Electrophilic ketones for the treatment of herpesvirus infections

Abstract

A class of compounds is described which can be used for the treatment of viral infections. Compounds of particular interest are defined by Formula II wherein each of R 1 , R 2 , and R 3 is independently selected from hydrido, halo, and nitro; wherein R 8 is selected from haloalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heteroaryl, optionally substituted arylalkoxy and optionally substituted aryloxyalkyl; wherein Y is selected from fluoroalkyl, and wherein R 9 is alkylamino; or a pharmaceutically-acceptable salt or tautomer thereof.

What is claimed is:  
     
         1 . A compound of Formula I  
       
         
           
           
               
               
           
         
         wherein each of R 1 , R 2 , R 3 , and R 4  is independently selected from hydrido, alkyl, aralkyl, halo, alkoxy, cyano, nitro, amino, alkylamino, N-acylamino, alkylsulfonyloxy, aminosulfonyl, N-(haloalkylcarbonyl)amino, peptidyl, amino acid residue,  
         
           
             
             
                 
                 
             
           
         
         wherein R 5  is selected from alkoxy, aryloxy, aralkyloxy, alkylthio, arylthio, aralkylthio, alkylamino, arylamino, aralkylamino, alkyl, aryl, aralkyl, heterocyclyl, and heterocyclylalkyl, wherein R 5  is optionally substituted at a substitutable position with one or more substituents selected from alkyl, alkoxy, aryloxy, alkylthio, arylthio, halo, nitro, N-acylamino, amino, alkylamino, alkoxycarbonyl, amino acid residue and peptidyl;  
         wherein R 6  is selected from alkyl, aryl, aralkyl, heterocyclyl and heterocyclylalkyl, wherein R 6  is optionally substituted at a substitutable position with a radical selected from alkoxy, aryloxy, alkylthio, arylthio, halo, nitro, N- acylamino, amino, alkylamino and alkoxycarbonyl;  
         wherein Y is selected from fluoroalkyl and  
         
           
             
             
                 
                 
             
           
         
         wherein Q is selected from alkoxy, aryloxy, aralkyloxy, amino acid residue, peptidyl, and —NHR7; and  
         wherein R 7  is a radical selected from alkyl, aralkyl, and heterocyclylalkyl, wherein R 7  is optionally substituted at a substitutable position with a radical selected from amino, nitrogen-containing heterocyclyl and alkylamino;  
         or a pharmaceutically-acceptable salt or tautomer thereof.  
       
     
     
         2 . Compound of  claim 1  wherein each of R 1 , R 2 , R 3 , and R 4  is independently selected from hydrido, lower alkyl, lower aralkyl, halo, lower alkoxy, cyano, nitro, amino, lower alkylamino, N-acylamino, lower alkylsulfonyloxy, aminosulfonyl, lower N-(haloalkylcarbonyl)amino, amino acid residue, peptidyl,  
       
         
           
           
               
               
           
         
         wherein R 5  is selected from lower alkoxy, phenyloxy, lower aralkyloxy, lower alkylthio, phenylthio, lower aralkylthio, lower alkylamino, arylamino, lower aralkylamino, lower alkyl, 6-10-membered aryl, lower aralkyl, 5-10-membered heterocyclyl, and lower heterocyclylalkyl, wherein R 5  is optionally substituted at a substitutable position with one or more substituents selected from lower alkyl, lower alkoxy, phenyloxy, lower alkylthio, phenylthio, halo, nitro, N-acylamino, amino, lower alkylamino, lower alkoxycarbonyl, amino acid residue and peptidyl; wherein R 6  is selected from lower alkyl, 6-10-membered aryl, lower aralkyl, 5-10-membered heterocyclyl and lower heterocyclylalkyl, wherein R 6  is optionally substituted at a substitutable position with a radical selected from lower alkoxy, phenyloxy, lower alkylthio, phenylthio, halo, nitro, N-acylamino, amino, lower alkylamino, and lower alkoxycarbonyl; wherein Y is selected from lower fluoroalkyl and  
         
           
             
             
                 
                 
             
           
         
         wherein Q is selected from lower alkoxy, phenyloxy, lower aralkyloxy, N-amino acid residue, N-peptidyl, and —NHR 7 ; and wherein R 7  is a radical selected from lower alkyl, lower aralkyl, and lower heterocyclylalkyl, wherein R 7  is optionally substituted at a substitutable position with one or more radical selected from amino, 5-6-membered nitrogen-containing heterocyclyl and lower N,N-dialkylamino; or a pharmaceutically-acceptable salt or tautomer thereof.  
       
     
     
         3 . Compound of  claim 2  wherein Y is lower fluoroalkyl; wherein each of R 1 , R 2 , R 3 , and R 4  is independently selected from hydrido, lower alkyl, halo, lower alkoxy, nitro, and amino; and wherein R 5  is selected from phenylalkoxy, lower alkyl substituted with halo or phenyloxy, phenyl, lower phenylalkyl, and five-ten membered heteroaryl, wherein R 5  is optionally substituted at a substitutable position of a phenyl or heteroaryl radical with one or more substituents selected from lower alkyl, lower alkoxy, phenyloxy, lower alkylthio, phenylthio, halo, nitro, N-acylamino, amino, lower alkylamino, lower alkoxycarbonyl, amino acid residue, and peptidyl; or a pharmaceutically-acceptable salt or tautomer thereof.  
     
