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.alpha.- and .beta.- amino acid hydroxyethylamino sulfonamides useful as retroviral protease inhibitors
RE42889 .alpha.- and .beta.- amino acid hydroxyethylamino sulfonamides useful as retroviral protease inhibitors
Patent Drawings:

Inventor: Vazquez, et al.
Date Issued: November 1, 2011
Application: 11/788,947
Filed: April 23, 2007
Inventors: Vazquez; Michael L. (Gurnee, IL)
Mueller; Richard A. (Glencoe, IL)
Talley; John J. (St. Louis, MO)
Getman; Daniel P. (Chesterfield, MO)
DeCrescenzo; Gary A. (St. Peters, MO)
Freskos; John N. (Clayton, MO)
Heintz; Robert M. (Ballwin, MO)
Bertenshaw; Deborah E. (Brentwood, MO)
Assignee: G.D. Searle LLC (New York, NY)
Primary Examiner: Saeed; Kamal
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; 544/335; 546/169; 546/316; 546/335; 546/336; 548/164; 548/204; 549/438; 549/501; 549/65
Field Of Search:
International Class: A61K 31/36; C07D 317/50
U.S Patent Documents:
Foreign Patent Documents: A-79823/87; 2045008; 2352452; 3635907; 0 104 041; 0 114 993; 0 172 347; 0 223 437; 0 264 795; 0 337 714; 0 342 541; 0 346 847; 356223; 389898; 389898; 393445; 393457; 402646; 0434365; 468641; WO94/05639; 2184730; 1435386; 2184730; 2200115; 2209752; 50041814; A-79823/87; WO 84/03044; WO 86/06726; WO 92/00750; WO 92/08688; WO 92/08701; WO 93/08184; WO 93/09096; WO 93/23388; WO-94/04492; WO 94/05300; WO 94/05639; WO 94/26749; WO 95/06030; WO 95/09843; WO 97/01349; WO 99/33792; WO 99/67417
Other References: Ghosh et al., "Structured-Based Design of HIV-1 Proteinase Inhibitors: Replacement of Two amides and a 10.pi.-Aromatic System by a FusedBis-tetrahydrofuran", J. Med. Chem. 37, pp. 2506-2508 (1994). cited by other.
Roberts, et al., "Rational Design of Peptide-based Proteinase Inhibitors," Science, vol. 248, p. 358 (1990). cited by other.
Erickson, et al., "Design Activity, and 2.BA Crystal Structure of a C.sub.2 Symmetric Inhibitor Complexed to HIV-1 Protease," Science, vol. 249, p. 527 (1990). cited by other.
Pearl, et al., "Sequence specificity of retroviral proteases," Nature, 328, (1987). cited by other.
Martin, "Drugs of the Future, 16" vol. 3, pp. 210-212 (1991). cited by other.
Meek, et al., "Letter to Nature," vol. 343, pp. 90-92 (1990). cited by other.
Rosenberg, et al., J. Med. Chem., vol. 30, pp. 1224-1228 (1987). cited by other.
U.S. Appl. No. 08/061,897, filed May 14, 1993, Merck & Co., Inc. cited by other.
U.S. Appl. No. 08/485,524, filed Jun. 7, 1995, Vazquez et al. cited by other.
U.S. Appl. No. 07/934,984, filed Aug. 25, 1992, Vazquez et al. cited by other.
Barry et al., "Protease Inhibitors in Patients with HIV Disease", Clinical Pharma., 1997, 32(3), 194-209. cited by other.
Darke et al., "Human Immunodeficiency Virus Protease", The Journal of Biological Chemistry, 1989, 264(4), 2307-2312. cited by other.
Ghosh et al., "3-Tetrahydrofuran and Pyran Urethanes as High-Affinity P.sub.2-Ligands for HIV-1 Protease Inhibitors", Journal of Medicinal Chemistry., 1993, 36(2), 292-294. cited by other.
