SULFONYLALKANOYLAMINO HYDROXYETHYLAMINO SULFONAMIDES USEFUL AS RETROVIRAL PROTEASE INHIBITORS

Abstract: Sulphonamide-containing hydroxyethylamine compounds represented by formula (I) where R, R<1>, R<2>, R<3>, R<4>, R<6>, R<20>, R<21>, Y, t and x are as defined in claim 1, are effective as retroviral protease inhibitors, and in particular as inhibitors of HIV protease.

Description: SULFONYLALKANOYLAMINO HYDROXYETHYLAMINO SULFONAMIDES USEFUL AS RETROVIRAL PROTEASE INHIBITORS RELATED APPLICATION This application is a continuation in part in U.S. Application Serial No. 07/935,071 filed August 25, 1992. BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to retroviral protease inhibitors and, more particularly, relates to novel compounds and a composition and method for inhibiting retroviral proteases. This invention, in particular, relates to sulfonamide-containing hydroxyethylamine protease inhibitor compounds, a composition and method for inhibiting retroviral proteases such as human immunodeficiency virus (HIV) protease and for treating a retroviral infection, e.g., an HIV infection. The subject invention also relates to processes for making such compounds as well as to intermediates useful in such processes. 2. Related Art During the replication cycle of retroviruses, gag and gag-pol gene products are translated as proteins. These proteins are subsequently processed by a virally encoded protease (or proteinase) to yield viral enzymes and structural proteins of the virus core. Most commonly, the gag precursor proteins are processed into the core proteins and the pol precursor proteins are processed into the viral enzymes, e.g., reverse transcriptase and retroviral protease. It has been shown that correct processing of the precursor proteins by the retroviral protease is necessary for assembly of infectious virons. For examυle, it has been shown that frameshifc mutations in the protease region of the pol gene of HIV prevents processing of the gag precursor protein. It has also been shown through site-directed mutagenesis of an aspartic acid residue in the HIV protease that processing of the gag precursor protein is prevented. Thus, attempts have been made to inhibit viral replication by inhibiting the action of retroviral proteases. Retroviral protease inhibition may involve a transition-state mimetic whereby the retroviral protease is exposed to a mimetic compound which binds to the enzyme in competition with the gag and gag-pol proteins to thereby inhibit replication of structural proteins and, more importantly, the retroviral protease itself. In this manner, retroviral replication proteases can be effectively inhibited. Several classes of compounds have been proposed, particularly for inhibition of proteases, such as for inhibition of HIV protease. Such compounds include hydroxyethylamine isosteres and reduced amide isoεteres. See, for example, EP 0 346 847; EP O 342,541; Roberts et al, "Rational Design of Peptide-Based Proteinase Inhibitors, "Science. 248. 358 (1990); and Erickson et al, "Design Activity, and 2.8A Crystal Structure of a C2 Symmetric Inhibitor Complexed to HIV-1 Protease, " Science. 249. 527 (1990) . Several classes of mimetic compounds are known to be useful as inhibitors of the proteolytic enzyme renin. See, for example, U.S. No. 4,599,198; U.K. 2,184,730; G.B. 2,209,752; EP 0 264 795; G.B. 2,200,115 and U.S. SIR H725. Of these, G.B. 2,200,115, GB 2,209,752, EP 0 264,795, U.S. SIR H725 and U.S. 4,599,198 disclose urea-containing hydroxyethylamine renin inhibitors. G.B. 2,200,115 also discloses sulfamoyl- containing hydroxyethylamine renin inhibitors and EP 0264795 discloses certain sulfonamide-containing hydroxyethylamine renin inhibitors. However, it is known that, although renin and HIV proteases are both classified as aspartyl proteases, compounds which are effective renin inhibitors generally cannot be predicted to be effective HIV protease inhibitors. BRIEF DESCRIPTION OF THE INVENTION The present invention is directed to virus inhibiting compounds and compositions. More particularly, the present invention is directed to retroviral protease inhibiting compounds and compositions, to a method of inhibiting retroviral proteases, to processes for preparing the compounds and to intermediates useful in such processes. The subject compounds are characterized as sulfonylalkanoylamino hydroxyethylamino sulfonamide inhibitor compounds. DETAILED DESCRIPTION OF THE INVENTION In accordance with the present invention, there is provided a retroviral protease inhibiting compound of the formula: or a pharmaceutically acceptable salt, prodrug or ester thereof wherein: R represents hydrogen, alkyl, alkenyl, alkynyl, hydroxyalkyl, alkoxyalkyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, heteroaryl, heterocycloalkylalkvl, aryl, aralkyl, heteroaralkyl, aminocarbonylalkyl, aminoalkylcarbonylalkyl, aminoalkyl, alkylcarbonylalkyl, aryloxyalkylcarbonylalkyl, aralkoxycarbonylalkyl radicals and mono- and disubstituted aminocarbonylalkyl, aminoalkylcarbonylalkyl and aminoalkyl radicals wherein said substituents are selected from alkyl, aryl, ' aralkyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroaralkyl, heterocycloalkyl, and heterbcycloalkylalkyl radicals, or in the case of a disubstituted radical, said substituents along with the nitrogen atom to which they are attached, form a heterocycloalkyl or a heteroaryl radical; each x independently represents 0, 1 or 2; t represents either 0 or 1; Rl, R20 and R^l independently represent hydrogen, -CH2SO2NH2, -CH2CO2CH3, -CO2CH3, -CONH2, -CH2C(0)NHCH3, -C(CH3)2(SH), -C(CH3)2(SCH3) , -C (CH3) 2 (S[0]CH3) , -C(CH3)2 (S[0]2CH3) , alkyl, haloalkyl, alkenyl, alkynyl and cycloalkyl radicals, and amino acid side chains selected from asparagine, S-methyl cysteine and the sulfoxide (SO) and sulfone (SO2) derivatives thereof, isoleucine, allo-isoleucine, alanine, leucine, tert-leucine, phenylalanine, ornithine, histidine, norleucine, glutamine, threonine, glycine, allo-threonine, serine, O-alkyl serine, aspartic acid, beta-cyano alanine and valine side chains; R 2 represents alkyl, aryl, cycloalkyl, cycloalkylalkyl and aralkyl radicals, which radicals are optionally substituted with a group selected from -NO2, CN, -C≡N,CF 3 -OR9, -SR9, haloalkyl and halogen and alkyl radicals, wherein R9 represents hydrogen and alkyl radicals; R3 represents hydrogen, alkyl, haloalkyl, alkenyl, alkynyl, hydroxyalkyl, alkoxyalkyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, heteroaryl, heterocycloalkylalkyl, aryl, aralkyl, heteroaralkyl, aminoalkyl and mono- and disubstituted aminoalkyl radicals, wherein said substituents are selected from alkyl, aryl, aralkyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroaralkyl, heterocycloalkyl, and heterocycloalkylalkyl radicals, or in the case of a disubstituted aminoalkyl radical, said substituents along with the nitrogen atom to which they are attached, form a heterocycloalkyl or a heteroaryl radical; R - represents radicals as defined by R3. excluding hydrogen; Y represents 0,S and NR15 wherein Rl5 represents hydrogen and radicals as defined for R3; and R6 represents hydrogen, and alkyl radicals. A preferred class of retroviral inhibitor compounds of the present invention are those represented by the formula: or a pharmaceutically acceptable salt, prodrug or ester thereof, preferably wherein the absolute stereochemistry about the hydroxy group is designated as (R) ; R represents alkyl, alkenyl, alkynyl, cycloalkyl, hydroxyalkyl, cycloalkylalkyl, heterocycloalkyl, heterocycloalkylalkyl, alkoxyalkyl, aryl, heteroaryl, aralkyl, heteroalkyl, heteroaralkyl, aminocarbonylalkyl, aminoalkylcarbonylalkyl, alkylcarbonylalkyl, aryloxyalkylcarbonyl, and aralkoxycarbonylalkyl radicals; Rl, R20 a nd R21 independently represent hydrogen, -CH2S02NH2, -CH2CO2CH3, -CO2CH3, -CONH2, -CH2C(0)NHCH3, -C(CH3)2(SCH3) , -C(CH3)2 (S[0]CH3) , -C(CH3)2 (S[0]2CH3) , alkyl, haloalkyl, alkenyl, alkynyl and cycloalkyl radicals, and amino acid side chains selected from aεparagine, S-methyl cysteine and the sulfoxide (SO) and sulfone (SO2) derivatives thereof, isoleucine, allo-isoleucine, alanine, leucine, tert-leucine, phenylalanine, ornithine, histidine, norleucine, glutamine, threonine, glycine, allo-threonine, serine, O-methyl serine, aspartic acid, beta-cyano alanine and valine side chains; R2 represents alkyl, aryl, cycloalkyl, cycloalkylalkyl, and aralkyl radicals, which radicals are optionally substituted with a group selected from alkyl and halogen radicals, NO2, CN, -C=N,CF 3 0R 9 and SR9 wherein R9 represents hydrogen and alkyl radicals, and halogen radicals; R3 represents alkyl, haloalkyl, alkenyl, hydroxyalkyl, alkoxyalkyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, heterocycloalkylalkyl, aryl, heteroaryl, aralkyl and heteroaralkyl radicals; and R - represents radicals as defined by R3 except for hydrogen; t represents 0 or 1; Y represents 0, S, and NR 15 wherein R15 represents hydrogen and radicals as defined for R3. Preferably, Y represents 0. A preferred class of compounds within Formula I are those represented by the formula: or a pharmaceutically acceptable salt, prodrug or ester thereof wherein R, Rl, R 2 , R3, and R - are as defined above, with respect to Formula (II) . As utilized herein, the term "alkyl", alone or in combination, means a straight-chain or branched-chain alkyl radical containing from 1 to about 10, preferably from 1 to about 8, carbon atoms. Examples of such radicals include methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, iso- amyl, hexyl, octyl and the like. The term "alkenyl", alone or in combination, means a straight-chain or branched-chain hydrocarbon radial having one or more double bonds and containing from 2 to about 18 carbon atoms preferably from 2 to about 8 carbon atoms. Examples of suitable alkenyl radicals include ethenyl, propenyl, 1,4-butadienyl and the like. The term alkynyl, alone or in combination, means a straight-chain hydrocarbon radical having one or more triple bonds'and containing from 2 to about 10 carbon atoms. Examples of alkynyl radicals include ethynyl, propynyl, propargyl and the like. The term "alkoxy", alone or in combination, means an alkyl ether radical wherein the term alkyl is as defined above. Examples of suitable alkyl ether radicals include methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, iso-butoxy, sec-butoxy, tert-butoxy and the like. The term "cycloalkyl", alone or in combination, means a saturated or partially saturated monocyclic, bicyclic or tricyclic alkyl radical wherein each cyclic moiety contains from about 3 to about 8 carbon atoms. The term "cycloalkylalkyl" means an alkyl radical as defined above which is substituted by a cycloalkyl radical containing from about 3 to about 8, preferably from about 3 to about 6, carbon atoms. Examples of such cycloalkyl radicals include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and the like. The term "aryl", alone or in combination, means a phenyl or naphthyl radical which optionally carries one or more substituents selected from alkyl, alkoxy, halogen, hydroxy, amino, nitro, cyano, haloalkyl and the like, such as phenyl, p-tolyl, 4-methoxyphenyl, 4- (tert-butoxy)phenyl, 4-fluorophenyl, 4-chlorophenyl, 4-hydroxypheny1, 1-naphthyl, 2-naphthyl, and the like. The term "aralkyl", alone or in combination, means an alkyl radical as defined above in which one hydrogen atom is replaced by an aryl radical as defined above, such as benzyl, 2-phenylethyl and the like. The term "aralkoxy carbonyl", alone or in combination, means a radical of the formula -C (0) -O-aralkyl in which the term "aralkyl" has the significance given above. An example of an aralkoxycarbonyl radical is benzyloxycarbonyl. The term "aryloxy" means a radical of the formula aryl-O- in which the term aryl has the significance given above. The term "alkanoyl", alone or in combination, means an acyl radical derived from an alkanecarboxylic acid, examples of which include acetyl, propionyl, butyryl, valeryl, 4-methylvaleryl, and the like. The term "cycloalkylcarbonyl" means an acyl group derived from a monocyclic or bridged cycloalkanecarboxylic acid such as cyclopropanecarbonyl, cyclohexanecarbonyl, adamantanecarbonyl, and the like, or from a benz-fused monocyclic cycloalkanecarboxylic acid which is optionally substituted by, for example, alkanoylamino, such as 1,2,3, 4-tetrahydro-2-naphthoyl,2-acetamido-l,2, 3,4- tetrahydro-2-naphthoyl . The term "aralkanoyl" means an acyl radical derived from an aryl-substituted alkanecarboxylic acid such as phenylacetyl, 3-phenylpropionyl (hydrocinnamoyl) , 4-phenylbutyryl, (2-naphthyl)acetyl, 4-chlorohyd ocinnamoy1, 4-aminohydrocinnamoyl, 4-methoxyhydrocinnamoyl, and the like. The term "aroyl" means an acyl radical derived from an aromatic carboxylic acid. Examples of such radicals include aromatic carboxylic acids, an optionally substituted benzoic or naphthoic acid such as benzoyl, 4-chlorobenzoyl, 4-carboxybenzoyl, 4- (benzyloxycarbonyl)benzoyl, 1-naphthoyl, 2-naphthoyl, 6-carboxy-2 naphthoyl, 6- (benzyloxycarbonyl) -2-naphthoyl, 3-benzyloxy-2-naphthoyl, 3-hydroxy-2-naphthoyl, 3- (benzyloxyformamido) -2-naphthoyl, and the like. The heterocyclyl or heterocycloalkyl portion of a heterocyclylcarbonyl, heterocyclyloxycarbonyl, heterocyclylalkoxycarbonyl, or heterocyclyalkyl group or the like is a saturated or partially unsaturated monocyclic, bicyclic or tricyclic heterocycle which contains one or more hetero atoms selected from nitrogen, oxygen and sulphur, which is optionally substituted on one or more carbon atoms by halogen, alkyl, alkoxy, oxo, and the like, and/or on a secondary nitrogen atom (i.e., -NH-) by alkyl, aralkoxycarbonyl, alkanoyl, phenyl or phenylalkyl or on a tertiary nitrogen atom (i.e. = N-) by oxido and which is attached via a carbon atom. The heteroaryl portion of a heteroaroyl, heteroaryloxycarbonyl, or a heteroaralkoxy carbonyl group or the like is an aromatic monocyclic, bicyclic, or tricyclic heterocycle which contains the hetero atoms and is optionally substituted as defined above with respect to the definition of heterocyclyl. Examples of such heterocyclyl and heteroaryl groups are pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, thiamorpholinyl, pyrrolyl, i idazolyl (e.g., imidazol 4-yl, l-benzyloxycarbonylimidazol-4-yl, etc.), pyrazolyl, pyridyl, pyrazinyl, pyrimidinyl, furyl, thienyl, triazolyl, oxazolyl, thiazolyl, indolyl (e.g., 2-indolyl, etc.), quinolinyl, (e.g., 2-quinolinyl, 3-quinolinyl, l-oxido-2-quinolinyl, etc.), isoquinolinyl (e.g., 1-isoquinolinyl, 3-isoquinolinyl, etc.) , tetrahydroquinolinyl (e.g., 1,2, 3 , 4-tetrahydro-2- quinolyl, etc.), 1, 2,3 , 4-tetrahydroisoquinolinyl (e.g., 1,2,3, 4-tetrahydro-l-oxo-isoquinolinyl, etc. ) , quinoxalinyl, β-carbolinyl, 2-benzofurancarbonyl, l-,2-,4- or 5-benzimidazolyl, and the like. The term "cycloalkylalkoxycarbonyl" means an acyl group derived from a cycloalkylalkoxycarboxylic acid of the formula cycloalkylalkyl-O-COOH wherein cycloalkylalkyl has the significance given above. The term "aryloxyalkanoyl" means an acyl radical of the formula aryl-O-alkanoyl wherein aryl and alkanoyl have the significance given above. The term "heterocyclyloxycarbonyl" means an acyl group derived from heterocyclyl-O-COOH wherein heterocyclyl is as defined above. The term "heterocyclylalkanoyl" is an acyl radical derived from a heterocyclyl-substituted