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.alpha.- and .beta.-amino acid hydroxyethylamino sulfonamides useful as retroviral protease inhibitors
RE43802 .alpha.- and .beta.-amino acid hydroxyethylamino sulfonamides useful as retroviral protease inhibitors
Patent Drawings:

Inventor: Vazquez, et al.
Date Issued: November 13, 2012
Application:
Filed:
Inventors:
Assignee:
Primary Examiner: Chu; Yong
Assistant Examiner:
Attorney Or Agent: Connolly Bove Lodge & Hutz LLP
U.S. Class: 514/275; 514/311; 514/314; 514/355; 514/357; 514/365; 514/367; 514/466; 514/471; 514/599; 514/601; 514/602; 514/605
Field Of Search:
International Class: A61K 31/36
U.S Patent Documents:
Foreign Patent Documents: A-79823/87; A 79823/87; 2026382; 2045008; 2352452; 3635907; 0104041; 0114993; 0172347; 0223437; 0264795; 0337714; 0342541; 0346847; 356223; 389898; 389898; 393445; 393457; 402646; 0434365; 468641; 468641; 0541168; 0560268; 0580402; 1435386; 2184730; 2200115; 2209752; 50041814; WO 84/03044; WO 86/06726; WO9003971; WO 92/00750; 92/08699; WO 92/08688; WO 92/08699; WO 92/08701; WO 93/07128; WO 93/008184; WO 93/09096; WO 93/23388; 94/04492; WO 94/04492; WO 94/05300; WO 94/05639; WO94/05639; WO 94/26749; WO 95/06030; WO 95/09843; WO95/33464; WO 97/01349; WO97/27319; WO97/27480; WO98/07888; WO98/56781; WO 99/33792; WO 99/67417
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Abstract: .alpha.- and .beta.-amino acid hydroxyethylamino sulfonamide compounds are effective as retroviral protease inhibitors, and in particular as inhibitors of HIV protease.
Claim: What is claimed is:

.[.1. A compound represented by the formula: ##STR00829## or a pharmaceutically acceptable salt[, prodrug] or ester thereof, wherein R.sup.2 is an alkyl, aryl, cycloalkyl,cycloalkylalkyl or aralkyl radical, which radical is optionally substituted with a radical selected from the group consisting of alkyl, halo, nitro, cyano, CF.sub.3, --OR.sup.9, and -SR.sup.9, wherein R.sup.9 is a radical selected from the groupconsisting of hydrogen and alkyl; R.sup.3 is a hydrogen, alkyl, haloalkyl, alkenyl, alkynyl, hydroxyalkyl, alkoxyalkyl, alkylthioalkyl, alkylsulfonylalkyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, heteroaryl, heterocycloalkylalkyl, aryl, aralkyl,heteroaralkyl, aminoalkyl or mono- or disubstituted aminoalkyl radicals, wherein said substituents are selected from the group consisting of alkyl, aryl, aralkyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroaralkyl, heterocycloalkyl andheterocycloalkylalkyl radicals; or where said aminoalkyl radical is disubstituted, said substituents along with the nitrogen atom to which they are attached, form a heterocycloalkyl or a heteroaryl radical; R.sup.4 is an alkyl, haloalkyl, alkenyl,alkynyl, hydroxyalkyl, alkoxyalkyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, heteroaryl, heterocycloalkylalkyl, aryl, aralkyl, aralkenyl, heteroaralkyl, aminoalkyl or mono- or disubstituted aminoalkyl radical, wherein said substituents are selectedfrom the group consisting of alkyl, aryl, aralkyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroaralkyl, heterocycloalkyl and heterocycloalkylalkyl radicals; or where said aminoalkyl radical is disubstituted, said substituents along with the nitrogenatom to which they are attached, form a heterocycloalkyl or a heteroaryl radical; R.sup.6 is a hydrogen or alkyl radical; x is 1 or 2; t is 0 or 1; and Y is O or S; and A is an alkoxy, alkenoxy, aralkoxy, alkyl, cycloalkyl, cycloalkylalkoxy,cycloalkylalkyl, aralkyl, aryl, aryloxy, heterocycloalkyl, heterocycloalkoxy, heterocycloalkylalkyl, heterocycloalkylalkoxy, heteroaralkyl, heteroaralkoxy, heteroaryloxy, heteroaryl, alkenyl, aryloxyalkyl, heteroaryloxyalkyl, hydroxyalkyl, amino, ormono- or disubstituted amino radical, wherein the substituents are selected from the group consisting of alkyl, aryl, aralkyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroaralkyl, heterocycloalkyl and heterocycloalkyalkyl radicals; or where saidamino radical is disubstituted, said substituents along with the nitrogen atom to which they are attached form a heterocycloalkyl or heteroaryl radical; or is represented by the formula ##STR00830## wherein R is a hydrogen, 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 disubstituted aminocarbonyl or mono- or disubstituted aminoalkanoyl radical, wherein the substituents are selected from the group consisting of alkyl, aryl, aralkyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroaralkyl,heterocycloalkyl and heterocycloalkyalkyl radicals; or wherein said aminocarbonyl or aminoalkanoyl radicals are disubstituted, said substituents along with the nitrogen atom to which they are attached form a heterocycloalkyl or heteroaryl radical; R'is a radical as defined for R.sup.3 or R''SO.sub.2--, wherein R'' is a radical as defined for R.sup.3; or R and R' together with the nitrogen to which they are attached form a heterocycloalkyl or heteroaryl radical; R.sup.1 is a hydrogen,--CO.sub.2CH.sub.3, --CH.sub.2CO.sub.2CH.sub.3, --CO.sub.2H, --CH.sub.2CO.sub.2H, --CH.sub.2CH.sub.2CONH.sub.2, --CH.sub.2CONH.sub.2, --CONH.sub.2, --CH.sub.2C (O) NHCH.sub.3, --CH.sub.2C(O)N (CH.sub.3).sub.2, --CONHCH.sub.3, --CONH(CH.sub.3).sub.2,--CH.sub.2SO.sub.2NH.sub.2, --CH.sub.2CH.sub.2SO.sub.2NH.sub.2, --CH.sub.2S[O]CH.sub.3, --CH.sub.2S[O].sub.2CH.sub.3, --C(CH.sub.3).sub.2(SCH.sub.3), --C(CH.sub.3).sub.2(S [O]CH.sub.3), --C(CH.sub.3).sub.2(S[O].sub.2CH.sub.3), alkyl, hydroxyalkyl,cyanoalkyl, haloalkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, alkylthioalkyl, aralkyl, heteroaralkyl, aminoalkyl or mono- or disubstituted aminoalkyl radical, wherein said substituents are selected from the group consisting of alkyl, aryl,aralkyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroaralkyl, heterocycloalkyl and heterocycloalkylalkyl radicals; or where said aminoalkyl radical is disubstituted, said substituents along with the nitrogen atom to which they are attached, form aheterocycloalkyl or a heteroaryl radical; and each of R.sup.1' and R.sup.1'' are independently a radical as defined for R.sup.1; or one of R.sup.1' and R.sup.1'' together with R.sup.1 and the carbon atoms to which R.sup.1, R.sup.1' and R.sup.1'' areattached, form a cycloalkyl radical; and wherein alkyl, alone or in combination, is a straight-chain or branched-chain hydrocarbon radical containing from 1 to 8 carbon atoms; alkenyl, alone or in combination, is a straight-chain or branched-chainhydrocarbon radical having at least one double bond and containing from 2 to 8 carbon atoms; alkynyl. alone or in combination. is a straight-chain or branched-chain hydrocarbon radical having at least one triple bond and containing from 2 to 10 carbonatoms; cycloalkyl, alone or in combination, is a hydrocarbon ring containing from 3 to 8 carbon atoms; aryl, alone or in combination, means a phenyl or naphthyl radical which optionally carries one or more alkyl, alkoxy, halogen, hydroxy, amino, nitro,cyano, haloalkyl, carboxy, alkoxycarbonyl, cycloalkyl, heterocycloalkyl, amido, alkylamino, dialkylamino, alkylamido or dialkylamido radicals; heterocyclyl and heterocycloalkyl, alone or in combination, mean a saturated or partially unsaturatedmonocyclic, bicyclic or tricyclic heterocycle having 3 to 12 ring members, which contains at least one nitrogen, oxygen, sulfur, sulfone, sulfoxide or N-oxide of a tertiary nitrogen heteroatom ring member, and which is optionally substituted on one ormore carbon atoms by halogen, alkyl, alkoxy, hydroxy, oxo or aryl, or on a secondary nitrogen atom by hydroxy, alkyl, aralkoxycarbonyl, alkanoyl, phenyl or phenylalkyl; and heteroaryl, alone or in combination, means an aromatic monocyclic, bicyclic, ortricyclic heterocycloalkyl radical which is optionally substituted as defined above with respect to the definitions of aryl and heterocycloalkyl..].