Merry et al., "Saquinavir Pharmacokinetics Alone and in Combination with Ritonavir in HIV-Infected Patients", AIDS, 1997 11(4), F29-F33. cited by other.
Toyoda et al., "Preparation of Dipeptide Renin Inhibitors", Jan. 29, 1992, CA117:449265. cited by other.
Yun et al. "Oxidation of the antihistaminic drug terfenadine in human liver microsomes. Role of Cytochrome P-450 3A(4) in N-dealkylation and C-hydroxylation," Drug Metabol. And Dispos. 21(3):403-409, 1993. cited by other.
Lewis et al "Role of cytochrome P-450 from the human CYP3A gene family in the potentiation of morpholino doxorubicin by human liver microsomes," Cancer Res. 52:4379-4384, 1992. cited by other.
Le Blanc et al. "Interaction of anticancer drugs with hepatic monooxygenase enzymes," Drug Metab. Rev. 20:395-439, 1989. cited by other.
Robins et al. "HIV Protease Inhibitors: Their Anti-HIV Activity and Potential Role in Treatment," J. of Acquired Immune Deficiency Syndromes 6:162-170, 1993. cited by other.
Wlodawer et al. "Structure-based inhibitors of HIV-1 Protease," Annual Review of Biochemistry, 62:543-585, 1993. cited by other.
Fittkau, J. Prakt. Chem. 1973, 315, 1037-1044 (No English translation available). cited by other.
Pauwels et al., "Rapid and Automated Tetrazolium-based Colorimetric Assay for the Detection of Anti-HIV Compounds", J. Virol. Methods, 1988, 20, 309-321. cited by other.
Hetero Drugs Ltd., "Certificate of Non-Infringement and/or Invalidity of United States Patent Nos. 5,843,946; 6,037,157; 6,248,775; 6,335,460; 6,703,403; 7,470,506 and 7,700,645", Feb. 2011, 73 pages. cited by other.
Teva Pharmaceuticals USA Inc., "Detailed Statement of the Factual and Legal Bases of Teva Pharmaceuticals USA Inc.'s Opinion that U.S. patent Nos. 6,037,157 and 6,703,403 are Invalid, Unenforceable or not Infringed and Detailed Statement of theFactual and Legal Bases for it's Opinion that U.S. Patent Nos. 5,843,946; 6,248,775; 7,470,506 and 7,700,645 are Invalid, Unenforceable or Not Infringed by the Manufacture, Use or Sale of its Darunavir Hydrate Tablets, Eq. 75 mg Base, Eq. 150 mg Base,Eq. 400 mg Base, and Eq. 600 mg base", Jan. 2011, 76 pages. cited by other.
Kwan Y. Hui et al., A rational approach in the search for potent inhibitors against HIV Proteinase, 5 FASEB J. 2606 (1991). cited by other.
Thomas D. Meek, Inhibitors of HIV-1 Protease, 6 J. Enzyme Inhibition 65 (1992). cited by other.
Tameo Iwasaki et al. Simultaneous Cleavage of N-Tosyl and S-Benzyl Groups in Amino Acid and Peptide by Electrolytic Reduction, 50(3) Bull. Inst. Chem. Res., Kyoto Univ, 220 (1972). cited by other.
Sigeru Torii et al. Indirect Electrochemical Radical Cyclization of Bromo Acetals by Cobaloxime(I) as an Electron-Transfer Catalyst, J. Org. Chem. 1985, 50, 5875-5877. cited by other.
Yasuhiro Kojima et al. Synthesis of Perhydrofuru [2.3-b] furan Compounds and the Structure-Activity Relationships of the Antifeeding Active Compounds, Agric. Biol. Chem. 44(4), 855-862, 1980. cited by other.
M. Pezechk et al. A New Route to Perhydro- and Tetrahydro-furo-2,3b Furans via Radical Cyclisation, Tet. Lett. vol. 27, No. 32 pp. 3715-3718 (1986). cited by other.