alkane carboxylic acid wherein heterocyclyl haε the significance given above. The term "heterocyclylalkoxycarbonyl" means an acyl radical derived from a heterocyclyl-subεtituted alkane-O-COOH wherein heterocyclyl haε the significance given above. The term "heteroaryloxycarbonyl" means an acyl radical derived from a carboxylic acid represented by heteroaryl- O-COOH wherein heteroaryl has the significance given above. The term "aminocarbonyl" alone or in combination, means an amino-subεtituted carbonyl (carbamoyl) group derived from an amino-substituted carboxylic acid wherein the amino group can be a primary, secondary or tertiary amino group containing substituents selected from hydrogen, and alkyl, aryl, aralkyl, cycloalkyl, cycloalkylalkyl radicals and the like. The term "aminoalkanoyl" means an acyl group derived from an amino-subεtituted alkanecarboxylic acid wherein the amino group can be a primary, secondary or tertiary amino group containing εubεtituents selected from hydrogen, and alkyl, aryl, aralkyl, cycloalkyl, cycloalkylalkyl radicals and the like. The term "halogen" means fluorine, chlorine, bromine or iodine. The term "leaving group" generally refers to groups readily displaceable by a nucleophile, such as an amine, a thiol or an alcohol nucleophile. Such leaving groups are well known in the art. Examples of such leaving groups include, but are not limited to, N-hydroxysuccinimide, N-hydroxybenzotriazole, halides, triflates, tosylates and the like. Preferred leaving groups are indicated herein where appropriate. Procedures for preparing the compounds of Formula I are set forth below. It should be noted that the general procedure is shown as it relates to preparation of compounds having the specified stereochemistry, for example, wherein the absolute stereochemiεtry about the hydroxyl group is deεignated as (R) . However, such procedures are generally applicable to thoεe compounds of oppoεite configuration, e.g., where the stereochemistry about the hydroxyl group is (S) . In addition, the compounds having the (R) stereochemiεtry can be utilized to produce thoεe having the (S) stereochemistry, and vice versa. For example, a compound having the (R) stereochemiεtry can be inverted to the (S) εtereochemistry using well-known methods. Preparation of Compounds of Formula I The compounds of the present invention represented by Formula II above can be prepared utilizing the following general procedure. An N-protected chloroketone derivative of an amino acid having the formula: wherein P representε an amino protecting group, and R2 is as defined above, is reduced to the corresponding alcohol utilizing an appropriate reducing agent. Suitable amino protecting groups are well known in the art and include carbobenzoxy, butyryl, t-butoxycarbonyl, acetyl, benzoyl and the like. A preferred amino protecting group is carbobenzoxy. A preferred N-protected chloroketone iε N-benzyloxycarbonyl-L-phenylalanine chloromethyl ketone. A preferred reducing agent is sodium borohydride. The reduction reaction is conducted at a temperature of from -10°C to about 25°C, preferably at about 0°C, in a suitable solvent system such as, for example, tetrahydrofuran, and the like. The N-protected chloroketones are commercially available, e.g., such as from Bache , Inc., Torrance, California. Alternatively, the chloroketones can be prepared by the procedure set forth in S. J. Fittkau, J. Prakt. Chem.. 315. 1037 (1973), and subεequently N-protected utilizing procedureε which are well known in the art. The halo alcohol can be used directly, as described below, or, preferably, is then reacted, preferably at room temperature, with a suitable base in a εuitable εolvent εyεtem to produce an N-protected amino epoxide of the formula: wherein P and R2 are as defined above. Suitable solvent syεtemε for preparing the amino epoxide include ethanol, methanol, isopropanol, tetrahydrofuran, dioxane, and the like including mixtures thereof. Suitable baseε for producing the epoxide from the reduced chloroketone include potassium hydroxide, sodium hydroxide, potaεεium t-butoxide, DBU and the like. A preferred base is potassium hydroxide. Alternatively, a protected amino epoxide can be prepared starting with an L-amino acid which iε reacted with a suitable amino-protecting group in a suitable solvent to produce an amino-protected L-amino acid ester of the formula: wherein P 1 and p2 independently represent hydrogen, benzyl and amino- protecting groupε (as defined above with reεpect to P) , provided that P 3 - and p are not both hydrogen; P3 is a carboxyl protecting group (such as methyl, ethyl, tertiary-butyl, benzyl and the like); and R 2 is as defined above. The amino-protected L-amino acid ester is then reduced, to the corresponding alcohol. For example, the amino-protected L-amino acid eεter can be reduced with diiεobutylaluminum hydride at -78° C in a εuitable solvent such as toluene. The resulting alcohol is then converted, for example, by way of a Swern oxidation, to the correεponding aldehyde of the formula: wherein P 1 , p and R2 are aε defined above. Thuε, a dichloromethane solution of the alcohol is added to a cooled (-75 to -68° C) εolution of oxalyl chloride in dichloromethane and DMSO in dichloromethane and εtirred for 35 minuteε. The aldehyde reεulting from the Swern oxidation is then reacted with a halomethyllithium reagent, which reagent is generated in εitu by reacting an alkyllithium or arylithium compound with a dihalomethane repreεented by the formula χ-CH2χ2 wherein X 1 and χ2 independently represent I, Br or Cl. For example, a solution of the aldehyde and chloroiodomethane in THF is cooled to -78° C and a solution of n-butyllithium in hexane is added. The reεulting product is a mixture of diastereomerε of the corresponding amino-protected epoxides of the formulaε: The diaεtereomers can be separated e.g., by chromatography, or, alternatively, once reacted in subsequent steps the diastereomeric products can be separated. For compounds having the (S) stereochemistry, a D-amino acid can be utilized in place of the L-amino acid. The amino epoxide is then reacted, in a suitable solvent εyεtem, with an equal amount, or preferably an excess of, a desired amine of the formula: wherein R is hydrogen or is as defined above. The reaction can be conducted over a wide range of temperatures, e.g., from about 10°C to about 100°C, but is preferably, but not necesεarily, conducted at a temperature at which the εolvent beginε to reflux. Suitable solvent systemε include protic, non-protic and dipolar aprotic organic solvents such as, for example, those wherein the solvent is an alcohol, εuch as methanol, ethanol, iεopropanol, and the like, etherε such as tetrahydrofuran, dioxane and the like, and toluene, N,N-dimethylformamide, dimethyl εulfoxide, and mixtureε thereof. A preferred εolvent iε iεopropanol. Exemplary amines corresponding to the formula R NH2 include benzyl amine, isobutylamine, n-butyl amine, isopentyl amine, isoamylamine, cyclohexanemethyl amine, naphthylene methyl amine and the like. The resulting product is a 3-(N- protected amino) -3- (R2) -1- (NHR3) -propan-2-ol derivative (hereinafter referred to as an amino alcohol) represented by the formulaε: wherein P, Pi, P2, R2 and R3 are aε described above. Alternatively, a haloalcohol can be utilized in place of the amino epoxide. The amino alcohol defined above is then reacted in a suitable solvent with a sulfonyl chloride (R 4 S02C1) or sulfonyl anhydride in the presence of an acid scavenger. Suitable solventε in which the reaction can be conducted include methylene chloride, tetrahydrofuran and the like. Suitable acid scavangers include triethylamino, pyridine and the like. Preferred εulfonyl chlorides are methane sulfonyl chloride and benzenesulfonyl chloride. The resulting sulfonamide derivative can be repreεented, depending on the epoxide utilized, by the formulaε wherein P, pi, P 2 , R2, R3 a nd R 4 are aε defined above. Theεe intermediateε are useful for preparing inhibitor compounds of the present invention and are also active inhibitors of retroviral proteases. The sulfonyl halides of the formula R^S02X can be prepared by the reaction of a suitable Grignard or alkyl lithium reagent with sulfuryl chloride, or εulfur dioxide followed by oxidation with a halogen, preferably chlorine. Also, thiols may be oxidized to εulfonyl.. chlorideε uεing chlorine in the preεence of water under carefully controlled conditionε. Additionally, sulfonic acids may be converted to sulfonyl halides using reagents such aε PCI5, and also to anhydrides using suitable dehydrating reagents. The sulfonic acids may in turn be prepared using procedures well known in the art. Such sulfonic acids are also commercially available. In place of the εulfonyl halides, εulfinyl halideε (R 4 SOCl) and εulfenyl halides (R SC1) can be utilized to produce compounds wherein the -SO2- moiety is replaced by -SO- and -S-, respectively. Following preparation of the sulfonamide derivative, the amino protecting group P iε removed, or the groupε P-- and p2 are removed, under conditionε which will not affect the remaining portion of the molecule. These methodε are well known in the art and include acid hydrolyεis, hydrogenolysiε and the like. A preferred method involveε removal of the protecting group, e.g., removal of a carbobenzoxy group, by hydrogenolyεis utilizing palladium on carbon in a suitable solvent system such aε an alcohol, acetic acid, and the like or mixtureε thereof. Where the protecting group is a t-butoxycarbonyl group, it can be removed utilizing an inorganic or organic acid, e.g., HCl or trifluoroacetic acid, in a suitable solvent syεtem, e.g., dioxane or methylene chloride. The reεulting product is the amine salt derivative. Where the protecting group is a benzyl radical, it can be removed by hydrogenolysis. Following neutralization of the εalt, the amine is then reacted with a sulfone of the formula: Wherein R, Rl, R20 7 R21 a nd t are as defined above. The sulfone is prepared according to the following procedure. A mercaptan of the formula RSH is reacted with a subεtituted methacrylate of the formula: by way of a Michael Addition. The Michael Addition iε conducted in a εuitable εolvent and in the preεence of a εuitable base, to produce the correεponding thiol derivative repreεented by the formula: wherein R and Rl repreεent radicalε defined above; R20 and R 1 repreεent hydrogen and radicals as defined for Rl; and R22 repreεents a carboxyl protecting group such as methyl, ethyl, benzyl, t-butyl or the like. Suitable solvents in which the Michael Addition can be conducted include protic, non-protic and dipolar aprotic organic solvents, e.g., alcohols such as, for example, methanol, ethanol, butanol and the like, aε well aε etherε, e.g., THF, and acetonitrile, DMF, DMSO, and the like, including mixtureε thereof. Suitable baεeε include Group I metal alkoxideε εuch aε, for example εodium methoxide, εodium ethoxide, εodium butoxide and the like aε well aε Group I metal hydrideε, εuch * aε εodium hydride, including mixtures thereof. The thiol derivative is converted into the correεponding εulfone or εulfoxide of the formula: by oxidizing the thiol derivative with a εuitable oxidation agent in a suitable solvent. Suitable oxidation agents include, for example, hydrogen peroxide, sodium meta-perborate. oxone (potaεsium peroxy monosulfate) , meta-chloroperoxvbenzoic acid, periodic acid and the like, including mixtures thereof. Suitable solventε include acetic acid (for εodium meta-perborate) and, for other peracidε, ethers such as THF and dioxane, and acetonitrile, DMF and the like, including mixtures thereof. The sulfone is then converted to the corresponding free acid of the formula: One method involves utilizing a suitable base, e.g., lithium hydroxide, sodium hydroxide, and the like, including mixtureε thereof, in a εuitable εolvent, such as, for example, THF, water, acetonitrile, DMF, DMSO, methylene chloride and the like, including mixtures thereof. Other methods which can be used for deprotection depend on the nature of R . For example, when R 22 is a tertiary-butyl group, one can uεe a εtrong acid such as hydrochloric acid or trifluoroacetic acid. When R22 is a benzyl group, it can be removed via hydrogenolysis. The free acid iε then coupled, utilizing procedureε well known in the art, to the sulfonamide derivative, or analog thereof, of an amino alcohol which is described above. The resulting product is a compound represented by Formula I. Alternatively, one can couple the εulfonamide iεoεtere to the commercially available acid, CH 3 remove the thioacetyl group with a εuitable base, such aε hydroxide, or an amine, such as ammonia, and then react the resulting thiol with an alkylating agent, such aε an alkyl halide, toεylate or meεylate to afford compoundε at the following structure: The sulfur can then be oxidized to the corresponding sulfone or εulfoxide uεing εuitable oxidizing agentε, aε deεcribed above, to afford the desired compounds of the following structure: Alternatively, to prepare -compounds of Formula I, a substituted methacrylate of the formula: wherein L representε a leaving group aε previouεly defined, R35 and R36 repreεent hydrogen and radicalε as defined for Rl; and R37 repreεents alkyl, aralkyl, cycloalkyl and cycloalkylalkyl radicalε, iε reacted with a εuitable sulfonating agent, such as, for example, a sulfinic acid represented by the formula RSO2M, wherein R representε radicals as defined above and M representε a metal adapted to form a salt of the acid, e.g., sodium, to produce the corresponding sulfone repreεented by the formula: wherein R, R 5, R36 and F.37 a re as defined above. The sulfone iε then hydrolyzed in the preεence of a εuitable base, εuch aε lithium hydroxide, εodium hydroxide and the like, to the compound repreεented by the formula: wherein R, R 5 and R36 represent radicals aε defined above. The reεulting compound iε then asymmetrically hydrogenated utilizing an aεymmetric hydrogenation catalyεt such as, for example, a ruthenium-BINAP complex, to produce the reduced product, εubεtantially enriched in the more active iεomer, repreεented by the formula: wherein R, R35 and R36 repreεent radicals as defined above. Where the more active isomer has the R-εtereochemistry, a Ru(R-BINAP) asymmetric hydrogenation catalyst can be utilized. Conversely, where the more active isomer has the S-sterochemistry, a Ru(S-BINAP) catalyεt can be utilized. Where both isomerε are active, or where it is desired to have a mixture of the two diastereomers, ' a hydrogenation catalyst εuch aε platinum, or palladium, on carbon can be utilized to reduce the above compound. The reduced compound iε then coupled to the εulfonamide iεoεtere, aε deεcribed above, to produce compoundε of Formula II. Alternatively, an acid or a derivative of an acid properly substituted with a leaving group (diεcuεsed above) can be treated with a Mercaptan and a base (see above) to provide an organic sulfide. Acid derivatives are defined above. The resulting sulfide can be oxidized to the correεponding εulfoxide or εulfone by methodε previously discussed. A preferred method to prepare 2 (S) -methyl-3- (methylsulfonyl)propionic acid is as follows. Beginning with the commercially available compounds of the following structure; CH. Where P 3 is a protecting group for sulfur, preferably a benzoyl or acetyl, and P 4 iε either hydrogen or a carboxylic