Retroviral protease inhibitors

A compound represented by the formula;

• 147
• including a pharmaceutically acceptable salt, prodrug or ester thereof, wherein:
• R′ represents radicals as defined for R3 and aminoalkyl radicals wherein said amino group may be mono- or disubstituted with substituents selected from alkyl, aryl, aralkyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroaralkyl, heterocycloalkyl and heterocycloalkyl alkyl radicals;
• t represents either 0 or 1;
• R1 represents hydrogen, —CH2SO2NH2, —CO2CH3, —CH2CO2CH3, —CONH2, CONHCH3, —CON(CH3)2, —CH2CONHCH3, —CH2CHCON(CH3)2, alkyl, alkenyl, alkynyl and cycloalkyl radicals and amino acid side chains selected from the group consisting of asparagine, S-methyl cysteine and the corresponding sulfoxide and sulfone derivatives thereof, glycine, leucine, isoleucine, allo-isoleucine, tert-leucine, alanine, phenylalanine, ornithine, histidine, norleucine, glutamine, valine, threonine, allo-threonine, serine, aspartic acid and beta-cyano alanine side chains;
• R2 represents alkyl, aryl, cycloalkyl, cycloalkylalkyl and aralkyl radicals, which radicals are optionally substituted with a substituent selected from the group consisting of —NO2, —OR9, —SR9, and halogen radicals, wherein R9 represents hydrogen and alkyl radicals;
• R3 represents alkyl, hydrogen, alkenyl, hydroxyalkyl, alkoxyalkyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, heteroaryl, heterocycloalkylalkyl, aryl, arlkyl, and heteroaralkyl radicals;
• Y′ represents O, S and NR3;
• R4 and R5 together with the nitrogen atom to which they are bonded represent a N-heterocyclic moiety;
• R6 represents hydrogen and alkyl radicals;
• and
• R20 and R21 represent radicals as defined for R1.

A compound represented by the formula:

• 151
• including a pharmaceutically acceptable salt, produg or ester thereof, wherein:
• t represents either 0 or 1;
• R1 represents hydrogen, —CH2SO2NH2, —CO2CH3, —CH2CO2CH3, —CONH2, —CONHCH3, —CON(CH3)2, —CH2CONHCH3, —CH2CHCON(CH3)2, alkyl, alkenyl, alkynyl and cycloalkyl radicals and amino acid side chains selected from the group consisting of asparagine, S-methyl cysteine and the corresponding sulfoxide and sulfone derivatives thereof, glycine, leucine, isoleucine, allo-isoleucine, tert-leucine, alanine, phenylalanine, ornithine, histidine, norleucine, glutamine, valine, threonine, allo-threonine, serine, aspartic acid and beta-cyano alanine side chains;
• R2 represents alkyl, aryl, cycloalkyl, cycloalkylalkyl and aralkyl radicals, which radicals are optionally substituted with a substituent selected from the group consisting of —NO2, —OR15, —SR15, and halogen radicals, wherein R15 represents hydrogen and alkyl radicals;
• R3 represents hydrogen, alkyl, alkenyl, hydroxyalkyl, alkoxyalkyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, heteroaryl, heterocycloalkylalkyl, aryl, aralkyl, and heteroaralkyl radicals;
• X′ represent O, N and C(R17) where R17 represents hydrogen and alkyl radicals;
• Y′ and Y″ independently represent O, S and NR3;
• R4 and R5 together with the nitrogen atom to which they are bonded represent a N-heterocyclic moiety;
• R6 represents hydrogen and alkyl radicals;
• R30, R31 and R32 independently represent radicals as defined for R1, or one of R1 and R30 together with one of R31 and R32 and the carbon atoms to which they are attached form a cycloalkyl radical;
• and
• R33 and R34 independently represent radicals as defined for R3, or R33 and R34 together with X′ represent cycloalkyl, aryl, heterocyclyl and heteroaryl radicals, provided that when X′ is O, R34 is absent.

A compound represented by the formula:

• 155
• including a pharmaceutically acceptable salt, prodrug or ester thereof, wherein:
• R and R′ independently represent hydrogen, alkyl, aryl, aralkyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroaralkyl, heterocycloalkyl, and heterocycloalkylalkyl radicals, or R and R′ along with the nitrogen atom to which they are attached form a heterocyclyl or heteroaryl radical;
• n represents 1 or 2;
• R′ represents hydrogen, —CH2SO2NH2, —CO2CH3, —CH2CO2CH3, —CONH2, —CONHCH3, —C(CH3)2SCH3, —CON(CH3)2, —CH2CONHCH3, —CH2CON(CH3)2, —C(CH3)2S(O)CH3, —C(CH3)2SO2CH3, alkyl, alkenyl, alkynyl, thioalkyl and cycloalkyl radicals and amino acid side chains selected from the group consisting of asparagine, S-methyl cysteine and the corresponding sulfoxide and sulfone derivatives thereof, glycine, leucine, isoleucine, allo-isoleucine, tert-leucine, alanine, phenylalanine, ornithine, histidine, norleucine, glutamine, valine, threonine, allo-threonine, serine, aspartic acid and beta-cyano alanine side chains;
• R1′ and R1″ independently represent hydrogen and radicals as defined for R1.
• R2 represents alkyl, aryl, cycloalkyl, cycloalkylalkyl and aralkyl radicals, which radicals are optionally substituted with a substituent selected from the group consisting of —NO2, —OR15, —SR15, and halogen radicals, wherein R15 represents hydrogen and alkyl radicals;
• R3 represents hydrogen, alkyl, alkenyl, hydroxyalkyl, alkoxyalkyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, heteroaryl, heterocycloalkylalkyl, aryl, aralkyl, and heteroaralkyl radicals;
• Y′ and Y″ independently represent O, S and NR3;
• R4 and R5 together with the nitrogen atom to which they are bonded represent a N-heterocyclic moiety;
• R6 and R6′ independently represent hydrogen and alkyl radicals.