RETROVIRAL PROTEASE INHIBITING COMPOUNDS

Abstract: A compound of formula (I) is disclosed as an HIV protease inhibitor. Methods and compositions for inhibiting an HIV infection are also disclosed.

Description: RETROVIRAL PROTEASE INHIBITING COMPOUNDS This is a contιnuatιon-ιn-part of U.S. Patent Application No. 08/572,226, filed December 13, 1995 Technical Field The present invention relates to novel compounds and a composition and method for inhibiting retroviral proteases and in particular for inhibiting human immunodeficiency virus (HIV) protease, a composition and method for inhibiting a retroviral infection and in particular an HIV infection, processes for making the compounds and synthetic intermediates employed in the processes Background of the Invention Retroviruses are those viruses which utilize a πbonucleic acid (RNA) intermediate and a RNA-dependent deoxyπbonucleic acid (DNA) polymerase reverse transcriptase, during their life cycle Retroviruses include, but are not limited to, the RNA viruses of the Retroviπdae family, and also the DNA viruses of the Hepadnavirus and Cauiimovirus families Retroviruses cause a variety of disease states in man, animals and plants. Some of the more important retroviruses from a pathological standpoint include human immunodeficiency viruses (HIV-1 and HIV-2), which cause acquired immune deficiency syndrome (AIDS) in man, human T-cell lymphotrophic viruses I, II, IV and V, which cause human acute cell leukemia, and bovine and feline leukemia viruses which cause ieukemia in domestic animals Proteases are enzymes which cleave proteins at specific peptide bonds Many biological functions are controlled or mediated by proteases and their complementary protease inhibitors For example, the protease renin cleaves the peptide angiotensinogen to produce the peptide angiotensin I Angiotensin I is further cleaved by the protease angiotensin converting enzyme (ACE) to form the hypotensive peptide angiotensin II. Inhibitors of renm and ACE are known to reduce high biood pressure in vivo. An inhibitor of a retroviral protease will provide a therapeutic agent for diseases caused by the retrovirus The genomes of retroviruses encode a protease that is responsible for the proteolytic processing of one or more polyprotem precursors such as the p_oJ and αaa gene products. See Wellmk, Arch. Virol. ≤£ 1 (1988). Retroviral proteases most commonly process the gag precursor into core proteins, and also process the QQ\ precursor into reverse transciptase and retroviral protease In addition, retroviral proteases are sequence specific. See Pearl, Nature 328 482 (1987) The correct processing of the precursor polyproteins by the retroviral protease is necessary for the assembly of infectious viπons It has been shown that in vitro mutagenesis that produces protease-defective virus leads to the production of immature core forms which lack infectivity. See Crawford, J Virol ϋ2 899 (1985); Katoh, et a!., Virology 1A5. 280 (1985). Therefore, retroviral protease inhibition provides an attractive target for antiviral therapy. See Mitsuya, Nature 225 775 (1987). Current treatments for viral diseases usually involve administration of compounds that inhibit viral DNA synthesis. Current treatments for AIDS involve administration of compounds such as 3'-azιdo-3'-deoxythymιdιne (AZT), 2', 3'- dideoxycytidme (DDC), 2',3'-dιdeoxymosιne (DDI), d4T and 3TC and compounds which treat the opportunistic infections caused by the immunosuppression resulting from HIV infection None of the current AIDS treatments have proven to be totally effective in treating and/or reversing the disease. In addition, many of the compounds currently used to treat AIDS cause adverse side effects including low platelet count, renal toxicity and bone marrow cytopenia. Recently the HIV protease inhibitors πtonavir, saqumavir and indmavir have been approved in the U.S. for treatment of HIV infections However, there is a continuing need for improved HIV protease inhibitors. Disclosure of the Invention In accordance with the present invention, there is a compound of the formula I: 1 wherein R 1 and R 2 are independently selected from the group consisting of loweralkyi, cycloalkylalkyi and arylalkyl; R 3 is loweralkyi, hydroxyalkyl or cycloalkylalkyi; R 4 is aryl or heterocyclic; R 5 .s b) h) or wherein n is 1 , 2 or 3, m is 1 , 2 or 3, nϊ is 1 or 2, X is O, S or NH, Y is -CH 2 -, -O- , -S- or -N(Rg)- wherein R 6 is hydrogen, loweralkyi, cycloalkyl, cycloalkylalkyi, aryl or arylalkyi, Y" is -CH 2 - or -N(R 6 »)- wherein R 6 .. is hydrogen, loweralkyi, cycloalkyl, cycloalkylalkyi, aryl or arylalkyi, Y' is -N(R 6 .)- wherein R 6 . is hydrogen, loweralkyi, cycloalkyl, cycloalkylalkyi, aryl or arylalkyi, and Z is O, S or NH; and a) -0-, b) -S-, c) -N(R 7 )- wherein R 7 is hydrogen, loweralkyi, cycloalkyl or cycloalkylalkyi, d) -O-alkylenyh e) -S-alkylenyl- f) -S(0)-alkylenyl-, g) -S(0) 2 -alkylenyl-, h) -N(R 7 )-alkylenyl- wherein R 7 is defined as above, i) -alkylenyl-O-, j) -alkylenyl-S-, k) alkylenyl-N(R 7 )- wherein R 7 is defined as above, I) alkylenyl or m) alkenyleπyl; or a pharmaceutically acceptable salt, ester or prodrug thereof. Preferred compounds are compounds of the formula I wherein R 1 and R 2 are arylalkyi, R 3 is loweralkyi, R 4 is aryl, R 5 is wherein X, Y, Y', Y", Z, R 6 -,, n, m and m' are defined as above and L 1 is -O-alkylenyl. More preferred compounds are compounds of the formula I wherein R 1 and R 2 are benzyl or R 1 is benzyl and R 2 is loweralkyi, R 3 is loweralkyi, R 4 is (a) phenyl which is substituted with two loweralkyi groups and which is optionally substituted with a third substituent selected from the group consisting of loweralkyi, hydroxy, ammo and halo or (b) pyridyl or pynmidmyl either of which is substituted with two loweralkyi groups and which is optionally substituted with a third substituent selected from the group consisting of loweralkyi, hydroxy, ammo and halo, R 5 is wherein n is 1 or 2, X is O or S and Y is -CH 2 or -NH-, wherein m is 1 or 2, X is 0, Y is -C H 2 - and Z is O, wherein m' is 1 , X is O, Z is O and Y is -NH-, wherein m' is 1 , X is O, Y" is -NH- and Y' is -NH- or wherein X is O and R 6 .. is hydrogen and Even more preferred compounds are compounds of the formula I wherein R 1 and R 2 are benzyl or R 1 is benzyl and R 2 is isopropyl, R 3 is loweralkyi, R 4 is 2,6-dιmethylphenyl which is optionally substituted with a third substituent selected from the group consisting of loweralkyi and halo, R 5 is wherein n is 1 or 2, X is O or S and Y is -CH 2 or -NH-, b) wherem m is 1 or 2, X is O, Y is -CH 2 - and Z is 0, wherein m' is 1 , X is O, Z is O and Y is -NH-, wherein m' is 1 , X is O, Y" is -NH- and Y' is -NH- or wherein X is 0 and R 6 .. is hydrogen and Most preferred compounds are compounds of the formula I wherein R 1 and R 2 are benzyl or R 1 is benzyl and R 2 is isopropyi, R 3 is loweralkyi, R 4 is 2,6-dιmethylphenyl which is optionally substituted with a third substituent selected from the group consisting of loweralkyi and halo, R 5 is wherein n is 1 or 2 X is 0 or S and Y is -CH 2 or -NH-, wherein m' is 1 , X is O, Z is O and Y is -NH- wherein m' is 1 , X is O, Y" is -NH- and Y' is -NH- or wherein X is O and Rg.. is hydrogen and Most highly preferred compounds are compounds of the formula I wherein R 1 and R 2 are benzyl or R 1 is benzyl and R 2 is isopropyl, R 3 is loweralkyi, R 4 is 2,6-dιmethylphenyl which is optionally substituted with a third substituent selected from the group consisting of loweralkyi and halo, R 5 is (CH 2 ) n J wherein n is 1 or 2, X is O or S and Y is -CH 2 or -NH- and Examples of highly and most highly preferred compounds of the formula I are selected from the group consisting of (2S, 3S, 5S)-2-(2,6-dιmethylphenoxyacetyl) amιno-3-hydroxy-5-[2S-(1 - tetrahydro-pyπmιd-2-onyl)-3-methyl butanoyl] amιno-1 .6-dιphenylhexane, (2S,3S,5S)-2-(2,6-Dιmethylphenoxyacetyl)amιno-3-hydroxy-5-(2S-(1 - ιmιdazolιdιn-2-onyl)-3,3-dιmethyl butanoyl)amιno-1 ,6-dιphenylhexane, (2S,3S,5S)-2-(2,6-dιmethylphenoxyacetyl)amιno-3-hydroxy-5-(2S-(1 - ιmιdazoiιdιn-2-thιonyl)-3-methyl butanoyl)amιno-1 ,6-dιphenylhexane; (2S,3S,5S)-2-(2,4,6-trιmethylphenoxyacetyl) ammo-3-hydroxy-5-(2S-(1 - ιmιdazolιdιn-2-onyl)-3-methylbutanoyl) amιno-1 ,6-dιphenylhexane, (2S,3S,5S)-2-(4-fluoro-2,6-dιmethylphenoxyacetyl) amιno-3-hydroxy-5-(2S-(1 - ιmιdazoiιdm-2-onyl)-3-methyl-butanoyl) amιno-1 ,6-dιphenylhexane, (2S,3S,5S)-2-(2,6-dιmethylphenoxyacetyl) amιno-3-hydroxy-5-(2S-(1- pyrrolιdιn-2-onyl)-3-methyl-butanoyl) amιno-1 ,6-dιphenylhexane, (2S,3S,5S)-2-(2,6-dιmethylphenoxyacetyl) amιno-3-hydroxy-5-(2S-(1 - pyrrolιdιn-2,5-dιonyl)-3-methyl-butanoyl) amιno-1 ,6-dιphenylhexane; (2S.3S,5S)-2-(trans-3-(2,6-dιmethylphenyl) propenoyi) amιno-3-hydroxy-5-(2S- 1 -tetrahydropyπmιdιn-2-onyl)-3-methyl-butanoyl) amιno-1 ,6-dιphenylhexane, (2S,3S,5S)-2-(3-(2,6-dιmethylphenyl) propanoyl) amιno-3-hydroxy-5-(2S-(1 - tetrahydropyπmιdιn-2-onyl)-3-methyl-butanoyl) amιno-1 .6-dιphenylhexane, (2S 3S,5S)-2-(2,6-Dιmethylphenoxyacetyl) ammo-3-hydroxy-5-(2S-(1 - tetrahydro-pyrιmιd-2,4-dιonyl)-3-methylbutanoyl)amιno-1 ,6-dιphenylhexane, (2S 3S.5S)-2-(2,6-Dιmethylphenoxyacetyl) amιπo-3-hydroxy-5-(2S-(4-aza-1 - tetrahydro-pyπmιd-2-onyl)-3-methyl-butanoyl)amιno-1 ,6-dιphenylhexane (2S,3S,5S)-2-(2,6-Dιmethylphenoxyacetyl) amιno-3-hydroxy-5-(2S-(1 - tetrahydro-pyrιmιd-2-onyl)-3-methylbutanoyl)amιno-1 -phenyl-6-methylheptane , (2S,3S,5S)-2-(2,6-Dιmethylphenoxyacetyl) amιno-3-hydroxy-5-(2S-(1 - tetrahydro-pyrιmιd-2,4-dιonyl)-3-methylbutanoyl)amιno-1 -phenyl-6- methylheptane; and (2S,3S,5S)-2-(2,6-Dιmethylphenoxyacetyl) amιno-3-hydroxy-5-(2S-(4-aza-4,5- dehydro-1 -pyrιmιd-2-onyl)-3-methyl-butanoyl)amιno-1 ,6-dιphenylhexane; or a pharmaceutically acceptable salt, ester or prodrug thereof. The most highly preferred compound of the formula I is (2S, 3S, 5S)-2- (2,6-Dιmethylphenoxyacetyl) amιno-3-hydroxy-5-[2S-(1 -tetrahydro-pyrιmιd-2- onyl)-3-methyl butanoyl] amιno-1 ,6-dιphenylhexane; or a pharmaceutically acceptable salt, ester or prodrug thereof. In some circumstances it is preferred to be able to prepare (2S, 3S, 5S)- 2-(2,6-Dιmethylphenoxyacetyl) amιno-3-hydroxy-5-[2S-(1 -tetrahydro-pyπmιd-2- onyl)-3-methyl butanoyl] amιno-1 ,6-dιphenylhexane (or a pharmaceutically acceptable salt, ester or prodrug thereof) as an amorphous solid. Such an amorphous solid can be prepared by dissolving (2S, 3S, 5S)-2-(2,6- Dimethylphenoxyacetyl) amιno-3-hydroxy-5-[2S-(1 -tetrahydro-pyrιmιd-2-onyl)- 3-methyl butanoyl] amιno-1 ,6-dιphenylhexane in an organic solvent (for example, ethanol, isopropanol, acetone, acetonitrile and the like) and then adding the solution to water. Preferably, (2S, 3S, 5S)-2-(2,6- Dimethylphenoxyacetyi) amιno-3-hydroxy-5-[2S-(1 -tetrahydro-pyrιmιd-2-onyl)- 3-methyl butanoyl] amιno-1 ,6-dιphenylhexane is dissolved in ethanol (from about 2 to about 4 mL/g) and the ethanolic solution is added with stirring to water (from about 10 about 100 mL/g) to provide amorphous (2S, 3S, 5S)-2- (2,6-Dιmethylphenoxyacetyl) amιno-3-hydroxy-5-[2S-(1-tetrahydro-pyπmιd-2- onyl)-3-methyl butanoyl] amιno-1 ,6-dιphenylhexane Another embodiment of the present invention comprises an HIV protease inhibiting compound comprising a substituent of the formula II: wherein R 3 is loweralkyi, hydroxyalkyl or cycloalkylalkyi; and R 5 is wherein n is 1 , 2 or 3, m is 1 , 2 or 3, m' is 1 or 2, X is O, S or NH, Y is -CH 2 -, -0- , -S- or -N(Rg)- wherein R 6 is hydrogen, loweralkyi, cycloalkyl, cycloalkylalkyi, aryl or arylalkyi, Y" is -CH 2 - or -N(R 6 »)- wherein R 6 .. is hydrogen, loweralkyi, cycloalkyl, cycloalkylalkyi, aryl or arylalkyi, Y' is -N(R 6 .)- wherein R 6 . is hydrogen, loweralkyi, cycloalkyl, cycloalkylalkyi, aryl or arylalkyi, and Z is O, S o NH. Preferred compounds are HIV protease inhibiting compounds comprising a substituent of the formula II wherein R 3 is loweralkyi and R 5 is or wherein X, Y, Y', Y", Z, R 6 «, n, m and m' are defined as above More preferred compounds are HIV protease inhibiting compounds compπsing a substituent of the formula II wherein R 3 is loweralkyi and R 5 is wherein n is 1 or 2, X is O or S and Y is -CH 2 or -NH- wherein m is 1 or 2, X is O, Y is -CH 2 - and Z is O, wherein m' is 1 , X is 0, Z is O and Y is -NH- wherein m' is 1 , X is 0, Y" is -NH- and Y' is -NH- or wherein X is O and R 6 .. is hydrogen. Even more preferred compounds are HIV protease inhibiting compounds compπsing a substituent of the formula II wherein R 3 is isopropyl and R 5 is wherein n is 1 or 2, X is O or S and Y is -CH 2 or -NH- wherein m is 1 or 2, X is O, Y is -CH 2 - and Z is O, wherein m' is 1 , X is O, Z is O and Y is -NH- wherein m' is 1 , X is O, Y" is -NH- and Y' is -NH- or wherein X is O and R 6 - is hydrogen. Most preferred compounds are HIV protease inhibiting compounds comprising a substituent of the formula II wherein R 3 is isopropyl and R 5 is wherein n is 1 or 2, X is O or S and Y is -CH 2 or -NH- b) wherem m' is 1 , X is O, Z is O and Y is -NH-, wherein m' is 1 , X is O, Y" is -NH- and Y" is -NH- or wherein X is 0 and R 6 » is hydrogen. Most highly preferred compounds are HIV protease inhibiting compounds comprising a substituent of the formula II wherein R 3 is isopropyl and R 5 is wherein n is 1 or 2, X is O or S and Y is -CH 2 or -NH- Examples of such HIV protease inhibiting compounds include: cιs-N-tert-butyl-decahydro-2-[ 2(R)-hydroxy-4-phenyl-3(S)-(2S-(1 - tetrahydropyπmid-2-onyl)-3-methylbutanoyl)amιnobutyl]-(4aS,8aS)- ιsoquιπolιne-3(S)-carboxamιde; cιs-N-tert-butyl-decahydro-2-[ 2(R)-hydroxy-4-thιophenyl-3(S)-(2S-(1 - tetrahydropyπmιd-2-onyI)-3-methylbutanoyl)amιnobutyl]-(4aS,8aS)- ιsoquιnoiιne-3(S)-carboxamιde; and 4-Amιno-N-(( 2syn, 3S)-2-hydroxy-4-phenyl-3-(2S-( 1 -tetrahydropyπmιd-2- onyl)-3-methylbutanoylamιno)-butyl)-N-ιsobutyl-benzenesuifonamιde, and the like, or pharmaceutically acceptable salts thereof Such HIV protease inhibiting compounds comprising a substituent of the formula II can be prepared by coupling a suitable intermediate or precursor having an ammo group (-NH 2 or -NHR * wherein R * is loweralkyi), a hydroxyl group (-OH) or a thiol group (-SH) to the compound of the formula III or a salt or an activated ester derivative thereof wherein R 3 is loweralkyi, hydroxyalkyl or cycloalkylalkyi; and R 5 ιs b) or wherein n is 1 , 2 or 3, m is 1 , 2 or 3, m' is 1 or 2, X is O, S or NH, Y is -CH 2 -, -O- , -S- or -N(Rg)- wherein R 6 is hydrogen, loweralkyi, cycloalkyl, cycloalkylalkyi, aryl or arylalkyi, Y" is -CH 2 - or -N(R 6 ..)- wherein R 6 .. is hydrogen, loweralkyi, cycloalkyl, cycloalkylalkyi, aryl or arylalkyi, Y' is -N(R 6 .)- wherein R 6 . is hydrogen, loweralkyi, cycloalkyl, cycloalkylalkyi, aryl or arylalkyi, and Z is O, S or NH. Preferred compounds are compounds of the formula III or an activated ester derivative thereof wherein R 3 is loweralkyi and R 5 is b) wherein X, Y, Y', Y", Z, R 6 .., n, m and rrϊ are defined as above. More preferred compounds are compounds of the formula III or an activated ester derivative thereof wherein R 3 is loweralkyi and R 5 is wherein n is 1 or 2, X is O or S and Y is -CH 2 or -NH-, wherein m is 1 or 2, X is O, Y is -CH 2 - and Z is O, wherein m' is 1 , X is O, Z is O and Y is -NH-, wherein m' is 1 , X is O, Y" is -NH- and Y' is -NH- or wherein X is O and R 6 » is hydrogen Even more preferred compounds are compounds of the formula 111 or an activated ester derivative thereof wherein R 3 is isopropyl and R 5 is wherein n is 1 or 2, X is O or S and Y is -CH or -NH- wherein m is 1 or 2, X is O, Y is -CH 2 - and Z is O, wherein m' is 1 , X is 0, Z is O and Y is -NH- wherein m' is 1 , X is 0, Y" is -NH- and Y' is -NH- or wherein X is O and Rg.. is hydrogen. Most preferred compounds are compounds of the formula III or an activated ester derivative thereof wherein R 3 is isopropyl and R 5 is wherein n is 1 or 2, X is O or S and Y is -CH 2 or -NH- wherein m' is 1 , X is O, Z is O and Y is -NH-, c) wherein m' is 1 , X is O, Y" is -NH- and Y' is -NH- or wherein X is 0 and R 6 - is hydrogen. Most highly preferred compounds are compounds of the formula III or an activated ester derivative thereof wherein R 3 is isopropyl and R 5 is wherein n is 1 or 2, X is O or S and Y is -CH 2 or -NH- The compounds of the invention can comprise asymmetrically substituted carbon atoms. As a result, all stereoisomers of the compounds of the invention are meant to be included in the invention, including racemic mixtures, mixtures of diastereomers, as well as single diastereomers of the compounds of the invention. The terms "S" and "R" configuration are as defined by the IUPAC 1974 Recommendations for Section E, Fundamental Stereochemistry, Pure Appl. Chem. (1976) 45, 13 - 30. The term "N-protecting group" or "N-protected" as used herein refers to those groups intended to protect the N-terminus of an amino acid or peptide or to protect an amino group against undersirable reactions during synthetic procedures. Commonly used N-protecting groups are disclosed in Greene and Wuts, "Protective Groups In Organic Synthesis," (John Wiley & Sons, New York (1991 )), which is hereby incorporated by reference. N-protecting groups comprise acyl groups such as formyl, acetyl, propionyl, pivaloyl, t-butylacetyl, 2-chloroacetyl, 2-bromoacetyl, trifluoroacetyl, trichloroacetyl, phthalyl, o-nitrophenoxyacetyl, α-chlorobutyryl, benzoyl, 4-chlorobenzoyl, 4-bromobenzoyl, 4-nitrobenzoyl, and the like; sulfonyl groups such as beπzenesulfonyl, p-toluenesulfonyl and the like; carbamate forming groups such as benzyloxycarbonyl, p-chlorobenzyloxycarbonyl, p-methoxybenzyloxycarbonyl, p-nitrobenzyloxycarbonyi, 2-nitrobenzyloxycarbonyl, p-bromobenzyloxycarbonyl, 3,4-dιmethoxybenzyloxycarbonyl, 3.5-dimethoxybenzyloxycarbonyl, 2.4-dimethoxybenzyioxycarbonyl, 4-methoxybenzyloxycarbonyl, 2-nιtro-4,5-dιmethoxybenzyloxycarbonyl, 3,4,5-tπmethoxybenzyloxycarbonyl, 1 -(p-biphenylyl)-l -methylethoxycarbonyl, α,α-dimethyl-3,5-dimethoxybenzyioxycarbonyl, benzhydryloxycarbonyl, t-butyloxycarbonyl, diisopropylmethoxycarbonyl, isopropyloxycarbonyl, ethoxycarbonyl, methoxycarbonyl, allyloxycarbonyl, 2,2,2,-trichloroethoxycarbonyl, phenoxycarbonyl, 4-nitrophenoxycarbonyl, fluorenyl-9-methoxycarbonyl, cyciopentyloxycarbonyl, adamantyioxycarbonyl, cyclohexyloxycarbonyl, phenylthiocarbonyl and the like; alkyl groups such as benzyl, triphenylmethyl, benzyloxymethyi and the like; and silyl groups such as trimethylsilyl and the like. Preferred N-protecting groups are formyl, acetyl, benzoyl, pivaloyi, t-butylacetyl, phenylsulfonyl, benzyl, t-butyloxycarbonyl (Boc) and benzyloxycarbonyl (Cbz). The term "activated ester derivative" as used herein refers to acid halides such as acid chlorides, and activated esters including, but not limited to, formic and acetic acid derived anhydrides, anhydrides derived from alkoxycarbonyl halides such as isobutyloxycarbonylchlonde and the like, N-hydroxysuccinimide derived esters, N-hydroxyphthalimide derived esters, N-hydroxybenzotriazole derived esters, N-hydroxy-5-norbornene-2,3-dicarboxamide derived esters, 2,4,5-trichlorophenol derived esters, thiophenol derived esters, propylphosphonic acid derived anhydrides and the like. The term "alkanoyl" as used herein refers to R 19 C(0)- wherein R 19 is a loweralkyi group. The term "alkenylenyl" as used herein refers to a divalent group derived from a straight or branched chain hydrocarbon containing from 2 to 10 carbon atoms and also containing at least one carbon-carbon double bond. Examples of alkenylene include -CH=CH-, -CH 2 CH=CH-, -C(CH 3 )=CH-, -CH 2 CH=CHCH 2 -, and the like. The terms "alkoxy" and "thioalkoxy" as used herein refer to - t ς O- and R-. E -S-, respectively, wherein R 1 5 is a loweralkyi group. The term "alkoxyalkoxy" as used herein refers to R22O-R23O- wherein R22 is loweralkyi as defined above and R23 is an alkylenyl group. Representative examples of alkoxyalkoxy groups include methoxymethoxy, ethoxymethoxy, t-butoxymethoxy and the like. The term "alkoxyalkyl" as used herein refers to an alkoxy group appended to a loweralkyi radical. The term "alkoxycarbonyl" as used herein refers to R 20 C(O)- wherein R 20 is an alkoxy group. The term "alkylamino" as used herein refers to -NHR 16 wherein R 16 is a loweralkyi group. The term "alkylaminocarbonyl" as used herein refers to R 21 C(0)- wherein R 21 is an alkylamino group. The term "alkylenyl" as used herein refers to a divalent group derived from a straight or branched chain saturated hydrocarbon having from 1 to 10 carbon atoms by the removal of two hydrogen atoms, for example methylene (-CH 2 -), 1 ,2-ethylene (-CH 2 CH 2 -), 1 ,1 -ethylene =CH-CH 3 , 1 ,3-propylene (-CH 2 CH 2 CH 2 -), 2,2-dιmethylpropylene (-CH 2 C(CH 3 ) 2 CH 2 -), and the like. The term "aminocarbonyl" as used herein refers to -C(0)NH 2 . The term "aryl" as used herein refers to a mono- or bicyclic carbocyclic ring system comprising 6 to 12 carbon atoms and having one or two aromatic rings including, but not limited to, phenyl, naphthyl, tetrahydronaphthyl, indanyl, indenyl and the like. Aryl groups can be unsubstituted or substituted with one, two or three substituents independently selected from loweralkyi, halo, haloalkyl, haloalkoxy, alkoxy, alkoxycarbonyl, thioalkoxy, amino, alkylamino, dialkylamino, aminocarbonyl, mercapto, nitro, carboxaldehyde, carboxy and hydroxy. The term "arylalkyi" as used herein refers to an aryl group as previously defined, appended to a loweralkyi radical, for example, benzyl and the like. The term "cycloalkyl" as used herein refers to an aliphatic ring system having 3 to 8 carbon atoms including, but not limited to, cyclopropyl, cyclopentyl, cyclohexyi, and the like. The term "cycloalkylalkyi" as used herein refers to a cycloalkyl group appended to a loweralkyi radical, including but not limited to cyclohexylmethyl. The term "dialkylamino" as used herein refers to -NR 1 6 R 1 7 wherein R 1 β and R 1 7 are independently selected from loweralkyi groups. The term "dialkylaminocarbonyl" as used herein refers to R 22 C(0)- wherem R 22 is a dialkylamino group The term "halo" or "halogen" as used herein refers to -Cl, -Br, -I or -F The term "haloalkoxy" as used herein refers to R- | 8 0- wherein R 18 is a haloalkyl group. The term "haloalkyl" as used herein refers to a loweralkyi group in which one or more hydrogen atoms are replaced by halogen, for example, chloromethyl, chloroethyl, tπfluoromethyl and the like The term "heterocyclic ring" or "heterocyclic" or "heterocycle" as used herein refers to any 3- or 4-membered ring containing a heteroatom selected from oxygen, nitrogen and sulfur; or a 5-, 6- or 7-membered ring containing one, two or three heteroatoms independently selected from the group consisting of nitrogen, oxygen and sulfur or a 5-membered ring containing 4 nitrogen atoms, and includes a 5-, 6- or 7-membered ring containing one, two or three nitrogen atoms, one oxygen atom; one sulfur atom; one nitrogen and one sulfur atom, one nitrogen and one oxygen atom; two oxygen atoms in non-adjacent positions, one oxygen and one sulfur atom in non-adjacent positions; two sulfur atoms in non-adjacent positions; two sulfur atoms in adjacent positions and one nitrogen atom; two adjacent nitrogen atoms and one sulfur atom; two non- adjacent nitrogen atoms and one sulfur atom; two non-adjacent nitrogen atoms and one oxygen atom The 5-membered ring has 0-2 double bonds and the 6- and 7-membered rings have 0-3 double bonds The nitrogen heteroatoms can be optionally quaternized The term "heterocyclic" also includes bicyclic groups in which any of the above heterocyclic rings is fused to a benzene ring or a cyclohexane ring or another heterocyclic ring (for example, mdolyl, qumolyl, isoqumolyl, tetrahydroqumolyl, benzofuryl, bistetrahydorfuranyl or benzothienyl and the like) Heterocyciics include azetidinyl, pyrrolyl, pyrrolinyl, pyrrolidmyl, pyrazolyl, pyrazolinyl, pyrazolidmyl, imidazolyl, imidazolinyl, imidazolidinyl, pyridyl, pipeπdinyl, homopipeπdinyl, pyrazmyl, piperazmyl, pynmidmyl, pyπdazinyl oxazolyl, oxazolidmyl, isoxazolyl, isoxazolidmyl, morpholmyl, thiazolyl, thiazolidinyl, isothiazolyl, isothiazoiidmyl, mdolyl, qumolmyl, isoqumolinyl, benzimidazolyl, benzothiazolyl, benzoxazolyl, furyl, thienyl, tetrahydrofuranyl, tetrahydrothienyl, thiazolidinyl, isothiazolyl, tπazolyl, tetrazolyl, isoxazolyl, oxadiazolyl, thiadiazolyl, pyrrolyl, pyπmidyl and benzothienyl Heterocyciics also include compounds of the formula wherein X * is -CH -, -NH- or -0-, Y * is -C(O)- or [-C(R") 2 -] V wherein R" is hydrogen or C-|-C4-alkyl and v is 1 , 2 or 3 and Z * is -O- or -NH-; such as 1 ,3- benzodioxolyl, 1 ,4-benzodιoxanyl and the like. Heterocyciics can be unsubstituted or substituted with one, two, three or four substituents independently selected from the group consisting of hydroxy, halo, oxo (=0), alkylimino (R * N= wherein R * is a loweralkyi group), ammo, alkylamino, dialkylamino, alkoxy, alkoxyalkoxy, haloalkyl, cycloalkyl, aryl, arylalkyi, -COOH, -SO3H and loweralkyi In addition, nitrogen containing heterocycles can be N-protected. The term "hydroxyalkyl" as used herein refers to a loweralkyi radical to which is appended an hydroxy group. The term "loweralkyi" as used herein refers to a straight or branched chain alkyl radical containing from 1 to 6 carbon atoms including, but not limited to, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, t-butyl, n- pentyl, 1 -methylbutyl, 2,2-dιmethylbutyl, 2-methylpentyl, 2,2-dιmethylpropyl, n- hexyl and the like The term "thioalkoxyalkyl" as used herein refers to a thioalkoxy group appended to a loweralkyi radical The compound of the invention of formula I can be prepared as shown in Schemes l-IV As outlined in Scheme I, intermediates 1 and 2 (wherein P 1 is an N-protecting group, for example, t-butyloxycarbonyl) can be coupled using standard peptide coupling reagents and methods, for example, reaction of 1 and Z in the presence of 1 -hydroxybenzotrιazole and a dnmide such as dicyclohexylcarbodnmide (DCC) or N-ethyl-N'-dimethylaminopropyl carbodiimide (EDAC) and the like to give 3_ Alternatively, a salt or an activated ester derivative of intermediate 1 (for example, the acid chloride, prepared by reaction of the carboxylic acid with thionyl chloride) can be reacted with intermediate Z Compound 2 can be N-deprotected to give compound 4. N-deprotection of 3_ wherein P 1 (especially wherein P- | is t-butyloxycarbonyl) is an acid labile N-protecting group can lead to formation of impurities resulting from migration of the acyl group R -L 1 -C(0)- from the amino group to the hydroxyl group. The formation of this impurity can be minimized or eliminated by performing the deprotection using (1 ) trifluoroacetic acid in methylene chloride or (2) concentrated hydrochloric acid (from about 2 molar equivalents to about 6 molar equivalents, preferably, from about 2 molar equivalents to about 4 molar equivalents) in acetic acid at about room temperature. A preferred N-deprotection method comprises reacting compound 3. (wherein P 1 is t-butyloxycarbonyl) with concentrated hydrochloric acid (from about 10 to about 20 molar equivalents) in acetonitrile (from about 2 to about 10 liters/kilogram of compound 3_ ) at a temperature of from about 0°C to about 5°C. Compound 5. or an activated ester derivative thereof can then be coupled to compound 4 to give the compound of the formula I (i.e., £). An alternative process is shown in Scheme IIA. Compound Z (wherein P 2 is an N-protecting group, for example, benzyloxycarbonyl) can be coupled to compound £, or a salt or an activated ester derivative thereof (for example, the acid chloride, prepared by reaction of the carboxylic acid with thionyl chloride), to give £. Compound £ can be N-deprotected to give £. Compound 2. can be coupled with compound 1, or an activated ester derivative thereof, to give the compound of the formula I (i.e., 6_). Scheme I1B shows a preferred alternative process wherein the N- protected amino alcohol 7a (P 3 is hydrogen and P 4 is an N-protecting group or both P 3 and P 4 are N-protecting groups, preferably, P 3 and P 4 are benzyl) is reacted with from about 1 to about 1.3 molar equivalents of carboxylic acid 5. or a salt or an activated ester derivative thereof (for example, the acid chloride, prepared by reaction of the carboxylic acid with thionyl chloride in ethyl acetate or THF or oxalyl chloride in toluene/DMF and the like) in the presence of from about 1.0 to about 4.0 molar equivalents (preferably, from about 2.5 to about 3.5 molar equivalents) of an organic amine base (for example, imidazole, 1-methylimidazole, 2-methylimidazole, 2-isopropylimidazole, 4-methylimidazole, 4-nitroimidazole, pyridine, N,N-dimethylaminopyridine, 1 ,2.4-triazole, pyrrole. 