acid protecting group such as methyl, ethyl, tertiary-butyl, benzyl and the like. Preferably, P 4 is tertiary-butyl. The εulfur protecting group P 3 can be εelectively removed uεing methodε known to thoεe εkilled in the art. For example, where P3 iε either benzoyl or acetyl, it can be removed by treatment with an inorganic base or an amine, preferably ammonia, in an appropriate solvent such as methanol, ethanol, isopropanol, toluene or tetrahydrofuran. The preferred solvent is methanol. Thiε provideε a compound of the following structure; which can be alkylated on the εulfur with a compound of the εtructure RX Where R is as defined above, and X is an appropriate leaving group, such as a halide (chloride, bromide, iodide) , mesylate, toεylate or triflate. The reaction is performed in the presence of a suitable base, such aε triethylamine, diisopropylethylamine, 1,8- diazabicyclo[5.4.0] undec-7-ene (DBu) and the like, in a suitable solvent such as toluene, tetrahydrofuran, or methylene chloride. The preferred base is DBU and the preferred solvent is toluene. Where R is a methyl group, RX can be methyl chloride, methyl bromide, methyl iodide, or dimethyl sulfate. Preferably RX iε methyl iodide. The product of the reaction iε a compound of the structure; CH. The εulfur can then be oxidized to either the εulfoxide or εulfone using methods known to those skilled in the art. Suitable oxidizing agents are meta-chloroperbenzoic acid, hydrogen peroxide, εodium perborate and the like. Appropriate εolventε are methylene chloride, toluene, acetic acid, propionic acid and the like. The preferred method iε uεing hydrogen peroxide or εodium perborate in acetic acid. The εulfone product haε the structure; The carboxylic acid protecting group P 4 can then be removed using methods well known to those in the art. For example, when P 4 is a tertiary-butyl group, it can be removed by treatment with an acid, such as hydrochloric acid or trifluoracetic acid. The preferred method iε using 4N hydrochloric acid in dioxane. This provides the desired final compound of the structure; It is envisioned that one εkilled in the art could utilize variationε on the synthetic sequence such as the use of different protecting groups for the sulfur (P 3 ) or for the carboxylic acid (P 4 ) , and different reagents to carry out the same transformationε. It is contemplated that for preparing compounds of the Formulas having R6, the compounds can be prepared following the procedure set forth above and, prior to coupling the εulfonamide derivative or analog thereof to the εulfone carried through a procedure referred to in the art aε reductive amination. Thuε, a εodium cyanoborohydride and an appropriate aldehyde or ketone can be reacted with the sulfonamide derivative compound or appropriate analog at room temperature in order to reductively aminate any of the compounds of Formulas I-III. It is also contemplated that where R3 of the amino alcohol intermediate is hydrogen, the inhibitor compounds can be prepared through reductive amination of the final product of the reaction between the amino alcohol and the amine or at any other stage of the synthesis for preparing the inhibitor compounds. Contemplated equivalents of the general formulas set forth above for the antiviral compounds and derivatives aε well aε the intermediates are compounds otherwise correεponding thereto and having the εame general propertieε wherein one or more of the various R groups are simple variations of the substituents as defined therein, e.g., wherein R is a higher alkyl group than that indicated. In addition, where a subεtituent iε designated as, or can be, a hydrogen, the exact chemical nature of a substituent which is other than hydrogen at that position, e.g., a hydrocarbyl radical or a halogen, hydroxy, amino and the like functional group, is not critical so long as it does not adversely affect the overall activity and/or synthesis procedure. The chemical reactions described above are generally discloεed in termε of their broadeεt application to the preparation of the compoundε of thiε invention. Occasionally, the reactions may not be applicable aε described to each compound included within the disclosed scope. The compoundε for which this occurs will be readily recognized by thoεe εkilled in the art. In all such cases, either the reactions can be succesεfully performed by conventional modifications known to those εkilled in the art, e.g., by appropriate protection of interfering groupε, by changing to alternative conventional reagents, by routine modification of reaction conditionε, and the like, or other reactions diεcloεed herein or otherwise conventional, will be applicable to the preparation of the corresponding compounds of this invention. In all preparative methodε, all εtarting materialε are known or readily preparable from known εtarting materialε. Without further elaboration, it iε believed that one εkilled in the art can, uεing the preceding deεcription, utilize the preεent invention to itε fulleεt extent. The following preferred εpecific embodimentε are, therefore, to be conεtrued aε merely illustrative, and not limitative of the remainder of the discloεure in any way whatεoever. All reagentε were uεed as received without purification. All proton and carbon NMR spectra were obtained on either a Varian VXR-300 or VXR-400 nuclear magnetic resonance spectrometer. Example IA Preparation of N[3 (S)-benzyloxycarbonylamino-2 (R) hydroxy-4-phenylbutyl] -N-isoamylamine. PART A- To a solution of N-benzyloxycarbonyl-L-phenylalanine chloromethyl ketone (75 g, 0.2 mol) in a mixture of 800 mL of methanol and 800 mL of tetrahydrofuran was added sodium borohydride (13.17 g, 0.348 mol, 1.54 equiv.) over 100 min. The solution was εtirred at room temperature for 2h and then concentrated in vacuo. The reεidue waε dissolved in 1000 mL of ethyl acetate and washed with IN KHSO4, saturated aqueous NaHC03, saturated aqueous NaCl, dried over anhyd MgS04, filtered and concentrated in vacuo to give an oil. The crude product was dissolved in 1000 mL of hexanes at 60 "C and allowed to cool to room temperature whereupon cryεtalε formed that were iεolated by filtration and waεhed with copiouε amountε of hexaneε. This solid waε then recryεtallized from hot ethyl acetate and hexaneε to provide 32.3 g 43% of N-benzyloxycarbonyl- 3 (S) -amino-l-chloro-4-phenyl-2(S)-butanol, mp 150-15 * 1 * c, FAB MS: MLi+=340. PART B A εolution of potaεεium hydroxide (6.52 g, 0.116 mol, 1.2 equiv.) in 970 mL of abεolute ethanol waε treated with N-benzyloxycarbonyl-3 (S) -amino-l-chloro-4- phenyl-2(S)-butanol (32.3 g, 0.097 mol). This solution was stirred at room temperature for 15 min and then concentrated in vacuo to give a white solid. The solid was diεεolved in dichloromethane and waεhed with water, dried over anhyd MgS04, filtered and concentrated in vacuo to give a white solid. The εolid waε cryεtallized from hexaneε and ethyl acetate to give 22.3 g, 77% of N-benzyloxycarbonyl-3 (S) -amino-1,2 (S) epoxy-4- phenylbutane, mp 102-103 'C, FAB MS: MH+=298. PART C A εolution of N-benzyloxycarbonyl-3 (S) -amino- 1,2 (S)epoxy-4-phenylbutane (11.54 g, 38.81 mmol) and isoamylamine (66.90 g, .767 mol, 19.9 equivalents) in 90 mL of isopropyl alcohol waε heated to reflux for 3.1h. The solution was cooled to room temperature and partially concentrated in vacuo and the remaining solution poured into 200 mL of stirring hexanes whereupon the product cryεtallized from εolution. The product waε iεolated by filtration and air dried to give 11.76 g, 79% of N[[3(S)- phenylmethylcarbamoyl)amino-2 (R) -hydroxy-4-phenylbutyl]N- [ (3-methylbutyl) lamine, mp 118-122' C, FAB MS: MH+=385. EXAMPLE IB Preparation of N- [ [3S- (phenylmethylcarbamoyl)amino] -2R- hydroxy-4-phenyl] -1- [ (2-methylpropyl)amino-2- (1,1- dimethylethoxyl) carbonyl]butane To a solution of 7.51g (20.3 mmol) of N-[[3S- (phenylmethylcarbamoyl) amino] -2R-hydroxy-4-phenylbutyl] N- (2-methylpropyl)]amine in 67 mL of anhydrous tetrahydrofuran waε added 2.25 g (22.3 mmol) of triethylamine. After cooling to 0 C, 4.4 g (20.3 mmol) of di-tert-butyldicarbonate was added and stirring continued at room temperature for 21 hours. The volatiles were removed in vacuo, ethyl acetate added, then washed with 5% citric acid, saturated sodium bicarbonate, brine, dried over magneεium sulfate, filtered and concentrated to-afford 9.6 g of crude product. Chromatography on silica gel using 30% ethyl acetate/hexane afforded 8.2 g of pure N-[[3S- (phenylmethylcarbamoyl)amino] -2R-hydroxy-4-phenyl] -1- [ (2- methylpropyl)amino-2- (1,1- dimethylethoxyl) carbonyl]butane, masε spectrum m/e = 477 (M+Li ) . Example 2 Preparation of Propanamide . N- r 2 -hvdroxv-3 - r ( 3 - methvlbutvl ) ( 4 -methoxvphenvlεulfonvl ) amino 1 -1- (phenvlmethvl ) propvl l -2-methvl-3 - (methvlsulfonvl ) - r iS- QR* (R* ) . 2S* 1 1 - PART A A solution of the amino alcohol from Example 1, Part C (1.1515 g, 2.99 mmol), and triethylamine (313.5 mg, 3.10 mmol) in 15 mL of dichloromethane was treated with 4-methoxybenzenesulfonyl chloride (630.6 mg, 3.05 mmol) via syringe. The solution was stirred at room temperature for 40 min and then concentrated in vacuo. The residue was dissolved in ethyl acetate and washed with IN KHSO4, saturated aqueous NaHC03 , brine, dried over anhyd MgS04, filtered and concentrated to give 1.5622 g, of a white foam. The crude product was purified by recryεtallization from a mixture of hexaneε and ethyl acetate to give 1.1047 g, 67% of pure product mp 95-98 'C. High reεolution FAB Maεε spectrum calc'd. for C30H38N2O6S: 555.2529. Found: 555.2559. PART B A solution of the product from Part A (970 mg, 1.68 mmol) in 30 mL of methanol was treated with 70 mg of 10% palladium on carbon catalyst and hydrogenated at 41 psig for 16h at room temperature. The catalyst was removed by filtration and the filtrate concentrated in vacuo to give a clear oil that solidified upon standing, mp- 81-85' C, FAB MS; MH+=421, 764.1 mg that was used directly in the next step. P RT C. A mixture of 2 (Ξ) -methyl-3-methylεulfonyl propionic acid (194 mg, 1.17 mmol), N-hydroxybenzotriazole (276 mg, 1.34 mmol) , and 1- (3-dimethylaminopropyl) -3- ethylcarbodiimide hydrochloride (EDO (256 mg, 1.34 mmol) waε dissolved in 3.5 mL of dimethylformamide (DMF) and allowed to react for 30 min at 0 'C. The amine from Part B (451.1 mg, 1.07 mmol) disεolved in 1.5 mL of DMF was added to the above mixture and stirred at room temperature for 16h. The solution waε then poured into 20 mL of εaturated aqueouε NaHCθ3 and extracted 4 timeε with ethyl acetate. The combined ethyl acetate extractε were waεhed with 5% aqueouε citric acid, saturated aqueous NaHCθ3 , brine, dried over anhyd MgS04, filtered and concentrated to give a clear oil that crystallized upon standing. The material was recrystallized from hexanes and ethyl acetate to give 517.6 mg, 85% of pure product with mp 125-129 'C. HRFAB MS; calc'd. for C27H40N2O7S2: 569.2355. Found: 569.2397. Example 3 Preparation of propanamide, N- r2-hvdroxy-3- r (2- methvlpronvl) (phenvlsulfonvl)amino1 -1- (phenvlmethvl)propvll -2-methvl-3- (methvlsulfonvl) -. US- PART A A solution of N-benzyloxycarbonyl-3 (S) -amino-1,2- (S) -epoxy-4-phenyl butane (50.0 g, 0.168 mol) and isobutylamine (246 g, 3.24 mol, 20 equivalents) in 650 mL of isopropyl alcohol was heated to reflux for 1.25 hours. The solution waε cooled to room temperature, concentrated in vacuo and then poured into 1 L of εtirring hexane whereupon the product crystallized from εolution. The product waε isolated by filtration and air dried to give 57.56 g, 92% of N[3 (S) -benzyloxycarbonylamino-2 (R) - hydroxy-4-phenyl]N-isobutylamine, mp 108.0-109.5 "C, MH+ m/z=371. PART B The amine from Part A (936.5 mg, 2.53 mmol) and triethylamine (288.5 mg, 2.85 mmol) waε dissolved in 20 mL of dichloromethane and treated with benzenesulfonyl chloride ( 461 mg, 2.61 mmoi) . The solution was stirred at room temperature for 16h and then concentrated in vacuo. The residue was disεolved in ethyl acetate and thiε solution was washed with IN KHSO4, saturated aqueous NaHC03 , brine, dried over anhyd MgSθ4, filtered, and concentrated to give a clear oil 1.234 g. The oil was crystallized from a mixture of ether and hexanes, 729.3 mg, 56.5%, mp 95-99'C, FAB MS; MH+=511. PART C A solution of phenylmethyl [ 2 (R) -hydroxy-3- [2- methylpropyl] (benzenesulfonyl) amino] 1-S- (phenylmethyl) propyl carbamate (671.1 mg, 1.31 mmol) from Part B in 10 mL of methanol was hydrogenated over 50 mg of 10% palladium on carbon at 40 psig at room temperature for 15h. The catalyεt waε removed by filtration through diatomaceouε earth and the filtrate concentrated to give a white foam, 474.5 mg, 96%, FAB MS; MH+=377, which waε uεed directly in the next step without further purification. PART D A mixture of 2 (S)methyl-3 (methylsulfonyl) propionic acid (210.6 mg, 1.27 mmol), N-hydroxybenzotriazole (260.4 mg, 1.70 mmol) and EDC (259 mg, 1.35 mmol) in 3.5 mL of DMF waε εtirred at 0'C for 0.5h. The amine from Part C (474 mg, 1.15 mmol) diεεolved in 2 mL of DMF waε added to the above εolution and εtirred at room temperature for 16h and then poured into 100 mL of 50% εaturated aqueouε NaHC03. The aqueous solution was extracted with ethyl acetate. The ethyl acetate solution was washed with 5% aqueous citric acid, saturated aqueous NaHCθ3 , brine, dried over anhyd MgS04, filtered and concentrated to give a white foam, 560.5 mg which was crystallized from ethyl acetate and hexanes to provide 440.3 mg of pure product, mp 112-116.5 " C, HR FAB MS; Calc'd for C25H36N2O6S2 : 525.2093. Found: 525.2077 Example 4 Preparation of propanamide, N- r2-hvdroxv-3- r (3- methylbutyl) (phenylsulfonyl) aminol -1- (phenvlme hyl)propyll-2-methvl-3-(methvlsulfonvl)-. flS- flR*(R*) .2S*11- PART A A mixture of N[3 (S) -benzyloxycarbonylamino-2 (R) - hydroxy-4-phenylbutyl]N- [ (3-methylbutyl) ] amine (Example 1, Part C) (3.89 g, 10.1 mmol) and triethylamine (1.02 g, 10.1 mmol) were diεεolved in 25 mL of tetrahydrofuran (THF) and treated with a solution of di-Cerϋ- butylpyrocarbonate (2.21 g, 10.1 mmol) dissolved in 10 mL of THF. The solution was εtirred at room temperature for 1.5h and then concentrated in vacuo. The reεidue waε diεεolved in ethyl acetate and waεhed with IN KHSO4, saturated aqueouε NaHC03, brine, dried over anhyd MgS04, filtered and concentrated to give a thick clear oil, -.4.66 g, 98.5%, Rf=0.23 on εilica gel eluting with 5:1 hexaneε:ethyl acetate. This material was used directly in the next step without further purification. PART B The product from Part A (4.66 g, 10.1 mmol) was diεεolved in 40 mL of anhyd ethanol and treated with 30 mg of 15% palladium on carbon catalyst. This mixture was then hydrogenated for 18h at room temperature and 40 psig. The catalyεt waε removed by filtration through diatomaceouε earth and the filtrate concentrated to give an oil that waε uεed directly in the next εtep without purification. PART C A mixture of 2 (S)-methyl—3-methylsulfonyl propionic acid (1.39 g, 8.3 mmol), N-hydroxybenzotriazole (1.84 g, 12.0 mmol), and 1- (3-dimethylaminopropyl) -3- ethylcarbodiimide hydrochloride (EDO (1.77 g, 9.2 mmol) waε disεolved in 10 mL of dimethylformamide (DMF) and allowed to react for 30 min at 0 'C. The amine from Part B (2.80 g, 8.0 mmol) diεεolved in 10 mL of DMF waε added to the above mixture and εtirred at room temperature for 24h. The solution was concentrated in vacuo and the reεidue taken