Alpha- and beta-amino acid hydroxyethylamino sulfonamides useful as retroviral protease inhibitors

A method of treating a retroviral infection comprising administering an effective amount of a pharmaceutical composition comprising a compound represented by the formula:

• or a pharmaceutically acceptable salt or ester thereof, wherein:
• R2 is a substituent selected from the group consisting of alkyl, aryl, cycloalkyl, cycloalkylalkyl, and aralkyl, which substituent is optionally substituted with alkyl, halo, nitro, cyano, —CF3, —OR9, or —SR9, wherein R9 is a hydrogen radical or alkyl;
• R4 is alkyl, haloalkyl, alkenyl, alkynyl, hydroxyalkyl, alkoxyalkyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, heteroaryl, heterocycloalkylalkyl, aryl, aralkyl, aralkenyl, heteroaralkyl, aminoalkyl, or mono- or di-substituted aminoalkyl that is substituted with one or two substituents independently selected from the group consisting of alkyl, aryl, aralkyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroaralkyl, heterocycloalkyl, and heterocycloalkylalkyl, or, in the case of a di-substituted aminoalkyl, said two substituents together with the nitrogen atom to which they are bonded form a heterocycloalkyl or a heteroaryl;
• R6 is a hydrogen radical or alkyl;
• Y is O or S;
• and
• A is alkoxy, alkenoxy, aralkoxy, alkyl, cycloalkyl, cycloalkylalkoxy, cycloalkylalkyl, aralkyl, aryl, aryloxy, heterocycloalkyl, heterocycloalkoxy, heterocycloalkylalkyl, heterocycloalkylalkoxy, heteroaralkyl, heteroaralkoxy, heteroaryloxy, heteroaryl, alkenyl, aryloxyalkyl, heteroaryloxyalkyl, hydroxyalkyl, amino, or mono- or di-substituted amino that is substituted with one or two substituents independently selected from the group consisting of alkyl, aryl, aralkyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroaralkyl, heterocycloalkyl, and heterocycloalkylalkyl, or, in the case of a di-substituted amino, said two substituents together with the nitrogen atom to which they are bonded form a heterocycloalkyl or a heteroaryl;
• or is A is a radical represented by the formula
• wherein:
• t is 0 or 1;
• R is a hydrogen radical, alkoxycarbonyl, aralkoxycarbonyl, alkylcarbonyl, cycloalkylcarbonyl, cycloalkylalkoxycarbonyl, cycloalkylalkanoyl, carboxyalkanoyl, alkanoyl, aralkanoyl, aroyl, aryloxycarbonyl, aryloxycarbonylalkyl, aryloxyalkanoyl, heterocyclylcarbonyl, heterocyclyloxycarbonyl, heterocyclylalkanoyl, heterocyclylalkoxycarbonyl, heteroaralkanoyl, heteroaralkoxycarbonyl, heteroaryloxycarbonyl, heteroaroyl, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, aralkyl, aryloxyalkyl, heteroaryloxyalkyl, hydroxyalkyl, aminocarbonyl, aminoalkanoyl, or mono- or di-substituted aminocarbonyl or mono- or di-substituted aminoalkanoyl, that are each substituted with one or two substituents independently selected from the group consisting of alkyl, aryl, aralkyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroaralkyl, heterocycloalkyl, and heterocycloalkylalkyl, or, in the case of a di-substituted aminocarbonyl or a di-substituted aminoalkanoyl, said two substituents together with the nitrogen atom to which they are bonded form a heterocycloalkyl or a heteroaryl;
• R′ is a hydrogen radical, alkyl, haloalkyl, alkenyl, alkynyl, hydroxyalkyl, alkoxyalkyl, alkylthioalkyl, alkylsulfonylalkyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, heteroaryl, heterocycloalkylalkyl, aryl, aralkyl, heteroaralkyl, aminoalkyl, or mono- or di-substituted aminoalkyl that is substituted with one or two substituents independently selected from the group consisting of alkyl, aryl, aralkyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroaralkyl, heterocycloalkyl, and heterocycloalkylalkyl, or, in the case of a di-substituted aminoalkyl, said two substituents together with the nitrogen atom to which they are bonded form a heterocycloalkyl or a heteroaryl;
• or R′ is R″SO2—, wherein R″ is a hydrogen radical, alkyl, haloalkyl, alkenyl, alkynyl, hydroxyalkyl, alkoxyalkyl, alkylthioalkyl, alkylsulfonylalkyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, heteroaryl, heterocycloalkylalkyl, aryl, aralkyl, heteroaralkyl, aminoalkyl, or mono- or di-substituted aminoalkyl that is substituted with one or two substituents independently selected from the group consisting of alkyl, aryl, aralkyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroaralkyl, heterocycloalkyl, and heterocycloalkylalkyl, or, in the case of a di-substituted aminoalkyl, said two substituents together with the nitrogen atom to which they are bonded form a heterocycloalkyl or a heteroaryl;
• or R and R′ together with the nitrogen to which they are bonded form a heterocycloalkyl or a heteroaryl;
• R1 is a hydrogen radical, —CO2CH3, —CH2CO2CH3, —CO2H, —CH2CO2H, —CH2CH2CONH2, —CH2CONH2, —CONH2, —CH2C(O)NHCH3, —CH2C(O)N(CH3)2, —CONHCH3, —CONH(CH3)2, —CH2SO2NH2, —CH2CH2SO2NH2, —CH2S[O]CH3, —CH2S [O]2CH3, —(CH3)2(SCH3), —C(CH3)2(S[O]CH3), —C(CH3)2(S[O]2CH3), alkyl, hydroxyalkyl, cyanoalkyl, haloalkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, alkylthioalkyl, aralkyl, heteroaralkyl, aminoalkyl, or mono- or di-substituted aminoalkyl that is substituted with one or two substituents independently selected from the group consisting of alkyl, aryl, aralkyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroaralkyl, heterocycloalkyl, and heterocycloalkylalkyl, or, in the case of a di-substituted aminoalkyl, said two substituents together with the nitrogen atom to which they are bonded form a heterocycloalkyl or a heteroaryl;
• and
• each of R1′ and R1″ are independently as defined for R1;
• or one of R1′ and R1″ together with R1 and the carbon atoms to which R1, R1′, R1″ are bonded, forms cycloalkyl.