3-methylpyrrole, triethylamine or N-methylmorphoiine and the like) or from about 1 to about 20 molar equivalents of an inorganic base (for example, sodium carbonate or sodium bicarbonate and the like) in an inert solvent (for example, ethyl acetate, dimethylformamide, THF, acetonitπle, isopropyl acetate or toluene and the like) at a temperature of from about 0°C to about 50°C to provide compound fia Preferred organic amme bases include imidazole and 1 ,2,4-tπazole. N-Debenzylation of £a (for example, using hydrogen and a hydrogenation catalyst or Pd/C and a formic acid salt (for example, ammonium formate and the like) or Pd/C and formic acid and the like) provides £. Compound 2 can be advantageously purified by crystallization with an organic carboxylic acid (for example, S-pyroglutamic acid, succinic acid or fumaπc acid and the like) A preferred organic carboxylic acid is S-pyroglutamic acid Compound 2 (or an organic carboxylic acid salt of compound £) is reacted with from about 1 0 to about 1.3 molar equivalents of carboxylic acid 1 or a salt or an activated ester derivative thereof (for example, the acid chloride) in the presence of (1 ) from about 4 to about 8 molar equivalents (preferably, from about 5 to about 7 molar equivalents) of an inorganic base (for example, NaHC0 3 , Na 2 C0 3 , KHC0 3 , K 2 C0 3 , NaOH or KOH and the like) in an inert solvent (for example, 1 1 ethyl acetate/water or isopropyl acetate/water or toluene/water or THF/water and the like) at about room temperature or (2) from about 1 0 to about 4 0 molar equivalents (preferably, from about 2 5 to about 3 5 molar equivalents) of an organic amme base (for example, imidazole, 1 -methylιmιdazole, 2-methylιmιdazole, 2-ιsopropylιmιdazole, 4-methylιmιdazole, 4-nιtroιmιdazole, pyridme, N,N-dιmethylamιnopyπdιne, 1 ,2,4-trιazole, pyrrole, 3-methylpyrrole, tπethylamine or N-methyimorpholme and the like) in an inert solvent (for example, ethyl acetate, isopropyl acetate, THF, toluene, acetonitπle, dimethylformamide and the like) at a temperature of from about 0°C to about 50°C to provide compound £. In a preferred embodiment of the invention (shown in Scheme III), intermediate compound ϋ has the formula of compound 1_Q (R 3 is as defined for the compound of formula I and is preferably isopropyl) Compound 10_ can be prepared in variety ways as shown in Scheme III In one method, ammo acid H (either as the free carboxylic acid or as the carboxylic acid ester (i e , loweralkyi ester)) is converted to carbamate 12 (R" is phenyl, loweralkyl-substituted phenyl, halo-substituted phenyl, nitro-substituted phenyl, tπfluoromethylphenyl and the like) by reaction with the appropriate chloroformate ester and the like. Reaction of carbamate 12 with from about 1.0 to about 1.5 molar equivalents of amme 12 or an acid addition salt thereof (Q is a leaving group, for example, Cl, Br or I, or a sulfonate such as methanesulfonate, tπflate, p-toluenesulfonate, benzenesulfonate and the like) in an inert solvent (for example, THF, methyl t-butyl ether, dimethoxyethane, THF/water, dimethoxyethane/water, toluene or heptane and the like) in the presence of a base (for example, LiOH, NaOH, Lι 2 C03, Na 2 C0 3 , lithium phenoxide or sodium phenoxide and the like) in the amount of from about 2.5 to about 3.5 molar equivalents provides urea 14 Urea 14 can be isolated and reacted further or can be converted in situ to cyclic urea 10 by reaction in an inert solvent (for example, THF, dimethoxyethane, methy! t-butyl ether, toluene or heptane and the like) with a base (for example, potassium t-butoxide, sodium hydride, potassium hydride or dimethylammopyridine and the like) in the amount of from about 2.0 to about 5.0 molar equivalents. If the ammo acid ester of JJ. was the starting material, the ester is then hydrolyzed to provide the carboxylic acid 1Q Alternatively, ammo acid 1_ (either as the free carboxylic acid or as the carboxylic acid ester) is converted to urea 14 by reaction with from about 1.0 to about 1.5 molar equivalents of isocyanate 15. (Q is a leaving group, for example, Cl. Br or I, or a sulfonate such as methanesulfonate, triflate, p-toluenesulfonate benzenesulfonate and the like) in an inert solvent (for example, THF, dimethoxyethane, methyl t-butyl ether, toluene or heptane and the like) in the presence of a base. In yet another alternative, ammo acid H (either as the free carboxylic acid or as the carboxylic acid ester) is converted to diamine 16 by reaction with from about 1.0 to about 1.5 molar equivalents of amme 13 or an N-protected derivative thereof (Q is a leaving group, for example, Cl, Br or I, or a sulfonate such as methanesulfonate, triflate, p-toluenesulfonate, benzenesulfonate and the like) in an inert solvent (for example, THF, dimethoxyethane, methyl t-butyl ether, toiuene or heptane and the like) in the presence of a base (for example, NaH or potassium t-butoxide and the like) in the amount of from about 1 0 to about 4.0 molar equivalents. N-deprotection is required if the N-protected derivative of 13 was used. Reaction of diamine 16 with a carbonyl equivalent 17 (for example, phosgene, carbonyldiimidazole and the like wherein Q' and Q" are leaving groups such as Cl, Br, I, -O-loweralkyl, -O-aryl or imidazolyl and the like) in an inert solvent (for example, THF, dimethoxyethane, methyl t-butyl ether, toluene or heptane and the like) in the presence of a base (for example, NaH or potassium t-butoxide and the like and the like) in the amount of from about 2.0 to about 4.0 molar equivalents provides cyclic urea 10. If the amino acid ester of H was the starting material, the ester is then hydrolyzed to provide the carboxylic acid 1Q. In yet another alternative shown in Scheme IV, compound H (either as the free carboxylic acid or as the carboxylic acid ester (i.e., loweralkyi ester)) is reacted with acrylonitrile according to J. Am. Chem. Soc. 72., 2599 (1950) to give aminonitrile 18.. Alternatively, acrylonitrile can be replaced with 3-chloropropionitrile to provide 18. N-protection of aminonitrile 18 as the carbamate (R 30 is loweralkyi or phenyl or haloalkyl (for example, 2-chloroethyl, 2-bromoethyl and the like) and the like) using standard conditions (for example, reaction of the amine with the appropriate chloroformate ester (CIC(O)OR 30 wherein R 30 is loweralkyi, phenyl, haloalkyl and the like) neat or in an inert solvent (for example, water, THF and the like) in the presence of an inorganic base (for example, NaOH, KOH, K 2 C0 3 and the like) or an organic base (for example, an alkylamine or dialkylamine and the like) and the iike) provides compound 19. Hydrogenation of 19 in the presence of a catalyst (for example, Ni-AI alloy (basic) or Raney nickel (neutral or basic) or Pt0 2 (acidic) and the like) in an inert solvent (for example, water or methanol or ethanol or THF and the like) provides cyclic urea 10.. In a preferred process, compound 19 is hydrogenated in the presence of a Ni-AI alloy catalyst in an inert solvent (for example, water or methanol or ethanol or THF and the like) in the presence of a base (for example, KOH or NaOH or LiOH or an organic amine base and the like) in the amount of from about 1.1 to about 5 molar equivalents to provide cyclic urea 10. If the amino acid ester of H was the starting material, the ester is then hydrolyzed to provide the carboxylic acid 10. Alternatively, hydrogenation of compound 1_g. (as described above for compound 12) provides diamine 1§. which can be converted to compound 10 as previously described. If the amino acid ester of H was the starting material, the ester is then hydrolyzed to provide the carboxylic acid 1Q_. Scheme 1 3 Scheme I1A \ Scheme MB OH R 2 O Scheme III Scheme IV 10 Key intermediates for the preparation of the compounds of the invention include compounds of the formula III as described above and compounds of the formula IV: IV or a salt thereof, wherein P 3 and P 4 are independently selected from hydrogen or an N-protecting group; R-, and R 2 are independently selected from the group consisting of loweralkyi, cycloalkylalkyi and arylalkyi; R 3 is loweralkyi, hydroxyalkyl or cycloalkylalkyi; and R 5 .s b) or wherein n is 1 , 2 or 3, m is 1 , 2 or 3, m' is 1 or 2, X is O, S or NH, Y is -CH 2 -, -O- , -S- or -N(R 6 )- wherein R 6 is hydrogen, loweralkyi, cycloalkyl, cycloalkylalkyi, aryl or arylalkyi, Y" is -CH 2 - or -N(R 6 ..)- wherein R 6 .. is hydrogen, loweralkyi, cycloalkyl, cycloalkylalkyi, aryl or arylalkyi, Y' is -N(R 6 .)- wherein R 6 , is hydrogen, loweralkyi, cycloalkyl, cycloalkylalkyi, aryl or arylalkyi, and Z is O, S or NH. Preferred compounds are compounds of the formula IV wherein P 3 and P 4 are hydrogen or benzyl, R 1 and R 2 are arylalkyi, R 3 is loweralkyi and R 5 is b) wherein X, Y, Y', Y", Z, Rg.., n, m and m' are defined as above. More preferred compounds are compounds of the formula IV wherein R 1 and R 2 are benzyl or R 1 is benzyl and R 2 is loweralkyi, R 3 is loweralkyi and R 5 is wherein n is 1 or 2, X is O or S and Y is -CH 2 or -NH-, wherein m is 1 or 2, X is O, Y is -CH 2 - and Z is O, wherein m' is 1 , X is O, Z is O and Y is -NH-, d) wherein m' is 1 , X is O, Y" is -NH- and Y' is -NH- or wherein X is O and Rg.. is hydrogen. Even more preferred compounds are compounds of the formula IV wherein R 1 and R are benzyl or R 1 is benzyl and R 2 is isopropyl, R 3 is loweralkyi and R 5 is wherein n is 1 or 2, X is O or S and Y is -CH 2 or -NH- wherein m is 1 or 2, X is O, Y is -CH 2 - and Z is O, wherein m' is 1 , X is O, Z is O and Y is -NH-, wherein m' is 1 , X is O, Y" is -NH- and Y' is -NH- or wherein X is O and Rg.. is hydrogen. Most preferred compounds are compounds of the formula IV wherein R 1 and R 2 are benzyl or R 1 is benzyl and R 2 is isopropyl, R 3 is loweralkyi and R 5 is wherein n is 1 or 2, X is O or S and Y is -CH 2 or -NH- wherein m' is 1 , X is O, Z is O and Y is -NH-, wherein m' is 1 , X is O, Y" is -NH- and Y' is -NH- or wherein X is O and Rg.. is hydrogen. Most highly preferred compounds are compounds of the formula IV wherein R 1 and R 2 are benzyl or R 1 is benzyl and R 2 is isopropyl, R 3 is loweralkyi and R 5 is wherein n is 1 or 2, X is O or S and Y is -CH 2 or -NH-. Preferred salts of the compound of formula IV are organic carboxylic acid salts, especially the (S)-pyroglutamic acid salt. The following examples will serve to further illustrate the preparation of the novel compounds of the invention. Example 1 ■ 2S. 3S. 5S,-2-f2.6-dimethylρhenoxyacetvn amino-3-hvdroxy-5-f2S-(1 - imidazolidin-2-onvh-3-methyl-butanoyl] amino- 1.6-diphenylhexane. A. N.N-Dibenzyl-(L)-phenylalanine Benzyl Ester. A solution containing L-phenylalanine (161 kg, 975 moles), potassium carbonate (445 kg, 3220 moles), water (675 L), ethanol (340 L), and benzyl chloride (415 kg, 3275 moles) was heated to 90±15°C for 10-24 hours. The reaction mixture was cooled to 60°C and the lower aqueous layer was removed. Heptane (850 L) and water (385 L) were added to the organics, stirred, and the layers separated. The organics were then washed once with a water/methanol mixture (150 L/150 L). The organics were then stripped to give the desired product as an oil, which was carried on in the next step without purification. IR (neat) 3090, 3050, 3030, 1730, 1495, 1450, 1 160 cm- ' , 1 H NMR (300 MHz, CDCI3) δ 7.5-7.0 (m, 20H), 5.3 (d, 1 H, J = 13.5 Hz), 5.2 (d, 1 H, J = 13.5 Hz), 4.0 (d, 2H, J = 15 Hz), 3.8 (t, 2H, J = 8.4 Hz), 3.6 (d, 2H, J = 15 Hz), 3.2 (dd, 1 H, J = 8.4, 14.4 Hz), 13c NMR (300 MHz, CDCI3) δ 172.0, 139.2, 138.0, 135.98.2, 128.1 , 128.1 , 126.9, 126.2, 66.0, 62.3, 54.3, 35.6. [α] D -79° (c = 0.9, DMF). B. (4S -(N.N-Dibenzvlamino,-3-oxo-5-phenvl-pentanonitrile. A solution containing the product of Example 1A (i.e., benzyl ester) (approx. 0.45 moles) in 520 mL tetrahydrofuran and 420 mL acetonitrile was cooled to -40°C under nitrogen. A second solution containing sodium amide (48.7g, 1.25 moles) in 850 mL tetrahydrofuran was cooled to -40°C. To the sodium amide solution was slowly added 75 mL acetonitrile and the resulting solution was stirred at -40°C for more than 15 minutes. The sodium amide/acetonitrile solution was then slowly added to the benzyl ester solution at -40°C. The combined solution was stirred at -40°C for one hour and then quenched with 1 150 mL of a 25% (w/v) citric acid solution. The resulting slurry was warmed to ambient temperature and the organics separated. The organics were then washed with 350 mL of a 25% (w/v) sodium chloride solution, then diluted with 900 mL heptane. The organics were then washed three times with 900 mL of a 5% (w/v) sodium chloride solution, two times with 900 mL of a 10% methanolic water solution, one time with 900 mL of a 15% methanoiic water solution, and then one time with 900 mL of a 20% methanolic water solution. The organics were stripped and the resulting material dissolved into 700 mL of hot ethanol. Upon cooling to room temperature, the desired product precipitated. Filtration gave the desired product in 59% yield from the L- phenylalanine. IR (CHCI3) 3090, 3050, 3030, 2250, 1735, 1600, 1490, 1450, 1370, 1300, 1215 cm" 1 , 1 H NMR (CDCI3) δ 7.3 (m, 15H), 3.9 (d, 1 H, J = 19.5 Hz), 3.8 (d, 2H, J = 13.5 Hz), 3.6 (d, 2H, J = 13.5 Hz), 3.5 (dd, 1 H, J = 4.0, 10.5 Hz), 3.2 (dd, 1 H, J = 10.5, 13.5 Hz), 3.0 (dd, 1 H, J = 4.0, 13.5 Hz), 3.0 (d, 1 H, J = 19.5 Hz), 13c NMR (300MHz, CDCI3) δ 197.0, 138.4, 138.0, 129.5, 129.0, 128.8, 128.6, 127.8, 126.4, 68.6, 54.8, 30.0, 28.4. [αJ D -95° (c = 0.5, DMF). C. ,5S 2-Amino-5-(N.N-dibenzvlaminoV4-oxo-1 .6-diphenvlhex-2-ene. To a -5°C solution of the nitrile product of Example 1 B (90 Kg, 244 moles) in tetrahydrofuran (288 L), was added benzylmagnesium chloride (378 Kg, 2M in THF, 708 moles). The solution was warmed to ambient temperature and stirred until analysis showed no starting material. The solution was then recooled to 5°C and slowly transferred to a solution of 15% citric acid (465 kg). Additional tetrahydrofuran (85 L) was used to rinse out the original container and the rinse was added to the citric acid quench container. The organics were separated and washed with 10% sodium chloride (235 kg) and stripped to a solid. The product was stripped again from ethanol (289 L) and then dissolved in 80°C ethanol (581 L)). After cooling to room temperature and stirring for 12 hours, the resulting product was filtered and dried in a vacuum oven at 30°C to give approx. 95 kg of the desired product, mp 101 -102°C, IR (CDCI3) 3630, 3500, 3110, 3060, 3030, 2230, 1620, 1595, 1520, 1495, 1450 cm- 1 , 1 H NMR (300 MHZ, CDCI3) d 9.8 (br s, 1 H), 7.2 (m, 20H), 5.1 (s, 1 H), 4.9 (br s, 1 H), 3.8 ( d, 2H, J = 14.7 Hz), 3.6 (d, 2H, J = 14.7Hz), 3.5 (m, 3H), 3.2 (dd, 1 H, J = 7.5, 14.4 Hz), 3.0 (dd, 1 H, J = 6.6, 14.4 Hz), ^ -C NMR (CDCI3) d 198.0, 162.8, 140.2, 140.1 , 136.0, 129.5, 129.3, 128.9, 128.7, 128.1 , 128.0, 127.3, 126.7, 125.6, 96.9, 66.5, 54.3, 42.3, 32.4. [αJ D -147° (c = 0.5, DMF). D. .2S. 3S. 5S,-5-Amino-2-fN.N-dibenzvlamino -3-hvdroxv-1.6-diohenyl- hexane i) A suspension of sodium borohydride (6.6 kg, 175 moles) in tetrahydrofuran (157 L) was cooled to less than -10±5°C. Methanesulfonic acid (41.6 kg, 433 moles) was slowly added and the temperature kept below 0°C during the addition. Once the addition was complete, a solution of water (6 L, 333 moles), the product of Example 1 C (20 kg, 43 moles) and tetrahydrofuran (61 L) was slowly added while maintaining the temperature below 0°C during the addition. The mixture was stirred for not less than 19h at 0±5°C. ii) To a separate flask was added sodium borohydride (6.6 kg, 175 moles) and tetrahydrofuran (157 L). After cooling to -5±5°C, trifluoroacetic acid (24.8 kg, 218 moles) was added while maintaining the temperature below 15°C. The solution was stirred 30 min at 15+5°C and was then added to the reaction mixture resulting from step i, keeping the temperature at less than 20°C. This was stirred at 20±5°C until reaction was complete. The solution was then cooled to 10±5°C and quenched with 3N NaOH (195 kg). After agitating with te/ -butyl methyl ether (162 L), the organic layer was separated and washed one time with 0.5N NaOH (200 kg), one time with 20% w/v aqueous ammonium chloride (195 kg), and two times with 25% aqueous sodium chloride (160 kg). The organics were stripped to give the desired product as an oil which was used directly in the next step. IR (CHCI3) 3510, 3400, 3110, 3060, 3030, 1630, 1 H NMR (300 MHz, CDCI3) δ 7.2 (m, 20H), 4.1 (d, 2H, J = 13.5 Hz), 3.65 (m, 1 H), 3.5 (d, 2H, J = 13.5 Hz), 3.1 (m, 2H), 2.8 (m, 1 H), 2.65 (m, 3H), 1.55 (m, 1 H), 1.30 (m, 1 H), 3c NMR (300 MHz, CDCI3) δ 140.8, 140.1 , 138.2, 129.4, 129 4, 128.6, 128.4, 128 3, 128 2, 126.8, 126.3, 125 7, 72.0, 63.6, 54 9, 53.3, 46.2, 40.1 , 30.2 E ( 2S.3S.5S ) -2-. N.N-Dιbeπzylamιπθ--3-hv roxy-5-.t-butyloxycarbonylamιno)- 1 .6-dιphenylhexane To a solution of the [2S,3S,5S]-2-N,N-dιbenzylamιno-3-hydroxy-5-amιno- 1 ,6-dιphenylhexane (approx. 105 kg, 226 moles) in MTBE (1096 L), was added BOC Anhydride (65 kg, 373 moles) and 10% potassium carbonate (550 kg) This mixture was stirred until reaction was complete (approx 1 hour) The bottom layer was removed and the organics were washed with water (665 L) The solution was then stripped to give the desired product as an oil 300 MHz 1 H NMR (CDCI3) δ 1 40 (s,9H), 1.58 (s, 2H), 2 45-2.85 (m, 4H), 3 05 (m, 1 H), 3 38 (d, 2H), 3.6 (m, 1 H), 3.79 (m, 1 H), 3 87 (d, 2H), 4.35 (s, 1 H), 4 85 (s, broad, 1 H), 7 0-7.38 (m, 20 H). F-1 (2S.3S.5SV2-Amino-3-hvdroxy-5-ft-butyloxycarbonylaminon .6- diphenylhexane To a stirred solution of [2S,3S,5S]-2-N,N-dιbenzylamιno-3-hydroxy-5-t- butyloxycarbonylamιno-1 ,6-dιphenylhexane (12 g, 21.3 mmol) in methanol (350 mL) was charged ammonium formate (8 05 g, 128 mmol, 6 0 eq) and 10% palladium on carbon (2.4 g) The solution was stirred under nitrogen at 60 °C for three hours and then at 75 °C for 12 hours. An additional amount of ammonium formate (6 g) and 10% palladium on carbon (1.5 g) was added as well as 1 mL of glacial acetic acid The reaction was driven to completion within 2 hours at a reflux temperature The reaction mixture was then cooled to room temperature and then filtered through a bed of celite. The filter cake was washed with methanol (75 mL) and the combined filtrates were concentrated under reduced pressure The residue was taken up in 1 N NaOH (300 mL) and extracted into methylene chloride (2 X 200 mL) The combined organic layers were washed with brine (250 mL) and dried over sodium sulfate Concentration of the solution under reduced pressure provided the desired product as a light colored oil which slowly crystallized upon standing (5 g). Further purification of the product could be accomplished by flash ehromatography (silica gel, 5% methanol in methylene chloride). 300 MHz 1 H NMR (CDCI3) δ 1 .42 (s, 9H), 1 .58 (m, 1 H), 1 .70 (m, 1 H), 2.20 (s, broad, 2H), 2.52 (m, 1 H), 2.76-2.95 (m, 4H) , 3.50 (m, 1 H), 3.95 (m, 1 H), 4.80 (d, broad, 1 H), 7.15-7.30 (m, 10H). F-2. r2S.3S.5S]-2-Amino-3-hvdroxv-5-t-butvloxvcarbonvlamino-1 .6- diphenvlhexane succinate salt To a solution of [2S,3S,5S]-2-N,N-dibenzylamino-3-hydroxy-5-t- butyloxycarbonylamino-1 ,6-diphenylhexane(approx. 1 27 kg, 225 moles) in methanol (437 L), was added a methanolic (285 L) slurry of 5% palladium on carbon (24 kg). To this was added a solution of ammonium formate (84 kg, 1332 moles) in methanol (361 L). The solution was heated to 75°C for 6-12 hours and then cooled to room temperature. Solids were filtered from the reaction mixture using a filter coated with filteraid (Celite) and the methanol was stripped from the reaction mixture using heat and vacuum (up to 70°C). The residue was dissolved in isopropyl acetate (4400 kg) with heat (40°C) and then washed with a 10% sodium carbonate solution (725 kg), and finally with water (665 L). Both of the washes were performed at 40°C to keep the product in solution. The solvent was removed under vacuum with heat (up to 70°C). Isopropyl alcohol (475 L) was then added and stripped off to remove residual solvents. Isopropanol (1200 L) was added to the residue and stirred until homogeneous. To this solution was added a solution of succinic acid (15-40 kg) in isopropanol (1200 L). The solution jacket was heated to 70°C to dissolve all of the solids and then allowed to slowly cool to room temperature and stir for 6 hours. The solution was then filtered to give the desired product as a white solid (55-80 kg). mp: 145-146 °C. 1 H NMR: (Me 2 SO-d 6 , 300 MHz) δ 0.97 (d, 3H, IPA), 1 .20 (s, 9H), 1 .57 (t, 2H), 2.20 (s, 2H, succinic acid), 2.55 (m, 2H), 2.66 (m, 2H), 2.98 (m, 1 H), 3.42 (m, 1 H), 3.70 (m, 1 H), 3.72 (m, 1 H, IPA), 6.60 (d, 1 H, amide NH), 7.0- 7.3 (m, 10H). 1 H NMR: (CD 3 OD, 300 MHz) δ 1.11 (d, 3H, J=7 Hz, IPA), 1.29 (s, 9H), 1.70 (m, 2H), 2.47 (s, 2H, succinic acid), 2.65 (m, 2H), 2.85 (m, 2H), 3.22 (m,1 H), 3.64 (m, 1 H), 3.84 (m, 1 H), 7.05-7.35 (m, 10H). G Ethyl 2.6-dimethylPhenoxy acetate. To a solution of 2,6-dιmethylphenol (8.0 g, 66 mmole) in dioxane (600 ml) was added ethyl bromoacetate (18.2 ml, 164 mmole) and cesium carbonate (58 g, 176 mmole). The reaction mixture was heated at reflux for 18 h, cooled to room temperature, filtered and concentrated in vacuo. Purification by silica gel column ehromatography (5% to 20% ether in hexane) provided the desired compound (80%). 300 MHz 1 H NMR (CDCI3) δ 1.35 (t, J = 7.5 Hz, 3H), 2.30 (s, 6H), 4.31 (q, J = 7.5 Hz, 2H), 4.40 (s, 2H), 7.0 (m, 3H) H. 2.6-Dιmethylphenoxy acetic acid. To a solution of the compound from Example 1 G (5.15 g, 24.7 mmole) in methanol (170 ml) and water (56 ml) was added 5.3 g of lithium hydroxide at 0°C, the solution was stirred for 1.5 h at RT and concentrated in vacuo. The residue was acidified with 0.5M HCl and extracted with ethyl acetate (300 ml). The organic layer was dried and concentrated to give a white solid (4.05 g, 91 %). 300 MHz 1 H NMR (CDCI3) δ 2.30 (s, 6H), 4.48 (s, 2H), 7 0 (m, 3H). I. .2S. 3S. 5S- -2-.2.6-Dιmethylphenc-xyacetyl) ammo-3-hvdroxy-5-.t- butyloxycarbonylamιnoH .6-diphenylhexane. Coupling of the amme from Example 1 F with the acid from Example 1 H using standard EDAC coupling procedure provided the desired compound (78%). 300 MHz 1 H NMR (CDCI3) δ 1.40 (s, 9H), 1.65 (m, 3H), 2.18 (s, 6H), 2.78 (m, 2H), 2.98 (d, J = 9 Hz, 2H), 3.75 (m, 1 H), 3.90 (m, 1 H), 4.15 (m, 1 H), 4.20 (s, 2H), 4.60 (m, 1 H), 7.0 (m, 3H), 7.25 (m, 10H). Mass spectrum: (M = H)+ = 547. J. 2-N-(Benzyloxycarbonyl) amino-acetaldehvde. To a solution of 1.45 ml of DMSO in 20 ml of CH2CI2 at -78°C was added dropwise 1.34 ml of oxalyl chloride After 15 minutes at -78°C, a solution of N-Cbz-amιnoethanol in 40 ml of CH2CI2 was added. After 15 minutes at -78°C and 2 minutes at 0°C, the solution was cooled to -78 C C and tπethylamine (6.14 ml) was added dropwise. The solution was stirred at -78°C for 30 minutes and poured into 50 ml of cold 10% aq. citric acid and extracted with ether (150 ml) The combined organic layer was washed with brine and dried with anhydrous Na2Sθ4; filtered and concentrated in vacuo. Purification of the crude product by silica gel column ehromatography (10% EtOAc/CH2Cl2) provided the desired compound (42%) 300 MHz H NMR (CDCI3) δ 4.17 (d, J = 6 Hz, 2H), 5.15 (s, 2H), 5.40 (br s, 1 H), 7.36 (m, 5H), 9.66 (s, 1 H). Mass spectrum. (M+NH4)+ = 211 . K N-(Benzyloxycarbonylamιno)-ethyl valme methyl ester To a solution of the aldehyde from Example 1 J (0.829 g, 4 29 mmole) in 17 ml of methanol was added valme methyl ester hydrochloride (0.72 g, 4.29 mmole), sodium acetate (0.7 g, 8.58 mmole), and sodium cyanoborohydride (0 54 g, 8.58 mmole. The mixture was stirred at RT overnight and the solvent was evaporated in vacuo. The residue was taken up in ethyl acetate (100 ml) and washed with satd. NaHCθ3 (10 ml) and the aq. layer was extracted with ethyl acetate (2 x 50 ml) The combined organic layer was washed with brine and dried with anhy. sodium sulfate, filtered and concentrated in vacuo. The residue was purified by silica gel column ehromatography (20% E.OAC/CH2CI2) to provide the desired compound (60%). 300 MHz 1 H NMR (CDCI3) δ 0.91 (d, J = 3 Hz, 3H), 0.94 (d, J = 3 Hz, 3H), 1 .90 (m, 1 H), 2.55 (m, 1 H), 2.80 (m, 1 H). 2.98 (d, J = 6 Hz, 1 H), 3.20 (m, 1 H), 3.30 (m, 1 H), 3.71 (s, 3H), 5.10 (s, 2H), 5.27 (br s, 1 H), 7, 37 (m, 5H) Mass spectrum: (M+H)+ = 309 L. 2S-(1 -lmιdazolιdιn-2-onyl ,-3-methyl butanoic acid methyl ester The Cbz-protectmg of the compound in Example 1 K was removed by hydrogenolysis and the crude product was treated with one equivalent of 1 ,1 - carbonyldiimidazole in CH2CI2 to provide the desired compound (64%), 300 MHz 1 H NMR (CDCI3) δ 0.95 (d, J = 7.5 Hz, 3H), 0 98 (d, J = 7.5 Hz, 3H), 2.15 (m, 1 H), 3 47 (m, 3H), 3.71 (s, 3H), 3.73 (m, 1 H), 4.23 (d, J = 10.5 Hz, 1 H), 4 81 (br s, 1 H), Mass spectrum. (M+H)+ = 201 M 2S-(1 -lmιdazolιdιn-2-onylV3-methyl butanoic acid To a solution of the compound from Example 1 L (151 mg, 0.75 mmole) in 2 5 ml of water and 5 ml of dioxane was added at 0°C lithium hydroxide monohydrate (2.0 eq ) The solution was stirred at 0°C for 1.5 h and RT for 1 h Acidification with 1 N HCl, extraction with EtOAc (100 ml + 2 x 50 ml), dπed with sodium sulfate and evaporation of the filtered solution in vacuo provided the desired compound (88%). 300 MHz 1 H NMR (DMSO-dβ) δ 0.85 (d, J = 12 Hz, 3H), 0 92 (d, J = 12 Hz, 3H), 2.05 (m, 1 H), 3.25 (m, 2H), 3 30 (m, 1 H), 3.50 (m, 1 H), 3 90 (d, J = 15 Hz, 1 H), 6.40 (br s, 1 H), 12.60 (br s, 1 H) Mass spectrum (M+H)+ = 187 N (2S. 3S. 5S. -2-.2.6-Dιmethylphenoxyacetyl. amιno-3-hvdroxy-5-amιno-1.6- diphenylhexane To 4 5 g of the compound from Example 11 was added 40 ml each of CH2CI2 and tπfluoroacetic acid. The solution was left at RT for 1 h Concentration of the solution in vacuo provided the desired compound (100%) 300 MHz 1 H NMR (CDCI3) δ 1 48 (m, 1 H), 1.62 (m, 1 H), 2 05 (m, 1 H), 2 24 (s, 6H), 2.50 (m, 1 H), 2.80 (m, 1 H), 3.0-3 10 (m, 4H), 3.90 (d, J = 10 Hz, 1 H), 4 17 (m, 1 H), 4.26 (ABq, J = 13.5 Hz, 2H), 7 0 (m, 3H), 7 10 (m, 2H), 7.30 (m, 7H), 7 41 (d, J = 10 Hz, 1 H) Mass spectrum (M+H)+ = 447 O (2S. 3S. 5S.