up in ethyl acetate. The ethyl acetate εolution waε washed with 5% aqueous citric acid, εaturated aqueouε NaHC03, brine, dried over anhyd MgS04, filtered and concentrated to give a clear oil, that waε purified by flash chromatography to give 3.00 g, 75%, this material was used directly in the next step. PART D The product from Part C (3.00 g, 6.02 mmol) was treated with 30 mL of 4N HCl in dioxane at room temperature for 24h. The εolution waε concentrated in vacuo and the semi-εolid residue was triturated with ether and dried under vacuum to give a white amorphous solid, mp > 250' C, turns yellow at 221' C, FAB MS, MH+=436. PART E The product from Part D was disεolved in dichloromethane and treated with εaturated aqueous NaHC03 to provide a solution of the free amine. The organic phase was dried over anhyd MgS04, filtered and concentrated in vacuo to give (610 mg, 1.75 mmol). Thiε amine was suεpended in 50 mL of THF and treated εequentially with triethylamine (1.01 g, 10 mmol) and benzeneεulfonyl chloride (283 mg, 1.75 mmol). The solution was stirred at room temperature for 19.5h. The εolidε were removed by filtration and the filtrate concentrated and diεsolved in dichloromethane. The dichloromethane εolution waε waεhed with IN KHSO4, εaturated aqueouε NaHC03, brine, dried over anhyd MgS04, filtered and concentrated to give an oil that was triturated with methanol to give a white εolid that was isolated by filtration. The crude εolid waε then cryεtallized from ethyl acetate and hexaneε to give 200 mg, 21% of material with mp 112-115 * C, HRFAB MS, calc'd. for C26H38N2O6S2: 538.2171. Found: 533.2180. Example 5. Preparation of propanamide. N-r2-hvdroxv-3- (propvl) (phenvlsulfonvl)aminol-1- (phenvlmethvl)oropvll -2- methyl-3-(methylεulfonyl)-. flS-FIR* (R*) -2S*11- PART A A εolution of N-benzyloxycarbonyl 3 (S) -amino-1,2- (S)-epoxy-4-phenylbutane (6.06 g, 20.4 mmol) and n-propylamine (20.9 g, 0.35 mmol) in 100 mL of iεopropyl alcohol waε heated to reflux for 3h. The εolution was then concentrated in vacuo to give a εolid that was crystallized from hexaneε and ethyl acetate to give 6.53 g, 90%, of the desired product, mp 120-123 * C, FAB MS: MH+=357. PART B The amine from Part A was reacted with benzenesulfonyl chloride in a manner εimilar to Example 3, Part B. The resulting compound (1.426 g, 2.87 mmol) diεεolved in 25 mL of methanol waε hydrogenated over 40 mg of 10% palladium on carbon at 40 pεig for 16h at room temperature. The solution was then filtered through diatomaceouε earth and the filtrate concentrated to give 1.04 g, 100%, of a clear oil that waε uεed directly in the next εtep without further purification, HRFAB MS Calc'd for C19H24N2O3S: 363.1742. Found: 363.1763. PART c A mixture of 2 (S)methyl-3 (methylsulfonyl)propionic acid (243.7 mg, 1.47 mmol), N-hydroxybenzotriazole (332.0 mg, 2.16 mmol), and EDC (304.8 mg, 1.59 mmol) in 2.5 mL of DMF was stirred at O'C for 0.5h and then treated with a solution of the free amine from Part B (513.3 mg, 1.42 mmol) in 1.5 mL of DMF. The εolution waε εtirred at room temperature for 16h and then poured into 80 mL of 50% εaturated aqueouε NaHC03. The εolution was extracted with ethyl acetate and the ethyl acetate solution was waεhed with 5% aqueouε citric acid, εaturated aqueoilε NaHC03 , brine, dried over anhyd MgS04 , filtered and concentrated to give- a white foam, 576.8 mg, that waε purified by cryεtallized ethyl acetate/hexaneε to give 441.1 mg, 61% of product with mp 134-136.5' C, HRFAB MS, Calc'd for C24H34N206S2+Li: 517.2019. Found: 517.1973. Example 6 Preparation of propanamide. N-r2-hvdroxy-3- (butvl) (phenvlsulfonvl)amino1-1-(phenvlmethvl)propvll -2- methvl-3-(me hvlsulfonyl)-. flS-flR R*) .2S*11- PART A From the reaction of (1.48 g, 5.0 mmol) of N-benzyloxycarbonyl 3 (S)-amino-1,2- (S)-epoxy-4- phenylbutane and (7.314 g, 100.0 mmol) of n-butylamine, one obtains 1.50 g (80%) of N-[3(S)- benzyloxycarbonylamino-2 (R)-hydroxy-4-phenylbutyl]-N- butyla ine, mp 125-128'C, FAB MS, Spectrum: MH+=371. PART B The amine from Part A (1.67 g, 4.5 mmol) and triethylamine (859.4 mg) , was dissolved in 60 mL of dichloromethane and treated with benzene sulfonyl chloride (822.3 mg, 4.66 mmol) at room temperature. After stirring for 15 min. the solution was concentrated in vacuo and the residue disεolved in ethyl acetate. The ethyl acetate εolution waε waεhed with IN KHSO4, εaturated aqueouε NaHC03, brine, dried over anhyd MgS04, filtered and concentrated to give an oil. The oil waε cryεtallized from hexanes and ether to give 2.04 g 89% of pure product, mp 68-77'C, FAB MS: MH+=511. PART C A solution of phenylmethyl [2 (R)-hydroxy-3-[n,- butyl] (benzeneεulfonyl) amino]-IS- (phenylmethyl) propyl carbamate from Part B (1.86 g, 3.64 mmol) in 40 mL of methanol waε hydrogenated over 110 mg of 10% palladium on carbon at 40 pεig for 4h. The εolution waε filtered through diamtomaceouε earth and concentrated in vacuo to give a εolid, mp 68-88 * C, FAB MS: MH+=377, that waε used in the next step without further purification. PART D A mixture of 2 (S)methyl-3 (methylsulfonyl)propionic acid(288.4 mg, 1.74 mmol), EDC (369.6 mg, 1.93 mmol), and N-hydroxybenzotriazole (368.1 mg, 2.41 mmol) was dissolved in 3.5 mL of DMF and stirred at 0 * C for 30 min. This εolution as then treated with the amine from PART C (621.9 mg, 1.65 mmol) disεolved in 2 mL of DMF. The mixture was allowed to stir at room temperature for 48h and then was concentrated in vacuo. The residue was dissolved in ethyl acetate, washed with IN KHSO4, saturated aqueouε NaHC03, brine, dried over anhyd MgS04, filtered and concentrated in vacuo to give an oil. The crude product waε purified by flaεh chromatography on εilica get eluting with hexanes/ethyl acetate mixtures to give the desired product as a white εolid, 353 mg, 41%, mp 99-103"C, HRFAB MS: Calc'd for C25H36N2O6S2: 531.2175. Found: 513.2176 Example 7 Preparation of propanamide. N-r2-hvdroxv-3- ϊ (2- methvlpropvl) (4-methoxvphenvlεulfonvl)amino1-1- (phenvlmethyl)propyll-2-methvl-3-(methvlsulfonvl)-. ns- PART A The amine from Example 3, Part A, N[3 (S)-benzyloxy- carbonylamino-2 (R)-hydroxy-4-phenyl]N-isobutyl amine (1.1131 g, 3.00 mmol) and triethylamine (324.0 mg, 3.20 mmol) in 20 mL of dichloromethane waε treated with 4-methoxy-benzenesulfonyl chloride (715.4 mg, 3.46 mmol). The εolution waε εtirred at room temperature for 6h and then was concentrated in vacuo. The reεidue waε diεεolved in ethyl acetate and washed with IN KHSO4, saturated aqueous NaHC03, brine, dried over anhyd MgS04, filtered, and concentrated to give a clear oil. The oil was crystallized from ether to give a white solid 1.-273 g, 78%, mp 97-101'C, of pure product, FAB MS; MH+=541. PART B The product from Part A (930 mg, 1.68 mmol) was disεolved in 30 mL of methanol and hydrogenated at 40 pεig over 70 mg of 10% palladium on carbon at room temperature for 17h. The catalyεt waε removed by filtration through diato aceous earth and the filtrate was concentrated in vacuo to give 704 mg of a clear oil, that solidified upon standing, mp 105-110"C, FAB MS, MH+=407, and was used directly in the next step without further purification. PART C A mixture of 2-methyl-3 (methylsulfonyl)propionic acid (174.9 mg, 1.05 mmol), N-hydroxybenzotriazole (230 mg, 1.50 mmol) and EDC (220.5 mg, 1.15 mmol) in 2 mL of DMF was stirred at O'C for 0.5 mL and then treated with the amine from Part B (401.2 mg, 0.99 mmol) in 1 mL of DMF. The solution was stirred at room temperature for 16h and then poured into 20 mL of saturated aqueous NaHC03. The aqueous solution was extracted with ethyl acetate and then the ethyl acetate solution was washed with 5% aqueouε citric acid, εaturated aqueouε NaHC03 , brine, dried over anhyd MgS04, filtered and concentrated in vacuo to give a clear oil, 260 mg, which waε purified by flaεh chromatography on Silica gel eluting with hexanes and ethyl acetate to provide 52.7 mg, 9.6%, mp 87-92' C, HRFAB MS; Calc'd for C26H38N2O7S2 : 555.2199. Found: 555.2234 E ample ϋ Preparation of propanamide. N- f2-hγdroxy-3- . (butyl) (4-methoxyphenylsulfonyl) aminol -1- (phenylmethyl)propyll 2-methyl-3- (methylεulfonyl) - . US- FIR* (R*) ,2S*11 - PART A The amine from Example 6, Part A (1.52 mg, 4.10 mmol) and triethylamine (488 mg, 4.82 mmol) in 30 mL of dichloromethane was treated with 4-methoxybenzenesulfonyl chloride (869 mg, 4.20 mmol) at room temperature for 3h. The εolution waε removed in vacuo and the residue waε taken up in ethyl acetate. The ethyl acetate solution waε waεhed with IN KHSO4, saturated aqueous NaHC03, brine, dried over anhyd MgS04, filtered and concentrated to give a white solid that was washed with ether and air dried to provide 1.71 g, 77%, mp 118-120'C, FAB MS; M+Li=547, of pure product. PART B The product from Part A (1.514 g, 2.80 mmol) in 30 mL of methanol waε hydrogenated at 40 psig over 110 mg of 10% palladium on carbon for 16h at room temperature. The catalyst was removed by filtration through diatomaceous earth and the filtrate concentrated to give a white solid, 1.20 g, 100%, mp 103-108'C, HRFAB MS; Calc'd for C21H30N2O4S: 413.2086. Found: 413.2121, which was used directly in the next εtep without further purification. PART C A mixture of 2 (S)-methyl-3 (methylεulfonyl)propionic acid (354.4 mg, 2.13 mmol), N-hydroxybenzotriazole (473.4 mg, 3.09 mmol) and EDC (445.3 mg, 2.33 mmol) in 1.5..mL of DMF waε εtirred at 0' C for 25 min. and then treated with the amine from Part B (815 mg, 2.00 mmol) in 2 mL of DMF. The mixture was εtirred at room temperature for 16h and then poured into 50 mL of saturated aqueous NaHC03 and then extracted with ethyl acetate. The ethyl acetate solution was washed with 5% aqueous citric acid, saturated aqueous NaHC03, brine, dried over anhyd MgSθ4, filtered and concentrated in vacuo to give 905 mg of a white foam. The product waε purified by flaεh chromatography on Silica gel eluting with ethyl acetate/hexanes to provide 711.6 mg, 65%, of pure product, mp 87-92'C, HRFAB MS, M+Li; Calc'd for 26H38N2θ7S2 i: 561.2281 Found: 561.2346 Example 9 Preparation of prooanamide . N- r 2 -hvdroxv-3 - r (propvl ) ( 4-methoxvphenvlsulfonvl ) amino 1 -1- (phenvlmethvl ) propvl l - 2-methvl-3 - (methvlsulfonvl ) - . f lS- T 1R* (R* ) . 2S* 1 l - PART A. A εolution of the product from Example 5, Part A (620 mg, 1.74 mmol) and triethylamine (250 mg, 2.47 mmol) in 15 mL of dichloromethane waε treated with 4-methoxybenzeneεulfonyl chloride (371 mg, 1.79 mmol) at room temperature for 2.33h. The εolvent waε removed in vacuo and the reεidue taken up in ethyl acetate and then waεhed with IN KHSO4, εaturated aqueouε NaHC03, brine, dried over anhyd MgS04, filtered and concentrated to give 1.0622 g, of a white foam. The crude product waε purified by flaεh chromatography over εilica gel eluting with hexanes and ethyl acetate to give 615 mg, 67%, of pure product with mp 88-92 * C, HRFAB MS; calc'd. for C28H34 2O6S: 533.2298. Found: 533.2329. PART B A solution of carbamic acid, product from Part A (519 mg, 0.98 mmol) in 30 mL of methanol was treated with 70 mg of 10% palladium on carbon catalyst and hydrogenated at 46 psig for 22h at room temperature. The catalyst was removed by filtration through diatomaceous earth and the filtrate concentrated in vacuo to give a clear oil that εolidified upon standing, mp 124-127 * C, FAB MS; M+Li+=399, 387 mg, 100%, that was used directly in the next step. PART C A mixture of 2 (S) -methyl-3-methylsulfonyl propionic acid (138.5 mg, 0.83 mmol), N-hydroxybenzotriazole (174.6 mg, 1.14 mmol), and 1- (3-dimethylaminopropyl) -3- ethylcarbodiimide hydrochloride (EDC) (171.8 mg, 0.90 mmol) was diεεolved in 2.5 mL of dimethylformamide (DMF) and allowed to react for 30 min at 0 'C. The amine from Part B (304.9 mg, 0.78 mmol) dissolved in 1.5 mL of DMF was added to the above mixture and stirred at room temperature for 14.5h. The solution was then poured into 20 mL of saturated aqueous NaHC03 and extracted with ethyl acetate. The ethyl acetate extracts were washed with 5% aqueous citric acid, saturated aqueous NaHC03, brine, dried over anhyd MgS04, filtered and concentrated to give a white solid. The material was recrystallized from hexaneε and ethyl acetate to give 228 mg, 54% of pure product with mp 115-118 * C. HRFAB MS; calc'd. for C27H 0N2O7S2: 541.2042. Found: 541.2064. Example 1_Q_ Preparation of propanamide. N- r2-hvdroxy-3- r (2- methvlpropyl) (4-acetamido)phenvlsulfonvl) amino1 -1- (phenvlmethvl)propvll -2-methvl-3- (methvlεulfonvl) - , flS- PART A A solution of the product from Example 3 , Part A (1.1082 g, 2.99 mmol) and triethylamine (713 mg, 3.05 mmol) in 20 mL of dichloromethane was treated with N-acetylsulfanilyl chloride (713.2 mg, 3.05 mmol) at room temperature for 3.67h. The solvent was removed in vacuo and the residue taken up in ethyl acetate and then washed with IN KHSO4, saturated aqueous NaHC03 , brine, dried over anhyd MgS04, filtered and concentrated to give 1.398 g, of a white solid, mp 155-158 * C, FAB MS; M+Li=574. PART B A solution of product from Part A (900 mg, 1.58 mmol) in 30 mL of methanol was treated with 90 mg of 10% palladium on carbon catalyst and hydrogenated at 32 psig for 15h at room temperature. The catalyst was removed by filtration through diatomaceous earth and the filtrate concentrated in vacuo to give a white foam, FAB MS; M+H+=334, 680 mg, 99%, that waε uεed directly in the next εtep without further purification. PART C A mixture of 2 (S) -methyl-3-methylεulfonyl propionic acid (159.7 mg, 0.96. mmol) , N-hydroxybenzotriazole (210.8 mg, 1.38 mmol), and 1- (3-dimethylaminopropyl) -3- ethylcarbodiimide hydrochloride (EDC) (203.9 mg, 1.06 mmol) waε diεsolved in 1.5 mL of dimethylformamide (DMF) and allowed to react for 30 min at 0 'C. The amine from Part B (401.9 mg, 1.06 mmol) disεolved in 0.5 mL of DMF was added to the above mixture and stirred at room temperature for 16.5h. The solution was then poured into 75 mL of saturated aqueous NaHC03 and extracted with ethyl acetate. The ethyl acetate extracts were washed with 5% aqueous citric acid, saturated aqueouε NaHC03, brine, dried over anhyd MgS04, filtered and concentrated to give a white foam, 490 mg. The material was crystallized from hexanes and ethyl acetate to give 428 mg, 80% of pure product with mp 123-127 * C. HRFAB MS; calc'd. for C27H39N3O7S2: 588.2398. Found: 588.2395. Example 11 Preparation of propanamide. N-r2-hvdroxv-3-r (3- methvlbutvl) (4-aminophenvlεulfonvl)amino1-1- (phenvlmethvl)propvll-2-methvl-3-(methvlεulfonvl)-. riS- PART A A εolution of product from Example 1, Part C (1.1812 g, 3.07 mmol) and triethylamine (325.7 mg, 3.22 mmol) in 20 mL of dichloromethane waε treated with 4- nitrobenzenεulfonyl chloride (767 mg, 90% purity 3.11 mmol) at room temperature for 10 min. The εolvent was removed in vacuo and the reεidue taken up in ethyl acetate and then waεhed with IN KHSO4, εaturated aqueous NaHC03, brine, dried over anhyd MgS04, filtered and concentrated to give 2.3230 g, of a tan εolid, that was crystallized from ethyl acetate and petroleum ether to provide 870 mg, 50%, mp 130-132' C of pure product, HRFAB S; M+Li, calc'd. for C29H35N3θ7SLi: 576.2316. Found: 576.2350. PART B A solution of product from Part A (574 mg, 1.01 mmol) in 40 mL of methanol, (the solution was not completely homogeneouε) , waε treated with 70 mg of 10% palladium on carbon catalyεt and hydrogenated at 42 pεig for 15h at room temperature. The catalyεt waε removed by filtration through diatomaceous earth and the filtrate concentrated in vacuo to give a white solid that waε crystallized from chloroform, mp 123-127' C, FAB MS; M+Li+=412, 400 mg, 91%, that was used directly in the next step without further purification. PART C A mixture of 2 (S) -methyl-3-methylεulfonyl propionic acid (112.3 mg, 0.675 mmol), N-hydroxybenzotriazole (159.1 mg, 1.04 mmol), and 1- (3-dimethylaminopropyl) -3- ethylcarbodiimide hydrochloride (EDC) (147.8 mg, 0.77 mmol) was dissolved in 1.0 mL of dimethylformamide (DMF) and allowed to react for 30 min at 0 'C. The amine from Part B (261.9 mg, 0.646 mmol) disεolved in 0.5 mL of DMF waε added to the above mixture and stirred at room temperature for 16.5h. The solution was then poured into 75 mL of saturated aqueouε NaHC03 and extracted with ethyl acetate. The ethyl acetate extractε were washed with 5% aqueous citric acid, saturated aqueouε NaHC03 , brine, dried over anhyd MgS04, filtered and concentrated to give a white foam, 326.3 mg. The material waε purified by flash chromatography over silica gel eluting with ethyl acetate to provide 213.6 mg, 64% of pure product aε a white foam, FAB MS; MH+=554. Example 12 Preparation of Propanamide , N- r2-hvdroxy-3 - F ( 2 - methvlpropvl ) ( 3 . 