Jan Vader et al. The Steroselective Synthesis of Substituted Furo[2,3b]furans, Tetrahedron, vol. 45, No. 7 pp. 2131-2142 (1989). cited by other.
Jean Boivin et al. Novel Radical Chain Reactions Based on O-Alkyl Tin Dithiocarbonates, J. Am. Chem. Soc. 1992, 114, 7909-7910. cited by other.
Claus Hackmann et al. New Methods for Reductive Free-Radical Cyclizations of a-Bromoacetals to 2-alkoxytetrahydrofurans with activated chromium(II)-Acetate, Tetrahedron vol. 49, No. 21, pp. 4559-4574 (1993). cited by other.
Tsutomu Inokuchi et al. Indirect Electrochemical Radical Cyclization of Bromo Acetals by the Combined use of Cobaloxime and Sacrificial Electrode, Bull. Chem. Soc. Jpn. 67, 595-598 (1994). cited by other.
Andrea Vaupel et al. Stereoselective Synthesis of Substituted Tetrahydrofurans and Butyrolactones by a New Nickel Catalyzed Carbozincation, Tet. Lett. vol. 35, No. 45 pp. 8349-8352 (1994). cited by other.
Steven A. Wrighton et al. The Human Hepatic Cytochromes P450 Involved in Drug Metabolism, 22 Critical Rev. Toxicology 1, 1-21 (1992). cited by other.
James R. Halpert et al. Contemporary Issues in Toxicology: Selective Inhibitors of Cytochromes P450, 125 Toxicology & Applied Pharmacology 163-175 (1994). cited by other.
J. Gregory Gillum et al. Pharmacokinetic Drug Interactions with Antimicrobial Agents, 25(6) Clinical Pharmacokinetics 450-82 (1993). cited by other.
Edward King, ABT-538 in Combination Trial, 28 AIDS Treatment Update 1 (1995). cited by other.
Arun K. Ghosh et al. Potent HIV Protease Inhibitors Incorporating High-Affinity P.sub.2-Ligands and (R)-(Hydroxyethylamino)Sulfonamide Isostere, 8 Bioorganic & Medicinal Chem. Letters 687-90 (1998). cited by other.
Yasuhiro Koh et al. Novel bis-Tetrahydrofuranylurethane-Containing Nonpeptidic Protease Inhibitor (PI) UIC-94017 (TMC114) With Potent Activity Against Multi-Pi-Resistant Human Immunodeficiency Virus in Vitro, 47 Antimicrobial Agents and Chemotherapy3123, 3124 (2003). cited by other.
Arun K. Ghosh et al. The Development of Cyclic Sulfolanes as Novel and High-Affinity P.sub.2 Ligands for HIV-1 Protease Inhibitors, J. Med. Chem. 1994, 37, 1177-1188. cited by other.
Wayne J. Thompson et al. 3'-Tetrahydrofuranylglycine as a Novel, Unnatural Amino Acid Surrogate for Asparagine in the Design of Inhibitors of the HIV Protease, J. Am. Chem. Soc. 1993, 115, 801-803. cited by other.
Arun K. Ghosh et al. Darunavir, a conceptually new HIV-1 protease inhibitor for the treatment of drug-resistant HIV, Bioorganic & Medicinal Chemistry 15 (2007) 7576-7580. cited by other.
Arun K. Ghosh et al. Chiral Auxiliary Mediated Conjugate Reduction and Asymmetric Protonation: Synthesis of High Affinity Ligands for HIV Protease Inhibitors, J. Org. Chem. 1995, 60, 6198-6201. cited by other.
Arun K. Ghosh et al. Cyclic Sulfolanes as Novel and High Affinity P.sub.2 Ligands for HIV-1 Protease Inhibitors, J. Med. Chem. 1993, 36, 924-927. cited by other.