-2-.2.6-DιmethylDhenoxyacetyl- amιno-3-hvdroxy-5-.2S-.1 - ιmιdazolιdιn-2-onv0-3-methyl-butanoyl] ammo-1 .6-dιphenylhexane Coupling of the ammo compound from Example 1 N with the acid from Example 1 M using standard coupling procedure [1 -(3-dιmethylamιnopropyl)-3- ethylcarbodnmide in DMF] provided the desired compound (80%) 300 MHz 1 H NMR (CDCI3) δ 0.83 (d, J = 6 Hz, 3H), 0 86 (d, J = 6 Hz, 3H), 1.75 (m, 2H), 2 16 (m, 1 H), 2 18 (s, 6H), 2 76 (m, 2H), 2 97 (d, J = 7 5 Hz, 2H), 3 14 (m, 2H), 3 30 (m, 2H), 3 70 (d, J = 1 - Hz, 1 H), 3 75 (m, 1 H), 4.20 (m, 4H), 4.50 (br s, 1 H), 6 70 (d, J = 7 5 Hz, 1 H), 7 0 (m, 3H), 7 25 (m, 10H) Mass Spectrum (M+H)+ = 615 Examole 2 (2S. 3S. 5S)-2-f2.6-DimethylDhenoxyacetvn amino-3-hvdroxy-5-.2S-.1 - tetrahvdro-Dyrimid-2-onyl.-3-methyl butanoyl] amino-1.6-diphenylhexane. A. 2S-π -Tetrahvdro-Dyrimid-2-onvπ-3-methyl butanoic acid. Using the procedures described in Examples U to 1 M, but replacing the N-Cbz-aminoethanol in Example 1J with N-Cbz-3-aminopropanol provided the desired compound. 300 MHz 1 H NMR (DMSO-d6) δ 0.82 (d, J = 7 Hz, 3H), 0.93 (d, J - 7 Hz, 3H), 1.77 (m, 2H), 2.10 (m, 1 H), 3.10-3.23 (m, 4H), 4.42 (d, J = 10.5 Hz, 1 H), 6.37 (br s, 1 H). Mass spectrum: (M+H)+ = 201. B. ,2S. 3S. 5S,-2-(2.6-Dimethylphenoxyacetvπ amino-3-hvdroxy-5-f2S-(1 - tetrahvdro-pyhmid-2-onvπ-3-methyl butaπoyl] amino-1 .6-diphenylhexane. Coupling of the amino compound from Example 1 N with the acid from Example 2A using standard procedure (EDAC in DMF) provided the desired compound (70%). 300 MHz 1 H NMR (CDCI3) δ 0.80 (d, J = 4.5 Hz, 3H), 0.83 (d, J = 4.5 Hz, 3H), 1.50 (m, 1 H), 1.65-1.72 (m, 6H), 2.20 (s, 6H), 2.68 (m, 1 H), 2.82 (m, 2H), 3.0 (d, J =7.5 Hz, 1 H), 3.05 (m, 4H), 3.77 (m, 1 H), 4.07 (d, J = 4.5 Hz, 1 H), 4.20 (m, 4H), 4.50 (br s, 1 H), 6.78 (br d, 1 H), 7.0 (m, 3H), 7.25 (m, 10H). Mass spectrum: (M+H)+ = 629. Example 3 (2S. 3S. 5S.-2-.2.6-Dimethv.Phenoxyacetyl. amino-3-hvdroxy-5-l2S-(3- oxazolidin-2-onyl,-3-methyl-butanoyl] amino-1 .6-diphenylhexane. A. 2S-(3-Qxazolidin-2-onvπ-3-methyl-butanoic acid methyl ester. To a solution of L-valine methyl ester hydrochloride (7.6 mmole) was added a solution of ethylene oxide in ethanol (1.5 equivalent). The solution was kept at 0°C for 0.5 h and then at RT for 18 h, at which time 0.01 equivalent of BF3Ε.2O was added. Fresh ethylene oxide was bubbled directly into the solution for 3 to 4 minutes. After 8 h the solution was concentrated to dryness and the residue was dissolved in CH2CI2 and cooled to 0°C. To this solution was added 1.2 equivalents of triethylamine and 1.0 equivalent of triphosgene. After 1 h, the solvent was removed in vacuo and the residue was washed with water (30 ml) and extracted with CH2CI2 (3x50 ml), dried and concentrated Purification of the crude product by silica gel column ehromatography (5% EtOAc/CH CI 2 ) provided the desired compound (42%, 2 steps) 300 MHz H NMR (CDCI3) δ 0.98 (d, J = 4.0 Hz, 3H), 1.0 (d, J = 4 0 Hz, 3H), 2 16 (m, 1 H), 3.60 (m, 2H), 3.73 (s, 3H), 4.20 (d, J = 10 Hz, 1 H), 4.37 (m, 2H). Mass spectrum. (M+H)+ = 202. B. 2S-(3-Oxazolιdιn-2-onvO-3-methyl-butanoιc acid Hydrolysis of the methyl ester from Example 3A, using the procedure described in Example 1 M provided the desired compound. 300 MHz 1 H NMR (DMSO-d6) δ 0.90 (d, J = 6 Hz, 3H), 0.95 (d, J = 6 Hz, 3H), 2.1 (m, 1 H), 3.55 (m, 1 H), 3.70 (m, 1 H), 3.88 (d, J = 9 Hz, 1 H), 4.30 (m, 2H), 13 0 (br s, 1 H) Mass spectrum- (M+NH. + = 205 C .2S. 3S. 5S.-2-.2.6-DιmethylDhenoxyac8tyl- amιno-3-hvdroxy-5-[2S-(3- oxazolιdin-2-onv0-3-methyl-butanoyl] amιno-1 ,6-dιphenylhexane. Coupling of the amme from Example 1 N with the acid from Example 3B using standard coupling procedures (EDAC in DMF) provided the desired compound. 300 MHz 1 H NMR (CDCI3) δ 0.83 (d, J = 4.5 Hz, 3H), 0.87 (d, J = 4.5 Hz, 3H), 1 75 (m, 1 H), 2.10 (m, 1 H), 2 20 (s, 6H), 2 65 (m, 1 H), 2.85 (m, 1 H), 3.0 (m, 3H), 3.30 (m, 1 H), 3.60 (m, 2H), 3 77 (m, 1 H), 4.20 (m, 4H), 6.25 (br d, J = 6 Hz, 1 H), 7.0 (m, 3H), 7.25 (m, 10H) Mass spectrum- (M+H)+ = 616 Example 4 f2S.3S.5S)-2-f(3R. 3aS. 6aR)-Bιs-tetrahvdrofuranyloxyl amιno-3-hvdroxy-5-r2S- (3-methyl-1 -ιmιdazolιdιn-2-onyl,-3-methyl butanoyl] amιno-1 ,6-dιphenylhexane A 2S-(3-Methyl-1 -ιmιdazolιdιn-2-onvO-3-methyl butanoic acid methyl ester To a suspension of 45 mg (60% oil dispersion) of sodium hydride in 0.5 ml of DMF was added a solution of 150 mg of the compound from Example 1 L in 4.5 ml of DMF After 20 minutes at RT, (1.5 equivalent, 0.07 ml) methyl iodide was added Reaction was complete in 1 h The reaction was quenched with satd. NH4CI solution and extracted with ether (100 ml + 50 ml x 2), dried and concentrated in vacuo. The crude product was purified by silica gel column ehromatography (20% E.OAC/CH2CI2) to provide the desired compound (61 %). 300 MHz 1 H NMR (CDCI3) δ 0.95 (d, J = 6 Hz, 3H), 0.97 (d, J = 6 Hz, 3H, 2.15 (m, 1 H), 2.80 (s, 3H), 3.32 (m, 3H), 3.60 (m, 1 H), 3.70 (s, 3H), 4.25 (d, J = 10.5 Hz, 1 H). Mass spectrum: (M+H) + = 215. B. 2S-f3-Methyl-1 -ιmidazolidin-2-onyl,-3-methyl butanoic acid. Hydrolysis of the methyl ester from Example 4A using the procedure described in Example 1 M provided the desired compound. 300 MHz 1 H NMR (DMSO-d6) δ 0.85 (d, J = 6 Hz, 3H), 0.92 (d, J = 6 Hz, 3H), 2.05 (m, 1 H), 2.65 (s, 3H), 3.25 (m, 3H), 3.42 (m, 1 H), 3.90 (d, J = 10 Hz, 1 H). Mass spectrum- (M+H)+ = 201. C. (3R,3aS,6aR,-Bιs-tetrahvdrofuranyl-(4-nitrophenyl) carbonate To a solution of 3R-hydroxy-(3aS,6aR)-bιs-tetrahydrofuran [J. Med. Chem. 37, 2506-2508 (1994)] (200 mg, 1.54 mmole) in 10 ml of CH CI 2 was added tπethylamine (0.26 ml, 1.85 mmole), and p-nitrophenyl chloroformate (341 mg, 1.69 mmole). The solution was kept at RT for 3 days, diluted with CH2CI2 (100 ml) and washed with satd. NaHCθ3 (15 ml). The organic layer was dried and concentrated in vacuo. Purification by silica gel column ehromatography (5% EtOAc/CH2Cl2) provided the desired compound (42%). 300 MHz 1 H NMR (CDCI3) δ 2.0 (m, 1 H), 2.20 (m, 1 H), 3 18 (m, 1 H), 4.0 (m, 3H), 4.17 (m, 1 H), 5.27 (m, 1 H), 5.80 (d, J = 6 Hz), 7 40 (d, J = 7.5 Hz, 2H), 8.30 (d, J = 7.5 Hz, 2H) Mass spectrum: (M+NH )+ = 313. D (2S.3S.5S)-2-f(3R.3aS.6aR ,-Bιs-tetrahvdrofuranyloxy1 amιno-3-hvdroxy-5-ft- butyloxy carbonvH amιno-1 .6-diphenylhexane. To a solution of the carbonate from Example 4C (100 mg, 0.34 mmole) in 3.4 ml of DMF was added the compound from Example 1 F (130 mg, 0.34 mmole) The solution was kept at RT overnight and then concentrated in vacuo. Purification of the crude product by silica gel column ehromatography (2% to 5% MeOH/CH 2 CI 2 ) provided the desired compound (93%). 300 MHz 1 H NMR (CDCI3) δ 1 40 (s, 9H), 1 64 (m, 3H), 2 76 (m, 2H), 2.87 (m, 2H), 3.66-4 0 (m, 7H), 4.53 (m, 1 H), 5.06 (m, 2H), 5.68 (d, J = 6 HZ, 1 H), 7.10-7.28 (m, 10H) Mass spectrum: (M+NH 4 )+ = 558. E (2S.3S.5SV2-r(3R.3aS.6aRVBιs-tetrahvdrofuranyloxy1 amιno-3-hvdroxy-5- amιno-1 ,6-diPhenylhexane. To a solution of the compound from Example 4D (170 mg, 0 31 mmole) in 5 ml of CH2CI2 was added 5 ml of tπfluoroacetic acid After 0.25 h, the solvent was removed in vacuo The residue was dissolved in 100 ml of EtOAc and washed with satd. NaHCOβ and then brine, dried and concentrated to provide the desired compound (91 %) 300 MHz 1 H NMR (CDCI3) δ 1.27-1 60 (m, 4H), 1 75 (m, 2H), 2 47 (m, 1 H), 2 80 (m, 1 H), 2 88 (m, 2H), 3.0 (m, 2H),3 80 (m 4H), 4.0 (m, 1 H), 5 10 (m, 1 H), 5.30 (d, J = 10 5 Hz, 1 H), 5 70 (d, J = 6 Hz, 1 H), 7 05- 7 25 (m, 10H) Mass spectrum (M+H)+ = 441 F .2S.3S.5S.-2-f.3R. 3aS. 6aRVBιs-tetrahvdrofuranyloxyl amιno-3-hvdroxy-5- f2S-.3-methv ιdazolιdιn-2-onyl.-3-methyl butanoyll amιno-1 .6- diphenylhexane Coupling of the carboxylic acid from Example 4B with the ammo compound from Example 4E using standard procedure (EDAC in DMF) provided the desired compound 300 MHz 1 H NMR (CDCI3) δ 0 82 (d, J = 3H, 3H), 0.85 (d, J = Hz, 3H), 1 65 (m, 1 H), 2.77 (s, 3H), 2.85 (m, 3H), 3 17 (m, 2H) 3 47 (m, 1 H), 3 60 (m, 2H), 3 75 (m, 1 H), 3 87 (m, 1 H), 4 0 (m, 1 H), 4 20 (m, 1 H), 5.05 (m, 2H), 5 68 (d, J = 6 Hz, 1 H), 6 45 (br d, J = 7 5 Hz, 1 H), 7.20 (m, 10H) Mass spectrum (M+H)+ = 623 Example 5 ■ 2S.3S.5S.-2-[.3R.3aS.6aR .-Bιs-tetrahvdrofuranyloxyl ammo-3-hvdroxy-5-.2S- (1 -ιmιdazolιdιn-2-onyl)-3-methyl butanoyll amιno-1 ,6-dιphenylhexane Coupling of the ammo compound from Example 4E with the carboxylic acid from Example 1 M using standard procedure (EDAC/DMF) provided the desired compound 300 MHz 1 H NMR (CDCI3) δ 0 85 (d, J = 7 Hz, 3H), 0 88 (d, J = Hz, 3H), 1 70 (m, 2H, 2 18 (m, 1 H), 2 80 (m, 3H), 2 95 (m, 1 H), 3.20 (m, 4H), 3.60 (m, 3H), 3.75 (m, 2H), 4.0 (m, 1 H), 4.20 (m, 1 H), 4.45 (s, 1 H), 5.10 (m, 2H), 5.67 (d, J = 6 Hz, 1 H) 6.60 (d, J = 7.5 Hz, 1 H), 7.20 (m, 10H). Mass spectrum: (M+H)+ = 609. Example 6 ■ 2S.3S.5S--2-.N-.(5-Thia2olvnm9thoxycarbonyl-amino ) -5-. f2S-M -imidazolidin- 2-onvπ-3-methyl-butanov0-amino)-3-hvdroxy-1 .6-diphenylhexane. A. Ethyl 2-Chloro-2-formylacetate. To a three neck 2L round bottom flask charged with potassium t-butoxide (0.5 mol, 500 mL of a 1 M solution in THF) and 500 mL of dry THF cooled to 0°C was added dropwise from an addition funnel a solution of ethyl chloroacetate (0.5 mol, 53.5 mL) and ethyl formate (0.5 mol, 40.4 mL), in 200 mL of THF over 3 hours. After completion of addition, the reaction mixture was stirred for 1 hour and allowed to stand overnight. The resulting solid was diluted with diethyl ether and cooled in an ice bath. Then, the pH was lowered to approximately 3 using 6N HCl. The organic phase was separated, and the aqueous layer was washed 3 times with diethyl ether. The combined ethereal portions were dried over NaS0 4 , and concentrated in vacuo. The crude desired compound was stored at -30°C and used without further purification. B. Ethyl Thiazole-5-carboxylate. To a round bottom flask was added 250 mL of dry acetone, 7.5 g (0.123 mol) of thioformamide, and 18.54 g (0.123 mol) of ethyl 2-chloro-2- formylacetate. The reaction was heated at reflux for 2 hours. The solvent was removed in vacuo, and the residue was purified by ehromatography (Siθ2, 6 cm o.d. column, 100% CHCI3, Rf = 0.25) to provide 1 1.6 g (60%) of the desired compound as a light yellow oil. NMR (CDCI3 δ 1.39 (t, J = 7 Hz, 3H), 4.38 (q, J = 7 Hz, 2H), 8.50 (s, 1 H), 8.95 (s, 1 H). C. 5-(Hvdroxymethvhthiazole. To a precooled (ice bath) three neck 500 mL flask containing lithium aluminum hydride (2.89 g, 76 mmol) in 250 mL of THF was added ethyl thiazole-5-carboxylate (11.82 g, 75.68 mmol) in 100 mL of THF dropwise over 1.5 hours to avoid excess foaming. The reaction was stirred for an additional hour, and treated cautiously with 2.9 mL of water, 2.9 mL of 15% NaOH, and 8.7 mL of water. The solid salts were filtered, and the filtrate set aside. The crude salts were heated at reflux in 100 mL of ethyl acetate for 30 minutes. The resulting mixture was filtered, and the two filtrates were combined, dried over Na2S0 , and concentrated in vacuo. The product was purified by silica gel ehromatography eluting sequentially with 0% - 2% - 4% methanol in chloroform, to provide the desired compound, Rf - 0.3 (4% methanol in chloroform), which solidified upon standing in 75% yield. NMR (CDCI3) δ 4.92 (s, 2H), 7.78 (s, 1 H), 8.77 (s, 1 H). Mass spectrum: (M+H)+ = 116. D. ((5-ThiazolvπmethylH4-nιtrophenyl)carbonate. A solution of 3.1 1 g (27 mmol) of 5-(hydroxymethyl)thiazole and excess N-methyl morpholine in 100 ml of methylene chloride was cooled to 0°C and treated with 8.2 g (41 mmol) of 4-nitrophenyl chloroformate. After being stirred for 1 h, the reaction mixture was diluted with CHCI3, washed successively with 1 N HCl, saturated aqueous NaHCθ3, and saturated brine, dried over NaS0 , and concentrated in vacuo. The residue was purified by silica gel ehromatography (Si0 2 , 1-2% MeOH/CHCI 3 , Rf = 0.5 in 4% MeOH/CHCi3) to yield 5.9 g (78%) of the desired compound as a yellow solid. NMR (CDCI3) δ 5.53 (s, 2H), 7.39 (dt, J = 9, 3 Hz, 2H), 8.01 (s, 1 H), 8.29 (dt, J = 9, 3 Hz, 2H), 8.90 (s, 1 H). Mass spectrum: (M+H)+ = 281. E. (2S.3S,5S)-5-Amino-2-(N-((5-thiazolyl)-methoxycarbonyl)amino)-3-hvdroxy- 1 .6-diphenylhexane. Coupling of the amino compound from Example 1 F with the carbonate from Example 6D using the procedure from Example 4D, followed by removal of the Boc-protecting group using TFA/CH2CI2 provided the desired compound. 300 MHz 1 H NMR (CDCI3) δ 1.3-1.6 (m, 2H), 2.40 (dd, J = 14, 8 Hz, 1 H), 2.78 (dd, J = 5 Hz, 1 H), 2.88 (d, J = 7 Hz, 2H), 3.01 (m, 1 H), 3.72 (br q, 1 H), 3.81 (br d, J = 10 Hz, 1 H), 5.28 (s, 2H), 5.34 (br d, J = 9 Hz, 1 H), 7.07 (br d, J = 7 Hz, 2H), 7.15-7.35 (m, 8H), 7.87 (s, 1 H), 8.80 (s, 1 H). Mass spectrum: (M+H)+ = 426. F. f2S.3S.5S)-2-.N-. -5-thia2olyl.methoxycarbonyl.amino .-5-r.2S-n - imidazolidin-2-onv0-3-methyl-butanoylr-amino ) -3-hvdroxy-1 .6-diphenylhexane. Coupling of the amino compound from Example 6E with the carboxylic acid from Example 1 M using standard procedure (EDAC in DMF) provided the desired compound (52%). 300 MHz H NMR (CDCI3) δ 0.82 (d, J = 7.5 Hz, 3H), 0.85 (d, J = 7.5 Hz, 3H), 1.65 (m, 2H), 2.15 (m, 1 H), 2.70 (m, 3H), 2.85 (d, 7.5 Hz, 2H), 3.08 (m, 1 H), 3.18 (m, 1 H), 3.30 (M, 2H), 3.60 (m, 3H), 3.80 (m, 1 H), 4.16 (m, 1 H), 4.40 (s, 1 H), 5.16 (d, J = 9 Hz, 1 H), 5.24 (s, 2H), 6.60 (d, J = 9 Hz, 1 H), 7.20 (m, 10H), 7.83 (s, 1 H), 8.80 (s, 1 H). Mass spectrum: (M+H)+ = 594. Example 7 (2S.3S.5S -2-(N-..5-Thiazolyl.-methoxycarboπyl.aminθ--3-hvdroxy-5-.2S-π - imidazolidin-2-onvπ-3,3-dimethyl butanoyl)amino-1.6-diphenylhexane. A. 2S-(1 -lmidazolidin-2-onyl)-3.3-dimethyl butanoic acid. Using the procedures described in Example 1J to 1 M, but replacing L- valine methyl ester with L-t-butyl-ieucine methyl ester provided the desired compound. 300 MHz H NMR (DMSO-d6) δ 1 .0 (s, 9H), 3.22 (t, J = 7.5 Hz, 2H), 3.55 (q, J = 7.5 Hz, 1 H), 3.65 (q, J = 7.5 Hz, 1 H), 4.14 (s, 1 H), 6.40 (s, 1 H), 12.62 (br s, 1 H). Mass spectrum: (M+H)+ = 201. B. (2S.3S.5S)-2-(N-(f5-Thiazolvh-methoxycarbonvnamino,-3-hvdroxy-5-(2S- (1 -imidazolidin-2-onvπ-3.3-dimethyl butanoyl)amino-1 .6-diphenylhexane. Coupling of the amino compound from Example 6E with the carboxylic acid from Example 7A using standard procedure (EDAC in DMF) provided the desired compound (77%). 300 MHz 1 H NMR (CDCI3) δ 1.0 (s, 9H), 1 .68 (m, 2H), 2.60-2.80 (m, 3H), 2.85 (d, J = 7.5 Hz, 1 H), 3.10 (m, 1 H), 3.30 (m, 1 H), 3.50 (m, 1 H), 4.56 (s, 1 H), 5.15 (d, J = 7.5 Hz, 1 H), 5.25 (ABq, 1 H), 6.50 (d, J = 7 Hz, 1 H), 7.20 (m, 10H), 7.83 (s, 1 H), 8.80 (s, 1 H). Mass spectrum: (M+H)+ = 609. Example 8 f2S.3S.5S)-2-,2.6-DιmethylDhenoxyacetvhamιno-3-hvdroxy-5-(2S-n - ιmιdazolιdιn-2-onvh-3.3-dιmethyl butanovhamιno-1 ,6-diphenylhexane Coupling of the ammo compound from Example 1 N with the carboxylic acid from Example 7A using standard procedure (EDAC in DMF) provided the desired compound (80%) 300 MHz 1 H NMR (CDCI3) δ 1 .0 (s, 9H), 2 18 (s, 6H), 2 68 (m, 1 H), 2 80 (m, 1 H), 2 98 (m, 3H), 3 10 (m, 1 H), 3 27 (q, J = 7 Hz, 1 H), 3 53 (m, 1 H), 3 77 (m, 1 H), 4 0 (s, 1 H), 4 20 (m, 4H), 6 72 (m, 1 H), 7 0 (m, 3H), 7 10-7 25 (m, 10H) Mass spectrum (M+H)+ = 629 Example 9 (2S.3S.5S.-2-.2.6-DιmethylDheπoxyacetvhamιno-3-hvdroxy-5-f2S-f1 - ιmιdazolιdιn-2-thιonyl)-3-methyl butanoyl. amιno-1 .6-dιphenylhexane A 2S-(1 -lmιdazolιdιn-2-thιonyl ι-3-methyl butanoic acid Using the same procedures described in Example U to 1 M, but replacing 1 ,1 -carbonyl-dιιmιdazole with 1 ,1 -thiocarbonyldiimidazole provided the desired compound 300 MHz H NMR (DMSO-d6) δ 0 87 (d, J = 6 Hz, 3H), 0 96 (d, J = 6 Hz, 3H), 2 1 1 (m, 1 H), 3 45 (m, 2H), 3 62 (m, 1 H), 3 80 (q, J = 9 Hz, 1 H), 4 80 (d, J = 1 0 Hz, 1 H), 8.30 (s, 1 H), 12 75 (br s, 1 H) B ■2S.3S.5S 2-.2.6-DιmethylDhenoxyacetyl.amιno-3-hvdroxy-5-.2S-(1 - ιmιdazolιdιn-2-thιonvπ-3-methyl butanoyl)amιno-1 .6-dιphenylhexane Coupling of the ammo compound from Example 1 N with the carboxylic acid from Example 9A using standard procedure (EDAC in DMF) provided the desired compound (53%) 300 MHz 1 H NMR (CDCI3) δ 0 82 (d, J = 6 Hz, 3H), 0 93 (d, J = 6 Hz, 3H), 1 75 (m, 1 H), 2 20 (s, 6H), 2 65 (m, 1 H), 2 84 (m, 1 H), 3 0 (m, 3H), 3.25 (m, 1 H), 3 40 (m, 2H), 3 54 (d, J = Hz, 1 H), 3 78 (m, 1 H), 4 22 (m, 4H) 4 56 (d, J = 10 5 Hz, 1 H), 5 65 (s, 1 H), 6 60 (d, J = Hz, 1 H), 7 0 (m 3H) 7 2 (m, 10H) Mass spectrum (M+H)+ = 631 Example 10 (2S.3S.5S -2-,4-Amino-2.6-dimethylphenoxyacetvπ amino-3-hvdro-xy-5-.2S-M - imιdazolidin-2-onyl.-3-methyl-butanoyl- amino-1 .6-di p henylhexane. A. 2.6-Dιmethyl-4-nιtro ohenoxyacetic acid ethyl ester. To a solution of 10.5 g (54.6 mmole) of ethyl 2,6-dιmethylphenoxy acetate and 7.5 g (109 mmole) of sodium nitrite in 100 ml of methylene chloride was added 50 ml of tπfluoroacetic acid slowly. The reaction mixture became solid after addition. Additional 35 ml of trifluoroacetic acid was added. After the reaction mixture was stirred at room temperature for 3 h, it was carefully partitioned between saturated sodium bicarbonate solution and methylene chloride The combined organic extracts were washed with brine and dried over anhydrous sodium sulfate, filtered and evaporated to dryness under reduced pressure. The residue was recrystalized in 30% ethyl acetate and hexaπes to give 4.75 g (36%) of ethyl 2,6-dιmethyl-4-nitro phenoxyacetate as light yellow prisms. 300 MHz 1 H NMR (CDCI3) δ 1.34 (3H, t, J = 7.5 Hz), 2.39 (6H, s), 4.31 (2H, q, J = 7.5 Hz), 7.93 (2H, s). B 2.6-Dimethyl-4-nιtro-phenoxyacetιc acid. To a solution of 0.962 g (4.06 mmole) of ethyl 2,6-dimethyl-4-nιtro phenoxy acetate in 10 ml of methanol was added 1 ml of 3 N sodium hydroxide. After the reaction mixture was stirred at room temperature for 30 minutes it was acidified with 3 N HCl and partitioned between water and methylene chloride. The combined organic extracts were washed with brine and dried over anhydrous sodium sulfate, filtered and evaporated to dryness under recduced pressure to give 0.82 g (97%) of 2,6-dιmethyl-4-nιtro phenoxy acetic acid as light yellow solid 300 MHz 1 H NMR (d3-DMSO) δ 2.35 (6H, s), 4 55 (2H, s) 7 97 (2H, s), 13.02 (1 H, bs). C. .2S.3S.5S--2- t-Butyloxycarbonyl. amιno-3-hvdroxy-5- ( 2S- ( 1 -ιmιdazolιdιn-2- onlv 3-methyl-butanoyl-amino-1 .6-diDhenylhexane. Coupling of (2S,3S,5S)-2-(t-butyloxycarbonyl) ammo-3-hydroxy-5- amιno-1 ,6-dιphenylhexane with the carboxylic acid from Example 1 M using standard procedure (EDAC in DMF) provided the desired compound (100%). 300 MHz 1 H NMR (CDCI3) δ 0.83 (d, J = 6 Hz, 3H), 0.87 (d, J = 6 Hz, 3H), 1.40 (s, 9H), 1 70 (m, 2H), 2.16 (m, 1 H), 2.58-2.80 (m, 4H), 3.10-3.30 (m, 4H), 3.65 (m, 2H), 4.20 (m, 1 H), 4.38 (s, 1 H), 4,83 (d, J= Hz, 1 H), 6.53 (d, J = 9 Hz, 1 H), 7.20 (m, 10H) Mass spectrum: (M+H) + = 553 D (2S.3S.5S 2-Amιno-3-hvdroxy-5-(2S-M -ιmιdazolιdιn-2-onyll-3-methyl- butanoyO amιno-1 .6-diphenylhexane Deprotection of the Boc-protecting group of the compound from Example 10C by standard procedure (TFA CH2CI2) provided the desired compound 300 MHz 1 H NMR (CDCI3) δ 0.87 (d, J = 6 Hz, 3H), 0.90 (d, J = 6 Hz, 3H), 1.33 (dd, J = 4.5, 9.0 Hz, 1 H) 2.18 (m, 1 H), 2.50 (m, 1 H), 2.80 (m, 5H), 3.20 (m, 4H) 3 72 (d, J = 10 Hz, 1 H), 4.30 (m, 1 H), 4.50 (s, 1 H), 6.67 (d, J = 7 Hz, 1 H), 7.20 (m, 10H) Mass spectrum. (M+H)+ = 453. E. .2S.3S.5S.-2-(4-Nιtro-2.6-dιmethylohenoxyacetyl . amιno-3-hvdroxy-5-(2S- (1 -ιmιdazolιdιn-2-onvπ-3-methyl-butanovh amιno-1 ,6-diphenylhexane Coupling of the ammo compound from Example 10D with the carboxylic acid from Example 10B using standard procedure (EDAC in DMF) provided the desired compound. 300 MHz 1 H NMR (CDCI3) δ 0.83 (d, 7 = Hz, 3H), 0.86 (d, J = 7 Hz, 3H), 1.70 (m, 3H), 2.18 (m, 2H), 2.28 (s, 6H) 2.75 (m, 3H), 2 95-3.30 (m, 6H), 3.67 (d, J = 10.5 Hz, 1 H), 3.75 (m, 1 H), 3.82 (d, J = 4 Hz, 1 H), 4.25 (m, 5H), 6.55 (d, J = 7 Hz, 1 H), 7.20 (m, 10H), 7.92 (s, 2H) Mass spectrum (M+H)+ = 660 F. (2S.3S.5SV2-(4-Amino-2.6-dimethylphenoxyacetvπ amino-3-hvdroxy-5-(2S- (1 -imidazolidin-2-onvD-3-methyl-butanovO amino-1 ,6-diPhenylhexane. To a suspension of 7 mg of 10% Pd/C in 5 ml of methanol was added a solution of 69 mg of the compound from Example 10E. The reaction mixture was stirred vigorously under a hydrogen atmosphere (balloon filled with hydrogen attached to a 3-way stopcock). After 1 h, reaction was complete by TLC analysis; the catalyst was filtered off and the filtrate was concentrated in vacuo. The crude product was purified by silica gel column ehromatography (2% to 5% MeOH/CH CI 2 ) to provide the desired compound (65%). 300 MHz 1 H NMR (CDCl3) δ 0.82 (d, J = Hz, 3H), 0.87 (d, J = 6 Hz, 3H), 1 .70 (m, 2H), 2.10 (s, 6H), 2.15 (m, 2H), 2.72 (m, 2H), 2.97 (d, J = 7.5 Hz, 2H), 3.08 (m, 1 H), 3.15 (m, 1 H), 3.30 (m, 2H), 3.45 (br s, 2H), 3.66 (d, J = 10 Hz, 1 H), 3.72 (m, 1 H), 3.90 (d, J = 3 Hz, 1 H), 4.10-4.20 (m, 4H), 4.30 (s, 1 H), 6.33 (s, 2H), 6.57 (d, J = 9 Hz, 1 H), 7.20 (m, 10H). Mass spectrum: (M+H)+ = 630. Example 1 1 ■ 2S.3S.5S .-2-.2.4.6-TrimethylDhenoxyacetyl . amino-3-hvdroxy-5-f2S-M - imidazolidin-2-onyl)-3-methylbutanoyl) amino-1 .6-diphenylhexane. A. 2,4,6-Trimethylphenoxyacetic acid. Using the procedures from Example 1 G and 1 H, but replacing 2,6- dimethylpheπol with 2,4,6-trimethylphenol provided the desired compound. 300 MHz 1 H NMR (CDCI3) δ 2.25 (s, 9H), 4.43 (s, 2H), 6.84 (s, 2H). Mass spectrum: (M+H)+ = 195. B. (2S.3S.5S ,-2-(2.4.6-Trimethylphenoxyacetvn amino-3-hvdroxy-5-(2S-f1 - imidazolidin-2-onvO-3-methylbutanovD amino-1 .6-diphenylhexane. Coupling of the amino compound from Example 10D with the carboxylic acid from Example 1 1 A using standard procedure (EDAC in DMF) provided the desired compound (51 %). 300 MHz 1 H NMR (CDCI3) δ 0.82 (d, J = 6 Hz, 3H), 0.85 (d, J = 6 Hz, 3H), 1 .70 (m, 4H), 2.13 (s, 6H), 2.25 (s, 3H), 2.75 (m, 2H), 2.97 (d, J = 7 Hz, 1 H), 3.13 (m, 2H), 3.28 (m, 2H), 3.68 (d, J = 10 Hz, 1 H), 3.72 (m, 1 H), 4.16 (m, 4H), 4.40 ( br s, 1 H), 6.67 (d, J = 8 Hz, 1 H), 6.80 (s, 2H), 7.20 (m, 10H). Mass spectrum: (M+H)+ = 629. Example 12 .2S.3S.5S--2-.4-Fluoro-2.6-dimsthylDhenoxyac9tyl. ammo-3-hvdroxy-5-.2S-.1 - ιmιdazolιdιn-2-onvπ-3-methyl-butanovπ amιno-1 .6-dιphenylhexane A. 4-Fluoro-2.6-dιmethylphenoxyacetιc acid. Using the procedure from Example 1 G and 1 H, but replacing 2,6- dimethyiphenol with 4-fluoro-2,6-dιmethylphenol provided the desired compound. 300 MHz 1 H NMR (CD3OD) δ 2.26 (s, 6H), 4.37 (s, 2H), 6.73 (d, J = 9 Hz, 2H). Mass spectrum: M+ = 198. B .2S.3S.5S--2-.4-Fluoro-2.6-dimethylDhenoxyacetvn amιno-3-hvdroxy-5-(2S- (1 -ιmιdazolιdin-2-onvπ-3-methyl-butanovh amιno-1 .6-dιphenylhexane Coupling of the ammo compound from Example 10D with the carboxylic acid from Example 12A provided the desired compound. 300 MHz 1 H NMR (CDCI3) δ 0.83 (d, J = 6 Hz, 3H), 0.86 (d, J = 6 Hz, 3H), 1.72 (m, 2H), 2.15 (s, 6H), 2.20 (m, 1 H), 2.76 (m, 2H), 2.98 (d, J = 7 Hz, 2H), 3.12 (m, 2H), 3.30 (m, 2H), 3.67 (d, J = 10 Hz, 1 H), 3.72 (m, 1 H), 4.13 (AB q, J = 8, 9 Hz, 2H), 4.20 (m, 2H), 4.37 (s, 1 H), 6.64 (d, J = 9 Hz, 1 H), 6.70 (d, J = Hz, 2H), 7.20 (m, 10H). Mass spectrum. (M+H)+ = 633 Example 13 (2S.3S.5S)-2-(4.6-Dιmethyl pyπmιdιn-5-oxy-acetvn amιno-3-hvdroxy-5-f2S-M - ιmιdazolιdιn-2-onyl)-3-methyl-butanoyl, amino-t .6-dιphenylhexane A 4.6-Dιmethyl pyπmιdιn-5-oxy-acetιc acid. Using the procedures from Example 1 G and 1 H, but replacing 2,6- dimethylphenol with 5-hydroxy-4,6-dιmethylpyπmιdιne (prepared according to Chem Ber. 93 pg. 1998, 1960) provided the desired compound. 300 MHz 1 H NMR (DMSO-d6) δ 2.45 (s, 6H), 4.55 (s, 2H), 8.50 (s, 1 H). Mass spectrum- (M+H)+ = 183 B. (2S.3S.5S)-2-f4.6-Dimethyl Dyrimidin-5-oxy-acetvh amino-3-hvdroxy-5-(2S- (1 -imidazolidin-2-onvπ-3-methyl-butanovπ amino-1 .6-diphenylhexanβ. Coupling of the amino compound from Example 10D with the carboxylic acid from Example 13A provided the desired compound. 300 MHz 1 H NMR (CDCI3) δ 0.82 (d, J = 6 Hz, 3H), 0.85 (d, J = 6 Hz, 3H), 1.70 (m, 2H), 2.15 (m, 1 H), 2.40 (s, 6H), 2.75 (m, 2H),2.97 (d, J = 7 Hz, 2H), 3.12 (m, 2H), 3.30 (m, 2H), 3.66 (d, J = 10 Hz, 1 H), 3.74 (m, 1 H), 3.88 (d, J = Hz, 1 H), 4.20 (m, 4H, 6.62 (d, J = 9 Hz, 1 H), 7.0 (d, J = 9 Hz, 1 H), 7.20 (m, 10H), 8.70 (s, 1 H). Mass spectrum: (M+H)+ = 617. Example 14 D. (2S.3S.5S -2-(2.4-Dimethyl-pyridin-3-oxy-acetvn amino-3-hvdroxy-5-(2S-M - imidazolidin-2-onyl)-3.3-dimethyl butanoyl) amino-1.6-diohenylhexane. A. 2.4-Dimethyl-Pyridin-3-oxy-acetic acid. Using the procedures from Example 1 G and 1 H, but replacing 2,6- dimethylphenol with 2,4 dimethyl-3-hydroxypyridine (prepared according to J. Med. Chem. 35, pg. 3667-3671 , 1992) provided the desired compound. 300 MHz H NMR (DMSO-d6) δ 2.26 (s, 3H), 2.42 (s, 3H), 4.44 (s, 2H), 7.08 (d, J = 5 Hz, 1 H), 8.07 (d, J = 5 Hz, 1 H). Mass spectrum: (M+H)+ = 182. B. .2S.3S.5S--2--2.4-Dimethyl-pyridin-3-oxy- acetyl, amino-3-hvdroxy-5-ft- butyloxycarbonyl) amino-1 .6-diphenylhexane. Coupling of the amino compound from Examplel F with the carboxylic acid from Example 14A using standard procedure (EDAC in DMF) provided the desired compound. 300 MHz 1 H NMR (CDCI3) δ 1.40 (s, 9H), 1.70 (m, 2H), 2.18 (s, 3H), 2.40 (s, 3H), 2.77 (m, 2H), 2.98 (d, J = 7 Hz, 2H), 3.75-3.95 (m, 3H), 4.20 (s, 2H), 4.22 (m, 1 H), 4.60 (br d, 1 H), 7.0 (d, J = 5H, 1 H), 7.10 (m, 3H), 7.25 (m, 7H), 8.16 (d, J = 5 Hz, 1 H). Mass spectrum: (M+H)+ = 548. C. (2S.3S.5S)-2-f2.4-Dimethyl-Pyridin-3-oxy-acetyl) amino-3-hvdroxy-5-amino- 1 .6-diphenylhexane. Deprotection of the Boc-group in the compound from Example 14B using standard procedure (TFA/CH2CI2) provided the desired compound. 300 MHz H NMR (CDCI3) δ 1.45 (m, 1 H), 1.62 (m, 1 H), 2.23 (s, 3H), 2.45 (s, 3H), 2.50 (m, 1 H), 2.80 (m, 1 H), 3.0 (m, 2H), 3.12 (m, 1 H), 3.90 (m, 1 H), 4.18 (m, 1 H), 4.25 (ABq, J = 9, 12 Hz, 2H), 6.98 (d, J = 5 Hz, 1 H), 7.10 (m, 2H), 7.30 (m, 8H), 8.17 (d, J = 5 Hz, 1 H). Mass spectrum: (M+H)+ = 448. D. (2S.3S.5S)-2-f2.4-Dimethyl-pyhdin-3-oxy-acetyl ' } amino-3-hvdroxy-5-(2S-( 1 - imidazolidin-2-onv0-3.3-dimethv[ butanoyll amino-1 .6-diphenylhexane. Coupling of the amino compound from Example 1 4C with the carboxylic acid from Example 7A using standard procedure (EDAC in DMF) provided the desired compound. 300 MHz 1 H NMR (CDCI3) δ 1 .0 (s, 9H), 1.70 (m, 3H), 2.18 (s, 3H), 2.42 (s, 3H), 2.75 (m, 2H), 3.0 (m, 4H), 3.30 (m, 1 H), 3.55 (m, 1 H), 3.80 (m, 1 H), 4.05 (s, 1 H), 4.20 (m, 4H), 4.60 (s, 1 H), 6.70 (d, J = 7 Hz, 1 H), 6.97 (d, J = 5 Hz, 1 H), 7.15 (m, 3H), 7.25 (m, 7H), 8.17 (d, J = Hz, 1 H), Mass spectrum: (M+H)+ = 630. Example 15 f2S.3S.5S)-2-(2.4-Dimethyl-pyridin-3-oxy-acetvh amino-3-hvdroxy-5-(2S-(1 - imidazolidin-2-onvπ-3-methyl-butanoyl) amino-1 ,6-diphenylhexane. Coupling of the amino compound from Example 14C with the carboxylic acid from Example 1 M using standard procedure (EDAC in DMF) provided the desired compound. 