4-dimethoxvphenvlεulfonvl ) amino 1 -1- (phenvlmethvl ) propvl 1 -2 -methvl-3 - (methvlεulfonvl ) - . r iS- PART A A εolution of the product from Example 3, Part A (1.5356 g, 4.14 mmol) and triethylamine (522 mg, 5.17 mmol) in 15 mL of dichloromethane waε treated with 3,4- dimethoxybenzenesulfonyl chloride (1.0087 g, 4.26 mmol) at room temperature for 14h. The solvent waε removed in vacuo and the reεidue taken up in ethyl acetate and then waεhed with IN KHSO4, εaturated aqueous NaHC03, brine, dried over anhyd MgS04, filtered and concentrated to give 2.147 g, 90.5%, of a white solid, mp 124-127' C, HRFAB MS; M+Li; calc'd. for C30H38N2θ7S+Li: 577.2560. Found: 577.2604. PART B A solution of carbamic acid, product from Part A (513 mg, 0.90 mmol) in 30 mL of methanol was stirred with 20 mg of palladium black catalyεt and 10 mL of formic acid for 15h at room temperature. The catalyεt waε removed by filtration through diatomaceous earth and the filtrate concentrated in vacuo and the residue taken up in ethyl acetate. The ethyl acetate solution was waεhed with εaturated aqueous NaHC03, brine and dried over anhyd MgS04, filtered and concentrated in vacuo to give a white εolid, 386 mg, 98%, mp 123-130' C, FAB MS; M+Li+=443, that waε used directly in the next step without further purification. PART C A mixture of 2 (S)-methyl-3-methylsulfonyl propionic acid (128 mg, 0.77 mmol), N-hydroxybenzotriazole (179.9 mg, 1.17 mmol), and 1- (3-dimethylaminopropyl)-3- ethylcarbodiimide hydrochloride (EDC) (177.3 mg, 0.92 mmol) waε dissolved in 1.5 mL of dimethylformamide (DMF) and allowed to react for 30 min at 0 'C. The amine from Part B (359 mg, 0.82 mmol) disεolved in 1 mL of DMF waε added to the above mixture and stirred at room temperature for 48h. The solution was then poured into 75 mL of saturated aqueous NaHC03 and extracted with ethyl acetate ' . The ethyl acetate extracts were washed with 5% aqueouε citric acid, εaturated aqueouε NaHC03, brine, dried over anhyd MgS04, filtered and concentrated to give a clear oil, 220 mg. The material waε cryεtallized from hexaneε and ethyl acetate to give 178 mg, 40% of pure product with mp 130-133 * C. HRFAB MS;M+Li+; calc'd. for C27H40N2θ8S2Li: 591.2386. Found: 591.2396. Example 13 Preparation of Propanamide, N-[2-hydroxy-3-[ (2- methylpropyl) (4-hydroxyphenylεulfonyl)amino] -1- (phenylmethyl)propyl] - 2-methyl-3-(methylsulfonyl)-, [IS-[IR* (R*) , 2S*]]- Part A: A solution of 0.98 g (1.85 mmol) of carbamic acid, [2R-hydroxy-3-[[ (4-fluorophenyl)εulfonyl] (2- methylpropyl)amino] -IS- (phenylmethyl)propyl] -phenylmethyl ester in 3.8 mL of anhydrous DMF was added to 22mg (7.4 mmol) of 80% εodium hydride in 2 mL of DMF. To thiε mixture was added 0.40g (3.7 mmol) of benzyl alcohol. After 2 hours, the solution waε cooled to O C, water added, and then ethyl acetate. The organic layer was washed with 5% cirtic acid, saturated sodium bicarbonate and brine, dried over magnesium sulfate, filtered and concentrated to afford 0.90g of crude material. This was chromatographed on baεic alumina uεing 3% methanol/methylene chloride to afford 0.70g of 2R- hydroxy-3-[ (2-methylpropyl) (4- benzyloxyphenyl)εulfonyl]amino-lS- (phenylmethyl)propylamine, cyclic carbamate; maεs spectrum m/e=509 (M+H) . Part B: To a solution of 0.65g (1.28 mmol) of the cyclic carbamate from part A in 15 mL of ethanol, was added 2.6 mL (6.4 mmol) of 2.5N εodium hydroxide εolution. After 1 hour at reflux, 4 mL of water waε added and the εolution refluxed for an additional eight hours. The volatileε were removed, ethyl acetate added, and washed with water, brine, dried over magnesium sulfate, filtered and concentrated to afford 550 mg of crude 2R-hydroxy-3-[ (2- methylpropyl) (4-benzyloxyphenyl) sulfonyl]amino-IS- (phenylmethyl)propylamine. Part C: A solution of crude 2R-hydroxy-3- [ (2- methylpropyl) (4-benzyloxyphenyl) sulfonyl]amino-lS- (phenylmethyl)propylamine in 10 mL of ethanol was hydrogenated in the preεence of 500 mg of a 10% palldium on carbon catalyεt under 50 pεig of hydrogen for 2 hourε. The catalyεt waε removed by filtration and the εolvent removed in vacuo to afford 330 mg of 2R-hydroxy-3- [ (2- methylpropyl) (4- hydroxyphenyl) εulfonyl]amino-IS- (phenylmethyl)propylamine, maεε εpectrum m/e = 393 (M+H) . Part D: To a solution of 337 mg (2.03 mmol) of 2(S)- methyl-3- (methylsulfonyl)propionic acid and 423 mg (2.21 mmol) of N-hydroxybenzotriazole in 4 mL of anhydrous DMF at 0 C, was added 423 mg (2.76 mmol) of l-(3- dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride. After stirring for 2 hours, 725 mg (1.84 mmol) of amine from part C above was added and the solution stirred at room temperature for 17 hours. The εolvent was removed in vacuo, ethyl acetate added, and then washed with saturated aqueouε εodium bicarbonate, brine, dried over magneεium εulfate, filtered and concentrated to afford 939 mg of crude product. Chromatography on εilica gel using 2-5% methanol/methylene chloride afforded 533 mg of propanamide, N- [2-hydroxy-3- [ (2-methylpropyl) (4- hydroxyphenylεulfonyl) amino] -1- (phenylmethyl)propyl] -2- methyl-3-(methylεulfonyl)-, [IS- [IR* (R*) , 2S*]]-, maεε εpectrum m/e = 547 (M+Li) . Example 14 The following general procedureε can be utilized to prepare additional compoundε within the scope of the present invention. General Procedure for the Synthesis of Amino Epoxides To a εolution of 0.226 mol of N-benzyloxycarbonyl-L-phenylalanine chloromethyl ketone in a mixture of 807 mL of methanol and 807 mL of tetrahydrofuran at -2°C, iε added 1.54 equiv. of εolid εodium borohydride over one hundred minuteε. The εolventε are then removed under reduced preεεure at 40°C and the reεidue iε diεεolved in ethyl acetate (approx. IL) . The εolution iε washed εequentially with IM potaεεium hydrogen εulfate, εaturated εodium bicarbonate and iε then εaturated εodium chloride solutions. After drying over anhydrous magnesium εulfate and filtering, the εolution iε removed under reduced preεεure. To the resulting oil iε added hexane (approx. ID and the mixture is warmed to 60°C with swirling. After cooling to room temperature, the εolids are collected and washed with 2L of hexane. The resulting solid is recrystallized from hot ethyl acetate and hexane to afford 32.3g (43% yield) of N-benzyloxycarbonyl-3 (S) -amino-l-chloro-4- phenyl-2 (S)-butanol, mp 150-151°C and M+Li+ = 340. PART B: To a solution of 1.2 equiv. of potasεium hydroxide in 968 mL of abεolute ethanol at room temperature, iε added 0.097 mol of N-CBZ-3 (S)-amino-1- chloro-4-phenyl-2 (S) -butanol. After εtirring for fifteen minutes, the solvent iε removed under reduced preεεure and the solids are disεolved in methylene chloride. After waεhing with water, drying over magneεium sulfate, filtering and stripping, one obtains a white εolid. Recryεtallization from hot ethyl acetate and hexane will afford N-benzyloxycarbonyl-3 (S) -amino-1,2 (S) -epoxy-4- phenylbutane. Alternate Procedure for the Synthesis of Amino Eooxideε Step A: A εolution of L-phenylalanine (50.0 g, 0.302 mol), εodium hydroxide (24.2 g, 0.605 mol) and potaεεium carbonate (83.6 g, 0.605 mol) in water (500 ml) is heated to 97°C. Benzyl bromide (108.5 ml, 0.912 mol) is then εlowly added (addition time -25 min) . The mixture iε then εtirred at 97°C for 30 minutes. The solution is cooled to room temperature and extracted with toluene (2 x 250 ml) . The combined organic alyers are then waεhed with water, brine, dried over magneεium εulfate, filtered and concentrated to give an oil product. The crude product iε then uεed in the next εtep without purification. Step p: The crude benzylated product of the above εtep is dissolved in toluene (750 ml) and cooled to -55°C. A 1.5 M solution of DIBAL-H in toluene (443.9 ml, 0.666 mol) is then added at a rate to maintain the temperature between -55° to -50°C (addition time - 1 hour) . The mixture is stirred for 20 minuteε at -55°C. The reaction iε quenched at -55°C by the slow addition of methanol (37 ml) . The cold solution iε then poured into cold (5°C) 1.5 N HCl εolution (1.8 L) . The precipitated εolid (approx. 138 g) iε filtered off and waεhed with toluene. The εolid material is suεpended in a mixture of toluene (400 ml) and water (100 ml) . The mixture iε cooled to 5°C, treated with 2.5 N NaOH (186 ml) and then εtirred at room temperature until the εolid is diεεolved. The toluene layer is separated from the aqueouε phaεe and waεhed with water and brine, dried over magneεium sulfate, filtered and concentrated to a volume of 75 ml (89 g) . Ethyl acetate (25 ml) and hexane (25 ml) are then added to the residue upon which the alcohol product begins to crystallize. After 30 min., an additional 50 ml hexane iε added to promote further cryεtallization. The εolid is filtered off and washed with 50 ml hexane to give approximately 35 g of material. A second crop of matrial can be isolated by refiltering the mother liquor. The solids are combined and recrystallized from ethyl acetate (20 ml) and hexane (30 ml) to give, in 2 crops, approximately 40 g (40% from L-phenylalanine) of analytically pure alcohol product. The mother liquorε are combined and concentrated (34 g) . The reεidue iε treated with ethyl acetate and hexane which provides an additional 7 g (-7% yield) of slightly impure εolid product. Further optimization in the recovery from the mother liquor is probable. Step : A εolution of oxalyl chloride (8.4 ml, 0.096 mol) in dichloromethane (240 ml) iε cooled to -74°C. A εolution of DMSO (12.0 ml, 0.155 mol) in dichloromethane (50 ml) is then slowly added at a rate to maintain the temperature at -74°C (addition time -1.25 hr) . The mixture is stirred for 5 min. followed by addition of a solution of the alcohol (0.074 mol) in 100 ml of dichloromethane (addition time -20 min., temp. -75°C to -68°C) . The solution is stirred at -78°C for 35 minutes. Triethylamine (41.2 ml, 0.295 mol) iε then added over 10 min. (temp. -78° to -68°C) upon which the ammonium salt precipitated. The cold mixture is stirred for 30 min. and then water (225 ml) is added. The dichloromethane layer iε separated from the aqueous phase and washed with water, brine, dried over magnesium sulfate, filtered and concentrated. The reεidue iε diluted with ethyl acetate and hexane and then filtered to further remove the ammonium εalt. The filtrate iε concentrated to give the deεired aldehyde product. The aldehyde waε carried on to the next εtep without purification. Temperatures higher than -70°C have been reported in the literature for the Swern oxidation. Other Swern modificationε and alternativeε to the Swern oxidationε are alεo possible. A solution of the crude aldehyde 0.074 mol and chloroiodomethane (7.0 ml, 0.096 mol) in tetrahydrofuran (285 ml) is cooled to -78°C. A 1.6 M solution of n-butyllithium in hexane (25 ml, 0.040 mol) is then added at a rate to maintain the temperature at -75°C (addition time - 15 min.). After the first addition, additional chloroiodomethane (1.6 ml, 0.022 mol) is added again, followed by n-butyllithium (23 ml, 0.037 mol), keeping the temperature at -75°C. The mixture is stirred for 15 min. Each of the reagentε, chloroiodomethane (0.70 ml, 0.010 mol) and n-butyllithium (5 ml, 0.008 mol) are added 4 more times over 45 min. at -75°C. The cooling bath is then removed and the solution warmed to 22°C over 1.5 hr. The mixture iε poured into 300 ml of εaturated aq. ammonium chloride solution. The tetrahydrofuran layer is εeparated. The aqueouε phaεe iε extracted with ethyl acetate (1 x 300 ml) . The combined organic layerε are washed with brine, dried over magnesium sulfate, filtered and concentrated to give a brown oil (27.4 g) . The product could be used in the next step without purification. The desired diaεtereomer can be purified by recryεtallization at the subsequent sulfonamide formation εtep. Alternately, the product could be purified by chromatography. General Procedure for the Synthesis of 1.3-Diamino 4- phenyl Bntan-2-ol Derivatives (Amino Alcohols) . A mixture of the amine R3NH2 (20 equiv. ) in dry isopropyl alcohol (20mL/mmol of epoxide to be converted) is heated to reflux and then iε treated with an N-Cbz amino epoxide of the formula: from a εolidε addition funnel over a 10-15 minute period. After the addition iε complete the εolution iε maintained at reflux for an additional 15 minuteε and the progreεε of the reaction monitored by TLC. The reaction mixture iε then concentrated in vacuo to give an oil and iε then treated with n-hexane with rapid εtirring whereupon the ring opened-material precipitateε from εolution. Precipitation iε generally complete within 1 hr and the product iε then iεolated by filtration on a Bϋchner funnel and iε then air dried. The product iε further dried in vacuo. This method affords amino alcohols of εufficient purity for moεt purposes. Table 1 shows representative amino alcohols prepared according to the above general procedureε. Table 1 Entry R 3 1 i-Butyl 2 CH3 3 i-Propyl 4 -CH2CH ( CH3 ) 2 5 i- Propyl 6 Phenyl 7 Benzyl 8 Cyclohexylmethyl 9 Cyclohexyl 10 2 -Naphthylmethyl 11 n-Butyl 12 n-Pentyl 13 n-Hexyl 14 p-Methyoxybenzyl 15 3-Pyridylmethyl 1 ' 6 4-Pyridylmethyl 17 n-Butoxy 18 p-Fluorobenzyl General procedure for the Reaction of Amino Alcohols with Sulfonyl Halides or Sulfonvl Anhydrides: Preparation of Sulfonamides To a solution of N[3 (S) -benzyloxycarbonylamino- 2 (R) -hydroxy-4-phenylbutyl] N-isoamylamine (2.0 gm, 5.2 mmol) and triethylamine (723 uL, 5.5 mmol) in dichloromethane (20 mL) iε added dropwiεe methaneεulfonyl chloride (400 uL, 5.2 mmol) . The reaction mixture iε stirred for 2 hours at room temperature, then the dichloromethane solution is concentrated to ca. 5 mL and applied to a silica gel column (100 gm) . The column is eluted with chloroform containing 1% ethanol and 1% methanol. Alternatively, from the reaction of N[3(S)- benzyloxycarbonylamino-2 (R) -hydroxy-4-phenylbutyl] N-isoamylamine (1.47 gm, 3.8 mmol) , triethylamine (528 uL, 3.8 mmol) and benzenesulfonyl chloride (483 uL, 3.8 mmol) one can obtain the appropriate (phenylεulfonyl)amino derivative. The following Table 2 showε repreεentative εulfonamideε prepared according to the above procedure. Table 2 Entry R4 TABLE 2 (Cont'd) Entry R^ TABLE 2 ( Cont ' d ) Entry General Procedure for the Removal of the Protecting Groups by Hvdroσenolvεiε with Palladium on Carbon A. Alcohol Solvent The Cbz-protected peptide derivative is disεolved in methanol (ca.20mL/mmol) and 10% palladium on carbon catalyst is added under a nitrogen atmosphere. The reaction vessel is sealed and flushed 5 times with nitrogen and then 5 times with hydrogen. The pressure is maintained at 50 psig for 1-16 hours and then the hydrogen is replaced with nitrogen and the solution is filtered through a pad of celite to remove the catalyst. The solvent is removed .in vacuo to give the free amino derivative of εuitable purity to be taken directly on to the next εtep. B. Acetic Acid Solvent The Cbz-protected peptide derivative iε diεεolved in glacial acetic acid (20mL/mmol) and 10% palladium on carbon catalyεt is added under a nitrogen atmoεphere. The reaction veεεel is flushed 5 times with nitrogen and 5 timeε with hydrogen and then maintained at 40 pεig for about 2h. The hydrogen iε then replaced with nitrogen and the reaction mixture filtered through a pad of ceϋte to remove the catalyεt. The filtrate iε concentrated and the reεulting product iε taken up in anhydrouε ether and is evaporated to drynesε 3 timeε. The final product, the acetate εalt, iε dried in vacuo and is of suitable purity for subεequent converεion. General Procedure for Removal of Boc-protectinα Group with 4N Hydrochloric Acid in Dioxane The Boc-protected amino acid or peptide derivative iε treated with a εolution of 4N HCl in dioxane with εtirring at room temperature. Generally the deprotection reaction is complete within 15 minutes, the progresε of the reaction is monitored by thin layer chromatography (TLC) . Upon completion, the excesε dioxane and HCl are removed by evaporation in vacuo. The last traces of dioxane and HCl are best removed by evaporation again from anhydrous ether or acetone. The hydrochloride salt thus obtained is thoroughly dried in vacuo and is suitable for further reaction. Procedures for Preparation of Sulfonyl Compounds The procedures described below in Examples 13A, 13B and 13C illustrate procedures for preparing sulfonyl alkanoyl compounds which can be coupled to the sulfonamideε aε prepared above. Example 14A Preparation of 2 (S) -methvl-3- (methvlεulfonvl)propionic ci . To a solution of lOg of D- (-) -S-benzoyl-b- mercaptioiεobutyric acid t-butyl eεter in 20 mL of methanol was bubbled in gaseous ammonia at 0°C. The reaction was allowed to then warm to room temperature, stirred overnight and concentrated under reduced pressure. The resulting mixture of a solid (benzamide) and liquid was filtered to provide 5.21g of a pale oil which then solidified. Thiε waε identified aε 2 (S) -methyl-3-mercaptopropionic acid t-butyl eεter. To a εolution of 5.21g of 2 (S) -methyl-3- mercaptopropionic acid t-butyl eεter in 75 mL of toluene at 0°C waε added 4.50g of 1, 8-diazabicyclo [5.40]undec-7- ene and 1.94 mL of methyl iodide. After εtirring at room temperature for 2.5 hourε, the volatileε were removed, ethyl acetate added, waεhed with dilute hydrochloric acid, water, brine, dried and concentrated to afford 2.82g of a pale oil, identified aε 2 (S) -methyl-3- (thiomethyl)propionic acid t-butyl eεter. To a εolution of 2.82g of 2 (S) -methyl-3- (thiomethyl)propionic acid t-butyl eεter in 50 mL of acetic acid was added 5.58g of sodium perborate and the mixture heated to 55°C for 17 hours. The reaction was poured into water, extracted with methylene chloride, washed with aqueous sodium bicarbonate, dried and concentrated to afford 2.68g of 2 (S) -methyl-3- ( ethylεulfonyl)propionic acid t-butyl eεter as a white εolid. To 2.68g of 2 (S) -methyl-3- (methylεulfonyl) - propionic acid t-butyl eεter waε added 20 mL of 4N hydrochloric acid/dioxane and the mixture εtirred at room temperature for 19 hourε. The εolvent waε removed under reduced preεεure to afford 2.18g of crude product, which waε recryεtallized from ethyl acetate/hexane to yield 1.44g of 2 (S) -methyl-3- (methylsulfonyl)propionic acid aε white cryεtalε. Example 14B PART A: A εolution of methyl methacrylate (7.25 g, 72.5 mmol) and phenethyl mercaptan (10.0 g, 72.5 mmol) in 100 mL of methanol waε cooled in an ice bath and treated with sodium methoxide (100 mg, 1.85 mmol) . The solution waε stirred under nitrogen for 3 h and then concentrated in vacuo to give an oil that waε taken up in ether and washed with 1 N aqueous pota≥εium hydrogen εulfate, εaturated aqueouε εodium chloride, dried over anhydrouε . magnesium εulfate, filtered and concentrated to give 16.83 g, 97.5% of methyl 2- (R,S) -methyl-4-thia-6-phenyl hexanoate as an oil. TLC on Siθ2 eluting with -20:1 hexane:ethyl acetate ' (v:v) Rf=0.41. Alternatively, one can use methyl 3-bromo-2-methyl propionate in place of methyl methacrylate. PART B: A solution of methyl 2- (R,S) -methyl-4-thia-6-phenyl hexanoate (4.00 g, 16.8 mmol) in 100 mL of dichloromethane was stirred at room temperature and treated portion wise with eta-chloroperoxybenzoic acid (7.38 g, 39.2 mmol) over approximately 40 m. The solution was stirred at room temperature for 16 h and then filtered and the filterate washed with saturated aqueouε εodium bicarbonate, IN εodium hydroxide, saturated aqueouε εodium chloride, dried over anhydrouε magnesium sulfate, filtered, and concentrated to give 4.50 g, 99% of desired εulfone. The unpurified εulfone waε diεεolved in 100 mL of tetrahydrofuran and treated with a solution of lithium hydroxide (1.04 g, 24.5 mmol) in 40 mL of water. The solution was stirred at room temperature for 2 m and then concentrated in vacuo. The residue was then acidified with IN aqueous potaεεium hydrogen sulfate to pH=l and then extracted three times with ethyl acetate. The combined ethyl acetate solution was washed with εaturated aqueouε εodium chloride, dried over anhydrouε. magneεium εulfate, filtered and concentrated to give a white εolid. The εolid waε taken up in boiling ethyl acetate/hexane and allowed to εtand undiεturbed whereupon white needleε formed that were isolated by filtration and air dried to give 3.38 g, 79% of 2-(R,S) -methyl-3 (β-phenethylsulfonyl) -propionic acid, mp 91-93°C. PART C: A εolution of 2-(R,S) -methyl-3 (β- phenethy1εulfonyl)-propionic acid (166.1 mg, 0.65 mmol), H-hydroxybenzotriazole (HOBT) (146.9 mg, 0.97 mmol), and 1- (3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC) (145.8 mg, 0.75 mmol) in 4 mL of anhydrous dimethylformamide (DMF) cooled to 0°C and stirred under nitrogen for 0.5 h. This εolution iε then treated with a desired sulfonamide isostere and εtirred at room temperature for 16 h. The εolution is poured into 30 mL of 60% εaturated aqueouε sodium bicarbonate solution. The aqueous solution is then decanted from the organic residue. The organic residue is taken up in dichloromethane and washed with 10% aqueous citric acid, brine, dried over anhydrous magnesium sulfate, filtered and concentrated. Flash chromatography of the mixture on silica gel eluting with 1:1 hexane:ethyl acetate can be utilized and will afford the separated diaεtereomerε. Example 14C PART A: A εolution of methyl 2- (bromomethyl) -acrylate (26.4 g, 0.148 mol) in 100 mL of methanol waε treated with . sodium methanesulfinate (15.1 g, 0.148 mol) portion wise over 10 m at room temperature. The εolution was then stirred at room temperature for a period of 1.25 h and the solution concentrated in vacuo. The residue was then taken up in water and extracted four times with ethyl acetate. The combined ethyl acetate solution was washed with saturated sodium chloride, dried over anhydrous magnesium sulfate, filtered and concentrated to give a white solid, 20.7 g which was taken up in boiling acetone/methyl tert-butvl ether and allowed to εtand whereupon cryεtalε of pure methyl 2- (methylεulfonylmethyl) acrylate 18.0 g, 68% formed, mp 65-68 0°C. PART B: A εolution of methyl 2- (methylsulfonylmethyl) acrylate (970 mg, 5.44 mmol) in 15 mL of tetrahydrofuran was treated with a εolution of lithium hydroxide (270 mg, 6.4 mmol) in 7 mL of water. The εolution was εtirred at room temperature for 5 m and then acidified to pH=l with 1 N aqueouε potaεεium hydrogen sulfate and the solution extracted three times with ethyl acetate. The combined ethyl acetate solution waε dried over anhydrouε magnesium sulfate, filtered, and concentrated to give 793 mg, 89% of 2- (methylsulfonylmethyl) acrylic acid, mp 147-149 0°C. PART C : A solution of 2- (methylsulfonylmethyl) acrylic acid (700 mg, 4.26 mmol) in 20 mL of methanol was charged into a Fiεher-Porter bottle along with 10% palladium on carbon catalyεt under a nitrogen atmoεphere. The reaction vessel was .sealed and flushed five timeε with nitrogen and then five timeε with hydrogen. The preεεure waε maintained at 50 pεig for 16 h and then the hydrogen waε replaced with nitrogen and the εolution filtered through a pad of celite to remove the catalyεt and the filterate concentrated in vacuo to give 682 mg 96% of 2- (R,S)-methyl-3-methylsulfonyl propionic acid. PART D: A εolution of 2- (R,S) -methyl-3 (methylsulfonyl) propionic acid (263.5 mg, 1.585 mmol), iJ-hydroxybenzptriazole (HOBT) (322.2 mg, 2.13 mmol), and 1- (3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC) (339.1 mg, 1.74 mmol) in 4 mL of anhydrouε dimethylformamide (DMF) iε cooled to 0°C and εtirred under nitrogen for 0.5 h. Thiε εolution iε then treated with a deεired sulfonamide and εtirred at room temperature for 16h. The εolution is poured into 60 mL of 60% saturated aqueous sodium bicarbonate solution. The aqueous solution is then decanted from the organic residue. The organic residue is taken up in dichloromethane and washed with 10% aqueous citric acid, brine, dried over anhydrous magnesium εulfate, filtered and concentrated to give the desired product. Example 14D Preparation of Sulfone Inhibitors From L- (+) -S-acetyl-β- mercaptoisobutyric Acid PART A : A round-bottomed flask is charged with the desired sulfonamide isoεtere (2.575 mmol), for example, the amine from Example 3, Part C, can be coupled to L- (+) -S-acetyl-β-mercapto butyric acid in the preεence of 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride (EDC) (339.1 mg, 1.74 mmol), in 10 mL of CH2CI2 and iε allowed to stir at room temperature for 16 h. The solution is concentrated in vacuo and the residue taken up in ethyl acetate, washed with IN KHSO4 sat. aq. NaHC03 , brine, dried over anhydrous MgS04, filtered and concentrated to give an oil which can be purified by radial chromatography on Siθ2 eluting with ethyl acetate to give the pure product. PART B: A solution of the product of Part A (0.85 mmol) in 10 mL of methanol iε treated with anhydrous ammonia for ca. 1 m at 0°C. The solution is stirred at that temperature for 16 h and then concentrated in vacuo to give the desired product that can be used directly in the next εtep without further purification. PART C: A εolution of the product of Part B (0.841 mmol) in 10 mL of dry toluene under nitrogen iε treated in rapid εucceεεion with 1, 8-diazabicyclo[5.4.0]undec-7- ene, (DBU) , (128.1 mg. 0.841 mmol) and iodomethane (119.0 mg, 0.841 mmol) . After 0.5 h at room temperature the reaction iε diluted with ethyl acetate washed with IN KHSO4, sat. aq. NaHC03, brine. After the solution is dried over anhydrous MgS04, filtered and concentrated in vacuo the desired product is obtained and can be uεed directly in the next εtep. 57 PART D : A solution of the product of Part C (0.73 mmol) and sodium perborate (500 mg, 3.25 mmol) in 30 mL of glacial acetic acid is warmed to 55°C for 16 h. The solution is conentrated in vacuo and then the reεidue iε taken up in ethyl acetate, waεhed with water, εat. aq. NaHC03, brine, dried over anhydrouε MgS04, filtered and concentrated to give the desired product. Repreεentative εulfoneε prepared according to the above general procedures are εhown in Table 3. Table 3 Entry 1 CH3 - 2 PhCH2CH2 - 3 Ph- General Procedure for Coupling Sulfonyl Compounds to Sulfonamides A mixture of the εulfonyl alkanoyl compoun (approximately 1 mmol), N-hydroxybenzotriazole (1.5 mmol), and 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride (EDO (1.2 mmol) is dissolved in a suitable solvent such as DMF and allowed to react for about 30 min. at 0°C. The εulfonamide (1.05 mmol) iε dissolved in DMF, added to the above mixture and stirred at room temperature for a period of time sufficient for the reaction to take place. The solution iε then poured into εaturated aqueous NaHC03 and extracted with, for example, ethyl acetate. The extracts are washed, dried, filtered and concentrated. The resulting material is then crystallized from a suitable solvent or solvent mixture such as hexaneε and ethyl acetate to produce the product. Repreεentative compoundε prepared according to theεe general procedureε are εhown in the following Table. Entry R 1 -CH- 2 -CH 2 CH 3 3 -CH(CH 3 ) 2 4 -C(CH 3 ) 3 Example 15 Utilizing the general and specific procedures shown in Examples 1-14, the compoundε εhown in Tables 4-8 could be prepared. TABLE 4 Entry R- TABLE 4 (Cont'd) Entry R3 R4 15 16 17 18 19 20 21 22 23 24 25 28 TABLE 4 (Cont'd) Entry R3 R4 29 30 31 32 33 34 35 36 37 38 39 40 TABLE 4 (Cont'd) Entry R 3 R 4 49 Phenyl 50 -CH2CH(CH3)2 Ethyl TABLE Entry 10 1 CH2SO2CH3 2 (R)-CH(OH)CH3 3 (R,S)CH2SOCH3 4 CH2S02NH2 5 CH2SCH3 15 6 CH2CH(CH3)2 7 CH2CH2C(0)NH2 (S) -CH(OH)CH3 -CH 2 C=CH TABLE 6 Entry 10 15 20 25 30 TABLE 7 Entry R 3 1 2 TABLE 8 Entry 10 15 20 Example 16 The compoundε of the preεent invention are effective HIV protease inhibitors. Utilizing an enzyme asεay as deεcribed below, the compoundε set forth in the examples herein discloεed inhibited the HIV enzyme. The preferred compoundε of the preεent invention and their calculated IC50 (inhibiting concentration 50%, i.e., the concentration at which the inhibitor compound reduceε enzyme activity by 50%) valueε are εhown in Table 16. The enzyme method iε described below. The substrate is 2-aminobenzoyl-Ile-Nle-Phe(p-N02) -Gln-ArgNH2. The positive control is MVT-101 (Miller, M. et al, Science, 246. 1149 (1989)] The asεay conditionε are aε follows: Asεay buffer: 20 mM εodium phoεphate, pH 6.4 20% glycerol 1 mM EDTA 1 mM DTT 0.1% CHAPS The above described subεtrate iε diεεolved in DMSO, then diluted 10 fold in aεεay buffer. Final substrate concentration in the asεay is 80 μM. HIV protease is diluted in the assay buffer to a final enzyme concentration of 12.3 nanomolar, based on a molecular weight of 10,780. The final concentration of DMSO iε 14% and the final concentration of glycerol iε 18%. The teεt compound iε diεεolved in DMSO and diluted in DMSO to lOx the teεt concentration; lOμl of the enzyme preparation iε added, the materialε mixed and then the mixture is incubated at ambient temperature for 15 minuteε . The enzyme reaction is initiated by the addition of 40μl of εubεtrate. The increaεe in fluorescence is monitored at 4 time points (0, 8, 16 and 24 minutes) at ambient temperature. Each aεεay is carried out in duplicate wells. TABLE 9 Example No. IC50 (nanomolar) 2 3.2 3 ' 3.2 4 3 5 13 6 8.8 7 1.9 8 3.1 9 4.1 10 2.2 11 7.8 12 38 Exam le 17. The effectivenesε of compounds of the present invention were determined in a CEM cell asεay. The HIV inhibition aεεay method of acutely infected cellε is an automated tetrazolium baεed colorimetric aεεay essentially that reported by Pauwles et al, J. Virol. Methods. 