     
         4 . Compound of  claim 3  wherein Y is selected from difluoromethyl, trifluoromethyl, pentafluoroethyl, heptafluoropropyl, 1,1-difluoroethyl, and 1,1-difluoropropyl; wherein each of R 1 , R 2 , R 3 , and R 4  is independently selected from hydrido, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, hexyl, fluoro, chloro, bromo, iodo, methoxy, ethoxy, propoxy, isopropoxy, butoxy, tert-butoxy, nitro, and amino; wherein R 5  is selected from phenylmethoxy, phenylethoxy, phenylpropoxy, fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl, pentafluoroethyl, heptafluoropropyl, difluorochloromethyl, dichlorofluoromethyl, difluoroethyl, difluoropropyl, dichloroethyl, dichloropropyl, phenyloxyethyl, phenyloxypropyl, phenyl, phenylmethyl, phenylethyl, furyl, pyrazinyl, oxazolyl, thiazolyl, thienyl, pyrrolyl, benzothienyl, benzofuranyl, indolyl, and pyridyl, wherein R 5  is optionally substituted at a substitutable position of a phenyl or heteroaryl radical with one or more substituents selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, hexyl, methoxy, ethoxy, propoxy, isopropoxy, butoxy, tert-butoxy, phenyloxy, methylthio, phenylthio, fluoro, chloro, bromo, iodo, nitro, N-formylamino, acetylamino, amino, N,N-dimethylamino and methoxycarbonyl; or a pharmaceutically-acceptable salt or tautomer thereof.  
     
     
         5 . Compound of  claim 2  wherein Y is  
       
         
           
           
               
               
           
         
         wherein Q is selected from lower alkoxy, phenyloxy, lower aralkyloxy, N-amino acid residue, N-peptidyl, and —NHR 7 ; and wherein R 7  is a radical selected from lower alkyl, lower aralkyl, and lower heteroaralkyl, wherein R 7  is optionally substituted at a substitutable position with a radical selected from amino, 5-6 membered nitrogen-containing heterocyclyl and lower N,N-dialkylamino; wherein each of R 1 , R 2 , R 3 , and R 4  is independently selected from hydrido, lower alkyl, halo, lower alkoxy, nitro, and amino; and wherein R 5  is selected from phenylalkoxy, lower alkyl substituted with halo or phenyloxy, phenyl, lower phenylalkyl, and five-ten membered heteroaryl, wherein R 5  is optionally substituted at a substitutable position of a phenyl or heteroaryl radical with one or more substituents selected from lower alkyl, lower alkoxy, phenyloxy, lower alkylthio, phenylthio, halo, nitro, N-acylamino, amino, lower alkylamino, lower alkoxycarbonyl, amino acid residue, and peptidyl; or a pharmaceutically-acceptable salt or tautomer thereof.  
       
     
     
         6 . Compound of  claim 5  wherein Y is  
       
         
           
           
               
               
           
         
         wherein Q is selected from methoxy, ethoxy, propoxy, isopropoxy, butoxy, phenyloxy, benzyloxy, phenylethoxy, and —NHR 7 ; and wherein R 7  is a radical selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, hexyl, benzyl, phenethyl, oxazolylmethyl, oxazolylethyl, imidazolylmethyl, imidazolylethyl, oxazolinylmethyl, oxazolinylethyl, indolylethyl, indolylmethyl, pyridylmethyl, thienylmethyl, and furylethyl, wherein R 7  is optionally substituted at a substitutable position with a radical selected from amino, piperidinyl, piperazinyl, pyrrolidinyl, morpholinyl, pyridyl, pyrimidyl and N,N-dimethylamino; wherein each of R 1 , R 2 , R 3 , and R 4  is independently selected from hydrido, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, hexyl, fluoro, chloro, bromo, iodo, methoxy, ethoxy, propoxy, isopropoxy, butoxy, tert-butoxy, nitro, and amino; and wherein R 5  is selected from phenylmethoxy, phenylethoxy, phenylpropoxy, fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl, pentafluoroethyl, heptafluoropropyl, difluorochloromethyl, dichlorofluoromethyl, difluoroethyl, difluoropropyl, dichloroethyl, dichloropropyl, phenyloxyethyl, phenyloxypropyl, phenyl, phenylmethyl, phenylethyl, furyl, pyrazinyl, oxazolyl, thiazolyl, thienyl, pyrrolyl, benzothienyl, benzofuranyl, indolyl, and pyridyl, wherein R 5  is optionally substituted at a substitutable position on a phenyl or heteroaryl radical with one or more substituents selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, hexyl, methoxy, ethoxy, propoxy, isopropoxy, butoxy, tert-butoxy, tert-butoxy, phenyloxy, methylthio, phenylthio, fluoro, chloro, bromo, iodo, nitro, N-formylamino, N-acetylamino, amino, N,N-dimethylamino and methoxycarbonyl; or a pharmaceutically-acceptable salt or tautomer thereof.  
       
     
     
         7 . A compound of Formula II  
       
         
           
           
               
               
           
         
         wherein each of R 1 , R 2 , and R 3  is independently selected from hydrido, halo, and nitro;  
         wherein R 8  is selected from haloalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heteroaryl, optionally substituted arylalkoxy and optionally substituted aryloxyalkyl;  
         wherein Y is selected from fluoroalkyl, and  
         
           
             
             
                 
                 
             
           
         
         wherein R 9  is alkylamino;  
         or a pharmaceutically-acceptable salt or tautomer thereof.  
       