300 MHz 1 H NMR (CDCI3) δ 0.82 (d, J = 6 Hz, 3H), 0.86 (d, J = 6 Hz, 3H), 1 .75 (m, 3H), 2.15 (m, 1 H), 2.18 (s, 3H), 2.40 (s, 3H), 2.75 (m, 2H), 2.97 (d, J = 7.5 Hz, 2H), 3.20 (m, 4H), 3.70 (d, J - 10 Hz, 1 H), 3.75 (m, 1 H), 4.20 (m, 6H), 4.52 (s, 1 H), 3.75 (m, 1 H), 4.20 (m, 6H), 4.52 (s, 1 H), 6.80 (d, J - 7 Hz, 1 H), 6.96 (d, J = 4.5 Hz, 1 H), 7.20 (m, 10 H), 8.17 (d, J = 4.5 Hz, 1 H). Mass spectrum: (M+H)+ = 616. Example 16 ,2S.3S.5S)-2-f2.6-Dιmethylthιophenoxyacetvn amιno-3-hvdroxy-5(2S-(1 - ιmιdazolιdιn-2-onvπ-3-methyl-butanov0 amιno-1 ,6-diphenylhexane A 2.6-Dιmethylthιophenoxy acetic acid Using the procedures from Example 1 G and 1 H, but replacing 2 6- dimethylphenol with 2,6-dιmethylthιophenol provided the desired compound 300 MHz 1 H NMR (CDCI3) δ 2.56 (s, 6H), 3 40 (s, 2H), 7 10 (m, 3H) Mass spectrum (M+H)+ = 197 B (2S.3S.5S 2-(2.6-Dimethylthiophenoxyacetvn amιno-3-hvdroxy-5-(2S-n - ιmιdazolιdιn-2-onvπ-3-methyl-butanovπ amιno-1 ,6-diphenylhexane Coupling of the carboxylic acid from Example 16A with the ammo compound from Example 10D provided the desired compound 300 MHz 1 H NMR (CDCI3) δ 0.82 (d, J = 6 Hz, 3H), 0.86 (d, J = 6 Hz, 3H), 2 15 (m, 1 H), 2 52 (s, 6H), 2 70 (m, 4H), 3.10 (m, 2H), 3.30 (m, 4H), 3.60 (m, 2H), 4 0 (m, 1 H), 4 10 (m, 1 H), 4.22 (s, 1 H), 6.39 (d, J = 7 Hz, 1 H), 6 58 (d, J = 9 Hz, 1 H), 7.20 ( , 13H) Mass spectrum (M+H)+ = 631 Example 17 (2S.3S.5S,-2-(2.6-Dιmethylphenoxyacetvn amιno-3-hvdroxy-5-f2S-(1 - pyrrolιdιn-2-onv0-3-methyl-butanoyl) amιno-1 ,6-dιphenylhexane A 4-Bromobutanoyl-L-valιne methyl ester To a solution of 1 08 g (8 4 mmole) of L-valine methyl ester in 30 ml of CH2CI2 was added 1.36 ml (16.8 mmole) of pyridme, cooled to 0°C and 1.55 g (8 4 mmole) of 4-bromobutanoyl chloride added The solution was stirred at 0°C for 40 minutes and at RT for 1 h The solution was washed with satd NaHC03, brine and dried with anhy Na2S0 4 , filtered and concentrated in vacuo The crude product was purified by silica gel column ehromatography (5% EtOAc/CH 2 CI 2 ) to provide 1.82 g (77%) of desired product 300 MHz 1 H NMR (CDCI3) δ 0 92 (d, J = 6 Hz, 3H), 0.96 (d, J = 6 Hz, 3H) 2.20 (m, 3H), 2 46 ( , 2H), 3.50 (m, 2H), 3.76 (s, 3H), 4.58 (dd, J = 4,7 Hz, 1 H), 5 97 (br d, J = 7 Hz, 1 H). Mass spectrum: (M+H)+ = 297. B. 2S-(1 -Pyrrolidιn-2-onvO-3-methyl-butanoιc acid. To a solution of 1.49 g (5.3 mmole) of the compound from Example 17A in a mixture of DMF/CH2CI2 cooled to 0°C was added 0.234 g (1.1 equivalent) of 60% sodium hydride in mineral oil. The mixture was slowly warmed up to RT and stirred overnight. The mixture was poured into satd. ammonium chloride and extracted with ethyl acetate, dried and concentrated in vacuo. The crude product was hydrolyzed using lithuim hydroxide as in Example 1 H to provide the desired compound. 300 MHz 1 H NMR (CDCI3) δ 0.96 (d, J = 7 Hz, 3H), 1.06 (d, J = 7 Hz, 3H), 2.10 (m, 2H), 2.40 (m, 1 H), 2.50 (t, J = 7 Hz, 2H), 3.56 (m, 2H), 4 14 (d, J = 10 Hz, 1 H) Mass spectrum: (M+H)+ = 186. C .2S.3S.5S.-2-.2.6-DιmethylDheπoxyacetyl. amino-3-hvdroxy-5-(2S-f 1 - pyrrolidιn-2-onvπ-3-methyl-butanoyl) amιno-1 .6-dιphenylhexane. Coupling of the carboxylic acid from Example 17B with the amme from Example 1 N using standard procedure (EDAC in DMF) provided the desired compound 300 MHz 1 H NMR (CDCI3) δ 0 77 (d, J = 7 Hz, 3H), 0.83 (d, J = 7 Hz, 3H), 1.75 (m, 3H), 2.10 (m, 1 H), 2.20 (s, 6H), 2.25 (m, 1 H), 2.65 (m, 1 H), 2.85 (m, 1 H), 3.0 (d, J = 7 Hz, 2H), 3.20 (m, 1 H), 3.77 ( , 2H), 3.88 (d, J = 10 Hz, 1 H), 4.20 (m, 3H), 6.30 (d, J = 7 Hz, 1 H), 6.98 (m, 3H), 7.20 (m, 10 H). Mass spectrum. (M+H)+ = 614. Example 18 ■ 2S.3S.5S ) -2-.2.6-DimethylDhenoxyacetvO amιno-3-hvdroxy-5-f2S- ( 1 - pyrrolιdιn-2,5-dιonv0-3-methvi-butanoyl) amιno-1 ,6-diphenylhexane. A 2S-π -Pyrrolidιn-2.5-dιonvD-3-methyl-butanoιc acid benzyl ester To a solution of 700 mg (3.38 mmole) of L-valine benzyl ester in 6 ml of chloroform was added 1 equivalent of succinic anhydride. After 1 h at RT, the solvent was removed in vacuo and the residue was dissolved in 20 ml of DMF To this solution was added 0.52 g of N-hydroxy-benzotπazole, 0.68 g of EDAC and 0.52 ml of tnethylamme. After 24 h at RT, 20 mg of 4-dimethylaminopyπdιne was added. The solution was left at RT for 3 days. After standard work-up, the crude product was purified by silica gel column ehromatography to provide 0.25 g of desired product (26%). 300 MHz 1 H NMR (CDCI3) δ 0.84 (d, J = 7 Hz, 3H), 1.12 (d, J = 7 Hz, 3H), 2.70 (m, 1 H), 2.71 (s, 4H), 4.45 (d, J = 9 Hz, 1 H), 5.15 (s, 2H), 7.30 (m, 5H). B. 2S-(1 -Pyrrolιdin-2.5-dιonvπ-3-methyl-butanoic acid. A mixture of 0.245 of the product from Example 18A, 30 mg of 10% palladium on charcoal in 50 ml of methanol was stirred vigorously under hydrogen atmosphere (balloon filled with hydrogen) for 1 h. The catalyst was filtered off and the solvent was removed under vacuum to provide 168 mg of the desired compound. 300 MHz 1 H NMR (CDCI3) δ 0.84 (d, J = 6 Hz, 3H), 1.13 (d, J = 6 Hz, 3H), 2.65 (m, 1 H), 2.80 (s, 4H), 4.45 (d, J = 8 Hz, 1 H). Mass spectrum: (M+H) + = 200. C (2S.3S.5S)-2-(2.6-Dimethylphenoxyacetyl , amιno-3-hvdroxy-5-f2S-M - pyrrolιdιn-2.5-dιonv0-3-methyl-butanoyl) amιno-1 .6-diphenylhexane. Coupling of the carboxylic acid from Example 18B with the amme from Example 1 N using standard procedure (EDAC in DMF) provided the desired product (75%). 300 MHz 1 H NMR (CDCI3) δ 0.70 (d, J = 4 Hz, 3H), 0.72 (d, J = 4 Hz, 3H), 1.70 (m, 1 H), 2.20 (s, 6H), 2.45 (m, 2H), 2.60 (s, 4H), 2.80 (m, 2H), 3.0 (m, 2H), 3.76 (m, 1 H), 4.20 (m, 6H), 7.0 (m, 3H), 7.20 (m, 10H). Mass spectrum- (M+Hh = 628. Example 19 f2S.3S.5S -2-fTrans-3-(2.6-dιmethylphenyl propenoyi) amιno-3-hvdroxy-5- (2S-1 -tetrahvdropyrιmιdin-2-onyl)-3-rnethyl-butanov0 amιno-1 ,6- diphenylhexane. A 2.6-Dιmethyl benzaldehyde. Oxidation of 2,6-dιmethyl benzyl alcohol by standard Swern oxidation procedure (oxalyl chloπde/DMSO) provided the desired compound. 300 MHz 1 H NMR (CDCl3) δ 2.62 (s, 6H), 7.10 (m, 2H), 7.33 (t, J = 7 Hz, 1 H), 10.63 (s, 1 H), Mass spectrum: (M+H)+ = 135. B Trans-3-(2.6-dιmethylphenvπ-propenoιc acid methyl ester. To a solution of tπmethyl phosphonoacetate (149 mg, 0.82 mmole) in 15 ml of THF was added 36 mg of sodium hydride (60% in oil). After 15 minutes 100 mg of the compound from Example 19A in 2 ml of THF was added After 2 h, the reaction was quenched carefully with water and extracted with ethyl acetate (70 ml), dried and concentrated. Purification of the crude product by silica gel column ehromatography (hexane/EtOAc 95:5) provided the desired compound (75%). 300 MHz 1 H NMR (CDCI3) δ 2.35 (s, 6 H), 3.82 (s, 3H), 6.07 (d, J = 16 Hz, 1 H). 7.10 (m, 3H), 7.85 (d, J = 16 Hz, 1 H) Mass spectrum- (M+NH 4 )+ = 191. C Trans-3-(2.6-dιmethylphenvπ-propenoic acid Hydrolys .> of the methyl ester from Example 19B using lithium hydroxide in a mixture of methanol and water provided the desired compound (84%) 300 MHz 1 H NMR (CDCI3) δ 2.38 (s, 6H), 6.13 (d, J = 16 Hz, 1 H), 7.10 (m, 3H), 7.96 (d, J = 16 Hz, 1 H). Mass spectrum: (M+H)+ = 194. D f2S.3S.5SV2-fTrans-3-(2.6-dιmethylphenvh prooenovπ amιno-3-hvdroxy-5- (t-butyloxycarbonyl amιno-1.6-dιpheny hexane. Coupling of the carboxylic acid from Example 19C with the amine from Example 1 F using standard procedure (EDAC/DMF) provided the desired compound (84%). 300 MHz 1 H NMR (CDCI3) δ 1.40 (s, 9H), 1.68 (m, 1 H), 2.34 (s, 6H), 2.75 (m, 2H), 2.96 (m, 2H), 3.72 (m, 1 H), 3.85 (m, 1 H), 4.08 (m, 2H), 4.60 (m, 1 H), 5.88 (d, J = 10 Hz, 1 H), 5.94 (d, J = 16 Hz, 1 H), 7.10 (m, 5H), 7.25 (m, 8H), 7.72 (d, J = 16 Hz, 1 H) Mass spectrum (M+H) + = 543 E. f2S.3S.5S>-2-π " rans-3-.2.6-dιmsthvlDhenvl. propenovl) amino-3-hvdroxv-5- .2S-1 -tetrahvdropvrimidin-2-onvn-3-methvl-butanovn amiπo-1.6- diphenylhexane. Removal of the Boc-protecting group of the compound from Example 19D (TFA/CH2CI2) and coupling of the resulting amine with the carboxylic acid from Example 2A using standard procedure (EDAC/DMF) provided the desired compound (73%). 300 MHz H NMR (CDCI3) δ 0.82 (d, J = 6 Hz, 3H), 0.87 (d, J = 6 Hz, 3H), 1.50 (m, 1 H), 1.70 (m, 2H), 2.20 (m, 1 H), 2.33 (s, 6H), 2.68 (m, 1 H), 2.78 (m, 1 H), 2.85 (m. 1 H), 3.05 (m, 5H), 3.73 (m, 1 H), 4.17 (m, 1 H), 4.30 (d, J = 3 Hz, 1 H), 4.60 (s, 1 H), 5.95 (d, J = 15 Hz, 1 H), 6.0 ( d, J = 9 Hz, 1 H), 6.80 (d, J = 7 Hz, 1 H), 7.25 (m, 13H), 7.70 (d, J = 15 Hz, 1 H). Mass spectrum: (M+H) + = 625. Exam le 2Q (2S.3S.5Si-2-f3-.2.6-Dimethvlphenvl. propanovl) amιno-3-hvdroxy-5-(2S-(1 - tetrahvdropvhmidin-2-onvn-3-methvl-butanovn amino-1 .6-diphenvlhexane. A. 3-.2.6-Dimethvlρhsnvn prooanoic acid methvl ester. A solution of 400 mg of the compound from Example 19B in 25 ml of methanol and 40 mg of 10% Pd/C was stirred vigorously under a hydrogen atmosphere (balloon pressure) for 3 h. The catalyst was filtered off and concentration of the filtrate in vacuo provided the desired compound (98%). 300 MHz 1 H NMR (CDCI3) δ 2.35 (s, 6H), 2.45 (m, 2H), 2.98 (m, 2H), 3.22 (s, 3H), 7.02 (s, 3H). Mass spectrum: (M+H)+ = 210. B. 3-(2.6-Dimethvlphenvl, propanoic acid. Hydrolysis of the methyl ester from Example 20A, using lithium hydroxide in methanol and water provided the desired compound (93%). 300 MHz 1 H NMR (CDCI3) δ 2.36 (s, 6H), 2.50 (m, 2H), 3.0 (m, 2H), 7.03 (s, 3H). Mass spectrum: (M+NH 4 )+ = 196. C .2S.3S.5S.-2-.3-2.6-Dιmethvlphenvl. propanovh amιno-3-hvdroxy-5-ft- butvloxvcarhonvl- amιno-1 .6-diPhenvlhexane. Coupling of the carboxylic acid from Example 20B with the amme from Example 1 F using standard coupling procedure (EDAC/DMF) provided the desired compound. 300 MHz 1 H NMR (CDCI3) δ 1 40 (s, 9H), 1.55 (m, 2H), 2.20 (m, 2H), 2.30 (s, 6H), 2.74 (m, 2H), 2.85 (m, 4H), 3.66 (m, 1 H), 3.82 (m, 1 H), 3 95 (m, 2H), 4.57 (br d, 1 H), 5.66 (d, J = 9 Hz, 1 H), 7.0 (s, 3H), 7.22 (m, 10H) Mass spectrum. (M+H)+ = 545. D .2S.3S.5S.-2-.3--2.6-Dim thylDher.vl. prooanovn amιno-3-hvdroxy-5-(2S- M -tetrahvdropvrimidin-2-onvn-3-methvl-butanovn amιno-1 .6-dιphenylhexane. Removal of the Boc-protecting group of the compound from Example 20C using tnfluoroaeetic acid m CH2CI2 and coupling of the resulting amme with the carboxylic acid from Example 2A using standard coupling procedure (EDAC/DMF) provided the desired compound 300 MHz H NMR (CDCI3) δ 0.82 (d, J = 6 Hz, 3H), 0.86 (d, J = 6 Hz, 3H), 1.55 (m, 2H), 1.65 (m, 1 H), 1 70 (s, 3H), 2.20 (m 3H), 2.30 (s, 6H), 2.65 (m, 1 H), 2.75 (m, 1 H), 2.86 (m, 5H), 3 10 (m, 3H), 3 68 (m, 1 H), 4.10 (m, 4H), 4.63 (s, 1 H), 5.75 (d, J = 7 Hz, 1 H), 6 76 (d, J = 7 Hz, 1 H), 7 0 (m, 3H), 7.20 (m, 10H) Mass spectrum. (M+H)+ = 627 Example 21 f2S.3S.5SV2-(2.6-Dιmethvl-4-hvdroxv-phenoxvacetvn amιno-3-hvdroxv-5-(2S- (1 -tetrahvdropyrιmιdιn-2-onylV3-methyl-butanoyl) amιno-1 ,6-dιphenylhexane A. 2.6-Dιmethyl-4-tert-butyldιmethylsιlyloxy phenol To a solution of 2.5 g (14 7 mmole) of 2,6-dιmethylquιnone in 5 ml of methanol was added 200 mg of Pd/C (20%) The reaction mixture was stirred under 1 atmosphere of hydrogen for overnight The Pd/C was removed over a celite pad, and the solvent was evaporated to dryness under reduced pressure to give 2.0 g (100%) of 2,6-dιmethyldιhydroquιnone as a light yellow oil To a solution of 2 0 g (14 7 mmole) of 2,6-dιmethyldιhydroquιnone in 10 ml of methylene chloride was added 1 2 g (17 6 mmole) of imidazole and 2.2 g (14 7 mmol) of tert-butyldimethylsilyl chloride subsequently at 0°C After the reactioπ was complete as indicated by TLC, it was partitioned between methylene chloride and 1 :1 mixture of 3 N hydrogen chloride and brine. The organic layer was washed with brine, dried over sodium sulfate, filtered and evaporated to dryness under reduced pressure. Silica gel ehromatography using 5% ethyl acetate :hexanes gave 1.8 g (49%) of 2,6-dimethyl-4-tert- butyldimethylsilyloxy phenol as a white solid. 300 MHz H NMR (CDCI3) δ 0.16 (s, 6H), 0.98 (s, 9H), 2.19 (s, 6H), 4.22 (s, 1 H), 6.48 (s, 2H). Mass spectrum: (M+H)+ = 253. B. Ethvl 2.6-Dimethvl-4-tert-Butvldimethvlsilvloxv phenoxvl acetate A solution of 1.8 g (7.1 mmole) of 2,6-dimethy!-4-tert-butyldimethylsiiyloxy phenol in 5 ml of dimethylformamide was treated with 2.0 g (1.43 mmole) of potassium carbonate and 830 μl (7.5 mmole) of ethyl bromoacetate. The resulting solution was heated at 70°C for 4 hr. After cooled to room temperature, the reaction mixture was partitioned between ethyl acetate and 3 N hydrogen chloride. The combined organic layer was washed with diluted brine, dried over magnesium sulfate, filtered, and evaporated in vacuo. Silica gel ehromatography using 5% ethyl acetate :hexanes gave 2.03 g (85%) of ethyl 2,6-dimethyl-4-tert-butyldimethylsilyloxy phenoxyl acetate as a light yellow oil. 300 MHz 1 H NMR (CDCI3) δ 0.17 (s, 6H), 0.97 s, 9H), 1.33 (t, 3H, J = 6.3 Hz), 2.22 (s, 6H), 4.30 (q, 2H, J = 6.3 Hz), 4.35 (s, 2H), 6.57 (s, 2H). Mass spectrum: (M+H) + = 356. C. 2.6-Dimethvl-4-Hvdroxvl phenoxvacetic acid To a solution of 2.03 g (6.0 mmole) of ethyl 2,6-dimethyl-4-tert- butyldimethysilyloxy phenoxy acetate in 10 ml of methanol was added 4 ml of 3 N sodium hydroxide. After the reaction mixture was stirred at room temperature for 30 minutes it was acidified with 3 N HCl. The reaction was allowed to stir for additional 1 h, and then partitioned between water and methylene chloride. The combined organic extracts were washed with brine and dried over anhydrous sodium sulfate, filtered, and evaporated to dryness under reduced pressure. Trituration with hexanes gave 910 mg (77%) of 2,6-dimethyl-4-hydroxyl phenoxyacetic acid as a white solid. 300 MHz " * H NMR (CD3OD) δ 2.18 (s, 6H), 4.31 (s. 2H), 6.41 (s, 2H). Mass spectrum: (M+H)+ = 214. D. .2S.3S.5S--2--2.6-Dimethvl-4-hvdroxv-Dhenoxvacstvl. amino-3-hvdroxy-5- ■ t-butvloxvcarbonvl. amino-1 .6-diphenvlhexane. Coupling of the carboxylic acid from Example 21 C with the amme from Example 1 F using standard coupling procedure (EDAC/DMF) provided the desired compound. 300 MHz 1 H NMR (CDCI3) δ 1.40 (s, 9H), 1.68 (m, 2H), 2.07 (s, 6H), 2.77 (d, J = 6 Hz, 2H), 2.98 (m, 2H), 3.74 (m, 1 H), 3.90 (m, 1 H), 4.10 (m, 3H), 4.58 (m, 1 H), 5.20 (m, 1 H), 6.44 (s, 2H), 7.10-7.30 (m, 10H). E. .2S.3S.5S--2-.2.6-Dimethvl-4-hvdroxv-Dhenoxvacetvl) amino-3-hvdroxv-5- ■ 2S-, 1 -tetrahvdroDvrimidin-2-onvl.-3-methvl-butanovl. amino-1.6- diphenylhexane. Removal of the Boc-protecting group of the compound from Example 21 D using TFA/CH2CI2 and coupling of the resulting amine with the carboxylic acid from Example 2A using standard procedure (EDAC/DMF) provided the desired compound. 300 MHz 1 H NMR (CDCI3) δ 0.78 (d, J = 5 Hz, 3H), 0.81 (d, J = 5 Hz, 3H), 1.47 (m, 1 H), 2.03 (s, 6H), 2.18 (m, 1 H), 2.62 (m, 1 H), 2.80 (m, 2H), 3.05 (m, 6H), 3.78 (m, 1 H), 4.12 (M, 6H), 4.37 (M, 1 H), 4.71 (s, 1 H), 6.47 (s, 2H), 6.94 (br d, 1 H), 7.20 (m, 10H). Mass spectrum: (M+H)+ = 645. Example 22 ( 2S.3S.5S .-2-fcisf+V1 .1 -dioxo-2-isopropvl-3-tetrahvdrothιo p henoxv.amιno-3- hvdroxv-5-(2S-f 1 -tetrahvdropvnmιd-2-onvl.-3-methvl butanovl .amιno-1 .6- dlphenylhex , ane, A. Cis (± -2-isopropvl-3-hvdroxv-tetrahvdrothiophene. To a solution of ethyl-3-mercaptopropιonate (27.25 ml, 0.246 mole) in 200 ml of ethanol was added carefully sodium ethoxide (16.75 g, 0.246 mole) in several portions. The resulting suspension was then cooled to -20°C and ethyl- 2-bromoisovalerate (50 g, 0.239 mole) in 50 ml of ethanol was added dropwise over 2 h. After addition was complete, the reaction was warmed to ambient temperature and stirred for 3 h. The mixture was poured into 600 ml of ethyl acetate and 600 ml of saturated NH Cl. The ethyl acetate layer was removed and the aqueous layer extracted (2 200 ml) with ethyl acetate. The combined organic layer was dried over sodium sulfate, filtered and concentrated in vacuo to give an orange oil. The oil was dissolved in 500 ml of toluene and sodium ethoxide (16.75 g, 0.246 mole) was added. The reaction mixture was heated to reflux for 6 h, cooled to RT, and then poured into an ice-cold solution of 1 N HCl (235 ml) and extracted with ethyl acetate (3 x 150 ml) The combined organic layers were dried over sodium sulfate, filtered and concentrated to an oil that was used in the next step without purification. The crude product was added to 500 ml of aqueous 10% sulfuπc acid and the resulting mixture heated to reflux for several hours, and then cooled to RT and neutralized with 6N sodium hydroxide and extracted with ethyl acetate (3 x 300 ml) The combined organic layer was dried, filtered and concentrated in vacuo to give a dark burgundy oil The crude product (ketone) was purified by vacuum distillation at 75°-80°C. 300 MHz 1 H NMR (CDCI3) δ 0.93 (d, J = 9 Hz, 3H), 1.03 (d, J = 9 Hz, 3H), 2.32 (m, 1 H), 2.55-2.70 (m, 2H), 2.93 (t, J = 7.5 Hz, 2H), 3.38 (d, J = 4 Hz, 1 H) Mass spectrum: (M+H) + = 145 To a stirred solution of the above ketone in 125 ml of CH2CI2 at 0°C was added diisobutylaluminum hydride (86 ml, 1 M in THF) dropwise over 20 minutes The reaction mixture was allowed to warm to room temperature and then was quenched by cautious addition of 1 N HCl (255 ml). The reaction mixture was extracted with ether (3 x 150 ml) and the combined ether solution was washed with satd. sodium bicarbonate, brine and dried over magnesium sulfate The solution was concentrated in vacuo and the resulting oil was purified by silica gel column ehromatography (10% EtOAc/hexane) 300 MHz 1 H NMR (CDCI3) δ 1.03 (d, J = 7 Hz, 3H), 1.08 (d, J = 7 Hz, 3H), 1.80 (d, J = 9 Hz, 1 H), 1.90 (m, 2H), 2.24 (m, 1 H), 2.90-3.10 (m, 3H), 4.36 (m, 1 H) Mass spectrum (M+H) + = 147. B Cιsf±H2-ιsoDropvl-3-thιoPhenvl l -2(2-Pvπdvncarbonate To the product from Example 22A (2.29 g, 15 7 mmole) in 40 ml of CH2CI2 was added dnsopropylethyl amme (4.65 ml, 26 7 mmole) and dι-(2- pyrιdyl)carbonate (5 42 g, 25 1 mmole) After 18 h at RT, the reaction mixture was diluted with chloroform and washed sequentially with 10% citric acid, satd sodium bicarbonate, brine and then dried over sodium sulfate; filtered and concentrated in vacuo. Purification of the crude product by silica gel column ehromatography (20% EtOAc/hexane) provided the desired compound 300 MHz 1 H NMR (CDCI3) δ 1.05 (d, J = 7 Hz, 3H), 1.08 (d, J = 7 Hz, 3H), 1.90 (m, 1 H), 2.05 (m, 2H), 2.58 (dd, J = 6, 15 Hz, 2H), 3.10 (m, 2H), 3.28 (dd, J = 3, 12 Hz, 1 H), 5 47 (m, 1 H), 7.12 (m, 1 H), 7.27 (m, 1 H), 7.80 (m, 1 H), 8.41 (m, 1 H) Mass spectrum: (M+H) + = 268. C. (2S. 3S. 5S)-2-fcιsf±V2-lsopropyl-3-tetrahvdrothιophenoxy amιno-3- hvdroxv-5-(t-butvloxvcarbonvnamιno-1 .6-dιphenvlhexane. To a solution of the compound from Example 22B (500 mg, 1.87 mmole) in 5 ml of CH2CI2 was added the amme from Example 1 F (791 mg, 2.06 mmole) The reaction was stirred at RT until all the compound from Example 22B was consumed The reaction mixture was diluted with chloroform and washed with 10% citric acid, satd sodium bicarbonate, brine and then dried with sodium sulfate; filtered and concentrated in vacuo. Purification of the crude product by silica gel column ehromatography (2% MeOH/CH2C(2) provided the desired compound (73%). 300 MHz 1 H NMR (CDCI3) δ 0.83-1.05 (m, 6H), 1.40 (s, 9H), 1.90 (m, 3H), 2.20 (m, 1 H), 2.75 (m, 2H), 2.85 (m, 4H), 2.95-3.15 (m, 3H), 3.67-3.90 (m, 4H), 4.55 (m, 1 H), 5.10 (m, 1 H), 5.30 (m, 1 H), 7.10-7 26 (m, 10H) Mass spectrum (M+H) + = 557. D (2S.3S.5S,-2-fcιs(±,-1 .1 -Dioxo-2-isopropvl-3-tetrahvdrothiophenoxv,amino- 3-hvdroxv-5-(t-butvloxvcarbonvnamιno-1 .6-diPhenvlhexane. To the compound from Example 22C (523 mg, 0.91 mmole) in 10 ml of acetone and 0.5 ml of water was added Oxone (839 mg, 1.37 mmole) and sodium bicarbonate (152 mg, 1.82 mmole). The resulting solution was stirred for 2 h, at which time a white precipitate appeared The reaction was quenched with aqueous sodium bisulfite and extracted with ethyl acetate (2 x 100 ml), dried with sodium sulfate, filtered and concentrated in vacuo. The crude product was purified by siiica gel column ehromatography (2% MeOH/CH2Cl2) to provide 422 mg of product. 300 MHz 1 H NMR (CDCI3) δ 1.20 (m, 6H), 1.40 (s, 9H), 1.60 (m, 4H), 2.10-2.32 (m, 4H), 2.67 (m, 2H), 2.75 (m, 2H), 2 85 (m, 2H), 3.15 (m, 2H), 3.70-3.90 (m, 3H), 4.56 (m, 1 H), 5.30 (m, 2H), 7.10-7.30 (m, 10H) E. f2S.3S.5S 2-.cιsf+.-1 .1 -Dioxo-2-isopropvl-3-tetrahvdrothiophenoxv,amino- 3-hvdroxv-5-f2S-f 1 -tetrahvdropvπmιd-2-onvn-3-methvl butanovhamιno-1 .6- diphenvlhexane. Removal of the Boc-protectmg group of the compound from Example 22D using TFA/CH 2 Cl 2 and coupling of the resulting amme with the carboxylic acid from Example 2A provided the desired compound (82%) 300 MHz 1 H NMR (CDCI3) δ 0.82 (m, 6H), 1.0-1.20 (m, 6H), 1.60 (, 2H), 2 07 (m, 1 H), 2.25 (m, 2H) 2 65-3.20 (m, 12H), 3 70 (m, 1 H), 3.90 (m, 1 H), 4 10-4.20 (m, 2H), 5 07 (m, 1 H), 5 37 (m, 1 H), 5 87-5.98 (m, 1 H), 6.95-7.05 (m, 1 H), 7.20 {m, 10H) Mass spectrum (M+H)+ = 671 Example 23 f2S.3S.5S,-2-(2-6-Dιmethvlphenoxvacetvn amιno-3-hvdroxv-5-(2S-M - dιhvdropyπmιd-2.4-dιonvπ-3-methyl-butanoyl) amιno-1 .6-dιphenylhexane A. N-f2-Ethoxvacrvlovn-N'-M S-carbomethoxv-2-methvl-propvn-urea. To 1 74 g (0 013 mole) of 2-ethoxy-acryloyl chloride in 18 ml of toluene was added 3 90 g (0.026 mole) of silver cyanate The mixture was heated to reflux for 0 75 h The mixture was allowed to cool to RT and the precipitate allowed to settle The supernatant (9 6 ml) was withdrawn and added to 18 m! of dry DMF and 5 ml of Et2θ, cooled to -15°C for 45 minutes and left in freezer overnight The solvent was evaporated in vacuo and the residue was purified by silica gel coiumn ehromatography (2% MeOH/CH2Cl2) to provide 1.59 g of desired compound (90 2%) 300 MHz 1 H NMR (CDCI3) δ 0.96 (d, J = 7 Hz, 3H), 1 0 (d, J = 7 Hz, 3H), 1 37 (t, J = 7.5 Hz, 3H), 2.25 (m, 1 H), 3 74 (s, 3H), 3 97 (q, J = 7 5 Hz, 2H), 4 42 (dd, J = 4.5, 8 0 Hz, 1 H), 5.25 (d, J = 12 Hz, 1 H), 7 68 (d, J = 12 Hz, 1 H), 8 55 (s, 1 H), 9.10 (d, J = 8 Hz, 1 H) Mass spectrum (M+H)+ = 273 B. 2S-(1 -Dιhvdropvrιmιd-2.4-dιonvl,-3-methvl butanoic acid A solution of 174 mg (0.64 mmole) of the compound from Example 23A in 10 ml of 2N sulfuπc acid was refluxed for 2 h, cooled to RT and left in freezer overnight The mixture was concentrated and the residue was extracted with ethyl acetate (2 x 100 ml), dried and concentrated in vacuo to give 122 mg of desired compound. 300 MHz H NMR (CDCI3) δ 1.06 (d, J = 7 Hz, 3H), 1.13 (d, J = 7 Hz, 3H), 2.25 (m, 1 H), 5 04 (d, J = 10 Hz, 1 H), 5 74 (d, J = 7 Hz, 1 H), 7.50 (d, J = 10 Hz, 1 H), 8 43 (s, 1 H) C. .2S.3S.5S)-2-.2.6-Dime-hvl p henoxvacetvl. amιno-3-hvdroxv-5-f2S-(1 - dιhvdroDyrιmιd-2.4-dιonvl--3-methvl-butanovlι amιno-1.6-dmhenylhexane. Coupling of the carboxylic acid from Example 23B with the amine from Example 1 N using standard coupling procedure (EDAC in DMF) provided the desired compound 300 MHz 1 H NMR (CDCI3) δ 0.81 (d, J = 7 Hz, 3H), 0.92 (d, J = 7 Hz, 3H), 2 18 (s, 6H), 2.23 (m, 1 H), 2.63 (m, 1 H), 2.85 (m, 1 H), 3 0 (m, 2H), 3 78 (m, 1 H), 4.20 (m, 4H), 4.58 (d, J = 10 Hz, 1 H), 5.68 (dd, J = 1.5, 7 5 Hz 1 H), 7 0-7.25 (m, 13H), 7 50 (d, J = 7.5 Hz, 1 H), 9 50 (s, 1 H) Mass spectrum (M+H) + = 640 Example 24 Alternate Preparation of (2S. 3S. 5S)-2-.2.6-Dimethvlohenoxvacetvn amιno-3- hvdroxy-5-[2S-(1 -tetrahvdro-pvrιmιd-2-onyl)-3-methvl butanovll amιno-1 .6- diphenyihexane, A. 2.6-Dιmethvlphenoxvacetιc acid 2,6-Dιmethylphenol (102.8 g, 0 842 mol) and chloroacetic acid (159 6 g, 1 68 mol) in 1000 ml of H2O was added to a 3-L, 3-necked round bottom flask with mechanical stirring and a water-cooled condenser A solution of NaOH (134.9 g, 3.37 mol) dissolved in 500 ml of water was slowly added to the above mixture via addition funnel and heat to reflux After 2 hours, additional chloroacetic acid (79 4 g, 0.84 mol) and NaOH solution (67 2 g, 1.68 mol in in 200 ml water) was added to the reaction mixture After 19 hours, additional chloroacetic acid (39 8 g, 0.42 mol) and NaOH solution (33 6 g, .84 mol in in 100 ml water) was added to the reaction mixture and refluxmg was continued until starting phenol was consumed The reaction flask was cooled in and ice- water bath and acidified to pH=1 with cone HCl, causing a precipitate to form The resulting slurry was stirred in the ice bath for 1 hour then filtered The solid was dissolved in hot (100°C) water and cooled to crystallize the product as white plates, mp= 136-137°C, yield = 78.8 g, 52%. B. .2S. 3S. 5S. -2-.2.6-Dimethvlphenoxvacetvl) amιno-3-hvdroxv-5-ft- bu.vloxvcarbonvlamino -1 .6-diphenvlhexane. Oxallyl chloride (36.3 ml, 0.42 mol) was added to a slurry of 2-6 dimethylphenoxyacetic acid (50 g, 0.28 mol) in 500 ml toluene followed by addition of 5 drops of DMF and stirred at room temperature for 30 mm, then at - 55°C for 1.5 hours. The toluene was removed on a rotary evaporator and remaining volatiles were removed in vacuo to afford 2,6-dιmethyl- pheπoxyacetyl chloride as an amber oil, 55 grams, 100%. [2S,3S,5S]-2-Amιno-3-hydroxy-5-t-butyloxycarbonylamιno-1 ,6- diphenylhexane x 0.5 succinate (111.9 g, 0.25 mol) was charged to a 2L, 3- necked round-bottomed flask with mechanical stirring. NaHC03 (106 g, 1.26 mol), 600 ml H2O and 600 ml EtOAc were added and stirred vigorously until all solids were dissolved (15 minutes). Stirring was slowed and a solution of the 2,6-dιmethyl-phenoxyacetyl chloride and EtOAc (100 ml) was added in a narrow stream via addition funnel. After 30 mm of stirring, starting materials were consumed (HPLC analysis) and the layers were separated. The aqueous layer was extracted with EtOAc, the organic layers were combined and washed with 200 ml of 1 M NaOH, 200 ml of 10% HCl, 200 ml of brine, dried over MgS04, filtered and concentrated to provide the desired product as a white solid. C (2S. 3S. 5S -2--2.6-Dιmethylphenoxvacetvl- amιno-3-hvdroxy-5-amιno-1 .6- diphenylhexane. (2S, 3S, 5S) -2-(2,6-Dimethylphenoxyacetyl) ammo-3-hydroxy-5-(t- butyloxycarbonylamιno)-1 ,6-diphenylhexane (175.1 g, 0.32 mol) and 500 ml CH2CI2 were mixed with stirring. CF3CO2H (249 ml, 3.2 mol) was added and stirred 20-25 minutes, then the reaction mixture was poured into a separatory funnel containing 1000 ml of water and 200 ml of CH2CI2 . The resulting mixture was shaken carefully and the layers were separated. The organic layer was washed again with 500 ml of water, then 3x 500 ml of NaHCθ3 and finally 500 ml of brine. The organic solution was dried over MgSθ4, filtered and concentrated to a golden oil that pulled into a foam 300 ml of diethyl ether was added to the crude product and shaken vigorously to dissolve. Within minutes solid began to crystallize and the mixture became thick. Enough diethyl ether was added to make the mixture stirrable and the mixture was stirred at room temperature for 1 hour. The solid was filtered and air dried to give the desired product as 1 15 g of white needles, 81 % yield. A solution of HCI/diethyl ether was added to the filtrate to precipitate the remaining product as the HCl salt. This pinkish solid was collected by filtration, taking care to keep the soiid flooded with N2 while it was wet with ether. When dry, transfered the amme salt to a separatory funnel and extracted with CH2CI2 and NaHCθ3 (aq). The organic layer was washed with brme, dried over MgSθ4, concentrated and treated as above to afford an additional 15 g of the desired product, the total yield is 91%. D. N-Carbonvlbenzvloxv-3-aminoρroDanol To a 12L 3-neck round bottom flask was added isopropyl acetate (6.5L). The solvent was cooled to 0°C in an ice-water bath and 3-amino-1 -propanol (1.14Kg, 15 1 mol, 2.15eq) was added in one portion. To this rapidly stirring solution, benzyl chloroformate (1.20Kg, 7.03mol, 1.0eq) was added dropwise over 2h while maintaining the internal temperature of the flask between 10°C and 15°C. After the addition was complete, the reaction mixture was allowed to stir between 10°C and 15°C for an additional 0.3h after which time water (3.5L) was added in one portion. The solution was then partitioned and washed with an additional 2X3.5L of water The organic layer was dried over potassium carbonate and concentrated to give a solid that was dissolved in excess isopropyl acetate and precipitated from solution by adding the compound to heptane. The solid was filtered under nitrogen to yield 1.20Kg (82%) of the desired product as a colorless soiid. E. N-Carbnnylbenzyloxy-3-ammopropanal 335 mL of dimethylsulfoxide and 9L of methylene chloride were combined and chilled to -48°C. 313 mL of oxalyl chloride was added over 25 minutes so that the temperature remained below -40°C. Cooled to -48°C, and added 500 grams of N-Cbz-3-amιno-1 -propanol dissolved in 1 L of methylene chloride so that the temperature remained below -40°C. Stirred for an additional hour at -45°C. 1325 mL of tnethylamme was added at such a rate that the temperature remained below -40°C. After stirring an additional 15 minutes at -40°C, the mixture was allowed to warm to -30°C, then added 2.5L of 20% aqueous potassium dihydrogen phosphate. Stirred for one hour, then separated the layers, washed the organic layer with brine, and dried with magnesium sulfate. The resulting aldehyde was kept in solution at -20°C until needed. F N-fN-(Benzyloxycarbonyl-3-ammo)-propyl) valme methyl ester To a 5L 3-neck round bottom flask was added the crude (uπchromatographed) product of Example 24E (115g, 0.555mol, 1.0eq) followed by addition of water (400mL) and methanol (1600mL). The reaction mixture was maintained at 25°C throughout the course of the reaction. After the solution became homogeneous, (S)-Valιne methyl ester hydrochloride (90.2g, 0 538mol, 0.97eq) was added in one portion followed by rapid addition of sodium acetate trihydrate (151 g, 1.11 mol, 2.0eq) and sodium cycanoborohydπde (73.2g, 1.17mol, 2.1 eq) in said order. The reaction mixture was allowed to stir at room temperature for 0.5h and was concentrated in vacuo to remove all methanol present. To this solution, saturated aq sodium bicarbonate (400mL) was added and the mixture was extracted with isopropyl acetate (1 L). The organic layer was washed with water (2X400mL), dried over sodium sulfate, and concentrated to yield 150g of crude product, which was dissolved in isopropyl acetate (300mL) and heptane (2400mL). Dry HCl was bubbled in and an oily solid precipitated out of solution. The liquid was decanted away from the solid and was dissolved in dichloromethane (3L) The solution was washed with water (600mL) and saturated aq sodium bicarbonate (600mL) and dried over sodium sulfate. It was concentrated in vacuo to yield 105g (59%) of the desired product as a light yellow oil. G. N-f3-amino.