2_Q_, 309-321 (1988) . Asεayε were performed in 96-well tiεεue culture plateε . CEM cellε, a CD4+ cell line, were grown in RPMI-1640 medium (Gibco) supplemented with a 10% fetal calf serum and were then treated with polybrene (2μg/ml) . An 80 μl volume of medium containing 1 x 10^ cellε was dispenεed into each well of the tissue culture plate. To each well was added a lOOμl volume of test compound dissolved in tisεue culture medium (or medium without teεt compound as a control) to achieve the deεired final concentration and the cellε were incubated at 37°C for 1 hour. A frozen culture of HIV-1 waε diluted in culture medium to a concentration of 5 x 104 TCID50 per ml (TCID50 = the doεe of viruε that infectε 50% of cellε in tiεεue culture) , and a 20μL volume of the viruε sample (containing 1000 TCID50 of virus) was added to wells containing test compound and to wells containing only medium (infected control cells) . Several wells received culture medium without viruε. (uninfected control cells) . Likewise, the intrinsic toxicity of the test compound waε determined by adding medium without viruε to several wells containing test .compound. In summary, the tisεue culture plateε contained the following experimentε: Cells Drug Virus 1. + 2. + 3. + + 4. + + In experimentε 2 and 4 the final concentrationε of teεt compounds were 1, 10, 100 and 500 μg/ml. Either azidothymidine (AZT) or dideoxyinosine (ddl) waε included as a positive drug control. Teεt compoundε were diεεolved in DMSO and diluted into tiεεue culture medium εo that the final DMSO concentration did not exceed 1.5% in any caεe. DMSO waε added to all control wells at an appropriate concentration. Following the addition of virus, cellε were incubated at 37°C in a humidified, 5% CO2 atmoεphere for 7 dayε. Teεt compoundε could be added on dayε 0, 2 and 5 if desired. On day 7, poεt-infection, the cellε in each well were reεuεpended and a lOOμl εample of each cell suspenεion was removed for asεay. A 20μL volume of a 5 mg/ml εolution of 3- (4, 5-dimethylthiazol-2-yl) -2, 5-diphenyltetrazolium bromide (MTT) waε added to each 100μL cell εuspension, and the cells were incubated for 4 hours at 27°C in a 5% C02 environment. During this incubation, MTT iε metabolically reduced by living cells resulting in the production in the cell of a colored formazan product. To each εample waε added lOOμl of 10% εodium dodecylεulfate in 0.01 N HCl to lyse the cells, and samples- were incubated overnight. The absorbance at 590 nm was determined for each εample uεing a Molecular Deviceε microplate reader. Abεorbance values for each set of wells is compared to asεeεε viral control infection, uninfected control cell reεponεe as well as test compound by cytotoxicity and antiviral efficacy. 1 Utilizing the procedures set forth above in the examples along with the general description, it is contemplated that the compounds listed below could be prepared and that such compounds would have activities aε HIV protease inhibitors subεtantially εimilar to the activitieε of the compoundε εet forth in the exampleε. The compoundε of the present invention are effective antiviral compounds and, in particular, are effective retroviral inhibitors aε εhown above. Thuε, the εubject compounds are effective HIV protease inhibitorε. It iε contemplated that the εubject compoundε will alεo inhibit other retroviruεeε such as other lentiviruses in particular other εtrainε of HIV, e.g. HIV-2, human T-cell leukemia viruε, reεpiratory syncitial viruε, simian immunodeficiency virus, feline leukemia virus, feline immuno-deficiency virus, hepadnaviruε, cytomegaloviruε and picornaviruε. Thuε, the subject compounds are effective in the treatment and/or proplylaxis of retroviral infections. Compounds of the present can posεess one or more asymmetric carbon atoms and are thus capable of existing in the form of optical isomers aε well as in the form of racemic or nonracemic mixtures thereof. The optical iεomerε can be obtained by reεolution of the racemic mixtureε according to conventional proceεεeε, for example by formation of diaεtereoiεomeric εaltε by treatment with an optically active acid or baεe. Exampleε of appropriate acids are tartaric, diacetyltartaric, dibenzoyltartaric, ditoluoyltartaric and camphorsulfonic acid and then separation of the mixture of diastereoisomerε by cryεtallization followed by liberation of the optically active baεeε from theεe εaltε. A different proceεε for εeparation of optical iεomers involves the use of a chiral chromatography column optimally chosen to maximize the separation of the enantiomers. Still another available method involves syntheεis of covalent diastereoiεomeric molecules by reacting compounds of Formula I with an optically pure acid in an activated form or an optically pure iεocyanate. The εynthesized diastereoisomers can be separated by conventional means such as chromatography, distillation, crystallization or sublimation, and then hydrolyzed to deliver the enantiomericaly pure compound. The optically active compounds of Formula I can likewise be obtained by utilizing optically active starting materials. These isomers may be in the form of a free acid, a free base, an ester or a salt. The compounds of the present invention can be used in the form of εaltε derived from inorganic or organic acidε. Theεe εalts include but are not limited to the following: acetate, adipate, alginate, citrate, aspartate, benzoate, benzenesulfonate, biεulfate, butyrate, camphorate, camphorεulfonate, digluconate, cyclopentanepropionate, dodecylεulfate, ethaneεulfonate, glucoheptanoate, glycerophosphate, hemisulfate, heptanoate, hexanoate, fumarate, hydrochloride, hydrobromide, hydroiodide, 2-hydroxy-ethanesulfonate, lactate, maleate, methaneεulfonate, nicotinate, 2-naphthaleneεulfonate, oxalate, palmoate, pectinate, perεulfate, 3-phenylpropionate, picrate, pivalate, propionate, succinate, tartrate, thiocyanate, tosylate, mesylate and undecanoate. Also, the baεic nitrogen- containing groupε can be quaternized with εuch agentε as lower alkyl halides, such as methyl, ethyl, propyl, and butyl chloride, bromideε, and iodideε; dialkyl εulfates like dimethyl, diethyl, dibutyl, and diamyl sulfates, long chain halides εuch aε decyl, lauryl, myristyl and stearyl chlorides, bromides and iodides, aralkyl ha ides like benzyl and phenethyl bromideε, and others. Water or oil-soluble or disperεible productε are thereby obtained. Exampleε of acidε which may be employed to form pharmaceutically acceptable acid addition εalts include εuch inorganic acidε as hydrochloric acid, sulphuric acid and phosphoric acid and εuch organic acidε aε oxalic acid, aleic acid, εuccinic acid and citric acid. Other exampleε include εalts with alkali metals or alkaline earth metalε, εuch aε sodium, potassium, calcium or magnesium or with organic baseε. Total daily doεe adminiεtered to a hoεt in εingle or divided doses may be in amounts, for example, from 0.001 to 10 mg/kg body weight daily and more usually 0.01 to 1 mg. Dosage unit compositions may contain such amounts of submultipleε thereof to make up the daily doεe. The amount of active ingredient that may be combined with the carrier materialε to produce a single dosage form will vary depending upon the host treated and the particular mode of administration. The doεage regimen for treating a diseaεe condition with the compoundε and/or compoεitions of this invention is selected in accordance with a variety of factors, including the type, age, weight, sex, diet and medical condition of the patient, the severity of the disease, the route of administration, pharmacological considerations such as the activity, efficacy, pharmacokinetic and toxicology profiles of the particular compound employed, whether a drug delivery εyεtem iε utilized and whether the compound is administered aε part of a drug combination. Thuε, the doεage regimen actually employed may vary widely and therefore may deviate from the preferred dosage regimen set forth above. The compoundε of the present invention may be administered orally, parenterally, by inhalation spray, rectally, or topically in dosage unit formulationε containing conventional nontoxic pharmaceutically acceptable carrierε, adjuvantε, and vehicleε aε deεired. Topical administration may alεo involve the use of transdermal administration such as transdermal patcheε or iontophoreεis deviceε. The term parenteral aε used herein includes subcutaneous injections, intravenous, intramuscular, intrasternal injection, or infusion techniques. Injectable preparations, for example, sterile injectable aqueous or oleaginous suεpenεionε may be formulated according to the known art uεing εuitable dispersing or wetting agentε and εuεpending agentε. The εterile injectable preparation may alεo be a εterile injectable εolution or suspenεion in a nontoxic parenterally acceptable diluent or εolvent, for example, aε a εolution in 1, 3-butanediol. Among the acceptable vehicleε and εolventε that may be employed are water, Ringer's solution, and iεotonic εodium chloride εolution. In addition, εterile, fixed oilε are conventionally employed aε a εolvent or εuεpending medium. For thiε purpoεe any bland fixed oil may be employed including synthetic mono- or diglycerides. In addition, fatty acidε εuch aε . oleic acid find use in the preparation of injectables. Suppositorieε for rectal ad iniεtration of the drug can be prepared by mixing the drug with a suitable nonirritating excipient εuch aε cocoa butter and polyethylene glycolε 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 capsuleε, tabletε, pills, powders, and granuleε. In εuch εolid dosage forms, the active compound may be admixed with at leaεt one inert diluent εuch aε εucroεe lactoεe or starch. Such dosage forms may also comprise, aε in normal practice, additional εubεtances other than inert diluentε, e.g., lubricating agentε εuch aε magneεium εtearate. In the caεe of capεuleε, tablets, and pills, the dosage forms may also comprise buffering agents. Tablets and pills can additionally be prepared with enteric coatings . Liquid dosage formε for oral adminiεtration may include pharmaceutically acceptable emulεionε, solutions, suspenεionε, syrups, and elixirs containing inert diluents commonly used in the art, εuch as water. Such compositions may also comprise adjuvants, such aε wetting agentε, emulεifying and suεpending agents, and sweetening, flavoring, and perfuming agents. While the compoundε of the invention can be adminiεtered aε the sole active pharmaceutical agent, they can also be used in combination with one or more immunomodulators, antiviral agentε or other antiinfective agentε. For example, the compoundε of the invention can be adminiεtered in combination with AZT, DDI, DDC or with N-butyl-1-deoxynojirimycin for the prophylaxis and/or treatment of AIDS. 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 diεcloεed compounds. Variations and changeε which are obviouε to one εkilled in the art are intended to be within the scope and nature of the invention which are defined in the appended claims . From the foregoing description, one skilled in the art can easily ascertain the esεential characteristics of this invention, and without departing from the spirit and scope thereof, can make various changes and modifications of the invention to adapt it to various usages and conditions.

Claims: WHAT IS CLAIMED IS ; 1. A compound represented by the formula: or a pharmaceutically acceptable εalt, prodrug or eεter thereof wherein: R repreεentε hydrogen, alkyl, alkenyl, alkynyl, hydroxyalkyl, alkoxyalkyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, heteroaryl, heterocycloalkylalkyl, aryl, aralkyl, heteroaralkyl, aminocarbonylalkyl, aminoalkylcarbonylalkyl, aminoalkyl, alkylcarbonylalkyl, aryloxyalkylcarbonylalkyl, aralkoxycarbonylalkyl radicals and mono- and disubstituted aminocarbonylalkyl, aminoalkylcarbonylalkyl and aminoalkyl radicals wherein said substituentε are selected from alkyl, aryl, aralkyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroaralkyl, heterocycloalkyl, and heterocycloalkylalkyl radicals, or in the case of a diεubεtituted radical, εaid εubεtituentε along with the nitrogen atom to which they are attached, form a heterocycloalkyl or a heteroaryl radical; each x independently represents 0, 1 or 2; t representε either 0 or 1; Rl, R20 nd R21 independently represent hydrogen, -CH2SO2NH2, -CH2CO2CH3, -CO2CH3, -CONH2, -CH2C(0)NHCH3, -C(CH3)2(SH) , -C(CH3)2(SCH3) , -C (CH3 ) 2 (S [0]CH3 ) , -C (CH3)2 (S[0]2CH3) , alkyl, haloalkyl, alkenyl, alkynyl and cycloalkyl radicals, and amino acid side chains εelected from asparagine, S-methyl cyεteine and the εulfoxide (SO) and εulfone (S02) derivativeε thereof, iεoleucine, allo-iεoleucine, alanine, leucine, tert-leucine, phenylalanine, ornithine, hiεtidine, norleucine, glutamine, threonine, glycine, allo-threonine, εerine, O-alkyl εerine, aspartic acid, beta-cyano alanine and valine side chains; R2 representε alkyl, aryl, cycloalkyl, cycloalkylalkyl and aralkyl radicalε, which radicalε are optionally substituted with a group selected from -NO2, "C =N, C F 3 -OR9'. -SR9, and halogen and alkylradicals, wherein R9 repreεentε hydrogen and alkyl radicals; R3 repreεents hydrogen, alkyl, haloalkyl, alkenyl, alkynyl, hydroxyalkyl, alkoxyalkyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, heteroaryl, heterocycloalkylalkyl, aryl, aralkyl, heteroaralkyl, aminoalkyl and mono- and diεubεtituted aminoalkyl radicals, wherein εaid εubstituents are selected from alkyl, aryl, aralkyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroaralkyl, heterocycloalkyl, and heterocycloalkylalkyl radicals, or in the case of a disubstituted aminoalkyl radical, said subεtituents along with the nitrogen atom to which they are attached, form a heterocycloalkyl or a heteroaryl radical; Y represents 0,S and R15 wherein Rl5 representε hydrogen and radicalε aε defined for R3; R4 repreεents radicalε as defined by R3 except for hydrogen' an d R6 represents hydrogen and alkyl radicals. 2. Compound represented by the formula: or a pharmaceutically acceptable salt, prodrug or ester thereof, wherein; R represents alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, heterocycloalkylalkyl, aryl,. heteroaryl, aralkyl, heteroalkyl, aminocarbonylalkyl, aminoalkylcarbonylalkyl, hydroxyalkyl, heteroaralkyl, alkylcarbonylalkyl, aryloxyalkylcarbonylalkyl and aralkoxycarbonylalkyl radicals; Rl, R20 and R^ 1 independently represent hydrogen, -CH2SO2NH2, -CH2C02CH3, -CO2CH3, -CONH2, -CH2C (0)NHCH3, -C(CH3)2(SCH3) , -C (CH3) 2 (S [O]CH3) , -C (CH3) 2 (S [0]2CH3) , alkyl, haloalkyl, alkenyl, alkynyl and cycloalkyl radicalε, and amino acid εide chains selected from asparagine, S-methyl cyεteine and the sulfoxide (SO) and sulfone (SO2) derivativeε thereof, iεoleucine, allo-iεoleucine, alanine, leucine, tert-leucine, phenylalanine, ornithine, hiεtidine, norleucine, glutamine, threonine, glycine, allo-threonine, εerine, 0-alkyl serine, aεpartic acid, beta-cyano alanine and valine εide chainε; R repreεentε alkyl, aryl, cycloalkyl, cycloalkylalkyl, and aralkyl radicals, which radicals are optionally subεtituted with a group εelected from halogen and alkyl radicals, NO2, "C≡N ' CF 3 , - 0 R9 and -SR9 wherein R9 represents hydrogen and alkyl radicalε, and halogen radicalε; R3 represents hydrogen, alkyl, haloalkyl, alkenyl, alkynyl, hydroxyalkyl, alkoxyalkyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, heteroaryl, heterocycloalkylalkyl, aryl, aralkyl, heteroaralkyl, aminoalkyl and mono- and disubεtituted aminoalkyl radicalε, wherein εaid εubstituents are selected from alkyl, aryl, aralkyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroaralkyl, heterocycloalkyl, and heterocycloalkylalkyl radicalε, or in the case of a disubstituted aminoalkyl radical, said subεtituentε along with the nitrogen atom to which they are attached, form a heterocycloalkyl or a heteroaryl radical; R 4 represents radicals as defined by R3 except for hydrogen; t representε 0 or 1; and Y represents 0, S, and NRl5 wherein Rl5 represents hydrogen and radicals as defined for R3. 