     
     
         8 . Compound of  claim 7  wherein R 1  is selected from hydrido, fluoro, chloro, bromo and iodo; wherein R 2  is selected from hydrido, fluoro, chloro, bromo and iodo; wherein R 3  is selected from hydrido, fluoro, chloro, bromo, iodo and nitro; wherein R 8  is selected from trifluoromethyl, phenyl, phenylmethyl, phenylethyl, furyl, pyridyl, pyrazinyl, thienyl, pyrrolyl, benzothienyl, benzofuranyl, indolyl, phenylmethyloxy, (phenyloxy)propyl and phenyloxymethyl; wherein Y is selected from trifluoromethyl and  
       
         
           
           
               
               
           
         
         wherein R 9  is selected from methylamino, ethylamino, propylamino, isopropylamino and N,N-dimethylamino; or a pharmaceutically-acceptable salt or tautomer thereof.  
       
     
     
         9 . Compound of  claim 8  selected from compounds and their pharmaceutically-acceptable salts, of the group consisting of 
 ?-phenoxy-N- [2-(2,2,2-trifluoro-1-oxo-ethyl)phenyl]butanamide;  
 N-[2-(2,2,2-trifluoro-1-oxoethyl)phenyl]furan-2-carboxamide;  
 N-[5-fluoro-2-(2,2,2-trifluoro-1-oxoethyl)phenyl]benzenepropanamide;  
 N-[3-chloro-2-(2,2,2-trifluoro-1-oxoethyl)phenyl]benzenepropanamide;  
 N-[2-(2,2,2-trifluoro-1-oxoethyl)phenyl]benzenepropanamide;  
 N-[2-(2,2,2-trifluoro-1-oxoethyl)phenyl]pyrazine-2-carboxamide;  
 phenylmethyl N-[2-(2,2,2-trifluoro-1-oxoethyl)phenyl]carbamate;  
 N-[5-nitro-2-[2,2,2-trifluoro-1-oxoethyl)phenyl]benzenepropanamide;  
 N-[4-fluoro-2-(2,2,2-trifluoro-1-oxoethyl)phenyl]furan-2-carboxamide;  
 N-[2-(2,2,2-trifluoro-1-oxoethyl)phenyl]-1-benzothiophene-2-carboxamide;  
 ?,?,?-trifluoro-N-[2-(2,2,2-trifluoro-1-oxoethyl)phenyl]acetamide;  
 N-[2-(2,2,2-trifluoro-1-oxoethyl)phenyl]pyridine-2-carboxamide;  
 N-[2-(2,2,2-trifluoro-1-oxoethyl)phenyl]2-methoxybenzamide;  
 N-[4-iodo-2-(2,2,2-trifluoro-1-oxoethyl)phenyl]furan-2-carboxamide;  
 N-[2-(2,2,2-trifluoro-1-oxoethyl)phenyl]4-chlorophenoxyacetamide;  
 N-[2-(2,2,2-trifluoro-1-oxoethyl)phenyl] indolyl-2-carboxamide;  
 N-[2-(2,2,2-trifluoro-1-oxoethyl)phenyl] benzofuranyl-2-carboxamide; and  
 N-[2-(3-(2-propylamino)-3-oxo-2,2-difluoro-1-oxopropyl)phenyl]2-methoxyphenylcarboxamide.  
 
     
     
         10 . A pharmaceutical composition comprising a therapeutically-effective amount of a compound and a pharmaceutically-acceptable carrier or diluent, said compound selected from a compound of Formula I  
       
         
           
           
               
               
           
         
         wherein each of R 1 , R 2 , R 3 , and R 4  is independently selected from hydrido, alkyl, aralkyl, halo, alkoxy, cyano, nitro, amino, alkylamino, N-acylamino, alkylsulfonyloxy, aminosulfonyl, N-(haloalkylcarbonyl)amino, peptidyl, amino acid residue,  
         
           
             
             
                 
                 
             
           
         
         wherein R 5  is selected from alkoxy, aryloxy, aralkyloxy, alkylthio, arylthio, aralkylthio, alkylamino, arylamino, aralkylamino, alkyl, aryl, aralkyl, heterocyclyl, and heterocyclylalkyl, wherein R 5  is optionally substituted at a substitutable position with one or more substituents selected from alkyl, alkoxy, aryloxy, alkylthio, arylthio, halo, nitro, N-acylamino, amino, alkylamino, alkoxycarbonyl, amino acid residue and peptidyl;  
         wherein R 6  is selected from alkyl, aryl, aralkyl, heterocyclyl and heterocyclylalkyl, wherein R 6  is optionally substituted at a substitutable position with a radical selected from alkoxy, aryloxy, alkylthio, arylthio, halo, nitro, N-acylamino, amino, alkylamino and alkoxycarbonyl;  
         wherein Y is selected from fluoroalkyl and  
         
           
             
             
                 
                 
             
           
         
         wherein Q is selected from alkoxy, aryloxy, aralkyloxy, amino acid residue, peptidyl, and —NHR 7 ; and  
         wherein R 7  is a radical selected from alkyl, aralkyl, and heterocyclylalkyl, wherein R 7  is optionally substituted at a substitutable position with a radical selected from amino, nitrogen-containing heterocyclyl and alkylamino;  
         or a pharnaceutically-acceptable salt or tautomer thereof.  
       
