Method for treating retroviral infections

Abstract

Compositions and methods of treating a retroviral infection in an afflicted host and/or inhibiting replication of a retrovirus involve administering a therapeutically effective amount of the following compound of formula I: A-L-B  (I) wherein A is a substituted or unsubstituted aryl compound, substituted or unsubstituted piperidyl, or substituted or unsubstituted thiopheneyl; L is sulfonyl, sulfinyl or thio; and B is a substituted or unsubstituted aromatic nitrogen containing heteroaryl compound; or pharmacologically acceptable acid-addition and base-addition salts thereof.

What is claimed is:  
     
         1 . A method of treating a retroviral infection by an HIV retrovirus in an afflicted host which comprises administering to the host a therapeutically effective amount of a compound represented by the following formula:  
       A-L-B  
       or a pharmaceutically acceptable acid-addition or base-addition salt thereof;  
       wherein: 
 component A is a substituted or unsubstituted aryl functional group, substituted or unsubstituted piperidyl, substituted or unsubstituted thiopheneyl;  
 component L is sulfonyl, sulfinyl or thio; and,  
 component B is a substituted or unsubstituted aromatic nitrogen containing heteroaryl functional group.  
 
     
     
         2 . The method of  claim 1  wherein the retroviral infection being treated is an infection by an HIV retrovirus selected from the group consisting of HIV-1 and HIV-2.  
     
     
         3 . The method of  claim 1  wherein the substituted or unsubstituted aryl functional group component A is a functional group of the following formula:  
       
         
           
           
               
               
           
         
         wherein Z is H, Cl, cyano, alkyl having from 1 to 15 carbon atoms, alkoxyalkyl having 2 or 3 carbon atoms; Y is H or a double bond to a carbon which is attached to R; and R is phenyl, biphenyl, benzyl, polycycloaryl, heteroaryl or phenyl substituted with 1 to 5 substituents which may be the same or different, the substituents being selected from the group consisting of lower alkyl having from 1 to 5 carbon atoms, halogen, nitro, methoxy, ethoxy, benzyloxy, methylenedioxy, 2,2-dichlorocyclopropyl, trifluoromethyl, methylsulfonyl, cyano and phenoxy.  
       
     
     
         4 . The method of  claim 1  wherein the substituted or unsubstituted aromatic nitrogen containing heteroaryl functional group component B is 4-methylquinolyl, 8-ethyl-4-methylquinolyl or a functional group of the following formula:  
       
         
           
           
               
               
           
         
       
       wherein n is 0 or 1, R 1  and R 2  may be the same or different and are H, halogen, lower alkyl having from 1 to 4 carbon atoms, hydroxy, or nitro.  
     
     
         5 . The method of  claim 1  wherein the compound is selected from the group consisting of 2-(phenylmethylsulfonyl) pyridine-N-oxide, 2-[1-(2,5-dimethylphenyl)octylsulfonyl]pyridine-N-oxide, 2-[(2,5-dimethylphenyl)methylsulfonyl]pyridine-N-oxide, 2-[[1-(2,5-dimethylphenyl)ethyl]sulfonyl]-3-methylpyridine-N-oxide, 2-[[1-(2,5-dimethylphenyl)chloromethyl]sulfonyl]-4-methylpyridine-N-oxide, 2-[1-(2,5-dimethylphenyl)chloromethyl]sulfonyl pyridine, 2-[1-(2,5-dimethylphenyl)methylthio]-3-chloropyridine-N-oxide, 2-[phenylmethyl]thio-3-hydroxypyridine, 2-[(2,5-dimethylphenyl)methylthio]pyridine, 2-[(2,3,4,5,6-pentachlorophenyl)methylsulfonyl]pyridine N-oxide, 2[1-(phenylethyl)sulfonyl]-8-ethyl-4-methylquinoline, 2-[(3,4-dichlorophenyl)methylsulfonyl]pyridine-N-oxide, 2-[(4-(2,2-dichlorocyclopropyl)phenyl)methylsulfonyl]pyridine-N-oxide, 2-[(2,4,6-trimethylphenyl)methylsulfinyl]pyridine-N-oxide, 2-[(3-nitro-4-chlorophenyl)methylsulfonyl]pyridine-N-oxide, 2-[phenylmethylsulfinyl]pyridine-N-oxide, 2-[[1-(2,5-dimethylphenyl)propyl]sulfonyl]-3-methylpyridine-N-oxide, 2-[(9-anthryl)methylsulfonyl]pyridine-N-oxide, 2-[4-((1,1dimethyl)propyl) phenyl)methylsulfonyl]pyridine-N-oxide, 2-[1-(2,5-dimethylphenyl)ethylthio]-4-methylquinoline, 2-[[(2,5dimethylphenyl)methyl]sulfonyl]-3-methylpyridine-N-oxide and pharmaceutically acceptable acid-addition and base-addition salts thereof.  
     
     
         6 . The method of  claim 1  wherein the compound is contained in a composition containing a pharmaceutically acceptable carrier.  
     
     
         7 . A method of inhibiting the replication of an HIV retrovirus, the method comprising contacting the HIV retrovirus with an effective amount a compound represented by the following formula:  
       A-L-B  
       or a pharmaceutically acceptable acid-addition or base-addition salt thereof;  
       wherein: 
 component A is a substituted or unsubstituted aryl functional group, substituted or unsubstituted piperidyl, substituted or unsubstituted thiopheneyl;  
 component L is sulfonyl, sulfinyl or thio; and,  
 component B is a substituted or unsubstituted aromatic nitrogen containing heteroaryl functional group.  
 
