2-Amino-benzoxazinones for the treatment of herpes simplex virus

Abstract

2-Amino-benzoxazinones are identified for use in the treatment of Herpes Simplex Virus. A subject is treated for Herpes Simplex Virus by treating with an effective amount of 2-amino-benzoxazinones.

1 . A compound of Formula II:  
       
         
           
           
               
               
           
         
         wherein R 28  is selected from amino substituted with two radicals selected from alkyl, aralkyl, heterocyclylalkyl, heterocyclyl, and aryl or the nitrogen can form a member of a heterocyclic ring;  
         wherein R 29  is selected from  
         
           
             
             
                 
                 
             
           
         
         wherein R 30  is selected from alkyl, alkoxy, alkylamino, carboxyalkyl,alkoxyalkyl, alkylaminoalkyl, cycloalkyl, heterocyclyl, heterocyclylalkyl,aralkyl, aralkoxy, aryloxy, cycloalkyloxy, arylamino, aralkenyl, heterocyclylalkoxy, alkylaminoalkoxy, alkylaminoalkylamino,heterocyclylalkylamino, N-aryl-Nalkylamino, N-aralkylamino and phenyl;  
         wherein R 31  is alkylene;  
         wherein R 32  is selected from alkyl and aryl; and  
         wherein R 33  is selected from hydrido, halo and alkyl;  
         or a pharmaceutically-acceptable salt thereof.  
       
     
     
         2 . Compound of  claim 1  wherein R 28  is selected from (a) amino substituted with two radicals selected from lower alkyl, lower aralkyl, lower heterocyclylalkyl, heterocyclyl, and aryl or the nitrogen can form a member of a heterocyclic ring, 
 wherein R 30  is selected from lower alkyl, lower alkoxy, lower alkylamino, lower carboxyalkyl, lower alkoxyalkyl, loweralkylaminoalkyl, lower cycloalkyl, heterocyclyl, lower heterocyckylalkyl, lower heterocyclylalkoxy, lower aralkenyl, loweraralkyl, lower aralkoxy, phenyloxy, phenylamino, lower cycloalkyloxy, lower N-phenyl-N-alkylamino, lower alkylaminoalkoxy, lower alkylaminoalkylamino, lowerheterocyclylalkylamino, lower N-aralkylamino and phenyl;    wherein R 31  is lower alkylene;    wherein R 32  is selected from lower alkyl and aryl; and    wherein R 33  is selected from hydrido and lower alkyl;    or a pharmaceuticallyacceptable salt thereof.    
     
     
         3 . Compound of  claim 2  wherein R 29  is  
       
         
           
           
               
               
           
         
         wherein R 30  is selected from lower alkyl, lower alkoxy, lower alkylamino, lower carboxyalkyl, lower alkoxyalkyl, loweralkylaminoalkyl, lower cycloalkyl, heterocyclyl, lower heterocyclylalkyl, lower heterocyclylalkoxy, lower aralkenyl, lower aralkyl, lower aralkoxy, phenyloxy, phenylamino, lower cycloalkyloxy, lower N-phenyl-N-alkylamino, lower alkylaminoalkoxy, lower alkylaminoalkylamino, lowerheterocyclylalkylamino, lowerN-aralkylamino and phenyl; and  
         wherein R 33  is hydrido;  
         or a pharmaceuticallyacceptable salt thereof.  
       
     
     
         4 . Compound of  claim 3  wherein R 30  is selected from lower alkoxy, lower alkoxyalkyl, or phenyl.  
     
     
         5 . Compound of  claim 4  wherein R 29  is selected from [(1,1-dimethylethoxy)carbonyl]amino, benzoylamino, (phenylmethoxyacetyl)amino and (2,4,6-trifluorobenzoylamino).  
     
     
         6 . Compound of  claim 1  wherein at least one substituent of R 28  is methyl.  
     
     
         7 . Compound of  claim 1  wherein at least one substituent of R 28  is optionally substituted phenylmethyl.  
     
     
         8 . Compound of  claim 1  wherein in R 28  the nitrogen forms a member of a heterocyclic ring.  
     
     
         9 . Compound of  claim 1  wherein R 28  is selected from methyl(phenylmethyl)amino, methyl[(4-methoxyphenyl)-methyl]amino, 1-(1,2,3,6-tetrahydro-pyridyl), isopropyl(methyl)amino, (4-furoyl)piperazinyl, [(2-cyano)ethyl]-(cyclopropyl)amino, (4-theonyl)piperazinyl, (4-benzene-sulfonyl)-piperazinyl, methyl(phenylmethyl)amino, diisopropylamino, [methyl(4-dimethylamino)-phenylmethyl]-amino, methyl(2-pyridylmethyl)-amino, methyl[2-(3-indoyl)ethylamino), 4-morpholyl, alkyl(methyl)amino, 1-decahydroquinolyl, and 4-(1-acetylpiperadinyl).  
     
     
         10 . Compound of  claim 9  wherein R 29  is selected from [(1,1-dimethylethoxy)carbonyl]amino, benzoylamino, (phenylmethoxyacetyl)amino and (2,4,6-trifluorobenzoylamino).  
     
     
         11 . A pharmaceutical composition comprising a therapeutically-effective amount of a compound of  claim 1  and a pharmaceutically acceptable carrier or diluent.  
     
     
         12 . A pharmaceutical composition comprising a therapeutically-effective amount of a compound of  claim 2  and a pharmaceutically acceptable carrier or diluent.  
     
     
         13 . A pharmaceutical composition comprising a therapeutically-effective amount of a compound of  claim 3  and a pharmaceutically acceptable carrier or diluent.  
     
     
         14 . A method or therapeutic or prophylactic treatment of Herpes Simplex Virus in a subject, said method comprising treating said subject with an effective amount of a compound of  claim 1 .  
     
     
         15 . A method or therapeutic or prophylactic treatment of Herpes Simplex Virus in a subject, said method comprising treating said subject with an effective amount of a compound of  claim 2 .  
     
     
         16 . A method or therapeutic or prophylactic treatment of Herpes Simplex Virus in a subject, said method comprising treating said subject with an effective amount of a compound of  claim 3.