     
     
         11 . A pharmaceutical composition of  claim 10  wherein each of R 1 , R 2 , R 3 , and R 4  is independently selected from hydrido, lower alkyl, lower aralkyl, halo, lower alkoxy, cyano, nitro, amino, lower alkylamino, N-acylamino, lower alkylsulfonyloxy, aminosulfonyl, lower N-(haloalkylcarbonyl)amino, amino acid residue, peptidyl,  
       
         
           
           
               
               
           
         
         wherein R 5  is selected from lower alkoxy, phenyloxy, lower aralkyloxy, lower alkylthio, phenylthio, lower aralkylthio, lower alkylamino, arylamino, lower aralkylamino, lower alkyl, 6-10-membered aryl, lower aralkyl, 5-10-membered heterocyclyl, and lower heterocyclylalkyl, wherein R 5  is optionally substituted at a substitutable position with one or more substituents selected from lower alkyl, lower alkoxy, phenyloxy, lower alkylthio, phenylthio, halo, nitro, N-acylamino, amino, lower alkylamino, lower alkoxycarbonyl, amino acid residue and peptidyl; wherein R 6  is selected from lower alkyl, 6-10-membered aryl, lower aralkyl, 5-10-membered heterocyclyl and lower heterocyclylalkyl, wherein R 6  is optionally substituted at a substitutable position with a radical selected from lower alkoxy, phenyloxy, lower alkylthio, phenylthio, halo, nitro, N-acylamino, amino, lower alkylamino, and lower alkoxycarbonyl; wherein Y is selected from lower fluoroalkyl and  
         
           
             
             
                 
                 
             
           
         
         wherein Q is selected from lower alkoxy, phenyloxy, lower aralkyloxy, N-amino acid residue, N-peptidyl, and —NHR7; and wherein R 7  is a radical selected from lower alkyl, lower aralkyl, and lower heterocyclylalkyl, wherein R 7  is optionally substituted at a substitutable position with one or more radical selected from amino, 5-6-membered nitrogen-containing heterocyclyl and lower N,N-dialkylamino; or a pharmaceutically- acceptable salt or tautomer thereof.  
       
     
     
         12 . A pharmaceutical composition of  claim 11  wherein Y is lower fluoroalkyl; wherein each of R 1 , R 2 , R 3 , and R 4  is independently selected from hydrido, lower alkyl, halo, lower alkoxy, nitro, and amino; and wherein R 5  is selected from phenylalkoxy, lower alkyl substituted with halo or phenyloxy, phenyl, lower phenylalkyl, and five-ten membered heteroaryl, wherein R 5  is optionally substituted at a substitutable position of a phenyl or heteroaryl radical with one or more substituents selected from lower alkyl, lower alkoxy, phenyloxy, lower alkylthio, phenylthio, halo, nitro, N-acylamino, amino, lower alkylamino, lower alkoxycarbonyl, amino acid residue, and peptidyl; or a pharmaceutically-acceptable salt or tautomer thereof.  
     
     
         13 . A pharmaceutical composition of  claim 12  wherein Y is selected from difluoromethyl, trifluoromethyl, pentafluoroethyl, heptafluoropropyl, 1,1-difluoroethyl, and 1,1-difluoropropyl; wherein each of R 1 , R 2 , R 3 , and R 4  is independently selected from hydrido, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, hexyl, fluoro, chloro, bromo, iodo, methoxy, ethoxy, propoxy, isopropoxy, butoxy, tert-butoxy, nitro, and amino; wherein R 5  is selected from phenylmethoxy, phenylethoxy, phenylpropoxy, fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl, pentafluoroethyl, heptafluoropropyl, difluorochloromethyl, dichlorofluoromethyl, difluoroethyl, difluoropropyl, dichloroethyl, dichloropropyl, phenyloxyethyl, phenyloxypropyl, phenyl, phenylmethyl, phenylethyl, furyl, pyrazinyl, oxazolyl, thiazolyl, thienyl, pyrrolyl, benzothienyl, benzofuranyl, indolyl, and pyridyl, wherein R 5  is optionally substituted at a substitutable position of a phenyl or heteroaryl radical with one or more substituents selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, hexyl, methoxy, ethoxy, propoxy, isopropoxy, butoxy, tert-butoxy, phenyloxy, methylthio, phenylthio, fluoro, chloro, bromo, iodo, nitro, N-formylamino, acetylamino, amino, N,N-dimethylamino and methoxycarbonyl; or a pharmaceutically-acceptable salt or tautomer thereof.  
     
     
         14 . A pharmaceutical composition of  claim 11  wherein Y is  
       
         
           
           
               
               
           
         
         wherein Q is selected from lower alkoxy, phenyloxy, lower aralkyloxy, N-amino acid residue, N-peptidyl, and —NHR 7 ; and wherein R 7  is a radical selected from lower alkyl, lower aralkyl, and lower heteroaralkyl, wherein R 7  is optionally substituted at a substitutable position with a radical selected from amino, 5-6 membered nitrogen-containing heterocyclyl and lower N,N-dialkylamino; wherein each of R 1 , R 2 , R 3 , and R 4  is independently selected from hydrido, lower alkyl, halo, lower alkoxy, nitro, and amino; and wherein R 5  is selected from phenylalkoxy, lower alkyl substituted with halo or phenyloxy, phenyl, lower phenylalkyl, and five-ten membered heteroaryl, wherein R 5  is optionally substituted at a substitutable position of a phenyl or heteroaryl radical with one or more substituents selected from lower alkyl, lower alkoxy, phenyloxy, lower alkylthio, phenylthio, halo, nitro, N-acylamino, amino, lower alkylamino, lower alkoxycarbonyl, amino acid residue, and peptidyl; or a pharmaceutically-acceptable salt or tautomer thereof.  
       