.[.2. The compound of claim 1 or a pharmaceutically acceptable salt, prodrug or ester thereof, wherein R.sup.2 is an alkyl, aryl, cycloalkyl, cycloalkylalkyl or aralkyl radical, which radical is optionally substituted with a radical selectedfrom the group consisting of alkyl, halo and --OR.sup.9, wherein R.sup.9 is a radical selected from the group consisting of hydrogen and alkyl; R.sup.3 is a hydrogen, alkyl, haloalkyl, alkenyl, alkynyl, hydroxyalkyl, alkoxyalkyl, alkylthioalkyl,alkylsulfonylalkyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, heteroaryl, heterocycloalkylalkyl, aryl, aralkyl, heteroaralkyl, aminoalkyl or mono- or disubstituted aminoalkyl radicals, wherein said substituents are selected from the group consistingof alkyl, aralkyl, cycloalkyl and cycloalkylalkyl radicals; or where said aminoalkyl radical is disubstituted, said substituents along with the nitrogen atom to which they are attached, form a heterocycloalkyl or a heteroaryl radical; R.sup.4 is analkyl, haloalkyl, alkenyl, alkynyl, hydroxyalkyl, alkoxyalkyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, heteroaryl, heterocycloalkylalkyl, aryl, aralkyl, aralkenyl or heteroaralkyl radical; R.sup.6 is a hydrogen or alkyl radical; x is 1 or 2; tis 0 or 1; and Y is O or S; and A is an alkoxy, alkenoxy, aralkoxy, alkyl, cycloalkyl, cycloalkylalkoxy, cycloalkylalkyl, aralkyl, aryl, aryloxy, heterocycloalkyl, heterocycloalkoxy, heterocycloalkylalkyl, heterocycloalkylalkoxy, heteroaralkyl,heteroaralkoxy, heteroaryloxy, heteroaryl, hydroxyalkyl, amino, or mono- or disubstituted amino radical, wherein the substituents are selected from the group consisting of alkyl, aralkyl, heteroaryl, heteroaralkyl, heterocycloalkyl andheterocycloalkyalkyl radicals; or where said amino radical is disubstituted, said substituents along with the nitrogen atom to which they are attached form a heterocycloalkyl radical; or is represented by the formula ##STR00831## wherein R is ahydrogen, alkoxycarbonyl, aralkoxycarbonyl, alkylcarbonyl, carboxyalkanoyl, alkanoyl, aralkanoyl, aroyl, heterocyclylcarbonyl, heterocyclyloxycarbonyl, heterocyclylalkanoyl, heterocyclylalkoxycarbonyl, heteroaralkanoyl, heteroaralkoxycarbonyl,heteroaryloxycarbonyl, heteroaroyl, alkyl, cycloalkyl, aralkyl, hydroxyalkyl, aminocarbonyl, aminoalkanoyl, or mono- or disubstituted aminocarbonyl or mono- or disubstituted aminoalkanoyl radical, wherein the substituents are selected from the groupconsisting of alkyl, aralkyl, heteroaryl, heteroaralkyl, heterocycloalkyl and heterocycloalkyalkyl radicals; or wherein said aminocarbonyl or aminoalkanoyl radicals are disubstituted, said substituents along with the nitrogen atom to which they areattached form a heterocycloalkyl or heteroaryl radical; R' is a hydrogen, alkyl or aralkyl radical or R''SO.sub.2--, wherein R'' is a radical as defined for R.sup.3; or R and R' together with the nitrogen to which they are attached form aheterocycloalkyl or heteroaryl radical; R.sup.1 is a hydrogen, --CO.sub.2CH.sub.3, --CH.sub.2CO.sub.2CH.sub.3, --CO.sub.2H, --CH.sub.2CO.sub.2H, --CH.sub.2CH.sub.2CONH.sub.2, --CH.sub.2CONH.sub.2, --CONH.sub.2, --CH.sub.2C (O) NHCH.sub.3,--CH.sub.2C(O)N (CH.sub.3).sub.2, --CONHCH.sub.3, --CONH(CH.sub.3).sub.2, --CH.sub.2SO.sub.2NH.sub.2, --CH.sub.2CH.sub.2SO.sub.2NH.sub.2, --CH.sub.2S[O]CH.sub.3, --CH.sub.2S[O].sub.2CH.sub.3, --C(CH.sub.3)2(SCH.sub.3), --C(CH.sub.3).sub.2(S [O]CH.sub.3),--C(CH.sub.3).sub.2(S[O].sub.2CH.sub.3), alkyl, hydroxyalkyl, cyanoalkyl, haloalkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, alkylthioalkyl, aralkyl, heteroaralkyl, aminoalkyl or mono- or disubstituted aminoalkyl radical, wherein said substituentsare selected from the group consisting of alkyl, aralkyl, heteroaryl, heteroaralkyl, heterocycloalkyl and heterocycloalkylalkyl radicals; or where said aminoalkyl radical is disubstituted, said substituents along with the nitrogen atom to which they areattached, form a heterocycloalkyl or a heteroaryl radical; and each of R.sup.1' and R.sup.1'' are independently a radical as defined for R.sup.1; or one of R.sup.1' and R.sup.1'' together with R.sup.1 and the carbon atoms to which R.sup.1, R.sup.1' andR.sup.1'' are attached, form a cycloalkyl radical..].

.[.3. The compound of claim 2 or a pharmaceutically acceptable salt or ester thereof, wherein R.sup.2 is an alkyl, aryl, cycloalkyl, cycloalkylalkyl or aralkyl radical, which radical is optionally substituted with a radical selected from thegroup consisting of alkyl, halo and --OR.sup.9, wherein R.sup.9 is a radical selected from the group consisting of hydrogen and alkyl; R.sup.3 is a hydrogen, alkyl, haloalkyl, alkenyl, alkynyl, hydroxyalkyl, alkoxyalkyl, alkylthioalkyl,alkylsulfonylalkyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, heteroaryl, heterocycloalkylalkyl, aryl, aralkyl, heteroaralkyl, aminoalkyl or mono- or dialkyl substituted aminoalkyl radical; R.sup.4 is an alkyl, haloalkyl, alkenyl, alkynyl,hydroxyalkyl, alkoxyalkyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, heteroaryl, heterocycloalkylalkyl, aryl, aralkyl, aralkenyl or heteroaralkyl radical; R.sup.6 is a hydrogen or alkyl radical; x is 1 or 2; t is 0 or 1; and Y is O or S; and Ais an alkoxy, alkenoxy, aralkoxy, alkyl, cycloalkyl, aryl, heterocycloalkyl, heterocycloalkoxy, heterocycloalkylalkyl, heteroaralkoxy, heteroaryl, amino, or mono- or disubstituted amino radical, wherein the substituents are selected from the groupconsisting of alkyl and aralkyl radicals; or is represented by the formula ##STR00832## wherein R is a hydrogen, alkoxycarbonyl, aralkoxycarbonyl, alkylcarbonyl, carboxyalkanoyl, alkanoyl, aroyl, heteroaroyl, alkyl, aralkyl, aminocarbonyl,aminoalkanoyl, or mono- or disubstituted aminocarbonyl or mono- or disubstituted aminoalkanoyl radical, wherein the substituents are selected from the group consisting of alkyl and aralkyl radicals; R' is a hydrogen, alkyl or aralkyl radical orR''SO.sub.2--, wherein R'' is a radical as defined for R.sup.3; or R and R' together with the nitrogen to which they are attached form a heterocycloalkyl or heteroaryl radical; R.sup.1 is a hydrogen, --CO.sub.2CH.sub.3, --CH.sub.2CO.sub.2CH.sub.3,--CO.sub.2H, --CH.sub.2CO.sub.2H, --CH.sub.2CH.sub.2CONH.sub.2, --CH.sub.2CONH.sub.2, --CONH.sub.2, --CH.sub.2C(O)NHCH.sub.3, --CH.sub.2C(O)N(CH.sub.3).sub.2, --CONHCH.sub.3, --CONH(CH.sub.3).sub.2, --CH.sub.2SO.sub.2NH.sub.2,--CH.sub.2CH.sub.2SO.sub.2NH.sub.2, --CH.sub.2S[O]CH.sub.3, --CH.sub.2S [O].sub.2CH.sub.3, --C(CH.sub.3).sub.2(SCH.sub.3), --C(CH.sub.3).sub.2(S[O]CH.sub.3), --C(CH.sub.3).sub.2(S[O].sub.2CH.sub.3), alkyl, hydroxyalkyl, cyanoalkyl, haloalkyl, alkenyl,alkynyl, cycloalkyl, cycloalkylalkyl, alkylthioalkyl, aralkyl, heteroaralkyl, aminoalkyl or mono- or disubstituted aminoalkyl radical, wherein said substituents are selected from the group consisting of alkyl and aralkyl radicals; and R.sup.1' is ahydrogen, alkyl or aralkyl; and R.sup.1'' is a hydrogen, alkyl, --CO.sub.2CH.sub.3 or --CONH.sub.2; or one of R.sup.1' and R.sup.1'' together with R.sup.1 and the carbon atoms to which R.sup.1, R.sup.1' and R.sup.1'' are attached, form a cycloalkylradical..].