-oro p vl) valine methvl ester. To a 3L flask was added the product of Example 24F (120g, 0.372mol) and methanol (1 L). This solution was allowed to stir in the presence of Raney Nickel (180g) for 1 h . After removal of Raney Nickel by filtration, Pd(OH)2 (24g) was added and the solution was allowed to stir under 60 psi of a hydrogen atmosphere for 12h. The solution was purged with nitrogen and repressurized with 60 psi of hydrogen for an additional 1 h. The solution was filtered and concentrated to give 63g of an oil (90%). To this oil toluene (120mL) was added and the solution was again concentrated in vacuo to give the desired product. H. 2S-(1 -tstrahvdro-pvrimid-2-onyl.-3-methvl butanoic acid methvl ester. To a 5L 3-neck round bottom flask with stir bar was added the crude product of Example 24G (150g, O.βmol) and dichloromethane (3.2L). Carboπyldiimidazole (232g, 1.44mol, 1 .8eq) was added slowly in portions over 25 min. The solution was allowed to stir at ambient temperature for 40h. Water (200mL) was added over 1 h with careful stirring untii no more gas evolution occurred. A solution of 35% HCl was slowly added to the stirring solution until the solution became acidic. The solution was then partitioned and was washed with water (2X300mL). The organic layer was dried over sodium sulfate and was concentrated to yield 126g (74%) of the desired product as a colorless solid. I. 2S-n -tetrahvdro-pvrimid-2-onvl.-3-methyl butanoic acid methvl ester. To a 12L 3-neck round bottom flask with stir bar was added the product of Example 24H (126g, 0.588mol), water (1.3L), and THF(3.9L). The solution was cooled to 0°C in an ice-water bath and lithium hydroxide monohydrate (74g, 1.76mol, 3.0eq) was added in one portion with rapid stirring. The solution was allowed to stir at 0°C for 14h. It was then acidified to pH 11 by slow addition of 50% aq phosphoric acid and the THF was removed in vacuo. The aqueous phase was washed with isopropyl acetate (2L) and was subsequently acidified to pH by slow addition of 35% aq HCl. The aqueous layer was then extracted with ethyl acetate (5X2.2L). The combined organic layers were concentrated to give the desired product (105g) as a white solid. The compound was then purified by addition of isopropyl acetate (500mL) and ethanol (15mL) and bringing the solution to a boil with rapid stirring until 50mL of solvent had evaporated. The solution was cooled to 0°C and filered to give 92g (75%) of pure desired product. J. (2S. 3S. 5S -2-(2.6-Dimethvlphenoxvacetvh amino-3- hvdroxv-5-r2S-M -tetrahydro-pvrimid-2-onvl,-3-methvl butanovl] amιno-1.6-diphenvlhexane. In a 2L, 3-necked round-bottomed flask were combined the product of Example 24C (100 g, 0.22 mol), the product of Example 24I (44.8 g, 0.22 mol) and 750 ml DMF and the mixture was cooled in an ice/water bath. HOBT (90.9 g, 0.67 mol), EDAC (86 g, 0.45 mol) and triethylamine (62.5 ml, 0.45 mol) were added and the ice bath was removed, allowing the reaction mixture to stir with warming to room temperature for 5h. The reaction was diluted with 1000 ml of IPAC and quenched with 1000 ml of water. The mixture was shaken and separated, the aq. layer was extracted 1 x 400 ml IPAC, the organics were washed with 1 x 400 ml 10% HCl, 1 x 500 ml NaHC03, diluted with 100 ml hexanes, then washed 4x 500 ml water, and 1 x 500 ml brine, dried over MgSθ4, filtered and concentrated to provide the desired product as a white foam. Example 25 ■ 2S.3S.5S^-2-.2.6-DιmethvlDhenoxvacetvl. amιno-3-hvdroxv-5-r2S-π - tetrahvdro-Dvnmid-2.4-dionvli-3-methvlbutanovl1amino-1 .6-diPhenvlhexanfi A N-(2-Carbomethoxy) ethyl-L-Valme t-butyl ester. To a solution of 1.73 g of L- Valme t-butyl ester in 10 ml of methanol was added 9.0 ml of methyl acrylate. The solution was heated to reflux overnight. Another 9.0 ml of methyl acrylate was added and continued the reflux for 24 h The solvent was evaporated in vacuo and the crude product was purified by silica gel column ehromatography (20% ethyl acetate in hexane) to provide 2 435 g of desired compound (93.9%). 300 MHz 1 H NMR (CDCI3) δ 0.91 (d, J=3.5 Hz, 3H), 0.93 (d, J=3.5 Hz, 3H), 1 47 (s, 9H), 1.85 (m, 1 H), 2 47 (t, J=7 Hz, 2H), 2.68 (m, 1 H), 2.81 (d, J=6 Hz, 1 H), 2.95 (m, 1 H), 3.68 (s, 3H) Mass spectrum. (M+H) + = 260. B. N-.2-Carboxamιdo ethvl-L-Va ne t-butvl ester. To a solution of 1.86 g of the product from Example 25A in 5 ml of THF was added 0 415 g of lithium hydroxide monohydrate in 10.8 ml of water After 40 mm, 10.8 ml of 1 N HCl was added The reaction mixture was evaporated to dryness and dry pyridme was added and evaporated to dryness two times The residue was dissolved in 25 ml of acetonitrile and 0.62 ml of dry pyridme added To this solution was added 2.02 g of N,N'-dιsuccιnιmιdyl carbonate The reaction mixture was stirred for 3.5 h. The solvent was removed in vacuo and 90 ml of THF added followed by 1.43 ml of cone, ammonium hydroxide The reaction was allowed to go overnight The reaction mixture was filtered and the filtrate concentrated in vacuo. The residue was dissolved in ethyl acetate and washed with sodium bicarbonate, brine and dried with anhy. sodium sulfate. After filtering off the drying agent, the filtrate was cone in vacuo and the crude product was purified by silica gel column ehromatography (5% MeOH in CH CI 2 ) to give 1 19 g (68%) of desired compound 300 MHz 1 H NMR (CDCI 3 ) δ 0.95 (d, J=7 Hz, 3H), 0 97 (d, J=7 Hz, 3H), 1 48 (s, 9H), 1.93 (m, 1 H), 2 37 (m, 2H), 2.65 (m, 1 H), 2 95 (m, 2H), 5 30 (br s, 1 H), 7.85 (br s, 1 H) Mass spectrum (M+H) + =245 C. 2S-(1 -Tetrahvdro-pvrimid-2.4-dionvn-3-methvlbutanoic acid t-butvl ester. A solution of 0.92 g of the product from Example 25B in 10 ml of THF and 1.83 g of carbonyldiimidazole (CDI) was refluxed for 26 h. Then 1.83 g of CDI was again added and the solution was refluxed for 72 h more. The solvent was evaporated in vacuo and the residue was dissolved in ethyl acetate and washed with water, satd. sodium bicarbonate, dilute hydrochloric acid and then brine. The organic layer was dried, filtered and cone, in vacuo. The crude product was purified by silica gel column ehromatography (2% to 5% MeOH in CH 2 Cl2) to give 0.54 g (52%) of desired compound. 300 MHz 1 H NMR (CDCI 3 ) δ θ.96 (d, J=7 Hz, 3H), 1.05 (d, J=7 Hz, 3H), 1.48 (s, 9H), 2.20 (m, 1 H), 2.66 (m, 2H), 3.43 (m, 1 H), 3.75 (m, 1 H), 4.63 (d, J=9 Hz, 1 H), 7.35 (br s, 1 H). Mass spectrum: (M+H) + =271. D. 2S-M -Tetrahvdro-pvrimid-2.4-dionvn-3-methvlbutanoic acid. A solution of 0.53 g of the compound from Example 25C in 5 ml of tnfluoroaeetic acid was stirred at 0°C for 1.25 h. Solvent was evaporated in vacuo, dried and purified by silica gel column ehromatography (2% MeOH/4% HOAc in CH 2 CI 2 ) to give 0.36 g of desired compound. 300 MHz H NMR (DMSO-d 6 ) δ 0.86 (d, J=7 Hz, 3H), 0.97 (d, J=7 Hz, 3H), 2.15 (m, 1 H), 3.40 (m, 4H), 4.39 (d, J=10 Hz, 1 H). Mass spectrum: (M+H)+=215. E. .2S.3S.5S)-2-.2.6-Dimethylphenoxyacetyl . amιno-3-hvdroxv-5-r2S-f1 - tetrahvdro-pvrimid-2.4-dionvn-3-methvlbutanovl] amino-1 .6-diphenvlhexane. Coupling of the amino compound from Example 1 N with the acid from Example 25D using standard coupling procedure (EDAC in DMF) provided the desired compound (68%). 300 MHz H NMR (CDCI3) δ 0.83 (d, J=7Hz, 3H), 0.88 (d, J=7Hz, 3H), 1.80 (m, 2H), 2.20 (s, 6H), 2.40 (m, 1 H), 2.58 (m, 1 H), 2.80 (m, 1 H), 2.92 (m, 1 H), 3.05 (m, 3H), 3.65 (d, J=5Hz, 1 H), 3.83 (m, 1 H), 4.20 (m, 5H), 6.18 (d, J=9Hz, 1 H), 7.0-7.38 (m, 14H). Mass spectrum: (M+H)+=643. Example 26 ■ 2S.3S.5S.-2-.2.6-Dimethvlphenoxvacetvlι amino-3-hvdroxv-5r2S-(4-aza-1 - tetrahvdro-Dvrimιd-2-onvn-3-methvl-butanovl|amιno-1.6-dιphenvlhexane. A. Nm-t-butvloxvcarbonvl-N,2Vallvl hvdrazine. To a solution of 18.18 g of t-butyloxycarbonyl protected hydrazine in 50 ml of acetonitrile was added 19.0 g of potassium carbonate, followed by 11.9 ml of allyl bromide. The reaction mixture was heated at reflux for a total of 3 h , filtered and cone, in vacuo. The residue was dissolved in ethyl acetate and washed with satd. sodium bicarbonate and dried with anhydrous sodium sulfate and filtered. After concentration in vacuo, the crude product was purified by silica gel column ehromatography (20% EtOAc/hexane) to give 4 47 g of desired compound 300 MHz 1 H NMR (CDCI 3 ) δ 1 45 (s, 9H), 3 46 (m, 2H), 4.0 (br s, 1 H), 5.10 (m, 2H), 5.83 (m, 1 H), 6.0 (br s, 1 H) Mass spectrum: (M+H)+=173. B N(1 Vt-butyloxvcarbonvl-N.2Vallvl-N.2ι-benzvloxvcarbonvl hvdrazme To a solution of 4.8 g of the compound from Example 26A in 15 ml of DMF was added 4.69 g of benzyloxycarbonyloxy-succinimide. The reaction mixture was stirred at RT for 72 h and the solvent was evaporated in vacuo. The residue was dissolved in ethyl acetate, washed with satd. sodium bicarbonate and dried with anhydrous sodium sulfate The crude product obtained after concentration was purified by silica gel column ehromatography (20% to 50% EtOAc in hexane) and provided 5.27 g of desired compound. 300 MHz H NMR (CDCI3) δ 1.43 (br s, 9H), 4.15 (br s, 2H), 5.18 (s, 2H), 5.20 (m, 2H), 5.82 (m, 1 H), 6.39 (br s, 1 H), 7.36 (m, 5H). Mass spectrum: (M+H)+=307. C. N(1 -t-butyloxvcarbonvl-Nf2Vformvlmethvl-N,2 -benzvloxvcarbonvl hydrazine. A solution of 6.5 g of the compound from Example 26B in 100 ml of methanol was cooled with a dry ice/acetone bath. Ozone was bubbled in for 1.75 h until a paie blue color persisted. Air was passed through the solution for 10 mm and then 15.6 ml of dimethyl sulfide was added and the reaction mixture was allowed to warm gradually to RT overnight. Solvent was evaporated in vacuo and the residue was dissolved in ethyl acetate and washed with water, then brine several times. The organic layer was dried with anhydrous sodium sulfate, filtered and cone, in vacuo to provide 7.2 g of the desired compound. 300 MHz 1 H NMR (CDCI3) δ 1.40 (br s, 9H), 4.35 (m, 2H), 5.20 (s, 2H), 6.65 (br s, 1 H), 7.36 (s, 5H), 9.70 (br s, 1 H). Mass spectrum. (M+NH 4 )+=326. D N-.2-. N-.2Vbenxvloxvcarbonvl-N-.1 Vt-butvloxvcarbonvlhvdrazinvl] ethvl-L- Valine methvl ester. To a solution of 7.2 g of the compound from Example 26C in 100 ml of methanol was added 3.55 g of L-valine methyl ester hydrochloride, followed by 3.48 g of sodium acetate and 1.33 g of sodium cyanoborohydride. The reaction mixture was stirred at RT overnight. The mixture was filtered and concentrated in vacuo. The crude product was purified by silica gel column ehromatography (2% MeOH in CH2CI2) to provide 5.8 g of desired compound. 300 MHz 1 H NMR (CDCI3) δ 0.90 (d, J=6Hz, 6H), 1.43 (br s, 9H), 1.87 (m, 1 H), 2.60-3.0 (m, 4H), 3.72 (s, 3H), 5.18 (s, 2H), 7.37 (m, 5H). Mass spectrum: (M+H)+=424. E. 2S-f4-benzvloxvcarbonvlaza-1 -tetrahvdro-Pvπmιd-2-onvn-3-methvi-butanoιc acid methvl ester. A solution of 2.4 g of the compound from Example 26D in 20 ml of HCl in dioxane was stirred at RT under argon for 1 h. Solvent was evaporated in vacuo and the residue was washed with satd. sodium bicarbonate and extracted with ethyl acetate. The organic layer was dried, filtered and concentrated in vacuo. The crude product was dissolved in 28 ml of CH2CI2 and 0.56 g of carbonyldiimidazole was added The solution was left at RT for 48 h. The solvent was removed and the residue was purified by silica gel column ehromatography (10% to 30% EtOAc in CH CI2) to give 0.78 g of desired compound. 300 MHz 1 H NMR (CDCI3) δ 0.90 (d, J=7Hz, 3H), 0.98 (d, J=7Hz, 3H), 2.17 (m, 1 H), 3.34 (m, 1 H), 3.61 (m, 2H), 3.72 (s, 3H), 3.98 (m, 1 H), 4.71 (d, J=10Hz, 1 H), 5.20 (s, 2H), 6.72 (br s, 1 H), 7.38 (m, 5H). Mass spectrum. (M+H) + =350. F. 2S- -Benzvloxvcarbonvlaza-1 -tetrahvdro-pvhmid-2-onvn-3-methyl-butanoic acid. Hydrolysis of 0.78 g of the compound from Example 26E using lithium hydroxide in aqueous dioxane provided 0.35 g of desired compound. 300 MHz 1 H NMR (CDCI 3 ) δ 0.85 (d, J=7Hz, 3H), 1.04 (d, J=7Hz, 3H), 2.40 (m, 1 H), 3.40 (m, 1 H), 3.50 (m, 1 H), 3.80 (m, 2H), 3.95 (d, J=10Hz, 1 H), 5.20 (s, 2H), 7.30 (s, 1 H), 7.36 (s, 5H). Mass spectrum: (M+H)+=336. G. f2S.3S.5S--2--2.6-Dimethvlphenoxvacetvl) ammo-3-hvdrnx -5[2S- ■ benzvloxvcarbonvlaza-1 -tetrahvdro-pvrimid-2-onvl.-3-methvl-butanyl]amino- 1 .6-diphenvlhexane. Coupling of the amino compound from Example 1 N with the acid from Example 26F using standard coupling procedure (EDAC/DMF) provided the desired compound (36%). 300 MHz 1 H NMR (CDCI3) δ 0.72 (d, J=7Hz, 3H), 0.83 (d, J=7Hz, 3H), 2.20 (s, 6H), 2.65 (m, 1 H), 2.83 (m, 1 H), 3.0-3.10 (m, 4H), 3.90 (m, 1 H), 6.65 (m, 1 H), 7.0-7.35 (m, 18H). Mass spectrum: (M+H)+=764. H. ,2S.3S.5S.-2-.2.6-Dime1hvlphenoxvacetvn amino-3-hvdroxv-5r2S-M-aza-1 - tetrahvdro-pvrimid-2-oxyn-3-methyl-butanoyl]amino-1 .6-diphenvlhexane. Removal of the benzyloxycarbonyl protecting group of the compound from Example 26G by hydrogenolysis using 10% palladium on carbon as catalyst provided the desired compound. 300 MHz 1 H NMR (CDCI3) δ 0.83 (d, J=4.5Hz, 3H), 0.86 (d, J=4.5Hz, 3H), 1.80 (m, 1 H), 2.20 (s, 6H), 2.58 ( , 1 H), 2.67 (m, 1 H), 2.90 (m, 2H), 3.0 (m, 2H), 3.80 (m, 1 H), 4.20 (m, 3H), 6.72 (m, 1 H), 7.0 (m, 2H), 7.20 (m, 1 1 H). Mass spectrum: (M+H)+=630. Example 27 f2S.3S.5S)-2-.2.6-Dιmethvl p henoxvacθtvl- amιno-3-hvdroxv-5-f2S-π - tetrahvdro-pyrιmid-2-onvlV3-methvlbutanovnamιno-1 -phenvl-6-methvlheptane A t ~ 2S.3S.5S .-2-Amιno-3-hvdroxv-5--t-butvloxvcarbonvlamιnoV1 -phenvl-6- methvlheptane. Following the procedures described in Example 1A to Example 1 F-1 , but substituting isopropylmagnesium chloride for benzylmagnesium chloride in Example 1 C provided the desired compound. 300 MHz " • H NMR (CDCI3) δ 0.88 (d, J=7Hz, 3H), 0.92 (d, J=7Hz, 3H), 1 43 (s, 9H), 1.50-1.80 (m, 4H), 2.55 (m, 1 H), 2.90 (m, 1 H), 3.0 (m, 1 H), 3.54 (m, 2H), 4.62 (m, 1 H), 7 30 (m, 5H) Mass spectrum- (M+H) + =337 B r2S.3S.5S--2-.2.6-Dιmethvlphenoxvacetvl- amιno-3-hvdroxv-5-.t- butvloxvcarbonvlammo)-1 -phenvl-6-methvlheptane. Coupling of the ammo compound from Example 27A with the acid from Example 1 H using standard EDAC coupling procedure provided the desired compound. 300 MHz 1 H NMR (CDCI3) δ 0.85 (d, J=7Hz, 3H), 0.90 (d, J=7Hz, 3H), 1.43 (s, 9H), 1.70 (m, 2H), 2.20 (s, 6H), 3.03 (d, J=8Hz, 2H), 3.42 (m, 1 H), 3.80 (m, 1 H), 4.20 (m, 2H), 4.22 (s, 2H), 4.55 (m, 1 H), 7.0 (m, 3H), 7 30 (m, 5H) Mass spectrum (M+H)+=499. £ -2S.3S.5S--2-.2.6-DιmethvlDhenoxvacetyl- amιno-3-hvdroxy-5-amιno-1 - phenvl-6-methvlheptane. Removal of the t-butyloxycarbonyl protecting group of the compound from Example 27B using the procedure of Example 1 N provided the desired compound 300 MHz 1 H NMR (CDCI3) δ 0.90 (d, J=3Hz, 3H), 0.94 (d, J=3Hz, 3H), 1.60 (m, 4H), 2.20 (s, 6H), 2.85 (m, 2H), 3 0 (m, 1 H), 3.85 (m, 1 H), 4.20 (m, 2H), 7 0 (m, 2H), 7.35 (m, 6H) Mass spectrum (M+H)+=399 D .2S.3S.5SV2-f2.6-nιmethvlDhenoxvanetvl- amιno-3-hvdroxv-5-f2S.π - tetrahvdro-pvπmιd-2-onvn-3-methvlbutanovl)amιno-1 -phenyl-6-methylheptane Coupling of the ammo compound from Example 27C with the acid from Example 2A using standard coupling procedure (EDAC/DMF) provided the desired compound. 300 MHz 1 H NMR (CDCI3) δ 0.88 (m, 12H), 1.67 (m, 2H), 1.90 (m, 1 H), 2.20 (s, 6H), 3.0 (d, J=8Hz, 2H), 3.22 (m, 4H), 3.67 (m, 1 H), 3 77 (m, 1 H), 4.20 (s, 2H), 4 40 (m, 1 H), 4.76 (m, 1 H), 7.0 (m, 3H), 7.30 (m, 5H) Mass spectrum (M+H)+=581. Example 26 (2S.3S.5S -2-f2.6-Dιmethvlphenoxvacetvh amιno-3-hvdroxv-5-[2S-f1 - tetrahvdro-pvπmιd-2.4-dιonvl--3-methvlbutanovl1amιno-1 -Dhenvl-6- met ylheptane, Coupling of the ammo compound from Example 27C with the acid from Example 25D using standard coupling procedure (EDAC/DMF) provided the desired compound 300 MHz 1 H NMR (CDCI3) δ 0.83 (d, J=7Hz, 6H), 0 92 (t, J=7Hz, 6H), 1.73 (m, 2H), 2.18 (s, 6H), 2.30 (m, 1 H), 2.62 (m, 2H), 3.03 (m, 2H), 3.45 (m, 1 H), 3.55 (m, 1 H), 4.72 (m, 2H), 4.20 (m, 4H), 6 40 (br d, J=9Hz, 1 H), 7.0 (m, 3H), 7.30 (m, 5H), 7.62 (br s, 1 H) Mass spectrum (M+H)+=595 Example 29, f2S.3S.5S.-2-.2.6-Dιmethylphenoxyacetvlιamιno-3-hvdroxv-5-r2S-n -DiDerazιn- 2.3-dιonyl--3-methylbutanovllamιno-1.6-dιphenvlhexane. A 2S-(4-benzyloxycarbonyl-1 -pιperazιn-2.3-dιonylV3-methvlbutanoιc acid methvl ester. To a solution of 0 77 g of N-(benzyloxycarbonylamιno)-ethyl-L-Valιne methyl ester in 20 ml of toluene and 10 ml of acetonitrile was added 0 79 g of oxalyl diimidazole The reaction mixture was kept at 50°C for 24 h and 0.2 g of oxalyl diimidazole was added The reaction mixture was kept at 50°C for another 72 h. Evaporation of solvent in vacuo and purification of the crude product by silica gel column ehromatography (10% EtOAc in CH2CI2) provided the desired compound 300 MHz 1 H NMR (CDCI3) δ 0.95 (d, J=7 Hz, 3H), 1.03 (d, J=7Hz, 3H), 2.20 (m, 1 H), 3.60 (m, 1 H), 3.73 (s, 3H), 3.85 (m, 1 H), 4.0 (m, 1 H), 4 10 (m, 1 H), 4.90 (d, J=10 Hz, 1 H), 5 36 (s, 2H), 7 20 (m, 5H) Mass spectrum (M+NH4) + =380 B 2S-f1 -pιperazιn-2.3-dιonvn-3-methylbutanoιc acid methyl ester Removal of the benzyloxycarbonyl protecting group of the compound from Example 29A by hydrogenolysis using 10% Pd/C as catalyst provided the desired compound. 300 MHz 1 H NMR (CDCI 3 ) δ 0.95 (d, J=7 Hz, 3H), 1.03 (d, J=7 Hz, 3H), 2.20 ( , 1 H), 3.50 (m, 3H), 3.74 (s, 3H), 3.83 (m, 1 H), 5.0 (d, J=10 Jz, 1 H), 7.30 (br s, 1 H). Mass spectrum: (M+H) + =229. C. ■2S.3S.5S.-2-.2.6-Dimethvlphenoxvacetvl . amino-3-hvdroxy-5[2S-π - piperazin-2.3-dionvn-3-methvlbutanovnamino-1 .6-diphenvlhexane. The methyl ester from Example 29B was hydrolyzed using the procedure of Example 1 M and the resulting acid was coupled to the amino compound from Example 1 N using standard EDAC coupling procedure to provide the desired compound. 300 MHz 1 H NMR (CDCI3) δ θ.82 (d, J=6 Hz, 3H), 0.85 (d, J=6 Hz, 3H), 1.80 (m, 2H), 2.18 (m, 1 H), 2.20 (s, 6H), 2.65 (m, 1 H), 2.82-3.0 (m, 4H), 3.30 (m, 3H), 3.70 (m, 1 H), 3.82 (m, 1 H), 4.22 (m, 3H), 4.54 (d, J=10 Hz, 1 H), 6.30 (br s, 1 H), 6.65 (br d, 1 H), 7.0-7.30 (m, 13H). Mass spectrum: (M+H)+=643. Example 30 f2S.3S.5SV2-f2.6-Dimethvlphenoxvace.vn amino-3-hvdroxv-5r2S-f4-aza-4.5- dehvdro-1 -pvrimid-2-onvn-3-methvl-butanovl1amino-1 .6-diphenvlhexane. A. 2S-f4-Aza-4.5-dehvdro-1 -Pvrimid-2-onvπ-3-methvl-butanoic acid. From the hydroysis product mixture of Example 26F, the desired product was isolated after column ehromatography (5% MeOH/5% AcOH in CH 2 CI 2 ) in 12.5% yield. 300 MHz 1 H NMR (CD 3 OD) δ 0.93 (d, J=7Hz, 3H), 1.04 (d, J=7Hz, 3H), 2.20 (m, 1 H), 3.92 (dd, J=15, 3 Hz„ 1 H), 4.09 (dd, J=15, 3 Hz, 1 H), 4.50 (d, J=10 Hz, 1 H), 6.95 (t, J=3Hz, 1 H). Mass spectrum: (M+H)+=334. B. f2S.3S.5S -2-f2.6-Dimethvlphenoxvacetvn amino-3-hvdroxv-5[2S-f4-aza- 4.5-dehvdro-1 -pvrimid-2-oxvll-3-methvl-butanovl)amino-1 .6-diphenylhexane. Coupling of the compound from Example 1 N with the acid from Example 30A using standard coupling procedure (EDAC/DMF) provided the desired compound (70%). 300 MHz H NMR (CDCI3) δ 0.80 (d, J=7Hz, 3H), 0.85 (d, J=7Hz, 3H), 1.75 (m, 2H), 2.15 (m, 1 H), 2.20 (s, 6H), 2.62 (m, 1 H), 2.85 (m, 1 H), 3 02 (m, 2H), 3.55 (m, 2H), 3.80 (m, 1 H), 4.20 (m, 4H), 6.38 (br d, 1 H), 6 72 (t, J=3 Hz,1 H), 7 0 (m, 3H), 7.22 (m, 10H), 7.63 (s, 1 H) Mass spectrum (M+H)+=628. Example 31 cιs-N-tert-butvl-decahvdro-2-r 2fR .-hvdroxv-4-phenvl-3fSVf2S-f1 - tetrahvdropyrιmιd-2-onvl--3-methvlbu1anovlιamιnobutvn-.4aS.8aR - ιsoαuιnolιne-3-S.-carooxamιde The title compound can be prepared by coupling the product of Example 2A with cιs-N-tert-butyl-decahydro-2-[ 2(R)-hydroxy-4-phenyl-3(S)-amιnobutyl]- (4aS,8aS)-ιsoquιnolιne-3(S)-carboxamιde (disclosed in PCT Patent Application No W09426749 and U.S Patent No. 5,196,438, issued March 23, 1993, both of which are incorporated herein by reference) using a standard coupling procedure (EDAC in DMF). Example 32 cιs-N-tert-butyl-decahvdro-2-f 2(RVhvdroxv-4-thioDhenvl-3fSW2S-f1 - tetrahvdropyπmιd-2-onvl--3-methvlbutanovl -amιnobutvl]- 4aS.8aS.- ιsoqumolιne-3.S--carboxamιde The title compound can be prepared by coupling the product of Example 2A with cιs-N-tert-butyl-decahydro-2-[ 2(R)-hydroxy-4-thιophenyl-3(S)- amιnobutyl]-(4aS,8aS)-ιsoquιnoiιne-3(S)-carboxamιde (disclosed in PCT Patent Application No WO95/09843, published April 13, 1995 and U S Patent No 5,484,926, issued January 16, 1996, both of which are incorporated herein by reference) using a standard coupling procedure (EDAC in DMF) Example 33 4-Ammo-N-.. 2svn. 3S)-2-hvdroxy-4-phenvl-3-f2S-f 1 -tetrahvdropvπmιd-2- onyl--3-methylbutanovlamιnθ --butvl.-N-ιsobutvl-benzenesulfoπamιde The title compound can be prepared by coupling the product of Example 2A with 4-Amιno-N-(( 2syn, 3S)-2-hydroxy-4-phenyl-3-amιno)-butyl)-N-tsobutyl- benzenesulfonamide (disclosed in PCT Patent Application No WO94/05639, published March 17, 1994, which is incorporated herein by reference) using a standard coupling procedure (EDAC in DMF) Examole 34 A Alternative Preparation of .2S. 3S. 5Si -2-.2.6-Dim9thylDhenoxyanetyl. amιno-3-hvdroxy-5-ammo-1 .6-diphenylhexane To a 1 liter 3-necked flask equipped with a mechanical stirrer, J-Kem® temperature probe, dropping addition funnel, and dry nitrogen line was charged 30.0 g (54.87 mmol) of the product of Example 11 and 120 mL of acetonitrile. The resultant slurry was cooled to 0-5°C and 54.1 g (549 mmol) of 37% aqueous hydrochloric acid was slowly added, maintaining an internal temperature of not more than +5°C during the addition. The reaction mixture was stirred at 0-5°C and samples were taken periodically to analyze for consumption of starting material by HPLC (Zorbax C-8 column, mobile phase = 1 :1 acetonιtιle/0.1 % aqueous phosphoric acid, flow rate = 1.5 mL/minute, detection at 205 nm). After stirring for 3 hours the reaction was complete. The reaction was quenched by the slow addition of 105 mL of 20% aqueous sodium hydroxide, again maintaining an internal temperature of not more than +5°C during the addition. Once the pH of the reaction mixture was confirmed to be basic, the solution was warmed to room temperature. Ethyl acetate (180 mL) was added with mixing and. after settling, the lower aqueous phase was separated and discarded The organic phase was then washed once with 105 mL of 10% aqueous sodium chloride. The title compound was crystallized from 12 mL/g of 1 :2 ethyl acetate/heptane (yield 80-85%). B Alternative Pre p aration of ( 2S. 3S. 5S ■ 2-.2.6-DιmethylDhenoxyacetyl) amιno-3-hvdroxy-5-amtno-1 ,6-diphenylhexane To a round-bottom 3-neck 1 L flask with attached mechanical stirbar and thermometer was added the product of Example 1 1 (51.6 g, 0.095 mol) and 100 mL of glacial acetic acid. To the resulting suspension was added 35% aqueous HCl (10.5 mL. 0.103 mol) in 1 portion. The solution was allowed to stir under a N2 atmosphere for 3h, at which time an additional 10.5 mL of 35% aqueous HCl was added. After an additional 1.5h. the reaction flask was immersed in an ice bath and a NaOH solution (16 mL, 0.198 mol) was added at a rate to maintain the internal temperature of the flask below 30 °C. Water (200 mL) was added and the mixture extracted with 4 x 200 mL of Isopropyl Acetate. The combined organic layers were washed with 2.5M NaOH (2 x 200 mL), 100 mL H2O, brine, dried over Na2S0 , filtered and evaporated in vacuo to yield 39.7g (94% crude) of product as a colorless solid in greater than 95% purity by HPLC. The product could be further purified by dissolving in 200 mL isopropanol heated over a steam bath, allowed to cool with stirring to 0-5 °C to yield 32.2g (76%) of the desired product, m.p. = 131 °C. Example 35 Alternative Preparation of 2S-(1 -Tetrahvdro-pyπmid-2-onyl)-3-methyl butanoic A. N-phenoxycarbonyl-L-valme N-phenoxycarbonyl-L-valine may be prepared according to the procedures disclosed in U.S. Patent Application No. 08/08/671 ,893, filed June 28, 1996, which is incorporated herein by reference, and which include the following method. Into a reactor equipped with an overhead stirrer, chiller, pH probe and thermocouple was added lithium chloride (15.6 kg, 368 moles), L-valine (26.0 kg, 222 moles), neutral alumina (8.1 kg, 150 mesh, Aldπch) and 156 kg of distilled water. The heterogeneous mixture was stirred and cooled to -14°C ± 5°C. The pH was adjusted to 10.1 with 10% aqueous lithium hydroxide. Precooied (-20°C) phenylchlorformate (36.6 kg, 234 moles) was added while maintaining a temperature of not more than -9 °C and the pH was controlled during the reaction (maintaining a pH within the range of 9.5 to 10.5 with a target of 10.0) using a continuous addition of 10% aqueous lithium hydroxide. The reaction was stirred for 2 hours at about -14°C The reaction mixture was filtered through Celite and the filter cake was washed with 42 kg of distilled water. The aqueous filtrate was extracted with methyl t-butyl ether (65 kg) to remove residual phenol. The aqueous phase was then cooled to 0-5°C and mixed with 200 kg of toluene. The stirred biphasic solution was adjusted to pH 1.8-2.0 with 25% (w/w) sulfuπc acid. The toluene layer was concentrated at not