Anti-viral triaza compounds

Abstract

A method of inhibiting viruses in which a virus is contacted with an antiviral amount of a compound of formula I. Activity is shown against HIV and other viruses. wherein W is a bridge carbon which has a polar or non-polar side group; X and Y independently are an aromatic group, an alkyl group, a sulfonyl group or a carbonyl group, said aromatic group is selected from the group consisting of Ar, Ar sulfonyl, Ar carboxy and Ar alkyl, where Ar is an aromatic cyclic or aromatic heterocyclic ring having from five to seven members; said alkyl group having from one to ten carbons; Z is a group listed for X and Y, a fused aryl moiety having from seven to ten carbons or hydrogen; a, d and e independently are a number from zero to 10; c and b independently are a number from one to 10; and the formula is cyclic or acyclic and includes sufficient hydrogens for a stable molecule.

What is claimed is:  
     
         1 . A method of inhibiting a virus which comprises contacting the virus, a virus-infectable cell or a virus-infected cell with a compound of formula I:  
       
         
           
           
               
               
           
         
       
       wherein 
 W is a bridge carbon which has a polar or non-polar side group;  
 X and Y independently are an aromatic group, an alkyl group, a sulfonyl group or a carbonyl group,  
 said aromatic group is selected from the group consisting of Ar, Ar sulfonyl, Ar carboxy and Ar alkyl, where Ar is an aromatic cyclic or aromatic heterocyclic ring having from five to seven members;  
 said alkyl groups having from one to ten carbons;  
 X and Y are not both an alkyl group;  
 Z is a group listed for X and Y, a fused aryl moiety having from seven to ten carbons or hydrogen;  
 a, d and e independently are a number from zero to 10;  
 c and b independently are a number from one to 10; the compound is cyclic or acyclic and includes sufficient hydrogens for a stable molecule.  
 
     
     
         2 . The method of  claim 1  wherein the polar or non-polar side group for W is selected from the group consisting of double-bonded carbon, double-bonded oxygen, hydroxyl, alkyl of one to about 10 carbons, alkoxy of one to about 10 carbons, aryl of about seven to about 10 carbons, halogen, methyl halogen, methylene halide, epoxide, acyl, CH 2 OH and hydrogen.  
     
     
         3 . The method-of  claim 1  wherein the Ar for X and Y is further substituted with a hydrophilic group.  
     
     
         4 . The method of  claim 1  wherein the Ar for X and Y is further substituted with NO, NO 2 , NH 2 , NHR, NHR 2 , OH, OR, SH, SR, SOR, SO 2 R, halo, C(halogen) 3 ,  
       
         
           
           
               
               
           
         
       
       where R is alkyl of C 1-10 .  
     
     
         5 . The method of  claim 1  wherein X and Y are independently  
       
         
           
           
               
               
           
         
       
     
     
         6 . The method of  claim 1  wherein c and b are three and a, d and e are independently zero or one.  
     
     
         7 . The method of  claim 1  wherein W is ethene, X and Y are both tosyl and Z is benzyl.  
     
     
         8 . The method of  claim 1  wherein the compound is 
 3-Methylene-1,5-ditosyl-1,5,9-triazacyclododecane  
 9-Benzyl-3-hydroxymethyl-1,5-ditosyl-1,5,9-triazacylododecane  
 9-Benzyl-3-chloromethyl-1,5-ditosyl-1,5,9-triazacyclododecane  
 3-Chloromethyl-1,5-ditosyl-1,5,9-triazacyclododecane  
 1,5,9-Tritosyl-1,5,9-triazacyclododecane  
 3-Methylene-1,5,9-tritosyl-1,5,9-triazacyclododecane  
 3-Hydroxymethyl-1,5,9-tritosyl-1,5,9-triazacyclododecane  
 3-Chloromethyl-1,5,9-tritosyl-1,5,9-triazacylododecane  
 9-Benzyl-3-keto-1,5-ditosyl-1,5,9-triazacyclododecane  
 9-Benzyl-3-methyl-1,5-ditosyl-1,5,9-triazacyclododecane  
 9-Benzyl-3-methylene-1,5-ditosyl-1,5,9-triazacyclododecane-9-oxide  
 9-Acyl-3-methylene-1,5-ditosyl-1,5,9-triazacyclododecane  
 9-Alkyl-3-methylene-1,5-ditosyl-1,5,9-triazacyclododecane  
 9-Acyl-3-methylene-1,5-ditosyl-1,5,9-triazacyclododecane epoxide  
 9-Benzyl-l-formyl-3-methylene-5-tosyl-1,5,9-triazacyclododecane  
 9-Benzyl-3-methylene-1-tosyl-1,5,9-triazacyclododecane  
 9-Benzyl-3-methylene-1-acyl-5-tosyl-1,5,9-triazacyclododecane  
 9-(Ethoxycarbonyl)-3-methylene-1,5-ditosyl-1,5,9-triazacyclododecane  
 N-Benzylbis(3-benzenesulfonamidopropyl)amine  
 9-Benzyl-3-methylene-1,5-dibenzenesulfonyl-1,5,9-triazacyclododecane  
 N-Benzylbis[3-(N′-2-propenyltoluenesulfonamido) propyl]amine dihydrogen sulfate  
 N-Benzyl-N-[3-(N′-2-methyl-2-propenyl-toluenesulfonamido)propyl]-N-(3-toluenesulfonamido-propyl)amine dihydrogen sulfate  
 N-Benzylbis[3-(N′-2-methyl-2-propenyltoluene-sulfonamido)propyl]amine dihydrogen sulfate; and the compound is in salt or non-salt form.  
 
     
     
         9 . The method of  claim 1  wherein the compound is 9-benzyl-3-methylene-1,5-ditosyl-1,5,9-triazacyclododecane, 
 N-benzylbis(3-toluenesulfonamidopropyl)amine, 3-methylene-1,5-ditosyl-1,5,9-triazacyclododecane,  
 9-(Ethoxycarbonyl)-3-methylene-1,5-ditosyl-1,5,9-triazacyclododecane,  
 N-Benzylbis(3-benzenesulfonamidopropyl)amine,  
 9-Benzyl-3-methylene-1,5-dibenzenesulfonyl-1,5,9-triazacyclododecane,  
 N-Benzylbis[3-(N′-2-propenyltoluenesulfonamido) propyl]amine dihydrogen sulfate,  
 N-Benzyl-N-[3-(N′-2-methyl-2-propenyl-toluenesulfonamido)propyl]-N-(3-toluenesulfonamido-propyl)amine dihydrogen sulfate,  
 N-Benzylbis[3-(N′-2-methyl-2-propenyltoluene-sulfonamido)propyl]amine dihydrogen sulfate, or salts of these compounds.  
 
     
     
         10 . The method of  claim 1  wherein the virus is a retrovirus, herpesvirus, influenza virus or rous sarcoma virus.  
     
     
         11 . The method of  claim 10  wherein the retrovirus is HIV.  
     
     
         12 . A method for treating humans or animals suffering from a viral infection comprising administering to said human or animal an antiviral effective amount of a compound of formula I.  
     
     
         13 . A pharmaceutical composition having pharmacological activity comprising a compound of formula I and a pharmaceutically acceptable carrier.