.[.4. The compound of claim 3 or a pharmaceutically acceptable salt or ester thereof, wherein R.sup.2 is an alkyl, cycloalkylalkyl or aralkyl radical, which radical is optionally substituted with a radical selected from the group consisting ofalkyl, halo and --OR.sup.9, wherein R.sup.9 is a radical selected from the group consisting of hydrogen and alkyl; R.sup.3 is a hydrogen, alkyl, alkenyl, alkynyl, hydroxyalkyl, alkoxyalkyl, alkylthioalkyl, alkylsulfonylalkyl, cycloalkyl,cycloalkylalkyl, heterocycloalkylalkyl, aryl, aralkyl, heteroaralkyl, aminoalkyl or mono- or dialkyl substituted aminoalkyl radical; R.sup.4 is an alkyl, haloalkyl, alkenyl, alkynyl, hydroxyalkyl, alkoxyalkyl, cycloalkyl, cycloalkylalkyl,heterocycloalkyl, heteroaryl, heterocycloalkylalkyl, aryl, aralkyl, aralkenyl or heteroaralkyl radical; R.sup.6 is a hydrogen or alkyl radical; x is 1 or 2; t is 0 or 1; and Y is O or S; and A is an alkoxy, alkenoxy, aralkoxy, alkyl, cycloalkyl,aryl, heterocycloalkyl, heterocycloalkoxy, heterocycloalkylalkyl, heteroaralkoxy, heteroaryl, amino, or mono- or disubstituted amino radical, wherein the substituents are selected from the group consisting of alkyl and aralkyl radicals; or isrepresented by the formula ##STR00833## wherein R is a hydrogen, alkoxycarbonyl, aralkoxycarbonyl, alkylcarbonyl, carboxyalkanoyl, alkanoyl, aroyl, heteroaroyl, alkyl, aralkyl, aminocarbonyl, aminoalkanoyl, or mono- or disubstituted aminocarbonyl ormono- or disubstituted aminoalkanoyl radical, wherein the substituents are selected from the group consisting of alkyl and aralkyl radicals; R' is a hydrogen, alkyl or aralkyl radical or R''SO.sub.2--, wherein R'' is a radical as defined for R.sup.3; or R and R' together with the nitrogen to which they are attached form a heterocycloalkyl or heteroaryl radical; R.sup.1 is a hydrogen, --CO.sub.2H, --CH.sub.2CO.sub.2H, --CH.sub.2CH.sub.2CONH.sub.2, --CH.sub.2CONH.sub.2, --CONH.sub.2,--CH.sub.2C(O)NHCH.sub.3, --CH.sub.2C(O)N(CH.sub.3).sub.2, --CONHCH.sub.3, --CONH(CH.sub.3).sub.2, --CH.sub.2SO.sub.2NH.sub.2, --CH.sub.2CH.sub.2SO.sub.2NH.sub.2, alkyl, hydroxyalkyl, cyanoalkyl, alkynyl, cycloalkylalkyl, alkylthioalkyl, aralkyl orheteroaralkyl radical; and R.sup.1' is a hydrogen, alkyl or aralkyl; and R.sup.1'' is a hydrogen, alkyl, --CO.sub.2CH.sub.3 or --CONH.sub.2; or one of R.sup.1 and R.sup.1'' together with R.sup.1 and the carbon atoms to which R.sup.1, R.sup.1' andR.sup.1'' are attached, form a cycloalkyl radical..].

.[.5. The compound of claim 4 or a pharmaceutically acceptable salt or ester thereof, wherein R.sup.2 is an alkyl, cycloalkylalkyl or aralkyl radical, which radical is optionally substituted with a radical selected from the group consisting ofalkyl, halo and --OR.sup.9, wherein R.sup.9 is a radical selected from the group consisting of hydrogen and alkyl; R.sup.3 is a hydrogen, alkyl, alkenyl, alkynyl, hydroxyalkyl, alkoxyalkyl, alkylthioalkyl, alkylsulfonylalkyl, cycloalkyl,cycloalkylalkyl, heterocycloalkylalkyl, aryl, aralkyl, heteroaralkyl, aminoalkyl or mono- or dialkyl substituted aminoalkyl radical; R.sup.4 is an alkyl, haloalkyl, alkenyl, alkynyl, hydroxyalkyl, alkoxyalkyl, cycloalkyl, cycloalkylalkyl,heterocycloalkyl, heteroaryl, heterocycloalkylalkyl, aryl, aralkyl, aralkenyl or heteroaralkyl radical; R.sup.6 is a hydrogen or alkyl radical; x is 1 or 2; t is 0 or 1; and Y is O or S; and A is an alkoxy, alkenoxy, aralkoxy, alkyl, cycloalkyl,aryl, heterocycloalkyl, heterocycloalkoxy, heterocycloalkylalkyl, heteroaralkoxy, heteroaryl, amino, or mono- or disubstituted amino radical, wherein the substituents are selected from the group consisting of alkyl and aralkyl radicals; or isrepresented by the formula ##STR00834## wherein R is a hydrogen, alkoxycarbonyl, aralkoxycarbonyl, alkylcarbonyl, carboxyalkanoyl, alkanoyl, aroyl, heteroaroyl, alkyl, aralkyl, aminocarbonyl, aminoalkanoyl, or mono- or disubstituted aminocarbonyl ormono- or disubstituted aminoalkanoyl radical, wherein the substituents are selected from the group consisting of alkyl and aralkyl radicals; R' is a hydrogen, alkyl or aralkyl radical or R''SO.sub.2--, wherein R'' is a radical as defined for R.sup.3; or R and R' together with the nitrogen to which they are attached form a heterocycloalkyl or heteroaryl radical; R.sup.1 is a hydrogen, --CO.sub.2H, --CH.sub.2CO.sub.2H, --CH.sub.2CH.sub.2CONH.sub.2, --CH.sub.2CONH.sub.2, --CONH.sub.2,--CH.sub.2C(O)NHCH.sub.3, --CH.sub.2C(O)N(CH.sub.3).sub.2, --CONHCH.sub.3, --CONH(CH.sub.3).sub.2, --CH.sub.2SO.sub.2NH.sub.2, --CH.sub.2CH.sub.2SO.sub.2NH.sub.2, alkyl, hydroxyalkyl, cyanoalkyl, alkynyl, cycloalkylalkyl, alkylthioalkyl, aralkyl orheteroaralkyl radical; and R.sup.1' is a hydrogen, alkyl or aralkyl; and R.sup.1'' is a hydrogen, alkyl, --CO.sub.2CH.sub.3 or --CONH.sub.2; or one of R.sup.1' and R.sup.1'' together with R.sup.1 and the carbon atoms to which R.sup.1, R.sup.1' andR.sup.1'' are attached, form a cycloalkyl radical; with the proviso that alkyl, alone or in combination, is a straight-chain or branched-chain hydrocarbon radical containing from one to five carbon atoms; alkenyl, alone or in combination, is astraight-chain or branched-chain hydrocarbon radical having at least one double bond and containing from two to five carbon atoms; alkynyl, alone or in combination, is a straight-chain or branched-chain hydrocarbon radical having at least one triplebond and containing from two to five carbon atoms; and cycloalkyl, alone or in combination, is a hydrocarbon ring containing from three to eight carbon atoms; and with the proviso that when R.sup.2 is cycloalkylalkyl and t is 0, R' is a group otherthan alkoxycarbonyl..].