     
     
         15 . A pharmaceutical composition of  claim 14  wherein Y is  
       
         
           
           
               
               
           
         
         wherein Q is selected from methoxy, ethoxy, propoxy, isopropoxy, butoxy, phenyloxy, benzyloxy, phenylethoxy, and —NHR 7 ; and wherein R 7  is a radical selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, hexyl, benzyl, phenethyl, oxazolylmethyl, oxazolylethyl, imidazolylmethyl, imidazolylethyl, oxazolinylmethyl, oxazolinylethyl, indolylethyl, indolylmethyl, pyridylmethyl, thienylmethyl, and furylethyl, wherein R 7  is optionally substituted at a substitutable position with a radical selected from amino, piperidinyl, piperazinyl, pyrrolidinyl, morpholinyl, pyridyl, pyrimidyl and N,N-dimethylamino; wherein each of R 1 , R 2 , R 3 , and R 4  is independently selected from hydrido, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, hexyl, fluoro, chloro, bromo, iodo, methoxy, ethoxy, propoxy, isopropoxy, butoxy, tert-butoxy, nitro, and amino; and wherein R 5  is selected from phenylmethoxy, phenylethoxy, phenylpropoxy, fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl, pentafluoroethyl, heptafluoropropyl, difluorochloromethyl, dichlorofluoromethyl, difluoroethyl, difluoropropyl, dichloroethyl, dichloropropyl, phenyloxyethyl, phenyloxypropyl, phenyl, phenylmethyl, phenylethyl, furyl, pyrazinyl, oxazolyl, thiazolyl, thienyl, pyrrolyl, benzothienyl, benzofuranyl, indolyl, and pyridyl, wherein R 5  is optionally substituted at a substitutable position on a phenyl or heteroaryl radical with one or more substituents selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, hexyl, methoxy, ethoxy, propoxy, isopropoxy, butoxy, tert-butoxy, tert-butoxy, phenyloxy, methylthio, phenylthio, fluoro, chloro, bromo, iodo, nitro, N-formylamino, N-acetylamino, amino, N,N-dimethylamino and methoxycarbonyl; or a pharmaceutically-acceptable salt or tautomer thereof.  
       
     
     
         16 . A pharmaceutical composition comprising a therapeutically- effective amount of a compound and a pharmaceutically-acceptable carrier or diluent, said compound selected from a compound of Formula II  
       
         
           
           
               
               
           
         
         wherein each of R 1 , R 2 , and R 3  is independently selected from hydrido, halo, and nitro;  
         wherein R 8  is selected from haloalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heteroaryl, optionally substituted arylalkoxy and optionally substituted aryloxyalkyl;  
         wherein Y is selected from fluoroalkyl, and  
         
           
             
             
                 
                 
             
           
         
         wherein R 9  is alkylamino;  
         or a pharmaceutically-acceptable salt or tautomer thereof.  
       
     
     
         17 . A pharmaceutical composition of  claim 16  wherein R 1  is selected from hydrido, fluoro, chloro, bromo and iodo; wherein R 2  is selected from hydrido, fluoro, chloro, bromo and iodo; wherein R 3  is selected from hydrido, fluoro, chloro, bromo, iodo and nitro; wherein R 8  is selected from trifluoromethyl, phenyl, phenylmethyl, phenylethyl, furyl, pyridyl, pyrazinyl, thienyl, pyrrolyl, benzothienyl, benzofuranyl, indolyl, phenylmethyloxy, (phenyloxy)propyl and phenyloxymethyl; wherein Y is selected from trifluoromethyl and  
       
         
           
           
               
               
           
         
         wherein R 9  is selected from methylamino, ethylamino, propylamino, isopropylamino and N,N-dimethylamino; or a pharmaceutically-acceptable salt or tautomer thereof.  
       
     
     
         18 . A pharmaceutical composition of  claim 17  wherein the compound is selected from compounds and their pharmaceutically-acceptable salts, of the group consisting of 
 ?-phenoxy-N- [2-(2,2,2-trifluoro-1-oxo-ethyl)phenyl]butanamide;  
 N-[2-(2,2,2-trifluoro-1-oxoethyl)phenyl]furan-2-carboxamide;  
 N-[5-fluoro-2-(2,2,2-trifluoro-1-oxoethyl)phenyl]benzenepropanamide;  
 N-[3-chloro-2-(2,2,2-trifluoro-1-oxoethyl)phenyl]benzenepropanamide;  
 N-[2-(2,2,2-trifluoro-1-oxoethyl)phenyl]benzenepropanamide;  
 N-[2-(2,2,2-trifluoro-1-oxoethyl)phenyl]pyrazine-2-carboxamide;  
 phenylmethyl N-[2-(2,2,2-trifluoro-1-oxoethyl)phenyl]carbamate;  
 N-[5-nitro-2-[2,2,2-trifluoro-1-oxoethyl)phenyl]benzenepropanamide;  
 N-[4-fluoro-2-(2,2,2-trifluoro-1-oxoethyl)phenyl]furan-2-carboxamide;  
 N-[2-(2,2,2-trifluoro-1-oxoethyl)phenyl]-1-benzothiophene-2-carboxamide;  
 ?,?,?-trifluoro-N-[2-(2,2,2-trifluoro-1-oxoethyl)phenyl]acetamide;  
 N-[2-(2,2,2-trifluoro-1-oxoethyl)phenyl]pyridine-2-carboxamide;  
 N-[2-(2,2,2-trifluoro-1-oxoethyl)phenyl]2-methoxybenzamide;  
 N-[4-iodo-2-(2,2,2-trifluoro-1-oxoethyl)phenyl]furan-2-carboxamide;  
 N-[2-(2,2,2-trifluoro-1-oxoethyl)phenyl]4-chlorophenoxyacetamide;  
 N-[2-(2,2,2-trifluoro-1-oxoethyl)phenyl] indolyl-2-carboxamide;  
 N-[2-(2,2,2-trifluoro-1-oxoethyl)phenyl] benzofuranyl-2-carboxamide; and  
 N-[2-(3-(2-propylamino)-3-oxo-2,2-difluoro-1-oxopropyl)phenyl]2-methoxyphenylcarboxamide.  
 
