Retroviral protease inhibitors

Abstract

N-heterocyclic moiety containing hydroxyethylamino compounds are effective as retroviral protease inhibitors, and in particular as inhibitors of HIV protease.

1 . A compound represented by the formula  
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof, wherein 
 R′ is a radical as defined for R 3  or aminoalkyl having an amino group that may be mono- or disubstituted with substituents selected from the group consisting of alkyl, aryl, aralkyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroaralkyl, heterocycloalkyl and heterocycloalkylalkyl;  
 t is either 0 or 1;  
 R 1  is a radical selected from the group consisting of a hydrogen radical, —CH 2 SO 2 NH 2 , —CO 2 CH 3 , —CH 2 CO 2 CH 3 , —CONH 2 , —CONHCH 3 , —CON(CH 3 ) 2 , —CH 2 CONHCH 3 , —CH 2 CHCON(CH 3 ) 2 , alkyl, alkenyl, alkynyl and cycloalkyl or a radical of a side chain of an amino acid selected from the group consisting of asparagine, S-methyl cysteine, the corresponding sulfoxide and sulfone derivatives of S-methyl cysteine, glycine, leucine, isoleucine, allo-isoleucine, tert-leucine, alanine, phenylalanine, ornithine, histidine, norleucine, glutamine, valine, threonine, allo-threonine, serine, aspartic acid and beta-cyano alanine;  
 R 3  is a radical selected from the group consisting of a hydrogen radical, alkyl, alkenyl, hydroxyalkyl, alkoxyalkyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, heteroaryl, heterocycloalkylalkyl, aryl, aralkyl, and heteroaralkyl;  
 Y′ is O, S, or NR 3 ;  
 R 4  and R 5  together with the nitrogen atom to which they are bonded form a five membered N-heterocyclic moiety;  
 R 6  is a hydrogen radical or an alkyl radical; and  
 R 20  and R 21  are radicals as defined for R.  
 
     
     
         2 . The compound of  claim 1  or a pharmaceutically acceptable salt thereof, wherein t is 0.  
     
     
         3 . The compound of  claim 1  or a pharmaceutically acceptable salt thereof, wherein Y′ is O.  
     
     
         4 . The compound of  claim 1  or a pharmaceutically acceptable salt thereof, wherein R 6  is a hydrogen radical.  
     
     
         5 . The compound of  claim 1  or a pharmaceutically acceptable salt thereof, wherein R 1  is a hydrogen radical or an alkyl radical having from 1 to about 4 carbon atoms.  
     
     
         6 . The compound of  claim 1  or a pharmaceutically acceptable salt thereof, wherein R 1  is a methyl radical.