Halovir, an antiviral marine natural product, and derivatives thereof

Abstract

The invention is a group of compounds named halovirs with antiviral activity that are structurally related to compounds isolated from a marine fungus CNL240. Halovirs are comprised of a short, amphipathic helical peptide with an extended lipid moiety on the N-terminal end of the peptide. The halovirs have demonstrated activity against herpes simplex virus, types I and II.

We claim:  
     
         1 . A compound of the structure  
       
         
           
           
               
               
           
         
       
       wherein, 
 R 1  is an alkyl chain comprising at least seven carbons;  
 R 2  is lower alkyl;  
 R 3  is lower alkyl;  
 R 4  and R 5  together form an alkyl bridge selected from the group consisting of propyl, butyl, hydroxypropyl, hydroxybutyl, and acetoxypropyl;  
 R 6  is selected from the group consisting of hydrogen and lower alkyl;  
 R 7  is selected from the group consisting of hydrogen and lower alkyl;  
 R 8  is selected from the group consisting of hydrogen, lower alkyl, and substituted lower alkyl;  
 R 9  is selected from the group consisting of hydrogen or lower alkyl;  
 R 10  is selected from the group consisting of —CH 2 —O—R 11  and —C(O)—R 12 , wherein R 11  is independently selected from the group consisting of hydrogen or lower alkyl, and substituted lower alkyl and R 12  is independently selected from the group consisting of hydrogen, NH 2 , methyl, hydroxyl, and —OR 13  wherein R 13  is lower alkyl:  
 
     
     
         2 . The compound of  claim 1 , wherein R 12  is selected from the group consisting of methoxy and ethoxy.  
     
     
         3 . A composition comprising the compound of  claim 1  and a pharmaceutically acceptable carrier.  
     
     
         4 . The composition of  claim 3 , wherein the composition comprises at least a second antiviral agent selected from the group consisting of acyclovir, pencyclovir, valacyclovir, famcyclovir, gangcyclovir, nonoxonol, docosonal and foscarnet.  
     
     
         5 . A method of prevention or treatment of viral infections in a host comprising: 
 administering the compound of  claim 1  and    observing the treated host for amelioration of the infection.    
     
     
         6 . The method of  claim 5 , wherein the viral infection is a herpes virus infection.  
     
     
         7 . The method of  claim 5 , wherein the compound is administered by a route selected from a group consisting of topical, oral, parenteral, intravenous, and intramuscular.  
     
     
         8 . The method of  claim 5 , wherein the compound is administered topically.  
     
     
         9 . A compound of the structure:  
       
         
           
           
               
               
           
         
       
       wherein, 
 R 1  is an alkyl chain comprising at least seven carbons;  
 R 2  is selected from the group consisting of methyl, 2-propyl, 2-methyl propyl, 2-butyl, and benzyl;  
 R 3  is selected from the group consisting of methyl, 2-propyl, 2-methyl propyl, 2-butyl, and benzyl;  
 R 4  and R 5  together form an alkyl bridge selected from the group consisting of propyl, butyl, hydroxypropyl, hydroxybutyl, and acetoxypropyl;  
 R 6  is selected from the group consisting of hydrogen, methyl, 2-propyl, 2-methyl propyl, 2-butyl, and benzyl;  
 R 7  is selected from the group consisting of hydrogen, methyl, 2-propyl, 2-methyl propyl, 2-butyl, and benzyl;  
 R 8  is selected from the group consisting of hydrogen, hydroxymethyl, 1-hydroxyethyl, thiomethyl, 4-hydroxyphenylmethyl, aminocarbonylmethyl, 3-propionyl acid amide, carboxyethyl, carboxymethyl, 4-aminobutyl, 3-guanylpropyl, and 4-imidazoylmethyl;  
 R 9  is selected from the group consisting of hydrogen, methyl, 2-propyl, 2-methyl propyl, 2-butyl, or benzyl; and  
 R 10  is selected from the group consisting of —CH 2 —O—R 11  and —C(O)—R 12 , wherein R 11  is independently selected from the group selected from hydrogen or alkyl, and R 12  is independently selected from the group consisting of hydrogen, NH 2 , methyl, hydroxyl, and —OR 13  wherein R 13  is lower alkyl.  
 
     
     
         10 . The compound of  claim 1 , wherein R 12  is selected from the group consisting of methoxy and ethoxy.  
     
     
         11 . A composition comprising the compound of  claim 9  and a pharmaceutically acceptable carrier.  
     
     
         12 . The composition of  claim 11 , wherein the composition comprises at least a second antiviral agent selected from the group consisting of acyclovir, pencyclovir, valacyclovir, famcyclovir, gangcyclovir, nonoxonol, docosonal, and foscarnet.  
     
     
         13 . A method of prevention or treatment of viral infections in a host comprising: 
 administering the compound of  claim 8  and    observing the treated host for amelioration of the infection.    
     
     
         14 . The method of  claim 13 , wherein the viral infection is a herpes virus infection.  
     
     
         15 . The method of  claim 13 , wherein the compound is administered by a route selected from a group consisting of topical, oral, parenteral, intravenous, intramuscular.  
     
     
         16 . The method of  claim 13 , wherein the compound is administered topically.  
     
     
         17 . The compound of  claim 9 , wherein: 
 R 1  is decanyl;    R 2  is methyl;    R 3  is methyl;    R 4  and R 5  together form a 2-hydroxypropyl bridge;    R 6  is 2-methyl propyl;    R 7  is 2-propyl;    R 8  is 3-propionyl acid amide;    R 9  is 2-methyl propyl; and    R 10  is hydroxymethyl    said compound having the name designation halovir F.    
     
     
         18 . The compound of  claim 9 , wherein: 
 R 1  is decanyl;    R 2  is methyl;    R 3  is methyl;    R 4  and R 5  together form a propyl bridge;    R 6  is 2-methyl propyl;    R 7  is 2-propyl;    R 8  is 3′-propionyl acid amide;    R 9  is 2-methyl propyl; and    R 10  is hydroxymethyl,    said compound having the name designation halovir G.    
     
     
         19 . The compound of  claim 9 , wherein: 
 R 1  is decanyl;    R 2  is methyl;    R 3  is methyl;    R 4  and R 5  together form a 2-hydroxypropyl bridge;    R 6  is 2-methyl propyl;    R 7  is methyl;    R 8  is 3′-propionyl acid amide;    R 9  is 2-methyl propyl; and    R 10  is hydroxymethyl,    said compound having the name designation halovir H.