.[.6. The compound of claim 5 or a pharmaceutically acceptable salt or ester thereof, wherein R.sup.2 is butyl, cyclohexylmethyl, benzyl, 4-fluorobenzyl or naphthylmethyl; R.sup.3 is methyl, ethyl, propyl, butyl, pentyl, hexyl, iso-butyl,iso-amyl, 3-methoxypropyl, 3-methylthiopropyl, 4-methylthiobutyl, 4-methylsulfonylbutyl, 2-dimethylaminoethyl, 2-(1-morpholino)ethyl, 4-hydroxybutyl, allyl, propargyl, cyclohexylmethyl, cyclopropylmethyl, phenyl, benzyl, 4-fluorobenzyl, 4-methoxybenzyl,1-phenylethyl, 2-phenylethyl, naphthylmethyl, 3-pyridylmethyl or 4-pyridylmethyl; R.sup.4 is methyl, ethyl, propyl, butyl, ethenyl, chloromethyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, naphthyl, chlorophenyl, fluorophenyl,hydroxyphenyl, methylphenyl, methoxyphenyl, ethoxyphenyl, methylthiophenyl, methylsulfoxyphenyl, methylsulfonylphenyl, acetamidophenyl, methoxycarbonylphenyl, dimethylaminophenyl, nitrophenyl, trifluoromethylphenyl, benzyl, 2-phenylethenyl or thienyl; R.sup.6 is hydrogen; x is 2; t is or 1; and Y is O; and A is methyl, cyclohexyl, cyclopentyl, cycloheptyl, 1,2,3, 4-tetrahydronaphthyl, naphthyl, quinolinyl, indolyl, pyridyl, methylpyridyl, furanyl, thiophenyl, oxazolyl, thiazolyl, phenyl,methylphenyl, ethylphenyl, dimethylphenyl, iso-propylphenyl, chlorophenyl, hydroxyphenyl, methoxyphenyl, methylsulfonylphenyl, methylsulfonylmethylphenyl, carboxyphenyl, aminocarbonylphenyl, methylhydroxyphenyl, methylnitrophenyl, methylaminophenyl,methyl-N,N-dimethylaminophenyl, t-butoxy, benzyloxy, pyridylmethoxy, 3-propenoxy, hydroxypyridylmethoxy, aminopyridylmethoxy, pyrimidinylmethoxy, N-oxo-pyrimidinylmethoxy, thiazolylmethoxy, tetrahydrothiophenoxy, 1,1-dioxotetrahydrothiophenoxy,tetrahydrofuranoxy, methylamino, benzylamino or isopropylamino; or is represented by the formula ##STR00835## wherein R is hydrogen, acetyl, phenoxyacetyl, methoxyacetyl, naphthaloxyacetyl, succinoyl, 2-methylpropionoyl, 2-hydroxypropionoyl,t-butoxycarbonyl, benzyloxycarbonyl, methoxybenzyloxycarbonyl, aminocarbonyl, quinolinylcarbonyl, N-methylglycinyl or N,N-dimethylglycinyl; R' is hydrogen, benzyl or methyl; or R and R' together with the nitrogen to which they are attached formpyrrolyl; R.sup.1 is hydrogen, --CO.sub.2H, --CH.sub.2CO.sub.2H, --CH.sub.2CH.sub.2CONH.sub.2, --CH.sub.2CONH.sub.2, --CONH.sub.2, --CH.sub.2C(O)NHCH.sub.3, --CH.sub.2C(O)N(CH.sub.3).sub.2, --CONHCH.sub.3, --CONH(CH.sub.3).sub.2,--CH.sub.2SO.sub.2NH.sub.2, --CH.sub.2CH.sub.2SO.sub.2NH.sub.2, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, 3-methylbutyl, cyclohexylmethyl, benzyl, hydroxybenzyl, imidazoyl, imidazoylmethyl, cyanomethyl, methylthiomethyl,propargyl or hydroxyethyl; and R.sup.1' is hydrogen, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, benzyl, phenylethyl, phenylpropyl, phenylbutyl or 4,4-diphenylbutyl; and R.sup.1'' is hydrogen, methyl, --CO.sub.2CH.sub.3 or --CONH.sub.2; or oneof R.sup.1' and R.sup.1'' together with R.sup.1 and the carbon atoms to which R.sup.1, R.sup.1' and R.sup.1'' are attached, form cyclobutyl, cyclopentyl or cyclohexyl; with the proviso that when R.sup.2 is cyclohexylmethyl and t is 0, R' is a groupother than t-butoxycarbonyl..].

.[.7. The compound of claim 1 which is: Phenylmethyl[2R-hydroxy-3-[(3-methylbutyl) (methylsulfonyl)amino]-1S-(phenylmethyl)propyl] carbamate; Phenylmethyl[2R-hydroxy-3-[(3-methylbutyl) (phenylsulfonyl)amino]-1S-(phenylmethyl)propyl] carbamate; N1-[2R-hydroxy-3-[(3-methylbutyl)(methylsulfonyl) amino]-1S-(phenylmethyl)propyl]-2S-[(2-quinolinylcarbonyl)amino] butanediamide; N1-[2R-hydroxy-3-[(3-methylbutyl)(methylsulfonyl) amino]-1S-(phenylmethyl)propyl]-2S-[(phenylmethyloxycarbonyl) amino]butanediamide; N1-[2R-hydroxy-3[(3-methylbutyl)(phenylsulfonyl) amino]-1S-(phenylmethyl)propyl]-2S-[(2-quinolinylcarbonyl)amino] butanediamide; N1-[2R-hydroxy-3[(3-methylbutyl)(phenylsulfonyl)amino]-1S-(phenylmethyl)propyl]-2S-[(phenylmethyloxycarbonyl) amino]butanediamide; 2S-[[(dimethylamino)acetyl]amino]-N-[2R-hydroxy-3-[(3-methyl-butyl)(pheny- lsulfonyl)amino]-1S-(phenylmethyl) propyl]-3,3-dimethylbutaneamide; 2S-[[(methylamino)acetyl]amino]-N-[2R-hydroxy-3-[(3-methyl-butyl)(phenyls- ulfonyl)amino]-1S-(phenylmethyl) propyl]-3,3-dimethylbutaneamide; N1-[2R-hydroxy-3-[(3-methylbutyl)(phenyl-sulfonyl)amino]-N4-methyl-1S-(phenylmethyl)propyl]-2S-[(2-quinolinylcarbonyl)amino- ]butanediamide; [3-[[2-hydroxy-3-[N-(3-methylbutyl)-N-(phenylsufonyl) amino]-1-(phenylmethyl)propyl]amino]-2-methyl-3-oxopropyl]-, (4-methoxyphenyl)methyl ester, [1S-[1R*(S*),2S*]]-; Carbamic acid, [2R-hydroxy-3-[(4-hydroxyphenylsulfonyl) (2-methylpropyl)amino]-1S-(phenylmethyl)propyl-, 3(S)-1,1-dioxotetrahydrothiophen-3-yl-ester; Carbamic acid, [2R-hydroxy-3-[(4-methoxyphenylsulfonyl)(2-methylpropyl)amino]-1S-(phenylmethyl)propyl-, 3(S)-1,1-dioxotetrahydrothiophen-3-yl-ester; Carbamic acid, [2R-hydroxy-3-[(4-methoxyyphenylsulfonyl) (2-methylpropyl)amino]-1S-(phenylmethyl)propyl-, 3-S-tetrahydrothiophen-3-yl-ester; Carbamic acid,[2R-hydroxy-3-[(4-hydroxyphenylsulfonyl) (2-methylpropyl)amino]-1S-(phenylmethyl)propyl-, 3-S-tetrahydrothiophen-3-yl-ester; Carbamic acid, [2R-hydroxy-3-[(4-hydroxyphenylsulfonyl) (2-methylpropyl)amino]-1S-(phenylmethyl)propyl-,3-S-tetrahydrofuran-3-yl-ester; Carbamic acid, [2R-hydroxy-3-[(4-methoxyphenylsulfonyl) (2-methylpropyl)amino]-1S-(phenylmethyl)propyl-, 3-S-tetrahydrofuran-3-yl-ester; Carbamic acid, [2R-hydroxy-3-[[(4-methoxyphenyl)sulfonyl](2-methylpropyl)amino]-1S-(phenylmethyl) propyl]-, 5-(thiazolyl)methyl ester; Carbamic acid, [2R-hydroxy-3-[[(4-hydroxyphenyl) sulfonyl](2-methylpropyl)amino]-1S-(phenylmethyl) propyl]-, 5-(thiazolyl)methyl ester; Benzamide,N-[2R-hydroxy-3-[[(4-hydroxyphenyl) sulfonyl](2-methylpropyl)amino]-1S-(phenylmethyl) propyl]-2-methyl; Carbamic acid, [2R-hydroxy-3-[[(4-methoxyphenyl) sulfonyl](2-methylpropyl)amino]-1S-(phenylmethyl) propyl]-, 3-(6-aminopyridyl)methyl ester; Carbamic acid, [2R-hydroxy-3-[[(4-hydroxyphenyl) sulfonyl](2-methylpropyl)amino]-1S-(phenylmethyl) propyl]-, 3-(6-aminopyridyl)methyl ester; Carbamic acid, [2R-hydroxy-3-[[(4-methoxyphenyl) sulfonyl] (2-methylpropyl)amino]-1S-(phenylmethyl) propyl]-,3-(6-hydroxypyridyl)methyl ester; Carbamic acid, [2R-hydroxy-3-[[(4-hydroxyphenyl) sulfonyl] (2-methylpropyl)amino]-1S-(phenylmethyl) propyl]-, 5-pyrimidylmethyl ester; or Benzamide, N-[2R-hydroxy-3-[[(4-methoxyphenyl) sulfonyl](2-methylpropyl)amino]-1S-(phenylmethyl) propyll-2-methyl..].