     
     
         19 . A method of treating herpes viral infection in a subject, said method comprising treating said subject with an effective amount of a compound of Formula I  
       
         
           
           
               
               
           
         
         wherein each of R 1 , R 2 , R 3 , and R 4  is independently selected from hydrido, alkyl, aralkyl, halo, alkoxy, cyano, nitro, amino, alkylamino, N-acylamino, alkylsulfonyloxy, aminosulfonyl, N-(haloalkylcarbonyl)amino, peptidyl, amino acid residue,  
         
           
             
             
                 
                 
             
           
         
         wherein R 5  is selected from alkoxy, aryloxy, aralkyloxy, alkylthio, arylthio, aralkylthio, alkylamino, arylamino, aralkylamino, alkyl, aryl, aralkyl, heterocyclyl, and heterocyclylalkyl, wherein R 5  is optionally substituted at a substitutable position with one or more substituents selected from alkyl, alkoxy, aryloxy, alkylthio, arylthio, halo, nitro, N-acylamino, amino, alkylamino, alkoxycarbonyl, amino acid residue and peptidyl;  
         wherein R 6  is selected from alkyl, aryl, aralkyl, heterocyclyl and heterocyclylalkyl, wherein R 6  is optionally substituted at a substitutable position with a radical selected from alkoxy, aryloxy, alkylthio, arylthio, halo, nitro, N-acylamino, amino, alkylamino and alkoxycarbonyl;  
         wherein Y is selected from fluoroalkyl and  
         
           
             
             
                 
                 
             
           
         
         wherein Q is selected from alkoxy, aryloxy, aralkyloxy, amino acid residue, peptidyl, and —NHR 7 ; and  
         wherein R 7  is a radical selected from alkyl, aralkyl, and heterocyclylalkyl, wherein R 7  is optionally substituted at a substitutable position with a radical selected from amino, nitrogen-containing heterocyclyl and alkylamino;  
         or a pharmaceutically-acceptable salt or tautomer thereof.  
       
     
     
         20 . A method of  claim 19  wherein each of R 1 , R 2 , R 3 , and R 4  is independently selected from hydrido, lower alkyl, lower aralkyl, halo, lower alkoxy, cyano, nitro, amino, lower alkylamino, N-acylamino, lower alkylsulfonyloxy, aminosulfonyl, lower N-(haloalkylcarbonyl)amino, amino acid residue, peptidyl,  
       
         
           
           
               
               
           
         
         wherein R 5  is selected from lower alkoxy, phenyloxy, lower aralkyloxy, lower alkylthio, phenylthio, lower aralkylthio, lower alkylamino, arylamino, lower aralkylamino, lower alkyl, 6-10-membered aryl, lower aralkyl, 5-10-membered heterocyclyl, and lower heterocyclylalkyl, wherein R 5  is optionally substituted at a substitutable position with one or more substituents selected from lower alkyl, lower alkoxy, phenyloxy, lower alkylthio, phenylthio, halo, nitro, N-acylamino, amino, lower alkylamino, lower alkoxycarbonyl, amino acid residue and peptidyl; wherein R 6  is selected from lower alkyl, 6-10-membered aryl, lower aralkyl, 5-10-membered heterocyclyl and lower heterocyclylalkyl, wherein R 6  is optionally substituted at a substitutable position with a radical selected from lower alkoxy, phenyloxy, lower alkylthio, phenylthio, halo, nitro, N-acylamino, amino, lower alkylamino, and lower alkoxycarbonyl; wherein Y is selected from lower fluoroalkyl and  
         
           
             
             
                 
                 
             
           
         
         wherein Q is selected from lower alkoxy, phenyloxy, lower aralkyloxy, N-amino acid residue, N-peptidyl, and —NHR 7 ; and wherein R 7  is a radical selected from lower alkyl, lower aralkyl, and lower heterocyclylalkyl, wherein R 7  is optionally substituted at a substitutable position with one or more radical selected from amino, 5-6-membered nitrogen-containing heterocyclyl and lower N,N-dialkylamino; or a pharmaceutically-acceptable salt or tautomer thereof.  
       