Arun K. Ghosh et al. Cyclic Sulfone-3-Carboxamides as Novel P.sub.2-Ligands for Ro 31/8959 Based HIV-1 Protease Inhibitors, Bioorganic & Medicinal Chemistry Letters, vol. 5, No. 1, pp. 83-88, 1995. cited by other.
Arun K. Ghosh et al. Highly Stereoselective Reduction of .alpha.-Keto Esters: Utility of Cis-1-Arylsulfonamido-2-indanols as Chiral Auxiliaries. Tetrahedron Letters, vol. 36, No. 38, pp. 6811-6814, 1995. cited by other.
Arun K. Ghosh et al. HIV-1 Protease Inhibitors: Synthesis and Biological Evaluation of Glycopeptidemimetics, Drug Design and Discovery, 1993, vol. 10, pp. 77-88, 1993. cited by other.
Arun K. Ghosh et al. Potent HIV Protease Inhibitors: The Development of Tetrahydrofuranylglycines as Novel P.sub.2-Ligands and Pyrazine Amides as P.sub.3-Ligands, J. Med. Chem. 1993, 36, 2300-2310. cited by other.
Arun K. Ghosh et al. Potent HIV-1 Protease Inhibitors: Stereoselective Synthesis of a Dipeptide Mimic, J. Org. Chem. 1993, 58, 1025-1029. cited by other.
Katharine Holloway et al. A Priori Prediction of Activity for HIV-1 Protease Inhibitors Employing Energy Minimization in the Active Site, J. Med. Chem. 1995, 38, 305-317. cited by other.
Arun K. Ghosh et al. Synthesis and Optical Resolution of High Affinity P.sub.2-Ligands for HIV-1 Protease Inhibitors, Tetrahedron Letters, vol. 36, No. 4 pp. 505-508, 1995. cited by other.
Arun K. Ghosh et al. Synthetic Studies of Antitumor Macrolide Laulimalide: Enantioselective Synthesis of the C.sub.3-C.sub.14 Segment by a Catalytic Hetero Diels-Alder Strategy, Tetrahedron Letters, vol. 38, No. 14, pp. 2427-2430, 1997. cited byother.
V.A. Eagling et al. The Metabolism of Zidovudine by Human Liver Microsomes In Vitro: Formation of 3'-Amino-3'Deoxythymidine, 48 Biochem. Pharmacology 267-76 (1994). cited by other.
Factual and Legal Basis for Mylan's Paragraph IV Certification(s) that U,S. Patent Nos. 5,843,946, 6,248,775, 6,037,157 and 6,703,403 are Invalid, Unenforceable and/or Will Not Be Infringed Jun. 20, 2011, (redacted) 148 pages. cited by other.
Factual and Legal Basis for Lupin's Paragraph IV Certification that U.S. Patent Nos. 5,843,946 and 6,248,775 are Invalid, Unenforceable and/or Will Not Be Infringed Jun. 21, 2011, (redacted) 85 pages. cited by other.
Teva Pharmaceuticals USA Inc., "Detailed Statement of the Factual and Legal Bases of Teva Pharmaceuticals USA Inc.'s Opinion that U.S. Patent Nos. 6,037,157 and 6,703,403 are Invalid, Unenforceable or not Infringed and Detailed Statement of theFactual and Legal Bases for Its Opinion that U.S. Patent Nos. 5,843,946; 6,248,775; 7,470,506; and 7,700,645 are Invalid, Unenforceable or Not Infringed by the Manufacture, Use or Sale of its Darunavir Hydrate Tablets, Eq. 75 mg Base, Eq. 150 mg Base,Eq. 400 mg Base, and Eq. 600 mg Base," (redacted) Jan. 2011 79 pages. cited by other.
McQuade, A Synthetic HIV-1 Protease Inhibitor with Antiviral Activity Arrests HIV-Like Particle Maturation, Science, vol. 247, 454-456, 1990. cited by other.