more than 40 °C to approximately 120 L, filtered (30 kg rinse of toluene) and then concentrated again at not more than 40 °C to approximately 120 L. To the resulting solution was added 44.2 kg of heptane and the resulting solution was heated to 40 °C ± 10°C for 15 minutes. The heat was removed and the solution was seeded and stirred overnight. The product crystallized on the walls of the reactor and was resuspended in 80 kg of toluene, reconcentrated at not more than 50 °C to approximately 130 L, then 45 2 kg of heptane was added The resulting solution was then heated to 40 °C ± 10°C for not less than 15 minutes and then cooled at not more than 20 °C/hour to 18 °C ± 5°C After not less than 12 hours, the resulting white slurry was cooled to 14 °C ± 5°C and stirred for not less than 3 hours The white slurry was filtered and the solid washed with 41 kg of 1 toluene/heptane The solid product was dried at not more than 50 °C to provide the desired product (47 8 kg) as a white powder B. 2S-f1 -Tetrahvdro-pvrιmιd-2-onvn-3-methvl butanoic acid A mixture of N-phenoxycarbonyl-L-valme (25 g, 0.106 mol) and 3-chloropropylamιne hydrochloride (15 2 g, 0 1 16 mol) in THF (250 mL) was cooled to 2°C Sodium hydroxide (12 7 g, 0.318 mol) was added to the stirring suspension After about 35 minutes, a slow exotherm to 10°C occurred The reaction was stirred at less than 10°C for 2 hours A solution of potassium t- butoxide (29 6 g, 0.265 mol) in 125 mL of THF was added over 10 minutes, followed by a 20 mL THF rinse The temperature of the reaction mixture was allowed to rise to 20°C during the addition The reaction mixture was stirred at room temperature for 19 hours. The reaction mixture was quenched with 200 mL of distilled water and then acidified to pH 9 using 26 2 g of concentrated hydrochloric acid, keeping the temperature below 30°C The aqueous layer was separated and washed with another 125 mL of THF Ethanol 3A (75 mL) was added to the separated aqueous layer and the mixture was acidified to pH < 3 with 12.3 g of concentrated hydrochloric acid, keeping the temperature below 25°C The acidified mixture was extracted twice with ethyl acetate (250 mL and 150 mL) The combined organic layers were evaporated to dryness on a rotary evaporator at a temperature below 50°C. The residual solids were flushed with 250 mL of ethyl acetate. The residual solid was dissolved in 150 mL of ethanol 3A at reflux temperature and filtered through a 5 g Darco-G60 bed over filteraid, followed by a 50 mL hot ethanol rinse. The filtrate was evaporated to dryness on a rotary evaporator at a temperature below 50°C. Ethyl acetate (75 mL) was added to the residue and refluxed for 30 minutes. The suspension was cooied to below 10°C for 2 hours. The solid was collected by filtration and washed with 20 mL of cold ethyl acetate (5-8°C). After drying at 40°C for 72 hours the desired product was obtained as a white solid (15.6 g, 74%). Example 36 Alternative Preparation of 2S-f1 -Tetrahvdro-pyrimid-2-onvn-3-methyl butanoic acid A mixture of phenoxycarbonyl-L-valine (250 g, 1.05 mol; prepared according to the procedure disclosed in U.S. Patent Application No. 08/671 ,893, filed June 28, 1996, which is incorporated herein by reference) and 3- chloropropylamine hydrochloride (151 g, 1.16 mol) in THF (2.5 L) is cooled to 2°C. Sodium hydroxide (127 g, 3.2 mol) is added to the stirring suspension. After about 45 minutes, a rapid exotherm to 10°C oceurrs. The reaction is stirred at 1 -5°C for 2 hours. Additional 3-chioropropylamine (10 g, 0.08 mol) is added and stirring is continued for 1 hour. A solution of potassium t-butoxide (296 g, 2.6 mol) in 1.25 L of THF is then added over 30 minutes, followed by a 100 mL THF rinse. The temperature of the reaction mixture was allowed to rise to 20°C during the addition. The reaction mixture is stirred at room temperature for 12- 16 hours. The reaction mixture is quenched with 2 L of distilled water and cooled to 12°C and then acidified to pH 9 using 258 g (2.6 mol) of concentrated hydrochloric acid, keeping the temperature below 30°C. The aqueous layer is separated. Ethanol 3A (625 mL) is added to the separated aqueous layer and the mixture was acidified to pH < 3 with 116 g (1.2 mol) of concentrated hydrochloric acid, keeping the temperature below 25°C. The acidified mixture is extracted twice with ethyl acetate (2.5 L and 1.5 L). The combined organic layers are evaproated to dryness on a rotary evaporator at a temperature below 50°C. The residual solids are dried by repeated distillation with ethyl acetate (4 x 1 L). The residual solid is dissolved in 750 mL of methanol and treated with decolorizing carbon (10 g Darco-G60 bed) at room temperature overnight. The carbon is removed by filtration through diatomaceous earth. The filtrate is evaporated to dryness on a rotary evaporator at a temperature below 50°C. Ethyl acetate (1.5 L) is added to the residue and approximately 500 mL is removed on the rotary evaporator. The suspension is cooled to below 10°C for > 1 hour. The solid is collected by filtration and washed with 2 x 100 mL of cold ethyl acetate (5-8°C). After drying at 50°C for 72 hours the desired product is obtained. Example 37 Alternative Preparation of 2S-f1 -Tetrahvdro-pyπmιd-2-onvO-3-methyl butanoic A fSH-)-N-carboxymethyl-Nfβ)cvanoethyl Valme To a 5L 3-neck round bottom flask with a mechanical stirrer was added (S)-vaiιne (170.1 g, 1.45mol) and water 145mL. The solution was cooled to 0°C with an ice-water bath and a solution of 1.Oeq of KOH (93g of 88% solid KOH) in 180mL water was added dropwise over 20 minutes. After the addition was complete, acrylonitrile 1.0eq (95.5mL) was added dropwise with vigorous stirring while maintaining the internal temperature of the flask below 5°C. The solution was allowed to stir between 0-5°C for 4.5h. Water (600mL) was added and a pH meter was inserted into the solution. Methyl chloroformate 1.0eq (112mL) was added dropwise while maintaining the pH of the solution between 9.5 and 10.5, with solution of 10% aq KOH The addition took place over 0.5h The solution was then acidified with cone. HCl and phosphoric acid to pH 2 and was subsequently extracted with 2L of isopropyl acetate. The organic layer was concentrated under vacuum to give 201 g (60%) of a colorless oil that solidified on standing, mp 65-66°C Optical rotation soαium D line at 25°C -0 44 (c=4.3, ethanol) IR (cm " 1 , CDCI3) 2960, 1740, 1710,1470. 1 H NMR (300 MHz,CDCl3), (δ TMS, 0.00) ppm 0.93 (d,3H J=7Hz); 1.07 (d,3H J=6Hz); 2 16-2.36 (m,1 H); 2.62-2.86 (m,2H), 3.62 (t,2H. J=7.5Hz), 3.77 (s,1.2H rotamer), 3.82 (s,1.8H rotamer); 4.15-4.30 (m,1 H); 9 76-9.96 (brs,1 H). ms (DCI/NH3) 246, 185, 146, 125. FAB hrms: cal for (M+H+): 229.1 188; found 229.1 185. B. 2S-f1 -Tetrahvdro-ovrimid-2-onvn-3-methvl butanoic acid To a 2L pressure vial was added the product of Example 37A (190g, 0.833 mol), water (900mL) and KOH (3eq, 140g). To this solution at ambient temperature was added Nickel Aluminum alloy (Raney-Type) 75g Note that this is the unactivated form The solution was sealed in a pressure bomb and was placed under 60 psi of hydrogen The resulting solution was heated to 100°C for 4h After cooimg the solution to ambient temperature, it was filtered, washed with 900mL of dichioromethane and subsequently acidified to pH 1 The aqueous solution was extracted with 2 X 900mL of dichloromethane The combined organic layers were concentrated to give 120g of crude product which was slurπed in isopropyl acetate to give 70g of the title compound. Example 38 Alternative Preparation of f2S. 3S. 5S,-2-f2.6-Dιmethvlphenoxvacetvn amιno-3- hvdroxy-5-[2S-f1 -tetrahvdro-pvπmιd-2-onvn-3-methvl butanovl] amιno-1 .6- diphenvlhexane A-1. 2S-f1 -Tetrahvdro-pyrιmιd-2-onvn-3-methvl butanovl chloride 2S-(1 -Tetrahydro-pyrιmιd-2-onyl)-3-methyl butanoic acid (17.6 g, 87 9 mmole) was slurπed in THF (240 mL) and cooled to <5 °C Thionyl chloride (14.3 g, 120 mmole) was added over 5 minutes (exothermic). The slurry was stirred at 20 °C for 70 mm. until complete by HPLC (samples quenched into methanol). THF was removed by rotary evaporation; heptane (90 mL) was added and removed by rotary evaporation, yielding a wet solid mass The material was slurπed in DMF (85 mL). A-2 Alternative Preparation of 2S-f1 -Tetrahvdro-pvπmιd-2-onvn-3-methyl butanoyl chloride 2S-(1 -Tetrahydro-pyrιmιd-2-onyl)-3-methyl butanoic acid (39.6 g, 198 mmole) was slurπed in THF (590 mL) and cooled to 1 °C Thionyl chloride (28.3 g, 238 mmole) was added over 5 minutes (exothermic). The slurry was stirred at 20 °C for 2 hours. THF was removed on the rotary evaporator; THF (200 mL) was added and removed on the rotary evaporator, yielding a wet solid mass. The material was slurried in DMF (225 mL). B-1. (2S. 3S. 5S -2-N.N-dibenzvlamιno-3-hvdroxv-5-[2S-f1 -tetrahvdro-pyrιmιri- 2-onyl)-3-methyl butanovl] amιno-1.6-diPhenvlhexane (2S, 3S, 5S)-2-N,N-dibenzylamιno-3-hydroxy-5-amιno-1 ,6- diphenylhexane (ca. 83 mmole; U.S. Patent No. 5,491 ,253, issued February 13, 1996, which is incorporated herein by reference) and imidazole (8.2 g, 120 mmole) were dissolved in ethyl acetate (350 mL, KF < 0.1%) and cooled to 2 °C The slurried product of Example 38A-1 was added (exothermic, maximum temp was 10 °C), followed by a DMF rinse (15 mL) The reaction was stirred cold initially then allowed to slowly warm to room temperature and stirred overnight The reaction was quenched with 100 mL water and stirred 30 minutes The organic layer was separated and washed with 3 x 125 mL 5% NaCl The organic solution was filtered and concentrated on rotary evaporator to a thick syrup, 62 g. HPLC purity approx. 85% (peak area). Isomer content approx 1 1.2% CIMS (NH 3 ) m/z 647 (M + H)+. 1 H NMR (300 MHz, CDCI 3 ) δ 7.35-7.13 (m, 10H), 7.13-7.06 (m, 1 H), 6.87 (br d, 1 H), 5.22 (br s, 1 H), 4.28 (d, 1 H), 4.20-4.05 (m, 1 H), 3.95 (d, 2H), 3.65-3.56 (m, 1 H), 3.37, (d, 2H), 3.12-2.89 (m, 5H), 2.83-2.53 (m, 4H), 2.23-2.08 (m, 1 H), 1 74-1 40 (m, 4H), 0.87-0.75 (m, 6H). 3C NMR (75 MHz, CDCI3) δ 170.0, 156.6, 140.2, 139 1 , 138.4, 129.3, 129 1 , 128.9, 128 4, 128.3, 128.0, 127.1 , 126.0, 125.8, 69.1 , 64.0, 63.1 (br), 54.2, 49.2, 41.2, 40.5, 40.0, 39 7, 31.5, 25 4, 21.6, 19.5, 18.6. B-2 Alternative Preparation of .2S. 3S. 5S,-2-N.N-dιbenzylamιno-3-hvdroxγ-5- f2S-(1 -tetrahvdro-pyπmιd-2-onyl)-3-methyl butanoyll amιno-1 .6-diphenylhexane (2S, 3S, 5S)-2-N,N-dιbenzylamιno-3-hydroxy-5-amιno-1 ,6- diphenylhexane (ca. 180 mmole; U.S. Patent No. 5,491 ,253, issued February 13, 1996, which is incorporated herein by reference) and imidazole (38.1 g, 560 mmole) were dissolved in ethyl acetate (675 mL, KF < 0.1 %) and cooled to 1 °C The slurried product of Example 38A-2 was added slowly over 30 minutes (exothermic, maximum temp, was 6 °C), followed by an ethyl acetate rinse (225 mL) The reaction was stirred cold for 1 5 hours, then allowed to slowly warm to about 27°C and stirred for about 20 hours. The reaction was quenched with a dilute solution of HCl (36.75 g concentrated HCl in 225 mL of water) and stirred 20 minutes The biphasic mixture was filtered with a 100 mL ethyl acetate rinse. The organic layer was separated and washed with 3 x 125 mL 5% NaCl The organic layer was separated and washed with 3 x 225 mL 5% NaCl and 2 x 225 mL 5% NaHC0 3 The organic solution was concentrated by rotary evaporation to provide the desired product as a thick syrup. C f2S. 3S. 5S)-2-Amιno-3-hvdroxy-5-f2S-f1 -tetrahvdro-pyrιmιd-2-onyl,-3- methyl butanoyll amιno-1 .6-dιphenylhexane The crude product of Example 38B (ca. 83 mmole) was dissolved in methanol (260 mL) Pd/C (50% wet Pearleman's catalyst, 10 4 g wet weight) and ammonium formate (15.1 g, 239 mmole) were added and the mixture was warmed to 50 °C After 2.5 hours the reaction was complete by TLC The mixture was cooled to 35 °C and catalyst was removed by filtration through diatomaceous earth followed by a methanol rinse (250 L) The combined filtrate was concentrated on the rotary evaporator The residue was dissolved in dioxane (150 mL) with warming Dioxane was removed on the rotary evaporator to yield 60 g of yellow oil HPLC purity approx 88.2% (peak area) Isomer content >7 9% (however, one isomer does not separate from the ma peak) CIMS (NH 3 ) m/z 467 (M + H) + 1 H NMR (300 MHz, CD 3 OD) δ 7.35-7.10 (m, 10H), 4.40-4.20 (m, 1H), 4.25 (d, 1H), 3.68-3.57 (m, 1H), 3.20-3.09 (m, 2H), 3.08-2.90 (m, 3H), 2.90-2.74 (m, 2H), 2.65-2.49 (m, 2H), 2.20-2.04 (m, 1H), 1.92-1.78 (m, 1H), 1.78-1.60 (m, 2H), 1.60-1.45 (m.1 H), 0.88-0.77 (m, 6H) 13 C NMR (75 MHz, CD3OD) δ 171.3, 158.4, 140.5, 139.8, 130.6, 130.4, 129.5, 129.3, 127.3, 127.0, 71.5, 63.9.57.1, 49.1, 41.8, 41.6, 41.4, 40.7, 40.5, 26.9, 22.5,20.0, 18.9 1 H NMR (300 MHz, CDCI3) δ 7.35-7.13 (m, 10H).5.35 (s, 1 H), 440-4.23 (m, 2H), 3.60-3.52 (m.1 H), 3.25-2.65 (m, 8H), 2.58-245 (dd, 1H), 2.30-2.10 (m, 1H), 1.90-165 (m.3H), 1.65-1.50 (m, 1H), 0.91 (d, 3H), 0.84 (d, 3H) 1 3 C NMR (75 MHz, CDCI3) δ 171.2, 156.6, 139.1, 138.5, 129.3, 129.2, 128.5, 128.2, 126.3, 126.0, 71.6, 63.1 (br), 56.3, 48.7, 41.6, 41.0, 40.6, 40.0, 39.6, 25.5,21.7, 19.7, 18.7 D. .2S.3S.5SV2-Ammo-3-hvdroxy-5-f2S-(1-tetrahvdro-pyπmid-2-onvn-3- ethyl butanoyl] amιno-1 6-dιphenylhexane (S)-Pyroαlutamtc acid salt The crude product of Example 38C was dissolved in dioxane (370 mL, KF = 0.07% moisture). S-Pyroglutamic acid (10.3 g, 80 mmole) was added and the suspension was warmed to 50 °C to give a clear solution. After stirring 1 hour the solution was seeded with a few crystals of the product salt. The salt slowly precipitated The slurry was slowly cooled and stirred overnight at room temperature The product was isolated by filtration and washed with dioxane (100 mL). Wet cake weight was 120 g Product was dried at 60 °C in a vacuum oven with nitrogen purge Yield 35.2 g off-white powder HPLC purity >98% (peak area including pyroglutamic acid). Isomer content approx.1% (however, one isomer does not separate from the mam peak). mp = 135-141 °C [a] D 25 = -21.9° (c=2.5, CH 3 OH) CIMS (NH3) m/z 467 (M + H for base) + , 147 (M + NH4 for pyroglutamic acid)+, 130 (M + H for pyroglutamic acid) + IR (KBr) 1586, 1655, 1682 cm ' 1 1H NMR (400 MHz, DMSO-d 6 ) δ 7.62 (s, 1H), 7.54 (d, 1H), 7.32-7.06 (m, 10 H), 6.33 (s, 1H), 4.26 (d, 1H), 4.11-3.99 (m, 1H), 3.82 (dd, 1H), 3.57-3.48 (m, 1H), 3.27-3.19 (m, 1H), 3.08-2.95 (m, 2H), 2.92-2.70 (m, 5H), 2.53-2.43 (m, 1H), 2.26-2.14 (m, 1H), 2.13-1.99 (m, 2H), 1.99-1.87 (m, 2H), 1.72-1.61 (m, 2H), 1.61-1.49 (m, 1H), 1.46-1.35 (m, 1 H), 0.70 (d, 3H), 0.64 (d, 3H). 13c NMR (100 MHz, DMSO-d 6 ) δ 176.9, 176.1, 169.2, 155.5, 138.8, 137.7, 129.3, 129.3, 128.3, 127.8, 126.4, 125.5, 66.9, 61.5, 56.9, 55.3, 46.8, 40.2, 39.6, 39.4, 38.8, 37.4, 29.8, 25.4, 25.3, 21.6, 19.6, 18.7. 1H NMR (300 MHZ, CD3OD) δ 7.32-7.03 (m, 10H), 4.23-4.12 (m, 1H), 4.12 (d, 1H), 3.98 (dd, 1 H), 3.71-3.63 (m, 1H), 3.46-3.37 (m, 1H), 3.11-2.98 (m, 2H), 2.97-2.80 (m, 4H), 2.70-2.59 (m, 1H), 2.49-2.38 (m, 1H), 2.38-2.12 (m, 3H), 2.07-1.92 (m, 2H), 1.75-1.63 (m, 2H), 1.63-1.50 (m, 1 H), 1.45-1.32 (m, 1 H), 0.74-0.65 (m,6H). 13C NMR (75 MHz, CD3OD) δ 181.0, 179.6, 171.6, 158.4, 139.5, 137.3, 130.5, 130.0, 129.4, 128.3, 127.2, 68.1, 64.0, 59.6, 57.7, 48.8, 41.7, 41.1, 40.7, 40.6, 37.9, 31.1, 26.9, 26.9, 22.5, 20.1, 18.9. 1 H NMR (300 MHz, D 2 0) δ 7.30-6.97 (m, 10H), 4.16-4.03 (m, 1 H), 3.99-3.91 (m, 2H).3.71-3.63 (m, 1H), 3.43-3.35 (m, 1H), 3.00-2.68 (m, 6H), 2.40-2.13 (m, 5H), 1.88-1.72 (m, 3H), 1.68-1.56 (m, 1H), 1.52-1.37 (m, 1H), 1.32-1.18 (m, 1H), 0.60-0.52 (m, 6H). 13C NMR (75 MHz, D 0) δ 181.6, 180.1 , 171.0, 157.3, 137.9, 135.2, 129.3, 129.2, 129.1 , 128.4, 127.6, 126.4, 67.3, 62.6, 58.2, 56.7, 47.5, 40.1 , 39.4, 39.2, 38.7, 35.7, 29.6. 25.3, 25.2, 20.5, 18.5, 17.6. E ^ (2S. 3S. 5S)-2-f2.6-DimethylPhenoxyacetvn amιno-3-hvdroxy-5--2S-M - tetrahvdro-pyrιmiri-2-onylV3-methyl butanoyll amιno-1 .6-dιohenylhexane The product of Example 1 H (7.26 g, 40.3 mmole) was slurried in ethyl acetate (22 mL) and thionyl chloride (5.75 g, 48.3 mmole) was added, followed by 1 drop DMF The mixture was warmed to 50 °C and stirred 5 hours. The solution of the resulting acid chloride was cooled to 22 °C and held for the subsequent coupling reaction. The product of Example 38D (20 g, 31.7 mmole, corrected for dioxane content), sodium bicarbonate (16.5 g, 197 mmole), ethyl acetate (150 mL) and water (150 mL) were combined in a flask and stirred until the product of Example 38D had dissolved (some salt remains undissolved). The solution of acid chloride prepared above was added over 5 minutes, followed by an ethyl acetate rinse (5 mL). Addition was mildly exothermic (maximum temperature 23 °C) The mixture was stirred overnight. The organic layer was separated and washed with 5% sodium bicarbonate (100 mL) and water (100 mL). Solvent was removed on the rotary evaporator. The residue was dissolved in ethyl acetate (100 mL) and filtered, rinsing with ethyl acetate (50 mL). The solvent was removed from the combined filtrate on the rotary evaporator. The residue was dissolved in hot ethyl acetate (105 mL) and heptane (105 mL) was added; product began to crystallize rapidly. The slurry was cooled and stirred at 20-23 °C for 5 hours. Product was collected by filtration and washed with 1/1 (v/v) ethyl acetate/heptane (30 mL). Product was dried under vacuum oven at 70 °C to provide 18.8 g of the desired product as a white powder. Example 39 Preoaration of Amorphous .2S. 3S. 5S.-2-.2.6-Dimethyl p henoxyacetyl. aminn- 3-hvdroxy-5-r2S-M -tetrahvdro-pyrimid-2-onyl l -3-methyl butanoyll amιno-1 .6- diohenylhexane A The product of Example 38E (2.5 g) was dissolved in 8 mL of absolute ethanol This solution was added slowly dropwise to 250 mL of chilled water at 9°C with vigorous stirring A white solid immediately appeared. The stirring was continued for 15 minutes and the solids were collected by filtration Vacuum drying at 50°C for 12 hours provided 2 32 g of the desired product as an amorphous solid B The product of Example 38E (2.5 g) was dissolved in 6 mL of absolute ethanol This solution was added slowly dropwise to 31 mL of chilled water at 7-9°C with vigorous stirring A white solid appeared The stirring was continued for 20 minutes and the solids were collected by filtration Vacuum drying at 50°C for 12 hours provided 2.24 g of the desired product as an amorphous solid C The product of Example 38E (0.5 g) was dissolved in 8 mL of isopropanol This solution was added slowly dropwise to 100 mL of chilled water at 10-15°C with vigorous stirring A white solid appeared The stirring was continued for 20 minutes and the solids were collected by filtration Air drying provided 0 48 g of the desired product as an amorphous solid D The product of Example 38E (0.5 g) was dissolved in 8 L of acetone and 0.2 mL of absolute ethanol This solution was added slowly dropwise to 100 mL of chilled water at 10-15°C with vigorous stirring A white solid appeared The stirring was continued for 10 minutes and the solids were collected by filtration Air drying provided 0 46 g of the desired product as an amorphous solid E The product of Example 38E (0.5 g) was dissolved in 2 mL of acetonitrile This solution was added slowly dropwise to 100 mL of chilled water at 10-15°C with vigorous stirring. A white solid appeared. The stirring was continued for 20 minutes and the solids were collected by filtration. Air drying provided 0.46 g of the desired product as an amorphous solid. Example 40 N-(3-Chloropropylaminocarbonv0-valine methyl ester 3-Chloropropylisocyanate (0.31 mL, 3.0 mmol) was added to a slurry of L-valine methyl ester hydrochloride (0.5 g, 3.0 mmol) and triethylamine (0.42 mL, 3.0 mmol) in THF (10 mL). The reaction mixture was stirred for 4 hours at room temperature and was then quenched with the addition of aqueous sodium bicarbonate. The quenched reaction mixture was extracted with ethyl acetate. The organic layer was separated, dried and evaporated to give the desired product. Example 41 (2S. 3S. 5S)-2-(2.6-DimethylPhenoxyacetyl) amino-3-hvdroxy-5-I2S-(1 - tetrahvdro-4-hvdroxy-pyrimid-2-onvπ-3-methyl butanoyll amino-1 .6- diphenylhexane Reaction of a solution of the product of Example 25E in methylene chloride with sodium borohydride provides the desired product. Example 42 ■ 2S. 3S. 5S.-2-.2.6-DimethylDhenc-xyacetyl. amino-3-hvdroxy-5-.2S-(1 - tetrahvdro-6-hvdroxy-pyrimid-2-onvO-3-methyl butanoyll amino-1 .6- diphenylhexane A 300-mL incubation of (2S, 3S, 5S)-2-(2,6- Dimethylphenoxyacetyl) amino-3-hydroxy-5-[2S-(1 -tetrahydro-6- hydroxy-pyrimid-2-onyl)-3-methyl butanoyl] amino-1 ,6-diphenylhexane labelled with 14 C in the carbonyl group of the acetyl moiety (50 μM, 6.0 μCi) was performed with rat liver microsomes (0.5 mg/mL microsomal protein) and an NADPH-generating system for 60 minutes at 37°C. The metabolic reaction was stopped by adding 300 mL of acetonitrile. The supernatant obtained after centrifugation at 3000 RPM for 10 minutes was evaporated to dryness in vacuo. The residue was reconstituted in 2 mL of HPLC mobile phase. Isolation of the desired product was achieved at ambient temperature with a Beckman Ultrasphere 5 μm 10 x 150 mm Cιβ column connected to an Alltech Ultrasphere 5 μm Ci8 cartridge guard column. A linear gradient of 25-55% acetonitrile in buffer (25 mM ammonium acetate, pH adjusted to 4.8 with formic acid) over 57 minutes was used as column eluent at a flow rate of 2.8 mL/minute. Fluoroπenic Assay for Screening Inhibitors of HIV Protease The inhibitory potency of the compound of the invention can be determined by the following method. The compound of the invention is dissolved in DMSO and a small aliquot further diluted with DMSO to 100 times the final concentration desired for testing. The reaction is carried out in a 6 X 50 mm tube in a total volume of 300 microliters. The final concentrations of the components in the reaction buffer are: 125 mM sodium acetate, 1 M sodium chloride, 5 mM dithiothreitol, 0.5 mg/ml bovine serum albumin, 1.3 μM fluorogenic substrate, 2% (v/v) dimethylsuifoxide, pH 4.5 After addition of inhibitor, the reaction mixture is placed in the fluorometer cell holder and incubated at 30°C for several minutes. The reaction is initiated by the addition of a small aliquot of cold HIV protease. The fluorescence intensity (excitation 340 nM, emmision 490 nM) is recorded as a function of time The reaction rate is determined for the first six to eight minutes. The observed rate is directly proportional to the moles of substrate cleaved per unit time The percent inhibition is 100 X (1 - (rate in presence of ιnhιbιtor)/(rate in absence of inhibitor)). Fluorogenic substrate: Dabcyl-Gaba-Ser-Gln-Asn-Tyr-Pro-lle-Val-Gln- EDANS wherein DABCYL = 4-(4-dιmethylamιno-phenyl)azobenzoιc acid, Gaba = γ-aminobutyπc acid, and EDANS = 5-((2-amιnoethyl)amιno)- naphthalene-1-sulfonιc acid. Compound of Example 1P 2B 3C 4F F B B 0F 1B 2B 3B 4D 5 7C 8C 9E 2E 3C 5E 6H 7D 8 9C 0B Antiviral Activity The anti-HIV activity of the compound of the invention can be determined in MT4 cells according to the following procedure. MT4 cells were infected with cell-free supernatant of HIVIIIB (previously frozen with known 50% tissue culture infectious dose (TCID50) at 0.003 multiplicity of infection (MOI) for one hour After one hour infection, cells were washed twice to remove residual viruses, resuspended in culture media and seeded into 96-well tissue culture plates at 1 x10 Λ 4 cells per well with various half-log dilutions of compounds Unmfected cells are included as toxicity and cell controls. RPMI 1640 media (Gibco ) with 10% fetal bovine serum were used as culture media Various concentrations of human serum (Sigma) 50%, 25% and 12.5% were added to culture media resulting in final concentration of 60%. 35% and 22 5% total serum All assay plates were incubated in 37 deg. cent incubator for 5 days MTT (sigma, 5 mg/ml stock in PBS) was added to all wells at 25 ul per well, incubate for 4 hours. 20%SDS with 0.02 N HCl in water was added at 50 ul per well to lyse cellls Plates incubated overnight for complete lyses were read on a microtitre plate reader at 570/650 nm wavelengths to determine cell optical density (O.D.) Raw data were analysed for percent inhibition by the following formula O.D. test well - O.D virus control x100 O.D cell control -O D virus control The 50% effective concentration (EC50) was calculated by the median effect equation (Chou, 1975,Proc. Int Cong Pharmacol. 