituted alkynylene with the exclusion of the following compounds: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
       and stereoisomers, or pharmaceutically acceptable salts thereof.