     
     
         21 . A method of  claim 20  wherein Y is lower fluoroalkyl; wherein each of R 1 , R 2 , R 3 , and R 4  is independently selected from hydrido, lower alkyl, halo, lower alkoxy, nitro, and amino; and wherein R 5  is selected from phenylalkoxy, lower alkyl substituted with halo or phenyloxy, phenyl, lower phenylalkyl, and five-ten membered heteroaryl, wherein R 5  is optionally substituted at a substitutable position of a phenyl or heteroaryl radical with one or more substituents selected from lower alkyl, lower alkoxy, phenyloxy, lower alkylthio, phenylthio, halo, nitro, N-acylamino, amino, lower alkylamino, lower alkoxycarbonyl, amino acid residue, and peptidyl; or a pharmaceutically-acceptable salt or tautomer thereof.  
     
     
         22 . A method of  claim 21  wherein Y is selected from difluoromethyl, trifluoromethyl, pentafluoroethyl, heptafluoropropyl, 1,1-difluoroethyl, and 1,1-difluoropropyl; wherein each of R 1 , R 2 , R 3 , and R 4  is independently selected from hydrido, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, hexyl, fluoro, chloro, bromo, iodo, methoxy, ethoxy, propoxy, isopropoxy, butoxy, tert-butoxy, nitro, and amino; wherein R 5  is selected from phenylmethoxy, phenylethoxy, phenylpropoxy, fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl, pentafluoroethyl, heptafluoropropyl, difluorochloromethyl, dichlorofl uoromethyl, difluoroethyl, difluoropropyl, dichloroethyl, dichloropropyl, phenyloxyethyl, phenyloxypropyl, phenyl, phenylmethyl, phenylethyl, furyl, pyrazinyl, oxazolyl, thiazolyl, thienyl, pyrrolyl, benzothienyl, benzofuranyl, indolyl, and pyridyl, wherein R 5  is optionally substituted at a substitutable position of a phenyl or heteroaryl radical with one or more substituents selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, hexyl, methoxy, ethoxy, propoxy, isopropoxy, butoxy, tert-butoxy, phenyloxy, methylthio, phenylthio, fluoro, chloro, bromo, iodo, nitro, N-formylamino, acetylamino, amino, N,N-dimethylamino and methoxycarbonyl; or a pharmaceutically-acceptable salt or tautomer thereof.  
     
     
         23 . A method of  claim 20  wherein Y is  
       
         
           
           
               
               
           
         
         wherein Q is selected from lower alkoxy, phenyloxy, lower aralkyloxy, N-amino acid residue, N-peptidyl, and —NHR 7 ; and wherein R 7  is a radical selected from lower alkyl, lower aralkyl, and lower heteroaralkyl, wherein R 7  is optionally substituted at a substitutable position with a radical selected from amino, 5-6 membered nitrogen-containing heterocyclyl and lower N,N-dialkylamino; wherein each of R 1 , R 2 , R 3 , and R 4  is independently selected from hydrido, lower alkyl, halo, lower alkoxy, nitro, and amino; and wherein R 5  is selected from phenylalkoxy, lower alkyl substituted with halo or phenyloxy, phenyl, lower phenylalkyl, and five-ten membered heteroaryl, wherein R 5  is optionally substituted at a substitutable position of a phenyl or heteroaryl radical with one or more substituents selected from lower alkyl, lower alkoxy, phenyloxy, lower alkylthio, phenylthio, halo, nitro, N-acylamino, amino, lower alkylamino, lower alkoxycarbonyl, amino acid residue, and peptidyl; or a pharmaceutically-acceptable salt or tautomer thereof.  
       
     
     
         24 . A method of  claim 23  wherein Y is  
       
         
           
           
               
               
           
         
         wherein Q is selected from methoxy, ethoxy, propoxy, isopropoxy, butoxy, phenyloxy, benzyloxy, phenylethoxy, and —NHR 7 ; and wherein R 7  is a radical selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, hexyl, benzyl, phenethyl, oxazolylmethyl, oxazolylethyl, imidazolylmethyl, imidazolylethyl, oxazolinylmethyl, oxazolinylethyl, indolylethyl, indolylmethyl, pyridylmethyl, thienylmethyl, and furylethyl, wherein R 7  is optionally substituted at a substitutable position with a radical selected from amino, piperidinyl, piperazinyl, pyrrolidinyl, morpholinyl, pyridyl, pyrimidyl and N,N-dimethylamino; wherein each of R 1 , R 2 , R 3 , and R 4  is independently selected from hydrido, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, hexyl, fluoro, chloro, bromo, iodo, methoxy, ethoxy, propoxy, isopropoxy, butoxy, tert-butoxy, nitro, and amino; and wherein R 5  is selected from phenylmethoxy, phenylethoxy, phenylpropoxy, fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl, pentafluoroethyl, heptafluoropropyl, difluorochloromethyl, dichlorofluoromethyl, difluoroethyl, difluoropropyl, dichloroethyl, dichloropropyl, phenyloxyethyl, phenyloxypropyl, phenyl, phenylmethyl, phenylethyl, furyl, pyrazinyl, oxazolyl, thiazolyl, thienyl, pyrrolyl, benzothienyl, benzofuranyl, indolyl, and pyridyl, wherein R 5  is optionally substituted at a substitutable position on a phenyl or heteroaryl radical with one or more substituents selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, hexyl, methoxy, ethoxy, propoxy, isopropoxy, butoxy, tert-butoxy, tert-butoxy, phenyloxy, methylthio, phenylthio, fluoro, chloro, bromo, iodo, nitro, N-formylamino, N-acetylamino, amino, N,N-dimethylamino and methoxycarbonyl; or a pharmaceutically-acceptable salt or tautomer thereof.  
       