6th p 619) to determine the efficacy of compound The 50% lethal concentration (LC50) was calculated using unmfected MT4 cells Under these conditions, the following data were obtained (n = 4 duplicate determinations The compounds of the present invention can be used in the form of salts derived from inorganic or organic acids. These salts include but are not limited to the following: acetate, adipate, alginate, citrate, aspartate, benzoate, benzenesulfonate, bisulfate, butyrate, camphorate, camphorsulfonate, digluconate, cyclopentanepropionate, dodecylsulfate, ethaπesulfonate, glucoheptanoate, glycerophosphate, hemisulfate, heptanoate. hexanoate, fumarate, hydrochloride, hydrobromide, hydroiodide, 2-hydroxy- ethanesulfonate (isethionate), lactate, maleate, methanesulfonate, nicotmate, 2-naphthalenesulfonate, oxalate, pamoate, pectinate, persulfate, 3-phenylpropιonate, picrate, pivalate, propionate, succinate, tartrate, thiocyanate, p-toluenesuifonate and undecanoate. Also, the basic nitrogen- containing groups can be quaternized with such agents as loweralkyi halides, such as methyl, ethyl, propyl, and butyl chloride, bromides, and iodides: dialkyl sulfates like dimethyl, diethyl, dibutyl, and diamyl sulfates, long chain halides such as decyl, lauryl, myπstyl and stearyl chlorides, bromides and iodides, aralkyl halides like benzyl and phenethyl bromides, and others Water or oil- soluble or dispersible products are thereby obtained Examples of acids which may be employed to form pharmaceutically acceptable acid addition salts include such inorganic acids as hydrochloric acid, sulphuric acid and phosphoric acid and such organic acids as oxalic acid, maleic acid, succinic acid and citric acid. Other salts include salts with alkali metals or alkaline earth metals, such as sodium, potassium, calcium or magnesium or with organic bases. Preferred salts of the compounds of the invention include hydrochloride, methanesulfonate, sulfonate, phosphonate and isethionate. The compounds of the present invention can also be used in the form of esters. Examples of such esters include compounds wherein a hydroxyl group in the compound of this invention has been acylated with an N-protected or unprotected ammo acid residue, a phosphate function, a hemisuccmate residue, an acyl residue of the formula RX(O)- or R * C(S)- wherein R * is hydrogen, loweralkyi, haloalkyl, alkoxy thioalkoxy, alkoxyalkyl, thioalkoxyalkyl or haloalkoxy, or an acyl residue of the formula Ra-C(Rb)(Rd)-C(0)- or R a -C(Rb)(Rd)-C(S)- wherein R and R < j are independently selected from hyαrogen or loweralkyi and R a is -N(R e )(Rf), OR e or -SR e wherein R e and Rf are independently selected from hydrogen loweralkyi and haloalkyl, or an ammo-acyl residue of the formula RιsoNH(CH2)2NHCH2C(0)- or Ri8θNH(CH2) 2 θCH2C(0)- wherein R-iso is hydrogen, loweralkyi, arylalkyi, cycloalkylalkyi, alkanoyl, beπzoyl or an α-ammo acyl group The ammo acid esters of particular interest are glycine and fysine; however, other amino acid residues can also be used, including those wherein the amino acyl group is -C(0)CH 2 NR ooR2θi wherein R200 and R201 are independently selected from hydrogen and loweralkyi or the group -NR200R201 forms a nitrogen containing heterocyclic ring. These esters serve as pro-drugs of the compound of the present invention and serve to increase the solubility of these substances in the gastrointestinal tract. These esters also serve to increase solubility for intravenous administration of the compound. Other prodrugs include compounds wherein a hydroxyl group in the compound of this invention is functionalized with a substituent of the formula -CH(R g )OC(0)R-i8i or -CH(R g )OC(S)Ri8i wherein R-181 is loweralkyi, haloalkyl, alkoxy. thioalkoxy or haloalkoxy and R g is hydrogen, loweralkyi, haloalkyl, alkoxycarbonyl, aminocarbonyl. alkylaminocarbonyl or dialkyiaminocarbonyl. Such prodrugs can be prepared according to the procedure of Schreiber (Tetrahedron Lett. 1983, 24, 2363) by ozonolysis of the corresponding methallyl ether in methanol followed by treatment with acetic anhydride. The prodrugs of this invention are metabolized in vivo to provide the compound of this invention . The preparation of the prodrug esters is carried out by reacting the compound of the invention with an activated amino acyl, phosphoryl, hemisuccinyl or acyl derivative as defined above. The resulting product is then deprotected to provide the desired pro-drug ester. Prodrugs of the invention can also be prepared by alkylation of the hydroxyl group with (haloalkyl)esters. transacetalization with bis-(alkanoyl)acetals or condensation of the hydroxyl group with an activated aldehyde followed by acylatioπ of the intermediate hemiacetal. The compounds of the invention are useful for inhibiting retroviral protease, in particular HIV protease, in vitro or in vivo (especially in mammals and in particular in humans). The compounds of the present invention are also useful for the inhibition of retroviruses in vivo, especially human immunodeficiency virus (HIV). The compounds of the present invention are also useful for the treatment or prophylaxis of diseases caused by retroviruses, especially acquired immune deficiency syndrome or an HIV infection in a human or other mammal. Total daily dose administered to a human or other mammal host in single or divided doses may be in amounts, for example, from 0.001 to 300 mg/kg body weight daily and more usually 0 1 to 20 mg/kg body weight daily Dosage unit compositions may contain such amounts of submultiples thereof to make up the daily dose. The amount of active ingredient that may be combined with the carrier materials to produce a single dosage form will vary depending upon the host treated and the particular mode of administration It will be understood, however, that the specific dose level for any particular patient will depend upon a variety of factors including the activity of the specific compound employed, the age, body weight, general health, sex, diet, time of administration, route of administration, rate of excretion drug combination and the severity of the particular disease undergoing therapy The compounds of the present invention may be administered orally, parenterally, sublingually, by inhalation spray, rectally, or topically in dosage unit formulations containing conventional nontoxic pharmaceutically acceptable carriers, adjuvants, and vehicles as desired Topical administration may also involve the use of transdermal administration such as transdermal patches or iontophoresis devices The term parenteral as used herein includes subcutaneous injections intravenous, intramuscular, mtrasternal injection, or infusion techniques Injectable preparations for example, sterile mjectable aqueous or oieagenous suspensions may be formulated according to the known art using suitable dispersing or wetting agents and suspending agents The sterile mjectable preparation may also be a sterile mjectable solution or suspension in a nontoxic parenterally acceptable diluent or solvent, for example, as a solution in 1 ,3-propanedιol Among the acceptable vehicles and solvents that may be employed are water Ringer s solution, and isotonic sodium chloride solution In addition, sterile, fixed oils are conventionally employed as a solvent or suspending medium For this purpose any bland fixed oil may be employed including synthetic mono- or diglyceπdes In addition, fatty acids such as oieic acid find use in the preparation of mjectables Suppositories for rectal administration of the drug can be prepared by mixing the drug with a suitable nonirπtating excipient such as cocoa butter and polyethylene glycols which are solid at ordinary temperatures but liquid at the rectal temperature and will therefore melt in the rectum and release the drug. Solid dosage forms for oral administration may include capsules tablets, pills, powders, and granules. In such solid dosage forms, the active compound may be admixed with at least one inert diluent such as sucrose lactose or starch Such dosage forms may also comprise, as is normal practice, additional substances other than inert diluents, e.g., lubricating agents such as magnesium stearate In the case of capsules, tablets, and piils, the dosage forms may also comprise buffering agents. Tablets and pills can additionally be prepared with enteric coatings. Liquid dosage forms for oral administration may include pharmaceutically acceptable emulsions, solutions, suspensions, syrups, and elixirs containing inert diluents commonly used in the art, such as water Such compositions may also comprise adjuvants, such as wetting agents, emulsifying and suspending agents, and sweetening, flavoring, and perfuming agents. The compounds of the present invention can also be administered in the form of liposomes. As is known in the art, liposomes are generally derived from phosphoiipids or other lipid substances. Liposomes are formed by mono- or multi-lamellar hydrated liquid crystals that are dispersed in an aqueous medium Any non-toxic, physiologically aceptable and metabolizable lipid capabale of forming liposomes can be used The present compositions in liposome form can contain in addition to the compound of the present invention stabilizers preservatives, excipients, and the like The preferred lipids are the phosphoiipids and phosphatidyl choiines (lecithins), both natureal and synthetic. Methods to form liposomes are known in the art. See, for example, Prescott. Ed , Methods in Cell Biology Volume XIV, Academic Press, New York, N Y (1976), p 33 et seq Some preferred dosage forms for the compounds of this invention are disclosed in U.S Patent Application No 08/ , filed November 21 , 1996, in the names of J Lipaπ, L A Al-Razzak, S Ghosh and R Gao and which is entitled Pharmaceutical Composition, which is incorporated herein by reference A preferred dosage form for the compounds of this invention comprises a solution of (a) a compound of the formula I in the amount of from about 1 % to about 50% (preferably, from about 5% to about 30%) by weight of the total solution and (b) poiyoxyl 35 castor oil in the amount of from about 0% to about 20% (preferably, from about 5% to about 10%) by weight of the total solution, in a pharmaceutically acceptable organic solvent which comprises (i) oleic acid in the amount of from about 20% to about 99% (preferably, from about 30% to about 70%; more preferably, from about 40% to about 65%) by weight of the total solution or (n) a mixture of (1 ) oleic acid in the amount of from about 20% to about 99% (preferably, from about 30% to about 70%; more preferably, from about 40% to about 65%) by weight of the total solution and (2) ethanol or propylene glycol or a mixture thereof in the amount of from about 0% to about 12% (preferably about 10%) by weight of the total solution In an even more preferred embodiment of the invention, the solution is encapsulated in a soft elastic gelatin capsule (SEC) or a hard gelatin capsule A most preferred composition of the invention comprises a solution of (a) a compound of the formula I in the amount of about 30% by weight of the total solution and (b) poiyoxyl 35 castor oil in the amount of about 10% by weight of the total solution, in a pharmaceutically acceptable organic solvent which comprises a mixture of (1 ) oleic acid in the amount of about 50% by weight of the total solution and (2) ethanol in the amount of about 10% by weight of the total solution In a most preferred embodiment of the invention, the solution is encapsulated in a soft elastic gelatin capsule (SEC) or a hard gelatin capsule and the solution also comprises an aπtioxidant (preferably, BHT (butylated hydroxytoluene)) in the amount of from about 0.01 % to about 0.08% by weight of the total solution (preferably, from about 0.01 % to about 0.05% by weight of the total solution) An example of such a composition and its preparation is provided below Comppnent % By Weight compound of Example 2B (free base) 30 Ethanol (USP, 200 proof) 10 poiyoxyl 35 castor oil (Cremophor® EL) 1 0 Oleic acid, 6321 , NF 50 Butylated hydroxy toluene (BHT), NF 0.01 Preparation of the above composition: The mixing tank was purged with nitrogen. Oleic acid (499.9 g) and ethanol (100g) were mixed in the tank. The butylated hydroxytoluene (0.1 g) was charged into the tank and mixed until the solution was clear. The Compound of Example 2B (300 g) was slowly charged into the tank and mixed until the solution was clear. The poiyoxyl 35 castor oil (100 g)was added to the tank and mixed. The resulting solution was filled into soft elastic capsules (0.333 g of solution/SEC) to provide a dosage of 100 mg of compound of Example 2B/SEC or 0.667 g/SEC to provide a dosage of 200 mg of compound of Example 2B/SEC. While the compound of the invention can be administered as the sole active pharmaceutical agent, it can also be used in combination with one or more immunomodulators, antiviral agents, other antiinfective agents or vaccines. Other antiviral agents to be administered in combination with a compound of the present invention include AL-721 , beta interferon, polymannoacetate, reverse transcriptase inhibitors ( for example, dideoxycytidine (ddC; zalcitabine), dideoxyinosine (ddl; didanosine), BCH-189, AzdU, carbovir, ddA, d4C, d4T (stavudine), 3TC (lamivudine) DP-AZT, FLT (fluorothymidine), BCH-189, 5-halo-3'-thia-dideoxycytidine, PMEA, bis- POMPMEA, zidovudine (AZT), nevirapine, delviridine, MSA-300, trovirdine and the like), non-nucleoside reverse transcriptase inhibitors (for example, R82193, L-697,661 , BI-RG-587 (nevirapine), retroviral protease inhibitors (for example, HIV protease inhibitors such as ritonavir, Ro 31 -8959 (saquinavir), SC-52151 , VX-478, AG1343 (nelfinavir), BMS 186,318, SC-55389a, BILA 1096 BS, DMP- 323, DMP-450, KNI-227, KNI-272, U-140690, N-(2(R)-hydroxy-1 (S)-indanyl)- 2(R)-phenylmethyl-4(S)-hydroxy-5-(1 -(4-(3-pyridylmethyl)-2(S)-N'-(t- butylcarboxamιdo)-pιperazιnyl))-pentaneamιde (MK-639; iπdinavir) , 5(S)-Boc- ammo-4(S)-hydroxy-6-phenyl-2(R)-phenyimethylhexanoyl-(L)-Val-(L)-Phe- morphoiιn-4-ylamιde, 1 -Naphthoxyacetyl-beta-methylthιo-Ala-(2S.3S)-3-amιπo- 2-hydroxy-4-butanoyl-1 ,3-thιazolidιne-4-t-butylamιde (i.e., 1 -Naphthoxyacetyl- Mta-(2S,3S)-AHPBA-Thz-NH-tBu), 5-ιsoquιnolιπoxyacetyl-beta-methylthιo-Ala- (2S,3S)-3-amιno-2-hydroxy-4-butanoyl-1 ,3-thιazolιdιne-4-t-butylamιde (i.e., iQoa-Mta-Apns-Thz-NHtBu) and the like), HEPT compounds, L,697,639, R82150, U-87201 E and the like), HIV mtegrase inhibitors (Zmtevir and the like), TAT inhibitors (for example, RO-24-7429 and the like), tπsodium phosphoπoformate, HPA-23, eflonithme, Peptide T, Reticulose (nucleophosphoprotein), ansamycin LM 427, tπmetrexate, UA001 , πbaviπn, alpha mterferon, oxetanocin, oxetanocm-G, cylobut-G, cyclobut-A ara-M BW882C87, foscarnet, BW256U87, BW348U87, L-693,989, BV ara-U, CMV tπcional antibodies, FIAC, HOE-602, HPMPC, MSL-109. TI-23, tπfluπdme, vidarabme, famciclovir, penciclovir, acyclovir, ganciclovir, castanospermme, rCD4/CD4-lgG, CD4-PE40, butyl-DNJ, hypeπcin, oxamyπstic acid, dextran sulfate and pentosan polysulfate Immunomodulators that can be administered in combination with the compound of the present invention include bropiπmine, Ampiigen, anti-human alpha mterferon antibody, colony stimulting factor, CL246,738, lmreg-1 , lmreg-2, diethydithiocarbamate, ιnterleukιn-2, alpha- mterferon, inosine pranobex, methionme enkepha n, muramyl-tπpeptide TP-5, erythropoietin, naltrexone, tumor necrosis factor, beta mterferon, gamma mterferon, ιnterleukιn-3, ιnterleukm-4, autologous CD8+ infusion, alpha mterferon immunoglobulin, IGF-1 , antι-Leu-3A, autovaccmation, biostimulation, extracorporeal photophoresis, cyclospoπn, rapamycin, FK-565, FK-506, G-CSF GM-CSF, hyperthermia, isopmosine, IVIG, HIVIG, passive immunotherapy and polio vaccine hypeπmmumzation. Other antimfective agents that can be administered in combination with the compound of the present invention include pentamidiπe isethionate Any of a variety of HIV or AIDS vaccines (for example, gp120 (recombmant), Env 2-3 (gp120), HIVAC-1 e (gp120), gp160 (recombinant), VaxSyn HIV-1 (gp160), Immuno-Ag (gp160), HGP-30, HIV- Immunogen, p24 (recombinant), VaxSyn HIV-1 (p24) can be used in combination with the compound of the present invention Other agents that can be used in combination with the compound of this invention are ansamycin LM 427, apunnic acid, ABPP, AI-721 , carπsyn, AS-101 , avarol, azimexoπ colchicine, compound Q, CS-85, N-acetyl cysteine, (2- oxothιazolιdιne-4-carboxylate), D-penicillamme, diphenylhydantom, EL-10, erythropoieteπ fusidic acid, glucan, HPA-23, human growth hormone, hydroxchloroqume, iscador, L-ofloxacm or other qumolone antibiotics, lentman, lithium carbonate. MM-1 , monolaunn, MTP-PE, naltrexone, neurotropin, ozone, PAI, panax ginseng, pentofyllme, pentoxifyllme, Peptide T, pine cone extract, polymannoacetate reticulose, retrogen, πbaviriπ, πbozymes, RS-47, Sdc-28, silicotungstate THA, thymic humoral factor, thymopentm, thymosin fraction 5, thymosin alpha one, thymostimuim, UA001 , undine, vitamin B12 and wobemugos Other agents that can be used in combination with the compound of this invention are antifungals such as amphoteπcin B, clotπmazole flucytosme, fluconazole itraconazoie, ketocoπazole and nystatm and the like Other agents that can be used in combination with the compound of this invention are antibacteπals such as amikacm sulfate, azithromycin, ciprofloxacin, tosufloxacin, claπthromycin, clofazimine, ethambutol, isoniazid, pyrazinamide πfabutin πfampin, streptomycin and TLC G-65 and the like Other agents that can be used in combination with the compound of this invention are aπti-neoplastics such as alpha mterferon, COMP (cyclophosphamide vmcristme, methotrexate and prednisone) etoposide, mBACOD (methotrexate, bleomycin, doxorubicin, cyclophosphamide vmcristme and dexamethasone) PRO-MACE/MOPP(prednιsone, methotrexate (w/leucovm rescue), doxorubicin, cyclophosphamide, taxol, etoposide/mechiorethamine, vmcristme, prednisone and procarbazine), vmcristme, vmblastme, angiomhibins peπtosar polysulfate, platelet factor 4 and SP-PG and the like Other agents that can be used in combination with the compound of this invention are drugs for treating neurological disease such as peptide T πtalin, lithium elavil phenytoin carbamazipine, mexitetine, hepaπn and cytosine arabmoside and the like Other agents that can be used in combination with the compound of this invention are anti-protozoals such as albeπdazole, azithromycin. claπthromycin, clmdamycin corticosteroids dapsone, DIMP eflornithme, 566C80 faπsidar, furazohdone, L.671 ,329, letrazuril, metronidazole, paromycm, pefloxacin, pentamidine, piπtrexim, pπmaquine, pynmethamine, somatostatm, spiramycin. sulfadiazme, tπmethopnm, TMP/SMX, tπmetrexate and WR 6026 and the like. Among the preferred agents for inhibition or treatment of HIV or AIDS in combination with the compound of this invention are reverse transcriptase inhibitors, especially, AZT (zidovudine), ddl (didanosme), ddC (zaicitabine), d4T (stavudme), 3TC (lamivudine), nevirapine, delviridine, trovirdine, PMEA, bis- POMPMEA and MSA-300. Other preferred agents for inhibition or treatment of HIV or AIDS in combination with the compound of this invention are HIV protease inhibitors, especially, ABT-538 (ritonavir) and related compounds, disclosed in U.S Patent No. 5.541 ,206, issued July 30, 1996 and U.S. Patent No. 5,491 .253. issued February 13, 1996 which are both incorporated by reference herein, N-(2(R)-hydroxy-1 (S)-ιndanyl)-2(R)-phenylmethyl-4(S)-hydroxy-5-(1 -(4-(3- pyπdylmethyl)-2(S)-N'-(t-butylcarboxamιdo)-pιperazιnyl))-pentaπeamιde (i.e., indmavir) and related compounds, disclosed in European Patent Application No. EP541 168, published May 12, 1993, and U.S. Patent No. 5.413,999, issued May 9, 1995 which are both incorporated herein by reference; N-tert-butyl-decahydro-2-[2(R)-hydroxy-4-phenyl-3(S)-[[N-(2-quιnolylcarbonyl)- L-asparagιnyl]amιno]butyl]-(4aS.8aS)-ιsoquιnolιne-3(S)-carboxamιde (i.e., saqumavir) and related compounds, disclosed in U.S. Patent No. 5.196.438, issued March 23, 1993, which is incorporated herein by reference, 5(S)-Boc-amιno-4(S)-hydroxy-6-phenyl-2(R)-phenylmethylhexanoyl-(L)-Val-(L)- Phe-morpholin-4-yiamιde and related compounds, disclosed in European Patent Application No. EP532466, published March 17, 1993, which is incorporated herein by reference; 1 -Naphthoxyacetyl-beta-methylthιo-A!a-(2S,3S)-3-amιno-2-hydroxy-4-butanoyl- 1 .3-thιazolιdιne-4-t-butylamιde (i.e., 1 -Naphthoxyacetyl-Mta-(2S,3S)-AHPBA- Thz-NH-tBu), 5-ιsoquιnolιnoxyacetyl-beta-methylthιo-Ala-(2S.3S)-3-amιπo-2- hydroxy-4-butaπoyl-1 ,3-thιazolιdιne-4-t-butylamιde (i e., iQoa-Mta-Apns-Thz- NHtBu) and related compounds, disclosed in European Patent Application No EP490667, published June 17, 1992 and Chem Pharm. Bull 40. (8) 2251 (1992). which are both incorporated herein by reference; [1 S-[1 R * (R * ),2S * ]}-N 1 [3-[[[(1 ,1 -dimethylethyl)amino]carbonyl](2- methylpropyl)amino]-2-hydroxy-1 -(phenylmethyl)propyl]-2-[(2- quinolinylcarbonyl)amino]-butanediamide (i.e., SC-52151 ) and related compounds, disclosed in PCT Patent Application No. WO92/08701 , published May 29, 1992 and PCT Patent Application No. W093/23368, published November 25, 1993, both of which are incorporated herein by reference; (i.e., VX-478) and related compounds, disclosed in PCT Patent Application No. WO94/05639, published March 17, 1994, which is incorporated herein by reference; (i.e., DMP-323) or and related compounds, disclosed in PCT Patent Application No. WO93/07128, published April 15, 1993, which is incorporated herein by reference (i.e., AG1343, (nelfmavir)), disclosed in PCT Patent Application No. WO95/09843, published April 13, 1995 and U.S. Patent No. 5.484,926, issued January 16, 1996. which are both incorporated herein by reference; disclosed in European Patent Application No. EP580402. published January 26. 1994, which is incorporated herein by reference, disclosed at 2nd National Conference on Human Retroviruses and Related Infections, (Washington, D.C., Jan. 29 - Feb. 2, 1995), Session 88; and (i.e., BILA 1096 BS) and related compounds disclosed in European Patent Application No. EP560268, published September 15, 1993, which is incorporated herein by reference; and (i.e., U-140690) and related compounds disclosed in PCT Patent Application No WO 9530670, published November 16, 1995, which is incorporated herein by reference; or a pharmaceutically acceptable salt of any of the above ln a most preferred combination, a compound of this invention is administered in combination with ritonavir. Such a combination is especially useful for inhibiting HIV protease in a human. Such a combination is also especially useful for inhibiting or treating an HIV infection in a human. When used in such a combination the compound of this invention and ritonavir can be administered as separate agents at the same or different times or they can be formulated as a single composition comprising both compounds When administered in combination with a compound of this invention, ritonavir causes an improvement in the pharmacokinetics (i.e., increases half- life increases the time to peak plasma concentration, increases blood levels) of the compound of this invention. Preferred dosage forms for ritonavir include (a) a liquid dosage form for oral administration as disclosed in U.S. Patent No. 5,484,801 , issued January 19. 1996, which is incorporated herein by reference, (b) an encapsulated solid or semi-solid dosage form as disclosed in PCT Patent Application No. WO95/07696, published March 23, 1995 and U.S. Serial No. 08/402,690, filed March 13, 1995, both of which are incorporated herein by reference and (c) an encapsulated solid dosage form as disclosed in PCT Patent Application No WO95/09614 published April 13, 1995 and U.S Patent No. 5,559,158. issued September 24 1996, both of which are incorporated herein by reference. Other examples of preferred dosage forms for ritonavir are disclosed in U S Patent Application No. 08/ , filed November 21 , 1996, in the names of J Lipaπ, L.A. Al-Razzak, S. Ghosh and R. Gao and which is entitled Pharmaceutical Composition, which is incorporated herein by reference. A preferred composition for ritonavir comprises a solution of (a) ritonavir in the amount of from about 1 % to about 30% (preferably, from about 5% to about 25%) by weight of the total solution and (b) poiyoxyl 35 castor oil in the amount of from about 0% to about 20% (preferably, from about 5% to about 10%) by weight of the total solution, in a pharmaceutically acceptable organic solvent which comprises (i) oleic acid in the amount of from about 15% to about 99% (preferably, from about 30% to about 70%; more preferably, from about 40% to about 65%) by weight of the total solution or (n) a mixture of (1 ) oleic acid in the amount of from about 15% to about 99% (preferably from about 30% to about 70%; more preferably, from about 40% to about 65%) by weight of the total solution and (2) ethanol or propylene glycol or a mixture thereof in the amount of from about 0% to about 12% (preferably, about 10%) by weight of the total solution. In an even more preferred embodiment of the invention, the solution is encapsulated in a soft elastic gelatin capsule (SEC) or a hard geiatin capsule and the solution also comprises an aπtioxidant (preferably, BHT (butylated hydroxytoluene)) in the amount of from about 0.01 % to about 0.08% by weight of the total solution (preferably, from about 0.01 % to about 0.05% by weight of the total solution). Examples of such a composition and its preparation are provided below. Component % Bv Weioht ritonavir (free base) 20 Ethanol (USP, 200 proof) 1 0 poiyoxyl 35 castor oil (Cremophor ® EL) 5 Oleic acid, 6321 , NF 65 Butylated hydroxy toluene (BHT), NF 0.01 Preparation of the above composition: The mixing tank was purged with nitrogen. Oleic acid (649.9 g) and ethanol (100g) were mixed in the tank. This solution was warmed to about 33°C (29-37°C) and maintained at that temperature. The butylated hydroxytoluene (0.1 g) was charged into the tank and mixed until the solution was clear. The ritonavir (200 g) was slowly charged into the tank and mixed until the solution was clear. The poiyoxyl 35 castor oil (50 g) was added to the tank and mixed. Heating was discontinued and the solution allowed to cool to amibient temperature (20-30°C). The resulting solution was filled into soft elastic capsules (0.5 g of solution/SEC) to provide a dosage of 100 mg of πtonavir/SEC or 1.0 g/SEC to provide a dosage of 200 mg of πtonavir/SEC. Comoonent % gy Weight ritonavir (free base) 20 Ethanol (USP, 200 proof) 1 0 poiyoxyl 35 castor oil (Cremophor ® EL) 1 0 Oleic acid, 6321 , NF 60 Butylated hydroxy toluene (BHT), NF 0.01 Preparation of the above composition- The mixing tank was purged with nitrogen Oleic acid (599.9 g) and ethanol (1 OOg) were mixed in the tank. This solution was warmed to about 33°C (29-37°C) and maintained at that temperature The butylated hydroxytoluene (0.1 g) was charged into the tank and mixed until the solution was clear The ritonavir (200 g) was slowly charged into the tank and mixed until the solution was clear The poiyoxyl 35 castor oil (100 g)was added to the tank and mixed. Heating was discontinued and the solution allowed to cool to amibient temperature (20-30°C). The resulting solution was filled into soft elastic capsules (0.5 g of solution/SEC) to provide a dosage of 100 mg of ritonavir/SEC or 1.0 g/SEC to provide a dosage of 200 mg of ritonavir/SEC. Examples of preferred single dosage forms comprising both ritonavir and a compound of the formula I are also disclosed in U.S. Patent Application No 08/ . filed November 21 , 1996, in the names of J. Lipan, L.A Al- Razzak, S. Ghosh and R. Gao and which is entitled Pharmaceutical Composition, which is incorporated herein by reference. A preferred composition for a single dosage form comprising both ritonavir and a compound of the formula J comprises a solution of (a) a mixture of ritonavir in the amount of from about 1 % to about 30% (preferably, from about 5% to about 25%) by weight of the total solution and a compound of the formula I in the amount of from about 1 % to about 50% (preferably, from about 5% to about 40%) by weight of the total solution and (b) poiyoxyl 35 castor oil in the amount of about 10% by weight of the total solution, in a pharmaceutically acceptable organic solvent which comprises a mixture of (1 ) oleic acid in the amount of from about 10% to about 88% (preferably, from about 40% to about 65%) by weight of the total solution and (2) ethanol in the amount of about 10% by weight of the total solution. In a most preferred embodiment of the invention, the solution is encapsulated in a soft elastic gelatin capsule (SEC) or a hard gelatin capsule and the solution also comprises an antioxidant (preferably, BHT (butylated hydroxytoluene)) in the amount of from about 0.01 % to about 0.08% by weight of the total solution (preferably, from about 0 01 % to about 0.05% by weight of the total solution). Examples of such a composition and its preparation are provided below Component % Bv Weight ritonavir (free base) 5 compound of Example 2B (free base) 30 Ethanol (USP, 200 proof) 1 0 poiyoxyl 35 castor oil (Cremophor® EL) 10 Oleic acid, 6321 , NF 45 Butylated hydroxy toluene (BHT), NF 0.01 Comπonent % Bv Weight ritonavir (free base) 15 compound Example 2B (free base) 1 5 Ethanol (USP, 200 proof) 10 poiyoxyl 35 castor oil (Cremophor ® EL) 1 0 Oleic acid. 6321 , NF 50 Butylated hydroxy toluene (BHT), NF 0.01 Comp nent % Bv Wei g ht ritonavir (free base) 15 compound Example 2B (free base) 1 5 Ethanol (USP. 200 proof) 10 poiyoxyl 35 castor oil (Cremophor® EL) 5 Oleic acid. 6321 , NF 55 Butylated hydroxy toluene (BHT), NF 0.01 Preparation of the above composition: The mixing tank was purged with nitrogen. Oleic acid (549.9 g) and ethanol (100g) were mixed in the tank The butylated hydroxytoluene (0.1 g) was charged into the tank and mixed until the solution was clear. The ritonavir (150 g) was slowly charged into the tank and mixed until the solution was clear. Compound Example 2B (150 g) was slowly charged into the tank and mixed until the solution was clear. The poiyoxyl 35 castor oil (100 g) was added to the tank and mixed. The resulting solution was filled into soft elastic capsules (1.0 g of solution/SEC) to provide a dosage of 150 mg each of ritonavir and compound Example 2B/SEC. Com p onent % By Weig ritonavir (free base) 1 5 compound Example 2B (free base) 5 Ethanol (USP, 200 proof) 10 poiyoxyl 35 castor oil (Cremophor® EL) 1 0 Oleic acid, 6321 , NF 60 Butylated hydroxy toluene (BHT), NF 0.01 Total daily dose of ritonavir (administered in combination with a compound of this invention) to be administered to a human or other mammal host in single or divided doses may be in amounts, for example, from 0.001 to 300 mg/kg body weight daily and more usually 0.1 to 10 mg of ritonavir Dosage unit compositions may contain such amounts of submultiples thereof to make up the daily dose. In the compositions which comprise a mixture of ritonavir and the compound of Example 2B, the ratio (w/w) of ritonavir to the compound of Example 2B ranges from about 1 '16 to about 5:1 (preferably, from about 1 :6 to about 3:1 ) In another most preferred combination, a compound of this invention is administered in combination with ritonavir and one or more reverse transcriptase inhibitors (preferably, one or more compounds selected from the group consisting of AZT (zidovudine), ddl (didanosme), ddC (zaicitabine), d4T (stavudme) and 3TC (lamivudme)). Such a combination is especially useful for inhibiting or treating an HIV infection in a human. When used in such a combination the compound of this invention and ritonavir and one or more reverse transcriptase inhibitors can be administered as separate agents at the same or different times or they can be formulated as compositions comprising two or more of the compounds A particularly preferred therapeutic combination comprises a compound of the formula I (especially, the compound of Example 2B) in combination with ritonavir, AZT and 3TC It will be understood that agents which can be combined with the compound of the present invention for the inhibition, treatment or prophylaxis of AIDS or an HIV infection are not limited to those listed above, but include in principle any agents useful for the treatment or prophylaxis of AIDS or an HIV infection When administered as a combination, the therapeutic agents can be formulated as separate compositions which are given at the same time or different times, or the therapeutic agents can be given as a single composition The foregoing is merely illustrative of the invention and is not intended to limit the invention to the disclosed compounds Variations and changes which are obvious to one skilled in the art are intended to be within the scope and nature of the invention which are defined in the appended claims