.[.8. A pharmaceutical composition comprising a compound of claim 1 and a pharmaceutically acceptable carrier..].

.[.9. Method of treating a retroviral infection comprising administering an effective amount of a composition of claim 8..].

.[.10. Method of inhibiting a retroviral protease comprising administering an effective amount of a compound of claim 1..].

.[.11. Method of inhibiting replication of a retrovirus comprising administering an effective amount of a compound of claim 1..].

.[.12. A compound represented by the formula: ##STR00836## or a pharmaceutically acceptable salt[, prodrug] or ester thereof, wherein each of P.sup.1 and P.sup.2 independently represent hydrogen, alkoxycarbonyl, aralkoxycarbonyl, alkylcarbonyl,cycloalkylcarbonyl, cycloalkylalkoxycarbonyl, cycloalkylalkanoyl, alkanoyl, aralkanoyl, aroyl, aryloxycarbonyl, aryloxycarbonylalkyl, aryloxyalkanoyl, heterocyclylcarbonyl, heterocyclyloxycarbonyl, heterocyclylalkanoyl, heterocyclylalkoxycarbonyl,heteroaralkanoyl, heteroaralkoxycarbonyl, heteroaryloxycarbonyl, heteroaroyl, alkyl, alkenyl, cycloalkyl, aryl, aralkyl, aryloxyalkyl, heteroaryloxyalkyl, hydroxyalkyl, aminocarbonyl, aminoalkanoyl, or mono- or disubstituted aminocarbonyl or mono- ordisubstituted aminoalkanoyl radical, wherein the substituents are selected from the group consisting of alkyl, aryl, aralkyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroaralkyl, heterocycloalkyl and heterocycloalkyalkyl radicals; or where saidaminoalkanoyl radical is disubstituted, said substituents along with the nitrogen atom to which they are attached form a heterocycloalkyl or heteroaryl radical; R.sup.2 is an alkyl, aryl, cycloalkyl, cycloalkylalkyl or aralkyl radical, which radicalsare optionally substituted with a group selected from alkyl and halogen radicals, nitro, cyano, CF.sub.3, --OR.sup.9, --SR.sup.9, wherein R.sup.9 is a hydrogen or alkyl radical; R.sup.3 is a hydrogen, alkyl, haloalkyl, alkenyl, alkynyl, hydroxyalkyl,alkoxyalkyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, heteroaryl, heterocycloalkylalkyl, aryl, aralkyl, heteroaralkyl, aminoalkyl or mono- or disubstituted aminoalkyl radical, wherein said substituents are selected from the group consisting ofalkyl, aryl, aralkyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroaralkyl, heterocycloalkyl and heterocycloalkylalkyl radicals; or where the aminoalkyl radical is disubstituted, said substituents along with the nitrogen atom to which they areattached, form a heterocycloalkyl or a heteroaryl radical; and R.sup.4 is a radical as defined by R.sup.3 except for hydrogen; and wherein alkyl, alone or in combination. is a straight-chain or branched-chain hydrocarbon radical containing from 1 to 8carbon atoms; alkenyl, alone or in combination, is a straight-chain or branched-chain hydrocarbon radical having at least one double bond and containing from 2 to 8 carbon atoms; alkynyl, alone or in combination, is a straight-chain or branched-chainhydrocarbon radical having at least one triple bond and containing from 2 to 10 carbon atoms; cycloalkyl, alone or in combination, is a hydrocarbon ring containing from 3 to 8 carbon atoms; aryl, alone or in combination, means a phenyl or naphthylradical which optionally carries one or more alkyl, alkoxy, halogen, hydroxy, amino, nitro, cyano, haloalkyl, carboxy, alkoxycarbonyl, cycloalkyl, heterocycloalkyl, amido, alkylamino, dialkylamino, alkylamido or dialkylamido radicals; heterocyclyl andheterocycloalkyl, alone or in combination, mean a saturated or partially unsaturated monocyclic, bicyclic or tricyclic heterocycle having 3 to 12 ring members, which contains at least one nitrogen, oxygen, sulphur, sulfone, sulfoxide or N-oxide of atertiary nitrogen heteroatom ring member, and which is optionally substituted on one or more carbon atoms by halogen, alkyl, alkoxy, hydroxy, oxo or aryl, or on a secondary nitrogen atom by hydroxy, alkyl, aralkoxycarbonyl, alkanoyl, phenyl orphenylalkyl; and heteroaryl, alone or in combination, means an aromatic monocyclic, bicyclic, or tricyclic heterocycloalkyl radical which is optionally substituted as defined above with respect to the definitions of aryl and heterocycloalkyl..].

.[.13. The compound of claim 12, wherein each of P.sup.1 and P.sup.2 independently represent a hydrogen, alkoxycarbonyl, aralkyloxycarbonyl, heteroaralkoxycarbonyl, aroyl, heteroaroyl, alkanoyl or cycloalkanoyl radical; R.sup.2 is acycloalkylalkyl, aralkyl or alkyl radical; R.sup.3 is an alkyl, cycloalkyl or cycloalkylalkyl radical; and R.sup.4 is an aryl, alkyl, heteroaryl or aryl radical..].

.[.14. The compound of claim 13, wherein P.sup.1 and P.sup.2 independently represent hydrogen, 3-pyridylmethyloxycarbonyl, 3-pyridylmethyloxycarbonyl N-oxide, 4-pyridylmethyloxycarbonyl, 4-pyridylmethyloxycarbonyl N-oxide,5-pyrimidylmethyloxycarbonyl, tert-butyloxycarbonyl, allyloxycarbonyl, 2-propyloxycarbonyl, benzyloxycarbonyl, cycloheptylcarbonyl, cyclohexylcarbonyl, cyclopentylcarbonyl, benzoyl, 4-pyridylcarbonyl, 2-methylbenzoyl, 3-methylbenzoyl, 4-methylbenzoyl,2-chlorobenzoyl, 2-ethylbenzoyl, 2,6-dimethylbenzoyl, 2,3-dimethylbenzoyl, 2,4-dimethylbenzoyl or 2,5-dimethylbenzoyl; R.sup.2 is benzyl, cyclohexylmethyl, 2-naphthylmethyl, para-fluorobenzyl, para-methoxybenzyl, isobutyl or n-butyl; R.sup.3 isisobutyl, isoamyl, cyclohexyl, cyclohexylmethyl, n-butyl or n-propyl; and R.sup.4 is phenyl, para-methoxyphenyl, para-cyanophenyl, para-chlorophenyl, para-hydroxyphenyl, para-nitrophenyl, para-fluorophenyl, 2-naphthyl, 3-pyridyl, 3-pyridyl N-oxide,4-pyridyl or 4-pyridyl N-oxide; with the proviso that when R.sup.2 is cyclohexylmethyl, each of P.sup.1 and P.sup.2 independently represent a group other than tert-butyloxycarbonyl..].