     
     
         8 . The method of  claim 7  wherein the HIV retrovirus whose replication is being inhibited is a retrovirus selected from the group consisting of HIV-1 and HIV-2.  
     
     
         9 . The method of  claim 7  wherein the substituted or unsubstituted aryl functional group component A is a functional group of the following formula:  
       
         
           
           
               
               
           
         
         wherein Z is H, Cl, cyano, alkyl having from 1 to 15 carbon atoms, alkoxyalkyl having 2 or 3 carbon atoms; Y is H or a double bond to a carbon which is attached to R; and R is phenyl, biphenyl, benzyl, polycycloaryl, heteroaryl or phenyl substituted with 1 to 5 substituents which may be the same or different, the substituents being selected from the group consisting of lower alkyl having from 1 to 5 carbon atoms, halogen, nitro, methoxy, ethoxy, benzyloxy, methylenedioxy, 2,2-dichlorocyclopropyl, trifluoromethyl, methylsulfonyl, cyano and phenoxy.  
       
     
     
         10 . The method of  claim 7  wherein the substituted or unsubstituted aromatic nitrogen containing heteroaryl functional group component B is 4-methylquinolyl, 8-ethyl-4-methylquinolyl or a functional group of the following formula:  
       
         
           
           
               
               
           
         
         wherein n is 0 or 1, R 1  and R 2  may be the same or different and are H, halogen, lower alkyl having from 1 to 4 carbon atoms, hydroxy, or nitro.  
       
     
     
         11 . The method of  claim 7  wherein the compound is selected from the group consisting of 2-(phenylmethylsulfonyl) pyridine-N-oxide, 2-[1-(2,5-dimethylphenyl)octylsulfonyl]pyridine-N-oxide, 2-[(2,5-dimethylphenyl)methylsulfonyl]pyridine-N-oxide, 2-[[1-(2,5-dimethylphenyl)ethyl]sulfonyl]-3-methylpyridine-N-oxide, 2-[[1-(2,5-dimethylphenyl)chloromethyl]sulfonyl]-4-methylpyridine-N-oxide, 2-[1-(2,5-dimethylphenyl)chloromethyl]sulfonyl pyridine, 2-[1-(2,5-dimethylphenyl)methylthio]-3-chloropyridine-N-oxide, 2-[phenylmethyl]thio-3-hydroxypyridine, 2-[(2,5-dimethylphenyl)methylthio]pyridine, 2-[(2,3,4,5,6-pentachlorophenyl)methylsulfonyl] pyridine N-oxide, 2[1-(phenylethyl)sulfonyl]-8-ethyl-4-methylquinoline, 2-[(3,4-dichlorophenyl)methylsulfonyl]pyridine-N-oxide, 2-[(4-(2,2-dichlorocyclopropyl)phenyl)methylsulfonyl]pyridine-N-oxide, 2-[(2,4,6-trimethylphenyl)methylsulfinyl]pyridine-N-oxide, 2-[(3-nitro-4-chlorophenyl)methylsulfonyl]pyridine-N-oxide, 2-[phenylmethylsulfinyl]pyridine-N-oxide, 2-[[1-(2,5-dimethylphenyl)propyl]sulfonyl]-3-methylpyridine-N-oxide, 2-[(9-anthryl)methylsulfonyl]pyridine-N-oxide, 2-[4-((1,1dimethyl)propyl) phenyl)methylsulfonyl] pyridine-N-oxide, 2-[1-(2,5-dimethylphenyl)ethylthio]-4-methylquinoline, 2-[[(2,5dimethylphenyl)methyl]sulfonyl]-3-methylpyridine-N-oxide and pharmaceutically acceptable acid-addition and base-addition salts thereof.  
     
     
         12 . The method of  claim 7  wherein the compound is contained in a composition containing a pharmaceutically acceptable carrier.  
     
     
         13 . A method of treating an HIV infection in an afflicted host which comprises administering to the host a therapeutically effective amount of a compound selected from the group consisting of 2-[[1-(2,5-dimethylphenyl)ethyl]sulfonyl]-3-methylpyridine-N-oxide, 2-[[1-(2,5-dimethylphenyl)chloromethyl]sulfonyl]-4-methylpyridine-N-oxide, 2-[1-(2,5-dimethylphenyl)chloromethyl]sulfonyl]pyridine, 2-[1-(2,5-dimethylphenyl)methylthio]-3-chloropyridine-N-oxide, 2-[phenylmethyl]thio-3-hydroxypyridine, 2-[(2,3,4,5,6-pentachlorophenyl) methylsulfonyl]pyridine N-oxide, 2[1-(phenylethyl)sulfonyl]-8-ethyl-4-methylquinoline, 2-[(3,4-dichlorophenyl)methylsulfonyl]pyridine-N-oxide, 2-[(4-(2,2-dichlorocyclopropyl)phenyl)methylsulfonyl]pyridine-N-oxide, 2-[(2,4,6-trimethylphenyl) methylsulfinyl]pyridine-N-oxide, 2-[(3-nitro-4-chlorophenyl)methylsulfonyl]pyridine-N-oxide, 2-[phenylmethylsulfinyl]pyridine-N-oxide, 2-[[(2,5dimethylphenyl)methyl]sulfonyl]-3-methylpyridine-N-oxide and pharmaceutically acceptable acid-addition and base-addition salts thereof.