     
     
         25 . A method of treating herpes viral infection in a subject, said method comprising treating said subject with an effective amount of a compound of Formula II  
       
         
           
           
               
               
           
         
         wherein each of R 1 , R 2 , and R 3  is independently selected from hydrido, halo, and nitro;  
         wherein R 8  is selected from haloalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heteroaryl, optionally substituted arylalkoxy and optionally substituted aryloxyalkyl;  
         wherein Y is selected from fluoroalkyl, and  
         
           
             
             
                 
                 
             
           
         
         wherein R 9  is alkylamino;  
         or a pharmaceutically-acceptable salt or tautomer thereof.  
       
     
     
         26 . A method of  claim 25  wherein R 1  is selected from hydrido, fluoro, chloro, bromo and iodo; wherein R 2  is selected from hydrido, fluoro, chloro, bromo and iodo; wherein R 3  is selected from hydrido, fluoro, chloro, bromo, iodo and nitro; wherein R 8  is selected from trifluoromethyl, phenyl, phenylmethyl, phenylethyl, furyl, pyridyl, pyrazinyl, thienyl, pyrrolyl, benzothienyl, benzofuranyl, indolyl, phenylmethyloxy, (phenyloxy)propyl and phenyloxymethyl; wherein Y is selected from trifluoromethyl and  
       
         
           
           
               
               
           
         
         wherein R 9  is selected from methylamino, ethylamino, propylamino, isopropylamino and N,N-dimethylamino; or a pharmaceutically-acceptable salt or tautomer thereof.  
       
     
     
         27 . A method of  claim 26  wherein the compound is selected from compounds and their pharmaceutically-acceptable salts, of the group consisting of 
 ?-phenoxy-N- [2-(2,2,2-trifluoro-1-oxo-ethyl)phenyl]butanamide;  
 N-[2-(2,2,2-trifluoro-1-oxoethyl)phenyl]furan-2-carboxamide;  
 N-[5-fluoro-2-(2,2,2-trifluoro-1-oxoethyl)phenyl]benzenepropanamide;  
 N-[3-chloro-2-(2,2,2-trifluoro-1-oxoethyl)phenyl]benzenepropanamide;  
 N-[2-(2,2,2-trifluoro-1-oxoethyl)phenyl]benzenepropanamide;  
 N-[2-(2,2,2-trifluoro-1-oxoethyl)phenyl]pyrazine-2-carboxamide;  
 phenylmethyl N-[2-(2,2,2-trifluoro-1-oxoethyl)phenyl]carbamate;  
 N-[5-nitro-2-[2,2,2-trifluoro-1-oxoethyl)phenyl]benzenepropanamide;  
 N-[4-fluoro-2-(2,2,2-trifluoro-1-oxoethyl)phenyl]furan-2-carboxamide;  
 N-[2-(2,2,2-trifluoro-1-oxoethyl)phenyl]-1-benzothiophene-2-carboxamide;  
 ?,?,?-trifluoro-N-[2-(2,2,2-trifluoro-1-oxoethyl)phenyl]acetamide;  
 N-[2-(2,2,2-trifluoro-1-oxoethyl)phenyl]pyridine-2-carboxamide;  
 N-[2-(2,2,2-trifluoro-1-oxoethyl)phenyl]2-methoxybenzamide;  
 N-[4-iodo-2-(2,2,2-trifluoro-1-oxoethyl)phenyl]furan-2-carboxamide;  
 N-[2-(2,2,2-trifluoro-1-oxoethyl)phenyl]4-chlorophenoxyacetamide;  
 N-[2-(2,2,2-trifluoro-1-oxoethyl)phenyl] indolyl-2-carboxamide;  
 N-[2-(2,2,2-trifluoro-1-oxoethyl)phenyl] benzofuranyl-2-carboxamide; and  
 N-[2-(3-(2-propylamino)-3-oxo-2,2-difluoro-1-oxopropyl)phenyl]2-methoxyphenylcarboxamide.  
 
     
     
         28 . The method of  claim 19  wherein the subject is infected with a herpesvirus selected from herpes simplex virus type-1(HSV-1), herpes simplex virus type-2 (HSV-2), cytomegalovirus (CMV), varicella-zoster virus (VZV),  Epstein-Barr  virus, herpesvirus-6 (HHV-6), herpesvirus-7 (HHV-7), herpesvirus-8 (HHV-8), pseudorabies and rhinotracheitis.  
     
     
         29 . A method of inhibiting a viral protease, said method comprising treating said subject with an effective amount of a compound of  claim 1 .  
     
     
         30 . Method of  claim 19  wherein the viral protease is a herpesvirus protease.  
     
     
         31 . Method of  claim 30  wherein the viral protease is selected from a CMV protease, an HSV-1 protease and a HSV-2 protease.  
     
     
         32 . Method of  claim 31  wherein the viral protease is a CMV protease, encoded by U L 80.  
     
     
         33 . A method of prophylactic treatment of herpes viral infection in a subject, said method comprising treating said subject with an effective amount of a compound of  claim 1 .  
     
     
         34 . The method of  claim 33  wherein the herpesvirus is selected from herpes simplex virus type-1 (HSV-1), herpes simplex virus type-2 (HSV-2), cytomegalovirus (CMV), varicella-zoster virus (VZV),  Epstein-Barr  virus, herpesvirus-6 (HHV-6), herpesvirus-7 (HHV-7), berpesvirus-8 (HHV-8), pseudorabies and rhinotracheitis.