.[.15. A compound of claim 12 which is: Phenylmethyl[2R-hydroxy-3-[(2-methylpropyl) (phenylsulfonyl)amino]-1S-(phenylmethyl)propyl] carbamate; Phenylmethyl[2R-hydroxy-3-[(2-methylpropyl)(4-methoxyphenylsulfonyl)amino- ]-1S-(phenylmethyl)propyl]carbamate; Phenylmethyl[2R-hydroxy-3-[(2-methylpropyl)(4-fluorophenylsulfonyl)amino]- -1S-(phenylmethyl) propyl] carbamate; Phenylmethyl[2R-hydroxy-3-[(2-methylpropyl)(4-nitrophenylsulfonyl)amino]-- 1S-(phenylmethyl)propyl] carbamate; Phenylmethyl[2R-hydroxy-3-[(2-methylpropyl)(4-chlorophenylsulfonyl)amino]- -1S-(phenylmethyl) propyl] carbamate; Phenylmethyl[2R-hydroxy-3-[(2-methylpropyl)(4-acetamidophenylsulfonyl)ami- no]-1S-(phenylmethyl) propyl]carbamate; Phenylmethyl[2R-hydroxy-3-[(2-methylpropyl)(4-aminophenylsulfonyl)ano]-1S- -(phenylmethyl) -propyl] carbamate; Phenylmethyl[2R-hydroxy-3-[(3-methylbutyl)(4-methoxyphenylsulfonyl)amino]- -1S-(phenylmethyl) propyl]carbamate; Phenylmethyl[2R-hydroxy-3-[(3-methylbutyl)(4-fluorophenyl sulfonyl)amino]-1S-(phenylmethyl)propyl] carbamate; Phenylmethyl[2R-hydroxy-3-[(3-methylbutyl)(4-nitrophenyl sulfonyl)amino]-1S-(phenylmethyl)propyl] carbamate; Phenylmethyl[2R-hydroxy-3-[(3-methylbutyl)(4-chlorophenyl sulfonyl)amino]-1S-(phenylmethyl)propyl] carbamate; Phenylmethyl[2R-hydroxy-3-[(2-methylpropyl)(4-methoxyphenyl sulfonyl)amino]-1S-(4-fluorophenylmethyl) propyl]carbamate; Phenylmethyl[2R-hydroxy-3-[(2-methylpropyl)(4-fluorophenylsulfonyl)amino]- -1S-(4-fluorophenylmethyl) propyl]carbamate; Phenylmethyl[2R-hydroxy-3-[(butyl)(phenylsulfonyl) amino]-1S-(phenylmethyl)propyl]carbamate; Phenylmethyl[2R-hydroxy-3-[(cyclohexylmethyl)(phenyl sulfonyl)amino]-1S-(phenylmethyl)propyl]carbamate; Phenylmethyl[2R-hydroxy-3-[(cyclohexyl)(phenylsulfonyl) amino]-1S-(phenylmethyl)propyl]carbamate; Phenylmethyl[2R-hydroxy-3-[(propyl)(phenylsulfonyl) amino]-1S-(phenylmethyl)propyl]carbamate; Pentanamide, 2S-[[(dimethylamino)acetyl]amino]-N-2R-hydroxy-3-[(3-methylpropyl)(4-meth- oxyphenylsulfonyl) amino]-1S-(phenylmethyl)propyl]-3S-methyl; Pentanamide, 2S-[[(methylamino)acetyl]amino]-N-2R-hydroxy-3-[(4-methylbutyl)(phenylsul- fonyl)amino]-1S-(phenylmethyl)propyl]-3S-methyl; Pentanamide, 2S-[[(dimethylamino)acetyl]amino]-N-2R-hydroxy-3-[(4-methylbutyl)(phenyls-ulfonyl)amino]-1S-(phenylmethyl)propyl]-3S-methyl; [2R-hydroxy-3-[[(4-methoxyphenyl)sulfonyl](2-methylpropyl)amino]-1S-(phen- ylmethyl)propylamine; 2R-hydroxy-3-[(2-methylpropyl)(4-hydroxyphenyl) sulfonyl] amino-1S-(phenylmethyl)propylamine; [2R-hydroxy-3-[(phenylsulfonyl)(3-methylbutyl)amino]-1S-(phenylmethyl)pro- pylamine; [2R-hydroxy-3-[(phenylsulfonyl)(2-methylpropyl)amino]-1S-(phenyl- methyl)propylamine; [2R-hydroxy-3-[(phenylsulfonyl)(cyclohexylmethyl)amino]-1S-(phenylmethyl)propylamine; [2R-hydroxy-3-[(phenylsulfonyl)(cyclohexyl)amino]-1S-(phenylmethyl)propyl- amine; 4-Pyridinecarboxamide, N-[2R-hydroxy-3-[[(4-methoxyphenyl)sulfonyl](2-methylpropyl)amino]-1S-(ph- enylmethyl)propyl]; Benzamide,N-[2R-hydroxy-3-[[(4-methoxyphenyl) sulfonyl] (2-methylpropyl)amino]-1S-(phenylmethyl) propyl]-2,6-dimethyl; Benzamide, N-[2R-hydroxy-3-[[(4-methoxyphenyl) sulfonyl] (2-methylpropyl)amino]-1S-(phenylmethyl) propyl]-2-methyl; Benzamide,N-[2R-hydroxy-3-[[(4-methoxyphenyl) sulfonyl] (2-methylpropyl)amino]-1S-(phenylmethyl) propyl]-2-ethyl; Benzamide, N-[2R-hydroxy-3-[[(4-methoxyphenyl) sulfonyl] (2-methylpropyl)amino]-1S-(phenylmethyl) propyl]-2-chloro; Carbamic acid,[2R-hydroxy-3-[[(4-methoxyphenyl) sulfonyl] (2-methylpropyl)amino]-1S-(phenylmethyl) propyl]-, 3-pyridylmethyl ester; Carbamic acid, [2R-hydroxy-3-[[(4-methoxyphenyl) sulfonyl] (2-methylpropyl)amino]-1S-(phenylmethyl) propyl]-, 3-pyridylmethyl ester,N-oxide; Carbamic acid, [2R-hydroxy-3-[[phenylsulfonyl](2-methylpropyl)amino]-1S-(phenylmethyl)pr- opyl]-, 3-pyridylmethyl ester; Carbamic acid, [2R-hydroxy-3-[[(4-methoxyphenyl) sulfonyl] (2-methylpropyl)amino]-1S-(phenylmethyl) propyl]-,4-pyridylmethyl ester; Carbamic acid, [2R-hydroxy-3-[[(4-methoxyphenyl) sulfonyl] (2-methylpropyl)amino]-1S-(phenylmethyl) propyl]-, 4-pyridylmethyl ester, N-oxide; Carbamic acid, [2R-hydroxy-3-[[(4-chlorophenyl)sulfonyl](2-methylpropyl)amino]-1S-(phenylmethyl)propyl]-, 3-pyridylmethyl ester; Carbamic acid, [2R-hydroxy-3-[[(4-nitrophenyl)sulfonyl] (2-methylpropyl)amino]-1S-(phenylmethyl)propyl]-, 3-pyridylmethyl ester; Carbamic acid,[2R-hydroxy-3-[[(4-fluorophenyl)sulfonyl] (2-methylpropyl)amino]-1S-(phenylmethyl)propyl]-, 3-pyridylmethyl ester; Carbamic acid, [2R-hydroxy-3-[[(4-hydroxyphenyl) sulfonyl] (2-methylpropyl)amino]-1S-(phenylmethyl) propyl]-, 3-pyridylmethyl ester; orCarbamic acid, [2R-hydroxy-3-[[(4-methoxyphenyl) sulfonyl] (2-methylpropyl)amino]-1S-(phenylmethyl) propyl]-, 5-pyrimidylmethyl ester..].