Rich, et al., "Peptide Inhibitors of Protease," Design of Protease Inhibitors, 511-520, 1984. cited by other.









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-(phen- ylmethyl)propyl]carbamate; Phenylmethyl[2R-hydroxy-3-[(3-methylbutyl)(phenylsulfonyl)amino]-1S-(phen- ylmethyl)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)p- ropyl]-2S-[(2-quinolinylcarbonyl)amino] butanediamide; N1-[2R-hydroxy-3[(3-methylbutyl)(phenylsulfonyl)amino]-1S-(phenylmethyl)p-ropyl]-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-(ph-enylmethyl)propyl]-2S-[(2-quinolinylcarbonyl)amino]butanediamide; [3-[[2-hydroxy-3[N-(3-methylbutyl)-N-(phenylsufonyl)amino]-1-(phenylmethy- l)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-(phenyl- methyl)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-(phenyl- methyl)propyl-, 3-S-tetrahydrothiophen-3-yl-ester; Carbamic acid, [2R-hydroxy-3-[(4-hydroxyphenylsulfonyl)(2-methylpropyl)amino]-1S-(phenyl- methyl)propyl-,3-S-tetrahydrofuran-3-yl-ester; Carbamic acid, [2R-hydroxy-3-[(4-methoxyphenylsulfonyl)(2-methylpropyl)amino]-1S-(phenyl- methyl)propyl-, 3-S-tetrahydrofuran-3-yl-ester; Carbamic acid,[2R-hydroxy-3-[[(4-methoxyphenyl)sulfonyl](2-methylpropyl)amino]-1S-(phen- ylmethyl)propyl]-, 5-(thiazolyl)methyl ester; Carbamic acid, [2R-hydroxy-3-[[(4-hydroxyphenyl)sulfonyl](2-methylpropyl)amino]-1S-(phen- ylmethyl)propyl]-, 5-(thiazolyl)methylester; Benzamide, N-[2R-hydroxy-3-[[(4-hydroxyphenyl)sulfonyl](2-methylpropyl)amino]-1S-(ph- enylmethyl)propyl]-2-methyl; Carbamic acid, [2R-hydroxy-3-[[(4-methoxyphenyl)sulfonyl](2-methylpropyl)amino]-1S-(phen- ylmethyl)propyl]-,3-(6-aminopyridyl)methyl ester; Carbamic acid, [2R-hydroxy-3-[[(4-hydroxyphenyl)sulfonyl](2-methylpropyl)amino]-1S-(phen- ylmethyl)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-(phe- nylmethyl)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-(phenylm- ethyl)propyl]carbamate; Phenylmethyl[2R-hydroxy-3-[(propyl)(phenylsulfonyl)amino]-1S-(phenylmethy- l)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-(phenylm- ethyl)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-(phe- nylmethyl)propyl-, phenylmethyl ester; 2R-hydroxy-3-[[(3-aminophenyl)sulfonyl](2-methylpropyl)amino]-1S-(phenylm- ethyl)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; Carbamicacid, [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]-1- S-(phenylmethyl)propyl]-3-amino-2-methyl; Benzamide,N-[2R-hydroxy-3-[[(1,3-benzodioxol-5-yl)sulfonyl](2-methylpropyl)amino]-1- S-(phenylmethyl)propyl]-4-hydroxy-2-methyl; Benzamide, N-[2R-hydroxy-3-[[(1,3-benzodioxol-5-yl)sulfonyl](2-methylpropyl)amino]-1- S-(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-methylpropypamino]-1S-(phenylmethyl)propyl]-2-(2,6-dimethylph- enylamino)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 pharmaceutical composition comprising a pharmaceutically acceptable carrier and a compound, or pharmaceutically acceptable salt or ester thereof, of the following formula: ##STR00840## .Iaddend.

.Iadd.25. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a compound of the following formula: ##STR00841## .Iaddend.
Description:
 
 
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