Claims: CLAIMS What is claimed is: 1. A compound of the formula: I wherein R 1 and R 2 are independently selected from the group consisting of loweralkyi, cycloalkylalkyi and arylalkyi; R 3 is loweralkyi, hydroxyalkyl or cycloalkylalkyi; R 4 is aryl or heterocyclic; b) e ) Y" Y' (CH 2 ) m - g) wherein n is 1 , 2 or 3, m is 1 , 2 or 3, πϊ is 1 or 2, X is O, S or NH, Y is -CH 2 -, -O- , -S- or -N(Rg)- wherein R 6 is hydrogen, loweralkyi, cycloalkyl, cycloalkylalkyi, aryl or arylalkyi, Y" is -CH 2 - or -N(R 6 -)- wherein R 6 ,. is hydrogen, loweralkyi, cycloalkyl, cycloalkylalkyi, aryl or arylalkyi, Y' is -N(R 6 .)- wherein R 6 . is hydrogen, loweralkyi, cycloalkyl, cycloalkylalkyi, aryl or arylalkyi, and Z is O, S or NH; and L 1 is a) -0-, b) -S-, c) -N(R )- wherein R 7 is hydrogen, loweralkyi, cycloalkyl or cycloalkylalkyi d) -O-alkylenyl-, e) -S-alkylenyl- f) -S(0)-alkyleπyl-, g) -S(0) 2 -alkylenyl-, h) -N(R 7 )-alkylenyl- wherein R 7 is defined as above, i) -alkylenyl-O-, j) -alkylenyl-S-, k) alkylenyl-N(R 7 )- wherein R 7 is defined as above, I) alkylenyl or m) alkenylenyl; or a pharmaceutically acceptable salt, ester or prodrug thereof. 2. A compound according to Claim 1 wherein R 1 and R 2 are arylalkyi, R 3 is loweralkyi, R 4 is aryl, R 5 is \ (CH 2 ); m \ Y" / Y' d) (CH 2 ) m ' or wherein X, Y, Y', Y", Z, R 6 „, n, m and m 1 are defined as therein and L 1 is -O-alkylenyl. Most highly preferred compounds are compounds of the formula I wherein R 1 and R 2 are benzyl or R 1 is benzyl and R 2 is isopropyl, R 3 is loweralkyi, R 4 is 2,6-dimethylphenyi which is optionally substituted with a third substituent selected from the group consisting of loweralkyi and halo, R 5 is wherein n is 1 or 2, X is O or S and Y is -CH 2 or -NH- and 3. A compound according to Claim 1 wherein R 1 and R 2 are benzyl or R 1 is benzyl and R 2 is loweralkyi, R 3 is loweralkyi, R 4 is (a) phenyl which is substituted with two loweralkyi groups and which is optionally substituted with a third substituent selected from the group consisting of loweralkyi. hydroxy, ammo and halo or (b) pyridyl or pynmidmyl either of which is substituted with two loweralkyi groups and which is optionally substituted with a third substituent selected from the group consisting of loweralkyi, hydroxy, amino and halo, R 5 is wherein n is 1 or 2, X is O or S and Y is -CH 2 or -NH- wherein m is 1 or 2, X is O, Y is -CH 2 - and Z is O, wherein m' is 1 . X is O, Z is O and Y is -NH- wherein m' is 1 , X is O, Y" is -NH- and Y' is -NH- or e) wherein X is O and Rg.. is hydrogen and L 1 is -0-CH 2 -. 4. A compound according to Claim 1 wherein R 1 and R 2 are benzyl or R 1 is benzyl and R 2 is isopropyl, R 3 is loweralkyi, R 4 is 2,6-dιmethylphenyl which is optionally substituted with a third substituent selected from the group consisting of loweralkyi and halo, R is wherein n is 1 or 2, X is O or S and Y is -CH 2 or -NH-, wherein m is 1 or 2, X is O, Y is -CH 2 - and Z is O, C) wherem m' is 1 , X is O, Z is O and Y is -NH-, wherein m' is 1 , X is O, Y" is -NH- and Y' is -NH- or wherein X is O and R g .. is hydrogen and L 1 is -0-CH 2 -. 5. A compound according to Claim 1 wherein R 1 and R 2 are benzyl or R 1 is benzyl and R 2 is isopropyl, R 3 is loweralkyi, R 4 is 2,6-dimethylphenyl which is optionally substituted with a third substituent selected from the group consisting of loweralkyi and halo, R 5 is wherein n is 1 or 2, X is O or S and Y is -CH 2 or -NH- and L 1 is -0-CH 2 -. 6. A compound selected from the group consisting of: (2S, 3S, 5S)-2-(2,6-dιmethylphenoxyacetyl) amιno-3-hydroxy-5-[2S-(1 - tetrahydro-pyrιmιd-2-oπyl)-3-methyl butanoyl] amιπo-1 ,6-dιphenylhexane; (2S,3S,5S)-2-(2,6-Dιmethylphenoxyacetyl)amιno-3-hydroxy-5-(2S-(1 - ιmιdazolιdιn-2-onyl)-3,3-dιmethyl butanoyl)amιno-1 ,6-dιphenylhexane, (2S,3S.5S)-2-(2,6-dιmethylphenoxyacetyl)amιno-3-hydroxy-5-(2S-(1 - ιmιdazolιdιn-2-thιonyl)-3-methyl butanoyl)amιno-1 ,6-dιphenylhexane, (2S,3S,5S)-2-(2,4,6-trιmethylphenoxyacetyl) amιno-3-hydroxy-5-(2S-(1 - ιmιdazolιdιn-2-onyl)-3-methylbutanoyl) amιno-1 ,6-dιphenylhexane, (2S,3S.5S)-2-(4-fluoro-2.6-dιmethylphenoxyacetyi) amιno-3-hydroxy-5-(2S-(1 - ιmιdazoiιdιn-2-onyl)-3-methyl-butanoyl) ami no- 1 ,6-dιphenylhexane, (2S,3S.5S)-2-(2.6-dιmethylphenoxyacetyl) amιno-3-hydroxy-5-(2S-(1 - pyrrolιdιn-2-onyl)-3-methyl-butanoyl) amιno-1 ,6-dιphenylhexane, (2S,3S,5S)-2-(2.6-dιmethylphenoxyacetyl) amιno-3-hydroxy-5-(2S-(1 - pyrrolιdιn-2.5-dιonyl)-3-methyi-butanoyl) amιno-1 ,6-dιphenylhexane; (2S,3S,5S)-2-(trans-3-(2,6-dιmethylphenyl) propenoyi) amιno-3-hydroxy-5-(2S- 1 -tetrahydropyπmιdin-2-onyl)-3-methyl-butanoyl) amιno-1 ,6-dιphenylhexane; (2S.3S,5S)-2-(3-(2,6-dιmethylphenyl) propanoyl) amιno-3-hydroxy-5-(2S-(1 - tetrahydropyrιmιdιn-2-onyl)-3-methyl-butanoyl) amιno-1 ,6-dιphenylhexane; (2S,3S,5S)-2-(2,6-Dιmethylρhenoxyacetyl) amιno-3-hydroxy-5-(2S-(1 - tetrahydro-pyrιmιd-2,4-dιonyl)-3-methylbutanoyl)amιno-1 ,6-dιphenylhexane, (2S.3S,5S}-2-(2.6-Dιmethylρhenoxyacetyl) ammo-3-hydroxy-5-(2S-(4-aza-1 - tetrahydro-pyrιmιd-2-onyl)-3-methyl-butaπoyl)amιno-1 ,6-dιphenylhexane, (2S,3S,5S)-2-(2,6-Dιmethylphenoxyacetyl) amιno-3-hydroxy-5-(2S-(1 - tetrahydro-pyrιmιd-2-onyl)-3-methylbutanoyl)amιno-1 -phenyl-6-methylheptane, (2S,3S,5S)-2-(2,6-Dιmethylphenoxyacetyl) amιno-3-hydroxy-5-(2S-(1 - tetrahydro-pyrιmιd-2,4-dιonyl)-3-methylbutanoyl)amιno-1 -pheny I-6- methylheptane: and (2S,3S,5S)-2-(2.6-Dιmethylphenoxyacetyl) amιno-3-hydroxy-5-(2S-(4-aza-4,5- dehydro-1 -pyrιmιd-2-onyl)-3-methyl-butanoyl)amιno-1 ,6-dιphenylhexane, or a pharmaceutically acceptable salt, ester or prodrug thereof 7 The compound (2S, 3S, 5S)-2-(2,6-dιmethylphenoxyacetyl) amιπo-3- hydroxy-5-(2S-(1 -tetrahydro-pyπmιd-2-onyl)-3-methyl butanoyl) amιno-1 ,6- diphenylhexane; or a pharmaceutically acceptable salt, ester or prodrug thereof. 8 A pharmaceutical composition for inhibiting HIV protease compπsing a pharmaceutical carrier and a therapeutically effective amount of the compound of Claim 1 9 A pharmaceutical composition for inhibiting HIV protease comprising a pharmaceutical carrier and a therapeutically effective amount of the compound of Claim 7 10 A method for inhibiting HIV protease comprising administering to a human in need of such treatment a therapeuctially effective amount of the compound of Claim 1 1 1 A method for inhibiting inhibiting HIV protease comprising administering to a human in need of such treatment a therapeuctially effective amount of the compound of Claim 7 12 A method for inhibiting an HIV infection comprising administering to a human in need of such treatment a therapeuctially effective amount of the compound of Claim 1 13 A method for inhibiting an HIV infection comprising administering to a human in need of such treatment a therapeuctially effective amount of the compound of Claim 7 14 A method for inhibiting an HIV infection comprising administering to a human in need of such treatment a therapeutically effective amount of the compound of Claim 1 in combination with a therapeutically effective amount of a reverse transcriptase inhibitor or a combination of reverse transcriptase inhibitors. 15 The method of Claim 14 wherein the reverse transcriptase inhibitor is selected from the group consisting of AZT (zidovudine), ddl (didanosme), ddC (zaicitabine), d4T (stavudme), 3TC (lamivudme), nevirapine, delviridine, trovirdine, PMEA, bis-POMPMEA and MSA-300 or a combination thereof 16 A method for inhibiting an HIV infection comprising administering to a human in need of such treatment a therapeutically effective amount of the compound of Claim 7 in combination with a therapeutically effective amount of a reverse transcriptase inhibitor or a combination of reverse transcriptase inhibitors 17 The method of Claim 16 wherein the reverse transcriptase inhibitor is selected from the group consisting of AZT (zidovudine), ddl (didanosme), ddC (zaicitabine), d4T (stavudme), 3TC (lamivudme), nevirapine, delviridine, trovirdine, PMEA, bis-POMPMEA and MSA-300 18 A method for inhibiting an HIV infection comprising administering to a human in need of such treatment a therapeutically effective amount of the compound of Claim 1 in combination with a therapeutically effective amount of another HIV protease inhibitor or a combination of HIV protease inhibitors 19 The method of Claim 18 wherein the other HIV protease inhibitor is selected from the group consisting of ritonavir, saqumavir, , indinavir, 5(S)-Boc-amιπo-4(S)-hydroxy-6-phenyl-2(R)-phenylmethylhexanoyl-(L)-Val-(L)- Phe-morpholιπ-4-ylamιde, 1 -Naphthoxyacetyl-beta-methylthιo-Ala-(2S,3S)-3-amιno-2-hydroxy-4-butanoyl- 1 ,3-thιazolιdιne-4-t-butylamιde, 5-ιsoquιnolιnoxyacetyl-beta-methylthιo-Ala-(2S,3S)-3-amιno-2-hydroxy-4- butanoyl-1 3-thιazolιdιne-4-t-butylamιde, (1S-(1R * (R * ),2S * )}-N 1 (3-((((1,1-dimethylethyl)amino)carbonyl)(2- methylpropyl)amino)-2-hydroxy-1-(phenylmethyl)propyl)-2-((2- quinolinylcarbonyl)amino)-butanediamide; ; and or a pharmaceutically acceptable salt thereof, or a combination of two or more'of these HIV protease inhibitors. 20 A method for inhibiting an HIV infection comprising administering to a human in need of such treatment a therapeutically effective amount of the compound of Claim 7 in combination with a therapeutically effective amount of another HIV protease inhibitor or a combination of HIV protease inhibitors 21 The method of Claim 20 wherein the other HIV protease inhibitor is selected from the group consisting of ritonavir, saqumavir, mdinavir, 5(S)-Boc-amιno-4(S)-hydroxy-6-phenyl-2(R)-phenylmethylhexanoyl-(L)-Val-(L)- Phe-morpholιn-4-ylamιde; 1 -Naphthoxyacetyl-beta-methylthιo-Ala-(2S,3S)-3-amιno-2-hydroxy-4-butanoyl- 1 ,3-thιazolιdιne-4-t-butylamιde; 5-ιsoquιnolmoxyacetyl-beta-methylthιo-Ala-(2S,3S)-3-amιno-2-hydroxy-4- butanoyl-1 ,3-thιazolιdιne-4-t-butylamιde; (1 S-(1 R * (R * ),2S * )}-N 1 (3-((((1 ,1 -dιmethylethyl)amιno)carbonyl)(2- methylpropyl)amιno)-2-hydroxy-1 -(phenylmethyl)propyl)-2-((2- quιnolιnylcarbonyl)amιno)-butanedιamιde; or a pharmaceutically acceptable salt thereof, or a combination of two or more of these HIV protease inhibitors. 22. A method for inhibiting an HIV infection comprising administering to a human in need of such treatment a therapeutically effective amount of the compound of Claim 7 in combination with a therapeutically effective amount of ritonavir or a pharmaceutically acceptable salt thereof. 23 An HIV protease inhibiting compound comprising a substituent of the formula: - wherein R 3 is loweralkyi, hydroxyalkyl or cycloalkylalkyi, and R 5 .s b) or wherein n is 1 , 2 or 3, m is 1 , 2 or 3, m' is 1 or 2, X is O, S or NH, Y is -CH 2 -, -O- , -S- or -N(Rg)- wherein R 6 is hydrogen, loweralkyi, cycloalkyl, cycloalkylalkyi, aryl or arylalkyi, Y" is -CH 2 - or -N(R 6 ..)- wherein R 6 .. is hydrogen, loweralkyi, cycloalkyl, cycloalkylalkyi, aryl or arylalkyi, Y' is -N(R 6 .)- wherein R g , is hydrogen, loweralkyi, cycloalkyl, cycloalkylalkyi, aryl or arylalkyi, and Z is O, S or NH 24 A compound according to Claim 23 wherein R 3 is loweralkyi and R 5 b) wherein X, Y, Y', Y", Z, R 6 », n, m and m' are defined as therein. 25. A compound according to Claim 23 wherein R 3 is loweralkyi and R 5 wherein n is 1 or 2, X is O or S and Y is -CH 2 or -NH-, wherein m is 1 or 2, X is O, Y is -CH 2 - and Z is O, wherein m' is 1 , X is O, Z is O and Y is -NH- wherein m' is 1 , X is O, Y" is -NH- and Y' is -NH- or wherein X is O and Rg.. is hydrogen. 26. A compound according to Claim 23 wherein R 3 is isopropyl and R 5 is wherein n is 1 or 2, X is O or S and Y is -CH 2 or -NH-, wherein m is 1 or 2, X is O, Y is -CH 2 - and 2 is O, wherein m' is 1 , X is O, Z is O and Y is -NH-, d) wherein m' is 1 , X is O, Y" is -NH- and Y * is -NH- or wherein X is O and R 6 .. is hydrogen. 27. A compound according to Claim 23 wherein R 3 is isopropyl and R 5 wherein n is 1 or 2, X is O or S and Y is -CH 2 or -NH- wherein nϊ is 1 , X is O, Z is O and Y is -NH-, wherein m' is 1 , X is O, Y" is -NH- and Y' is -NH- or d) wherein X is O and Rg.. is hydrogen 28 A compound according to Claim 23 wherein R 3 is isopropyl and R 5 is wherein n is 1 or 2, X is O or S and Y is -CH 2 or -NH- 29 A compound according to Claim 23 selected from the group consisting of cιs-N-tert-butyl-decahydro-2-( 2(R)-hydroxy-4-phenyl-3(S)-(2S-(1 - tetrahydropyrιmιd-2-onyl)-3-methylbutanoyl)amιnobutyl)-(4aS,8aS)- ιsoquιnolιne-3(S)-carboxamιde, cιs-N-tert-butyl-decahydro-2-( 2(R)-hydroxy-4-thιophenyl-3(S)-(2S-(1 - tetrahydropyrιmιd-2-onyl)-3-methylbutanoyl)amιnobutyl)-(4aS,8aS)- ιsoquιnolιne-3(S)-carboxamιde; and 4-Amιno-N-(( 2syn, 3S)-2-hydroxy-4-phenyl-3-(2S-( 1-tetrahydropyπmιd-2- onyl)-3-methylbutanoylamιno)-butyl)-N-ιsobutyl-benzenesulfonamιde, or pharmaceutically acceptable salts thereof 30 A compound of the formula wherein R 3 is loweralkyi, hydroxyalkyl or cycloalkylalkyi; and R 5 ,s wherein n is 1 , 2 or 3, m is 1 , 2 or 3, m' is 1 or 2, X is O, S or NH, Y is -CH 2 -, -O- , -S- or -N(R 6 )- wherein R 6 is hydrogen, loweralkyi, cycloalkyl, cycloalkylalkyi, aryl or arylalkyi, Y" is -CH 2 - or -N(R 6 ..)- wherein R 6 .. is hydrogen, loweralkyi, cycloalkyl, cycloalkylalkyi, aryl or arylalkyi, Y' is -N(R 6 .)- wherein R 6 . is hydrogen, loweralkyi, cycloalkyl, cycloalkylalkyi, aryl or arylalkyi, and Z is O, S or NH; or a salt or an activated ester derivative thereof. 31. A compound according to Claim 30 wherein R 3 is loweralkyi and R 5 wherein X, Y, Y', Y", Z, R 6 ... n, m and m' are defined as above. 32. A compound according to Claim 30 wherein R 3 is loweralkyi and R 5 wherein n is 1 or 2, X is O or S and Y is -CH 2 or -NH- wherein m is 1 or 2, X is O, Y is -CH 2 - and Z is O, wherein m' is 1 , X is O, Z is O and Y is -NH-, wherein m' is 1 , X is O, Y" is -NH- and Y' is -NH- or θ) wherein X is O and Rg.. is hydrogen. 33. A compound according to Claim 30 wherein R 3 is isopropyl and R 5 is wherein n is 1 or 2, X is O or S and Y is CH 2 or -NH- wherein m is 1 or 2, X is O, Y is -CH 2 - and Z is O, wherein m' is 1 , X is O, Z is O and Y is -NH- d) wherein m' is 1 , X is O, Y" is -NH- and Y' is -NH- or wherein X is O and R 6 .. is hydrogen. 34. A compound according to Claim 30 wherein R 3 is isopropyl and R 5 wherein n is 1 or 2, X is O or S and Y is -CH 2 or -NH-, wherein m' is 1 , X is O, Z is O and Y is -NH-, c) wherein m' is 1 , X is O, Y" is -NH- and Y' is -NH- or wherein X is O and Rg.. is hydrogen. 35. A compound according to Claim 30 wherein R 3 is isopropyl and R 5 is wherein n is 1 or 2, X is O or S and Y is -CH 2 or -NH-. 36 The compound according to Claim 30 which is 2S-(1 -Tetrahydro- pyπmιd-2-onyl)-3-methyl butanoic acid or a salt or an activated ester derivative thereof. 37. A compound of the formula: wherein P 3 and P 4 are independently selected from hydrogen or an N-protecting group; R 1 and R 2 are independently selected from the group consisting of loweralkyi, cycloalkylalkyi and arylalkyi; R 3 is loweralkyi, hydroxyalkyl or cycloalkylalkyi; and R 5 ιs wherein n is 1 , 2 or 3, m is 1 , 2 or 3, m' is 1 or 2, X is O, S or NH, Y is -CH 2 -, -O- , -S- or -N(R 6 )- wherein R 6 is hydrogen, loweralkyi, cycloalkyl, cycloalkylalkyi, aryl or arylalkyi, Y" is -CH 2 - or -N(R 6 ..)- wherein R 6 .. is hydrogen, loweralkyi, cycloalkyl, cycloalkylalkyi, aryl or arylalkyi, Y' is -N(R 6 .)- wherein R 6 . is hydrogen, loweralkyi, cycloalkyl, cycloalkylalkyi, aryl or arylalkyi, and Z is O, S or NH; or a salt thereof 38. A compound according to Claim 37 wherein P 3 and P 4 are hydrogen or benzyl, R 1 and R 2 are arylalkyi, R 3 is loweralkyi and R 5 is wherem X, Y, Y', Y", Z, R 6 .., n, m and m' are defined as therein 39. A compound according to Claim 37 wherein P 3 and P 4 are hydrogen or benzyl, R 1 and R 2 are benzyl or R 1 is benzyl and R 2 is loweralkyi, R 3 is loweralkyi and R 5 is wherein n is 1 or 2, X is O or S and Y is -CH or -NH- wherein m is 1 or 2, X is O, Y is -CH 2 - and Z is O, wherein m' is 1 , X is O, Z is O and Y is -NH- wherein m' is 1 , X is O, Y" is -NH- and Y' is -NH- or wherein X is O and Rg.. is hydrogen. 40. A compound according to Claim 37 wherein P 3 and P 4 are hydrogen or benzyl, R 1 and R 2 are benzyl or R-, is benzyl and R 2 is isopropyl, R 3 is loweralkyi and R 5 is wherein n is 1 or 2, X is O or S and Y is -CH 2 or -NH- wherein m is 1 or 2, X is O, Y is -CH 2 - and Z is O, wherein m' is 1 , X is O, Z is O and Y is -NH-, wherein m 1 is 1 , X is O, Y" is -NH- and Y' is -NH- or wherein X is O and R 6 .. is hydrogen. 41. A compound according to Claim 37 wherein P 3 and P 4 are hydrogen or benzyl, R 1 and R 2 are benzyl or R 1 is benzyl and R 2 is isopropyl, R 3 is loweralkyi and R 5 is wherein n is 1 or 2, X is O or S and Y is -CH 2 or -NH-, wherein m' is 1 , X is O, Z is O and Y is -NH-, wherein rrϊ is 1 , X is O, Y" is -NH- and Y' is -NH- or wherein X is O and Rg.. is hydrogen. 42. A compound according to Claim 37 wherein P 3 and P 4 are hydrogen or benzyl, R 1 and R 2 are benzyl or R 1 is benzyl and R 2 is isopropyl, R 3 is loweralkyi and R 5 is wherein n is 1 or 2, X is O or S and Y is -CH 2 or -NH-. 43. A compound according to Claim 37 selected from the group consisting of: (2S, 3S, 5S)-2-N ,N-dibenzyiamino-3-hydroxy-5-(2S-(1 -tetrahydro-pyrimid-2- onyl)-3-methyl butanoyl) amino-1 ,6-diphenylhexane; and (2S, 3S, 5S)-2-Amino-3-hydroxy-5-(2S-(1 -tetrahydro-pyrimid-2-onyl)-3-methyl butanoyl) amino-1 ,6-diphenylhexane; or a salt thereof. 44. The compound according to Claim 43 which is (2S, 3S, 5S)-2- Amino-3-hydroxy-5-(2S-(1 -tetrahydro-pyrimid-2-onyl)-3-methyl butanoyl) amino-1 ,6-diphenylhexane (S)-Pyroglutamic acid salt. 45. A process for the preparation of a compound of the formula: or a salt or ester thereof, wherein R 3 is loweralkyi, hydroxyalkyl or cycloalkylalkyi, comprising (a) reacting a compound of the formula: (b) reacting a compound of the formula: or a salt or ester thereof, wherein R 3 is as defined above with a carbonyl equivalent; or (c) hydrogenating a compound of the formula: wherem R 3 is as defined above and R 30 is loweralkyi, phenyl or haloalkyl. 46 The process of Claim 45 wherein R 3 is loweralkyi. 47 The process of Claim 45 wherein R 3 is isopropyl and Q is chloro 48 The process of Claim 45 wherein R 3 is loweralkyi and the carbonyl equivalent is Q'-C(0)-Q" wherein Q' and Q" are Cl, Br, I, -O-loweralkyl, -O-aryl or imidazolyl 49 The process of Claim 48 wherein R 3 is isopropyl. 50 The process of Claim 45 wherein R 3 is loweralkyi and R 30 is loweralkyi 51 The process of Claim 50 wherein R 3 is isopropyl and R 30 is methyl 52 A process for the preparation of a compound of Claim 1 comprising reacting a compound of the formula wherein R 1 , R 2 , R 3 and R 5 are as defined therein with a compound of the formula or a salt or activated ester derivative thereof, wherein R 4 and L- | are as defined therein 53. A process for the preparation of (2S, 3S, 5S)-2-(2,6- dimethylphenoxyacetyl) ammo-3-hydroxy-5-(2S-(1 -tetrahydro-pyπmιd-2-onyl)- 3-methyl butanoyl) amιno-1 ,6-dιphenylhexane; or a pharmaceutically acceptable salt, ester or prodrug thereof, comprising reacting (2S, 3S, 5S)-2-amιno-3-hydroxy-5-(2S-(1 -tetrahydro-pyrιmιd-2-onyi)-3- methyl butanoyl) amιno-1 ,6-dιphenylhexane with 2,6-dιmethylphenoxyacetιc acid, or a salt of activated ester derivative thereof. 54 The process according to Claim 53 wherein (2S, 3S, 5S)-2-amιno-3- hydroxy-5-(2S-(1 -tetrahydro-pyrιmιd-2-onyl)-3-methyl butanoyl) amιno-1 ,6- diphenylhexane is reacted with 2,6-dιmethylphenoxyacetyl chloride 55 A process for the preparation of a compound of Claim 1 comprising (a) reacting a compound of the formula- wherein P 3 is hydrogen and P 4 is an N-protecting group or both P 3 and P 4 are N-protecting groups and R 1 and R 2 are as defined therein with a compound of the formula or a salt or activated ester derivative thereof, wherein R 3 and R 5 are as defined therein, to provide a compound of the formula- wherem P 3 , P 4 , R., , R 2 , R 3 and R 5 are as defined above; (b) N-deprotectmg the product of step (a) to provide a compound of the formula: wherein R 1 τ R 2 , R 3 and R 5 are as defined above; and (c) reacting the product of step (b) with a compound of the formula: or a salt or activated ester derivative thereof, wherein R and L 1 are as defined therein 56 A process for the preparation of (2S, 3S, 5S)-2-(2,6- dimethylphenoxyacetyl) amιno-3-hydroxy-5-(2S-(1 -tetrahydro-pyπmιd-2-onyl)- 3-methyl butanoyl) amιno-1 ,6-dιphenylhexane; or a pharmaceutically acceptable salt, ester or prodrug thereof, comprising (a) reacting (2S, 3S, 5S)-2-N,N-dιbenzylamιno-3-hydroxy-5-amιno-1 ,6- diphenylhexane with 2S-(1 -tetrahydro-pyπmιd-2-onyl)-3-methyl butanoic acid or a salt or activated ester derivative thereof to provide (2S, 3S, 5S)-2-N,N- dιbenzylamιno-3-hydroxy-5-(2S-(1 -tetrahydro-pyπmid-2-onyl)-3-methyl butanoyl) amιno-1 ,6-dιphenylhexane; (b) debenzylatmg the product of step (a) to provide (2S, 3S, 5S)-2-amιno-3- hydroxy-5-(2S-(1-tetrahydro-pyπmιd-2-onyl)-3-methyl butanoyl) amιno-1 ,6- diphenylhexane; and (c) reacting the product of step (b) with 2,6-dιmethylphenoxyacetιc acid, or a salt of activated ester derivative thereof. 57. The process according to Claim 56 wherein (a) (2S, 3S, 5S)-2-N,N-dibenzyfamino-3-hydroxy-5-amino-1 ,6-dιphenylhexane is reacted with 2S-(1 -tetrahydro-pyrimid-2-onyl)-3-methyl butanoyl chloride to provide (2S, 3S, 5S)-2-N,N-dibenzylamino-3-hydroxy-5-(2S-(1 -tetrahydro- pyrimid-2-onyl)-3-methyl butanoyl) amino-1 ,6-diphenylhexane; (b) the product of step (a) is hydrogenated to provide (2S, 3S, 5S)-2-amιno-3- hydroxy-5-(2S-(1 -tetrahydro-pyrimid-2-onyl)-3-methyl butanoyl) amιno-1 ,6- diphenylhexane; and (c) the product of step (b) is reacted with 2,6-dimethylphenoxyacetyl chloride. 58. A process for the preparation of (2S, 3S, 5S) -2-(2,6- Dimethylphenoxyacetyl) amino-3-hydroxy-5-amιno-1 ,6-diphenylhexane or a salt thereof, comprising reacting (2S, 3S, 5S) -2-(2,6-Dimethylphenoxyacetyl) amιno-3-hydroxy-5-t-butyloxycarbonylamιno-1 ,6-diphenylhexane with tnfluoroaeetic acid in methylene chloride, aqueous hydrochloric acid in acetonitrile or aqueous hydrochloric acid in acetic acid. 59. A process for the preparation of a compound of the formula: or a salt or ester thereof , wherein R 3 is loweralkyi, hydroxyalkyl or cycloalkylalkyi and Q is a leaving group, comprising (a) reacting a compound of the formula: or a salt or ester thereof, wherein R 3 is as defined above with a compound of the formula: O=C=N. wherem Q is as defined above; or (b) reacting a compound of the formula: or a salt or ester thereof, wherein R 3 is as defined above and R" is phenyl, loweralkyl-substituted phenyl, halo-substituted phenyl, nitro-substituted phenyl or tπfluoromethylphenyl with a compound of the formula. wherein Q is as defined above. 60 The process of Claim 59 wherein R 3 is loweralkyi and Q is chloro 61. The process of Claim 59 wherein R 3 is isopropyl and Q is chloro 62 A process for the preparation of (2S, 3S, 5S)-2-(2,6- Dimethylphenoxyacetyl) amιno-3-hydroxy-5-(2S-(1 -tetrahydro-pyrιmιd-2-onyl)- 3-methyl butanoyl) amιno-1 ,6-diphenylhexane, or a pharmaceutically acceptable salt, ester or prodrug thereof, as an amorphous solid, comprising dissolving (2S, 3S, 5S)-2-(2,6-Dιmethylpheπoxyacetyl) amιno-3-hydroxy-5-(2S- (1 -tetrahydro-pyπmιd-2-onyl)-3-methy! butanoyl) amιno-1 ,6-dιphenylhexane in an organic solvent , followed by adding the solution to water. 63 The process according to Claim 62 wherein (2S, 3S, 5S)-2-(2,6- Dimethylphenoxyacetyl) amιno-3-hydroxy-5-(2S-(1 -tetrahydro-pyπmιd-2-onyl)- 3-methyl butanoyl) amιno-1 ,6-dιphenylhexane is dissolved in ethanol (from about 2 to about 4 mL/g) and the ethanolic solution is added to water (from about 10 about 100 mL/g).

Inventors: BETEBENNER DAVID A, CHEN XIAOQI, CONDON STEPHEN L, COOPER ARTHUR J, DICKMAN DANIEL A, HANNICK STEVEN M, HERRIN THOMAS R, KEMPF DALE J, KOLACZKOWSKI LAWRENCE, KUMAR GONDI N, LIU JIH-HUA, NORBECK DANIEL W, OLIVER PATRICIA A, PATEL KETAN M, PLATA DANIEL J, SHAM HING LEUNG, STENGEL PETER J, STONER ERIC J, TIEN JIEH-HEH J, BETEBENNER, DAVID, A., CHEN, XIAOQI, CONDON, STEPHEN, L., COOPER, ARTHUR, J., DICKMAN, DANIEL, A., HANNICK, STEVEN, M., HERRIN, THOMAS, R., KEMPF, DALE, J., KOLACZKOWSKI, LAWRENCE, KUMAR, GONDI, N., LIU, JIH-HUA, NORBECK, DANIEL, W., OLIVER, PATRICIA, A., PATEL, KETAN, M., PLATA, DANIEL, J., SHAM, HING, LEUNG, STENGEL, PETER, J., STONER, ERIC, J., TIEN, JIEH-HEH, J.
Applicants: ABBOTT LAB, ABBOTT LABORATORIES
Application year: 1996
Main classification: C07D239
IPC codes: A61K31, A61K38, A61K45, A61P31, A61P43, C07C231, C07C235, C07C273, C07C275, C07D207, C07D211, C07D223, C07D233, C07D239, C07D241, C07D243, C07D253, C07D263, C07D265, C07D267, C07D277, C07D279, C07D281, C07D401, C07D403, C07D405, C07D409, C07D413, C07D417