.[.16. A compound of claim 12 which is: Carbamic acid, [2R-hydroxy-3-[[(4-methoxyphenyl) sulfonyl] (methylpropyl)amino]-1S-(phenylmethyl) propyl]-, 5-thiazolylmethyl ester; Carbamic acid, [2R-hydroxy-3-[[(4-hydroxyphenyl) sulfonyl](2-methylpropyl)amino]-1S-(phenylmethyl) propyl-, 5-thiazolylmethyl ester; Carbamic acid, [2R-hydroxy-3-[[(4-methoxyphenyl) sulfonyl] (2-methylpropyl)amino]-1S-(phenylmethyl) propyl-, 3-furanylmethyl ester; Benzamide,N-[2R-hydroxy-3-[[(4-methoxyphenyl) sulfonyl] (2-methylpropyl)amino]-1S-(phenylmethyl) propyl]-3-hydroxy-2-methyl; 2R-hydroxy-3-[[(4-aminophenyl)sulfonyl](2-methylpropyl) amino]-1S-(phenylmethyl)propylamine; Carbamic acid,2R-hydroxy-3-[[(4-aminophenyl)sulfonyl] (2-methylpropyl)amino]-1S-(phenylmethyl)propyl-, 3-furanylmethyl ester; Carbamic acid, 2R-hydroxy-3-[[(4-aminophenyl)sulfonyl] (2-methylpropyl)amino]-1S-(phenylmethyl)propyl-, 5-thiazolylmethyl ester; Benzamide,N-[2R-hydroxy-3-[[(4-aminophenyl)sulfonyl] (2-methylpropyl)amino]-1S-(phenylmethyl)propyl]-2-methyl; Benzamide, N-[2R-hydroxy-3-[[(4-aminophenyl)sulfonyl] (2-methylpropyl)amino]-1S-(phenylmethyl)propyl]-3-hydroxy-2-methyl; Carbamic acid,2R-hydroxy-3-[[(2-aminobenzothiazol-6-yl) sulfonyl](2-methylpropyl)amino]-1S-(phenylmethyl) propyl-, phenylmethyl ester; Carbamic acid, 2R-hydroxy-3-[[(benzothiazol-6-yl) sulfonyl](2-methylpropyl)amino]-1S-(phenylmethyl) propyl-, phenylmethyl ester; 2R-hydroxy-3-[[(3-aminophenyl)sulfonyl](2-methylpropyl) amino]-1S-(phenylmethyl)propylamine; Carbamic acid, 2R-hydroxy-3-[[(3-aminophenyl)sulfonyl] (2-methylpropyl)amino]-1S-(phenylmethyl)propyl-, 5-thiazolylmethyl ester; Benzamide,N-[2R-hydroxy-3-[[(3-aminophenyl)sulfonyl] (2-methylpropyl)amino]-1S-(phenylmethyl)propyl]-3-hydroxy-2-methyl; Carbamic acid, 2R-hydroxy-3-[[(2-amino benzothiazol-5-yl) sulfonyl](2-methylpropyl)amino]-1S-(phenylmethyl) propyl-, phenylmethyl ester; Carbamic acid, 2R-hydroxy-3-[[(2-aminobenzothiazol-7-yl) sulfonyl] (2-methylpropyl)amino]-1S-(phenylmethyl) propyl-, phenylmethyl ester; 2R-hydroxy-3-[[(2,3-dihydrobenzofuran-5-yl)sulfonyl](2-methylpropyl)amino- ]-1S-(phenylmethyl) propylamine; Carbamic acid, [2R-hydroxy-3-[[(2,3-dihydrobenzofuran-5-yl)sulfonyl](2-methylpropyl)amin- o]-1S-(phenylmethyl) propyl-, 3-pyridylmethyl ester; Carbamic acid, [2R-hydroxy-3-[[(2,3-dihydrobenzofuran-5-yl)sulfonyl](2-methylpropyl)amin- o]-1S-(phenylmethyl)propyl-, 5-thiazolylmethyl ester; Benzamide, N-[2R-hydroxy-3-[[(2,3-dihydrobenzofuran-5-yl) sulfonyl](2-methylpropyl)amino]-1S-(phenylmethyl) propyl]-3-amino-2-methyl-; 2R-hydroxy-3-[[(1,3-benzodioxol-5-yl)sulfonyl](2-methylpropyl)amino]-1S-(-phenylmethyl) propylamine; Carbamic acid, 2R-hydroxy-3-[[(1,3-benzodioxol-5-yl) sulfonyl](2-methylpropyl)amino]-1S-(phenylmethyl) propyl-, 3-pyridylmethyl ester; Carbamic acid, 2R-hydroxy-3-[[(1,3-benzodioxol-5-yl)sulfonyl](2-methylpropyl)amino]-1S-(phenylmethyl) propyl-, 5-thiazolylmethyl ester; Benzamide, N-[2R-hydroxy-3-[[(1,3-benzodioxol-5-yl) sulfonyl](2-methylpropyl)amino]-1S-(phenylmethyl) propyl]-3-amino-2-methyl; Benzamide,N-[2R-hydroxy-3-[[(1,3-benzodioxol-5-yl) sulfonyl](2-methylpropyl)amino]-1S-(phenylmethyl) propyl]-4-hydroxy-2-methyl; Benzamide, N-[2R-hydroxy-3-[[(1,3-benzodioxol-5-yl) sulfonyl](2-methylpropyl)amino]-1S-(phenylmethyl) propyl]-3-hydroxy-2-methyl; N-[2R-hydroxy-3-[[(4-methoxyphenyl) sulfonyl](2-methylpropyl)amino]-1S-(phenylmethyl)propyl]-(2,6-dimethylphe- noxy)acetamide; N-[2R-hydroxy-3-[[(4-methoxyphenyl)sulfonyl](2-methylpropyl)amino]-1S-(ph- enylmethyl)propyl]-(2-methylphenoxy)acetamide; N-[2R-hydroxy-3-[[(4-methoxyphenyl) sulfonyl](2-methylpropyl)amino]-1S-(phenylmethyl)propyl]-2-(2,6-dimethylp- henylamino)acetamide; or N-[2R-hydroxy-3-[[(4-methoxyphenyl) sulfonyl](2-methylpropyl)amino]-1S-(phenylmethyl)propyl]-2-aminobenzothia-zole-6-carboxamide..].

.[.17. A compound represented by the formula: ##STR00837## or a pharmaceutically acceptable salt or ester thereof, wherein R.sup.2 is an alkyl, aryl, cycloalkyl, cycloalkylalkyl or aralkyl radical, which radical is optionally substituted with aradical selected from the group consisting of alkyl, halo, nitro, cyano, CF.sub.3, --OR.sup.9, and --SR.sup.9, wherein R.sup.9 is a radical selected from the group consisting of hydrogen and alkyl; R.sup.3 is a hydrogen, alkyl, haloalkyl, alkenyl,alkynyl, hydroxyalkyl, alkoxyalkyl, alkylthioalkyl, alkylsulfonylalkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, aminoalkyl or mono- or disubstituted aminoalkyl radical, wherein said substituents are selected from the group consisting of alkyl, aryl,aralkyl, cycloalkyl, and cycloalkylalkyl radicals; R.sup.4 is an alkyl, haloalkyl, alkenyl, alkynyl, hydroxyalkyl, alkoxyalkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, aralkenyl, aminoalkyl, mono- or disubstituted aminoalkyl radical, wherein saidsubstituents are selected from the group consisting of alkyl, aryl, aralkyl, cycloalkyl, and cylcloalkylalkyl; and a saturated or partially unsaturated monocyclic, bicyclic or tricyclic heterocycle having 3 to 12 ring members, which contains at leastone nitrogen, oxygen, sulphur, sulfone, sulfoxide or N-oxide or a tertiary nitrogen heteroatom ring member, and which is optionally substituted on one or more carbon atoms by halogen, alkyl, alkoxy, hydroxy, oxo or aryl, or on a secondary nitrogen atomby hydroxy, alkyl, aralkoxycarbonyl, alkanoyl, phenyl or phenylalkyl; or an aromatic monocyclic, bicyclic, or tricyclic heterocycloalkyl radical which is optionally substituted with one or more alkyl, alkoxy, halogen, hydroxy, amino nitro, cyano,haloalkyl, carboxy, alkoxycarbonyl, cycloalkyl, amido, alkylamino, dialkylamino, alkylamido or dialkylamido radicals; R.sup.6 is a hydrogen or alkyl radical; x is 2; t is 0 or 1; Y is O; and A is an alkoxy, alkenoxy, aralkoxy, alkyl, cycloalkyl,cycloalkylalkoxy, cycloalkylalkyl, aralkyl, aryl, aryloxy, alkenyl, aryloxyalkyl, hydroxyalkyl, amino, or mono- or disubstituted amino radical, wherein the substituents are selected from the group consisting of alkyl, aryl, aralkyl, cycloalkyl, andcycloalkylalkyl radicals, or is represented by the formula ##STR00838## wherein R is a hydrogen, alkoxycarbonyl, aralkoxycarbonyl, alkylcarbonyl, cycloalkylcarbonyl, cycloalkylalkoxycarbonyl, cycloalkylalkanoyl, carboxyalkanoyl, alkanoyl, aralkanoyl,aroyl, aryloxycarbonyl, aryloxycarbonylalkyl, aryloxyalkanoyl, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, aralkyl, aryloxyalkyl, hydroxyalkyl, aminocarbonyl, aminoalkanoyl, or mono- or disubstituted aminocarbonyl or mono- or disubstituted aminoalkanoylradical, wherein the substituents are selected from the group consisting of alkyl, aryl, aralkyl, cycloalkyl, and cycloalkylalkyl radicals; R.sup.1 is a radical as defined for R.sup.3 or R''SO.sub.2--, wherein R'' is a radical as defined for R.sup.3; R.sup.1 is a hydrogen, --CO.sub.2CH.sub.3, --CH.sub.2CO.sub.2CH.sub.3, --CO.sub.2H, --CH.sub.2CO.sub.2H, --CH.sub.2CH.sub.2CONH.sub.2, --CH.sub.2CONH.sub.2, --CONH.sub.2, --CH.sub.2(O)NHCH.sub.3, --CH.sub.2CH.sub.2SO.sub.2NH.sub.2,--CH.sub.2S[O]CH.sub.3, CH.sub.2S[O].sub.2CH.sub.3, --C(CH.sub.3).sub.2(SCH.sub.3), --C(CH.sub.3).sub.2(S[O]CH.sub.3), --C(CH.sub.3).sub.2(S[O].sub.2CH.sub.3), alkyl, hydroxyalkyl, cyanoalkyl, haloalkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl,alkylthioalkyl, aralkyl, aminoalkyl or mono- or disubstituted animoalkyl radical, wherein said substituents are selected from the group consisting of alkyl, aryal, aralkyl, cycloalkyl, and cycloalkylalkyl radicals; and each of R.sup.1' and R.sup.1'' areindependently a radical as defined for R.sup.1; or one of R.sup.1' and R.sup.1'' together with R.sup.1 and the carbon atoms to which R.sup.1, R.sup.1' and R.sup.1'' are attached, form a cycloalkyl radical; and wherein alkyl, alone or in combination, isa straight-chain or branched-chain hydrocarbon radical containing from 1 to 8 carbon atoms; alkenyl, alone or in combination, is a straight-chain or branched-chain hydrocarbon radical having at least one double bond and containing form 2 to 8 carbonatoms; alkynyl, alone or in combination, is a straight-chain or branched-chain hydrocarbon radical having at least one triple bond and containing form 2 to 10 carbon atoms; cycloalkyl, alone or in combination, is a hydrocarbon ring containing from 3 to8 carbon atoms; aryl, alone or in combination, means a phenyl or napthyl radical which optionally carries one or more alkyl, alkoxy, halogen, hydroxy, amino, nitro, cyano, haloalkyl, carboxy, alkoxycarbonyl, cycloalkyl, amido, alkylamino, dialkylamino,alkylamido or dialkylamido radicals; a saturated or partially unsaturated monocyclic, bicyclic or tricyclic heterocycle having 3 to 12 ring members, which contains at least one nitrogen, oxygen, sulphur, sulfone, sulfoxide or N-oxide or a tertiarynitrogen heteroatom ring member, and which is optionally substituted on one or more carbon atoms by halogen alkyl, alkoxy, hydroxy, oxo or aryl, or on a secondary nitrogen atom by hydroxy, alkyl, aralkoxycarbonyl, alkanoyl, phenyl or phenylalkyl; or anaromatic monocyclic, bicyclic, or tricyclic heterocycloalkyl radical which is optionally substituted with one or more alkyl, alkoxy, halogen, hydroxy, amino nitro, cytano, haloalkyl, carboxy, alkoxycarbonyl, cycloalkyl, amido, alkylamino, dialkylamino,alkylamido or dialkylarnido radicals..].

.[.18. The compound of claim 17 or a pharmaceutically acceptable salt or ester thereof, wherein R.sup.2 is an aralkyl radical, which is optionally substituted with a radical selected from the group consisting of alkyl, halo and --OR.sup.9,wherein R.sup.9 is a radical selected from the group consisting of hydrogen and alkyl; R.sup.3 is a hydrogen, alkyl, aryl, or aralkyl radical; R.sup.4 is an alkyl, haloalkyl, alkenyl, alkynyl, hydroxyalkyl, alkoxyalkyl, cycloalkyl, cycloalkylalkyl,aryl, aralkyl, aralkenyl, a saturated or partially unsaturated monocyclic, bicyclic or tricyclic heterocycle having 3 to 12 ring members, which contains at least one nitrogen, oxygen, sulphur, sulfone, sulfoxide or N-oxide or a tertiary nitrogenheteroatom ring member, and which is optionally substituted on one or more carbon atoms by halogen, alkyl, alkoxy, hydroxy, oxo or aryl, or on a secondary nitrogen atom by hydroxy, alkyl, aralkoxycarbonyl, alkanoyl, phenyl or phenylalkyl; or an aromaticmonocyclic, bicyclic, or tricyclic heterocycloalkyl radical which is optionally substituted with one or more alkyl, alkoxy, halogen, hydroxy, amino, nitro, cyano, haloalkyl, carboxy, alkoxycarbonyl, cycloalkyl, amido, alkylamino, dialkylamino, alkylamidoor dialkylamido radicals; R.sup.6 is a hydrogen or alkyl radical; t is 0 or 1; and A is an alkoxy, alkenoxy, aralkoxy, alkyl, cycloalkyl, aryl, amino, or mono- or disubstituted amino radical, wherein the substituents are selected from the groupconsisting of alkyl and aralkyl radicals..].

.[.19. A compound represented by the formula: ##STR00839## or a pharmaceutically acceptable salt or ester thereof, wherein A is a phenyl or napthyl radical which is optionally substituted with one or more alkyl, alkoxy, halogen, hydroxy, amino,nitro, cyano, haloalkyl, carboxy, alkoxycarbonyl, cycloalkyl, amido, alkylamino, dialkylamino, alkylamido or dialkylamido radicals; R.sup.2 is an aralkyl radical, which is optionally substituted with a radical selected from the group consisting ofalkyl, halo, nitro, cyano, --CF.sub.3, --OR.sup.9 and --SR.sup.9, wherein R.sup.9 is a radical selected from the group consisting of hydrogen and alkyl; R.sup.3 is an alkyl, and R.sup.4 is an aromatic monocyclic, bicyclic or tricyclic heterocycle whichcontains at least one nitrogen, oxygen or sulfur and which is optionally substituted on one or more carbon atoms by halogen, alkyl, alkoxy, hydroxy, oxo or aryl, or on a secondary nitrogen atom by hydroxy, alkyl, aralkoxycarbonyl, alkanoyl, phenyl orphenylalkyl..].

.[.20. pharmaceutical composition comprising a compound of claim 19 and a pharmaceutically acceptable carrier..].

.[.21. Method of treating a retroviral infection comprising administering an effective amount of a composition of claim 20..].

.[.22. Method of inhibiting a retroviral protease comprising administering an effective amount of a compound of claim 19..].

.[.23. Method of inhibiting replication of a retrovirus comprising administering an effective amount of a compound of claim 19..].

.Iadd.24. A method of treating human immunodeficiency virus (HIV-1) infection in a patient comprising administering to the patient a therapeutically effective amount of a compound of the following formula ##STR00840## .Iaddend.

.Iadd.25. A method of treating human immunodeficiency virus (HIV-1) infection in a patient comprising co-administering to the patient a therapeutically effective amount of a first antiviral compound of the following formula ##STR00841## with atherapeutically effective amount of a second antiviral compound. .Iaddend.

.Iadd.26. The method of claim 25, wherein the second antiviral compound is an antiretroviral compound. .Iaddend.

.Iadd.27. A method of treating a retroviral infection in a patient comprising administering to the patient a therapeutically effective amount of a compound of the following formula ##STR00842## .Iaddend.

.Iadd.28. A method of inhibiting a retroviral protease in a patient comprising administering to the patient a therapeutically effective amount of a compound of the following formula ##STR00843## .Iaddend.

.Iadd.29. A method of inhibiting replication of a retrovirus in a patient comprising administering to the patient a therapeutically effective amount of a compound of the following formula ##STR00844## .Iaddend.

.Iadd.30. A method of treating human immunodeficiency virus (HIV-1) infection in a patient comprising administering to the patient a pharmaceutical composition comprising a pharmaceutically acceptable carrier and a therapeutically effectiveamount of a compound, or pharmaceutically acceptable salt or ester thereof, of the following formula: ##STR00845## .Iaddend.

.Iadd.31. A method of treating human immunodeficiency virus (HIV-1) infection in a patient comprising co-administering to the patient a pharmaceutical composition comprising a pharmacetuically acceptable carrier and a therapeutically effectiveamount of a first antiviral compound, or pharmaceutically acceptable salt or ester thereof, of the following formula ##STR00846## with a therapeutically effective amount of a second antiviral compound. .Iaddend.

.Iadd.32. The method of claim 31, wherein the second antiviral compound is an antiretroviral compound. .Iaddend.

.Iadd.33. A method of treating a retroviral infection in a patient comprising administering to the patient a pharmaceutical composition comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound, orpharmaceutically acceptable salt or ester thereof, of the following formula ##STR00847## .Iaddend.

.Iadd.34. A method of inhibiting a retroviral protease in a patient comprising administering to the patient a pharmaceutical composition comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound, orpharmaceutically acceptable salt or ester thereof, of the following formula ##STR00848## .Iaddend.

.Iadd.35. A method of inhibiting replication of a retrovirus in a patient comprising administering to the patient pharmaceutical composition comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound,or pharmaceutically acceptable salt or ester thereof, of the following formula ##STR00849## .Iaddend.

.Iadd.36. A method of treating human immunodeficiency virus (HIV-1) infection in a patient comprising administering to the patient a pharmaceutical composition comprising a pharmaceutically acceptable carrier and a therapeutically effectiveamount of a compound of the following formula ##STR00850## .Iaddend.

.Iadd.37. A method of treating human immunodeficiency virus (HIV-1) infection in a patient comprising co-administering to the patient a pharmaceutical composition comprising a pharmacetuically acceptable carrier and a therapeutically effectiveamount of a first antiviral compound of the following formula ##STR00851## with a therapeutically effective amount of a second antiviral compound. .Iaddend.

.Iadd.38. The method of claim 37, wherein the second antiviral compound is an antiretroviral compound. .Iaddend.

.Iadd.39. A method of treating a retroviral infection in a patient comprising administering to the patient a pharmaceutical composition comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound of thefollowing formula ##STR00852## .Iaddend.

.Iadd.40. A method of inhibiting a retroviral protease in a patient comprising administering to the patient a pharmaceutical composition comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound ofthe following formula ##STR00853## .Iaddend.

.Iadd.41. A method of inhibiting replication of a retrovirus in a patient comprising administering to the patient pharmaceutical composition comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of a compoundof the following formula ##STR00854## .Iaddend.
Description:
 
 
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