3. Compound of Claim 2 wherein R representε alkyl, aryl and aralkyl radicalε. 4. Compound of Claim 2 wherein R repreεents methyl and phenethyl radicals. 5. Compound of Claim 2 wherein R represents methyl. Compound of Claim 2 wherein R represents phenethyl 7. Compound of Claim 2 wherein Rl repreεents hydrogen, alkyl, alkenyl and alkynyl radicals. 8. Compound of Claim 2 wherein Rl represents methyl, ethyl, propargyl, t-butyl, isopropyl and sec- butyl radicals. 9. Compound of Claim 2 wherein Rl representε methyl, ethyl and t-butyl radicals. 10. Compound of Claim 2 wherein Rl represents a methyl radical when t is 0. 11. Compound of Claim 2 wherein Rl repreεents an ethyl radical when t is 0. 12. Compound of Claim 2 wherein Rl represents alkyl radicals having from 1 to about 4 carbon atoms. 13.. Compound of Claim 2 wherein R and Rl both represent a methyl radical. 14. Compound of Claim 2 wherein R represents a methyl radical and R! representε an ethyl radical. 15. Compound of Claim 2 wherein R representε a methyl radical, Rl repreεents a methyl radical and t is 0. 16. Compound of Claim 2 wherein t is 0. 17. Compound of Claim 2 wherein t is 1. 18. Compound of Claim 2 wherein R2 representε alkyl, cycloalkylalkyl and aralkyl radicalε, which radicalε are optionally εubεtituted with halogen radicalε and radicals represented by the formula -0R9 and -SR9 wherein R9 represents alkyl radicals. 19. Compound of Claim 2 wherein R2 representε alkyl, cycloalkylalkyl and aralkyl radicals. 20. Compound of Claim 2 wherein R represents aralkyl radicals. 21. Compound of Claim 2 wherein R representε CH3SCH2CH2-, iso-butyl, n-butyl, benzyl, 4-fluorobenzyl, 2-naphthylmethyl and cyclohexylmethyl radicalε. 22. Compound of Claim 2 wherein R2 repreεentε an n-butyl and iεo-butyl radicalε. 23. Compound of Claim 2 wherein R2 repreεentε benzyl, 4-fluorobenzyl and 2-naphthylmethyl radicalε. 24. Compound of Claim 2 wherein R2 repreεentε a cyclohexylmethyl radical. 25. Compound of Claim 2 wherein R3 and R4 independently.represent alkyl, alkenyl, hydroxyalkyl, alkoxyalkyl, haloalkyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, heteroaryl, heterocycloalkylalkyl, aryl, aralkyl and heteroaralkyl radicals. 26. Compound of Claim 25 wherein R3 representε an alkyl radical and R 4 repreεents an aryl radical. 27. Compound of Claim 25 wherein R3 and R4 independently represent alkyl and aryl radical . 28. Compound of Claim 25 wherein R3 and R- independently repreεent alkyl, cycloalkyl, cycloalkylalkyl, aralkyl and aryl radicalε. 29. Compound of Claim 25 wherein R and R independently represent alkyl, cycloalkyl and cycloalkylalkyl radicalε. 30. Compound of Claim 25 wherein R3 and R4 independently represent alkyl, heterocycloalkyl and heterocycloalkylalkyl radicalε. 31. Compound of Claim 25 wherein R and R 4 independently repreεent alkyl, aryl and aralkyl radicalε. 32. Compound of Claim 25 wherein R 4 repreεentε phenyl, p-fluorophenyl, p-nitrophenyl, p-methoxyphenyl, p-chlorophenyl and p-aminophenyl radicalε. 33. Compound of Claim 2 wherein R3 represents alkyl radicals having from about 2 to about 5 carbon atoms. 34. Compound of Claim 2 wherein R representε n-pentyl, n-hexyl, n-propyl, i-butyl, neo-pentyl, i-amyl, and n-butyl radicalε. 35. Compound of Claim 2 wherein R3 repreεents alkyl radicals having from about 2 to about 5 carbon atoms, and cycloalkyl and cycloalkylalkyl radicals having from about 6 to about 10 carbon atoms; and R4 representε aryl and heteroaryl radicalε which may be εubεtituted with εubεtituentε εelected from chloro, fluoro, nitro, methoxy and amino εubεtituents. 36. Compound of Claim 2 wherein R3 repreεents benzyl, para-fluorobenzyl, para-methoxybenzyl, para- methylbenzyl, and 2-naphthylmethyl radicals and R4 represents phenyl radicals and subεtituted phenyl radicalε, wherein εubεtituents of the substituted phenyl radical are selected from chloro, fluoro, nitro, methoxy and amino subεtituentε. 37. Compound of Claim 2 wherein R3 is cyclohexylmethyl and R IS phenyl. 38. Compound of Claim 2 wherein R3 is i-amyl and R 4 iε phenyl. 39. Compound of Claim 2 wherein R3 iε i-butyl and R - iε phenyl. 40. Compound of Claim 2 wherein R3 iε n-butyl and R4 is phenyl. 41. Compound of Claim 2 wherein R3 is neo¬ pentyl and R4 is phenyl. 42. Compound of Claim 2 wherein R4 represents aryl radicals. 43. Compound of Claim 2 wherein R- represents substituted aryl and heteroaryl radicals wherein substituents are selected form halo, nitro, alkoxy, and amino radicals. 44. Compound of Claim 2 wherein R3 and R- independently represent alkyl, cycloalkyl, cycloalkylalkyl, aryl and aralkyl radicals. 45. Compound of Claim 2 wherein R3 representε heteroaralkyl radicals and R 4 iε an aryl radical. 46. Compound of Claim 2 wherein R3 iε a p-fluorobenzyl radical and R - iε an aryl radical. 47. Compound of Claim 2 wherein R3 iε a 4-pyridylmethyl radical or itε N-oxide and R - iε an aryl radical. 48. Compound of Claim 2 wherein R repreεents methyl and cyclohexyl radicalε and R represents an alkyl radical. 49. Compound of Claim 2 wherein R3 and R - independently represent aryl radicals optionally εubstituted with εubεtituentε selected from amino, alkoxy, halo, and nitro substituents. 50. Compound of Claim 2 wherein R20 and R21 are both hydrogen and Rl representε an alkyl radical having from 1 to about 4 carbon atomε. 51. Compound of Claim 2 wherein R20 and R21 are both hydrogen and R repreεentε -CH2SO2NH2, CO2NH2, CO2CH3, alkyl and cycloalkyl radicalε and amino acid εide chainε εelected from asparagine, S-methyl cysteine and the εulfone and εulfoxide derivatives thereof, histidine, norleucine, glutamine, glycine, allo-isoleucine, alanine, threonine, isoleucine, leucine, tert-leucine, phenylalanine, ornithine, allo-threonine, serine, O-methyl serine, aspartic acid, beta-cyano alanine and valine side chains. 52. Compound of Claim 2 wherein t is 0, Rl represents an alkyl radical and R represents an alkyl, cycloalkyl, cycloalkylalkyl or an aryl radical. 53. Compound of Claim 2 wherein R representε a heteroaryl radical. 54. Compound of Claim 2 wherein R repreεents an alkyl or aryl radical. 55. Compound of Claim 2 wherein t is 0, Rl repreεentε a methyl or ethyl radical and R repreεentε a methyl or phenethyl radical. 56. Compound of Claim 2 wherein R repreεentε an aralkylcarbonylalkyl, aryloxycarbonylalkyl, alkanoylalkyl, aminocarbonylalkyl, or a mono- or dialkylaminocarbonylalkyl radical. 57. Compound of Claim 2 wherein R represents an aryloxycarbonylalkyl or alkanoylalkyl radical. 58. Compound of Claim 2 wherein R represents an aminocarbonylalkyl radical, a monosubstituted aminoalkanoylalkyl radical or disubstituted aminoalkanoylalkyl radical. 59. Compound of Claim 2 where R representε an aralkylcarbonylalkyl radical. 60. Compound of Claim 2 where t iε 1 and Rl iε a methyl radical. 61. Compound of Claim 60 where R repreεentε an alkyl, cycloalkyl, cycloalkylalkyl, aryl or aralkyl radical. 62. Compound of Claim 60 where R represents a methyl, cyclohexyl, cyclohexylmethyl, phenyl, benzyl or phenethyl radical. 63. Compound of Claim 2 wherein t is 1, R20 and R21 are both hydrogen and Rl is methyl or ethyl. 64. Compound of Claim 60 wherein R represents an aminocarbonylalkyl or a mono- or dialkylaminocarbonylalkyl radical. 65. Compound of Claim 60 where R represents an N,N-dimethylaminocarbonylalkyl radical. 66. A pharmaceutical composition comprising a compound of Claim 1 and a pharmaceutically acceptable carrier. 67. A pharmaceutical composition comprising a compound of Claim 2 and a pharmaceutically acceptable carrier. 68. Method of inhibiting a retroviral protease comprising administering a protease inhibiting amount of a composition of Claim 66. 69. Method of Claim 68 wherein the retroviral proteaεe iε HIV proteaεe. 70. Method of treating a retroviral infection compriεing adminiεtering an effective amount of a composition of Claim 66. 71. Method of Claim 70 wherein the retroviral infection is an HIV infection. 72. Method for treating AIDS compriεing adminiεtering an effective amount of a compoεition of Claim 66. 73. Method of inhibiting a retroviral proteaεe compriεing adminiεtering a proteaεe inhibiting amount of a compoεition of Claim 67. 74. Method of Claim 73 wherein the retroviral proteaεe iε HIV proteaεe. 75. Method of treating a retroviral infection compriεing adminiεtering an effective amount of a compoεition of Claim 67. 76. Method of Claim 75 wherein the retroviral infection iε an HIV infection. 77. Method for treating AIDS comprising administering an effective amount of a composition of Claim 67. 78. Compound repreεented by the formula: or a pharmaceutically acceptable salt, prodrug or ester thereof, preferably wherein the stereochemiεtry about the hydroxy group iε deεignated aε (R) ; R repreεentε alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, heterocycloalkylalkyl, aryl, heteroaryl, aralkyl, heteroaralkyl, aminocarbonylalkyl, aminoalkylcarbonylalkyl, hydroxyalkyl, alkoxyalkyl, alkylcarbonylalkyl, aryloxyalkylcarbonylalkyl and aralkoxycarbonylalkyl radicalε; Rl represents hydrogen, -CH2SO2NH2, -CH2CO2CH3, -CO2CH3 , -CONH2, -CH2C(0)NHCH3, -C (CH3) 2 (SCH3) , -C (CH3 ) 2 (S[0]CH3) , -C(CH 3 ) 2 (SH) , -C(CH3)2(S[0]2CH3) , alkyl, haloalkyl, alkenyl, alkynyl and cycloalkyl radicals, and amino acid side chains selected from asparagine, S-methyl cyεteine and the εulfoxide (SO) and εulfone (SO2) derivativeε thereof, isoleucine, _ allo-isoleucine, alanine, leucine, tert-leucine, phenylalanine, orni hine, hiεtidine, norleucine, glutamine, threonine, glycine, allo-threonine, εerine, O-methyl serine, aεpartic acid, beta-cyano alanine and valine εide chainε; R2 repreεentε alkyl, aryl, cycloalkyl, cycloalkylalkyl, and aralkyl radicals, which radicalε are optionally εubεtituted with a group εeiected from halogen and alkyl radicals, NO2, ~C=N ' CF3, QR9 and SR9 wherein R9 represents hydrogen and alkyl radicals; R3 represents hydrogen, alkyl, halolkyl, alkenyl, alkynyl, hydroxyalkyl, alkoxyalkyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, heteroaryl, heterocycloalkylalkyl, aryl, aralkyl, heteroaralkyl, aminoalkyl and mono- and disubstituted aminoalkyl radicals, wherein said εubεtituentε are εelected from alkyl, aryl, aralkyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroaralkyl, heterocycloalkyl, and heterocycloalkylalkyl radicalε, or in the case of a disubεtituted aminoalkyl radical, said εubεtituentε along with the nitrogen atom to which they are attached, form a heterocycloalkyl or a heteroaryl radical; and R4 repreεents radicals as defined by R except for hydrogen. 79. Compound of Claim 78 wherein R represents alkyl, alkenyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, heterocycloalkylalkyl, aryl, heteroaryl, aralkyl, heteroaralkyl, aminocarbonylalkyl, aminoalkylcarbonylalkyl, alkylcarbonylalkyl, aryloxyalkylcarbonylalkyl and aralkoxycarbonylalkyl radicals. 80. Compound of Claim 78 wherein Rl represents hydrogen, alkyl and alkenyl and alkynyl radicals. 81. Compound of Claim 78 wherein Rl representε alkyl radicals having from 1 to about 4 carbon atomε, alkenyl radicals having from 2 to 8 carbon atoms, and alkynyl radicals having from 2 to about 8 carbon atoms. 82. Compound of Claim 78 wherein Rl representε methyl, ethyl, iεopropyl, t-butyl and propargyl radicalε. 83. Compound of Claim 78 wherein R! represents methyl, ethyl and t-butyl radicals. 84. Compound of Claim 78 wherein R! representε methyl and ethyl radicalε. 85. Compound of Claim 78 wherein R! represents a methyl radical. 86. Compound of Claim 78 wherein R representε alkyl, cycloalkl, cycloalkylalkyl, aryl and aralkyl radicalε. 87. Compound of Claim 78 wherein R iε εelected from alkyl and aralkyl radicalε. 88. Compound of Claim 78 wherein R2 representε alkyl, cycloalkylalkyl and aralkyl radicalε, which radicalε are optionally εubεtituted with halogen radicalε and radicalε represented by the formula -OR9 and -SR9 wherein R9 repreεents alkyl radicals. 89. Compound of Claim 78 wherein R represents alkyl, cycloalkylalkyl and aralkyl radicals. 90. Compound of Claim 78 wherein R2 represents aralkyl radicals. 91. Compound of Claim 78 wherein R2 represents CH3SCH2CH2-, iso-butyl, n-butyl, benzyl, 4-fluorobenzyl, 2-naphthylmethyl and cyclohexylmethyl radicalε. 92. Compound of Claim 78 wherein R2 represents an n-butyl and iso-butyl radicals. 93. Compound of Claim 78 wherein R2 represents benzyl, 4-fluorobenzyl, and 2-naphthylmethyl radicals. 94. Compound of Claim 78 wherein R representε a cyclohexylmethyl radical. 95. Compound of Claim 78 wherein R3 and R 4 independently represent alkyl, haloalkyl, alkenyl, hydroxyalkyl, alkoxyalkyl cycloalkyl, cycloalkylalkyl, heterocycloalkyl, heterocycloalkylalkyl, aryl, aralkyl, heteroaryl and heteroaralkyl radicalε. 96. Compound of Claim 95 wherein R3 and R4 independently repreεent alkyl, aralkyl, cycloalkyl, cycloalkylalkyl and aryl radicalε. 97. Compound of Claim 95 wherein R3 and R 4 independently repreεent alkyl and aryl radicalε. 98. ' Compound of Claim 95 wherein R and R- independently represent alkyl and alkoxyalkyl radicals. 99. Compound of Claim 95 wherein R3 and R4 independently represent alkyl, cycloalkyl and cycloalkylalkyl radicals. 100. Compound of Claim 95 wherein R3 and R - independently represent alkyl, heterocycloalkyl and heterocycloalkylalkyl radicalε. 101. Compound of Claim 95 wherein R3 and R 4 independently repreεent alkyl, aryl and aralkyl radicalε. 102. Compound of Claim 95 wherein R3 and R 4 independently repreεent alkyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, heterocycloalkylalkyl, aryl, aralkyl, heteroaryl and heteroaralkyl radicals. 103. Compound of Claim 78 wherein R repreεentε alkyl radicalε having from about 2 to about 5 carbon atomε. 104. Compound of Claim 96 wherein R - repreεentε methyl, ethyl, i-propyl, t-butyl and 1,1-dimethylpropyl radicalε. 105. Compound of• Claim 78 wherein R3 and R4 independently represent alkyl radicalε having from about 2 to about 5 carbon atomε, cycloalkylalkyl radicals, aralkyl radicals, heterocycloalkylalkyl radicalε and heteroaralkyl radicalε. 106. Compound of Claim 78 wherein R3 represents benzyl, para-fluorobenzyl, para-methoxybenzyl, para-methylbenzyl, and 2-naphthylmethyl radicalε and R - represents phenyl. 107. Compound of Claim 78 wherein R3 iε cyclohexylmethyl or cyclohexyl and R - iε phenyl. 108. Compound of Claim 78 wherein R3 is i-amyl and R is phenyl. 109. Compound of Claim 78 wherein R3 is i-butyl and R4 iε phenyl. 110. Compound of Claim 78 wherein R3 is n-butyl and R 4 iε phenyl. 111. Compound of Claim 78 wherein R3 is neo-pentyl and R4 is phenyl. 112. Compound of Claim 78 wherein R4 represents aryl radicalε which are εubεtituted with εubεtituentε εelected from alkoxy, alkyl, carboalkoxy, carboxy, amino, halo, and nitro εubεtituentε. 113. Compound of Claim 78 wherein R 4 repreεentε aryl radicals which are subεtituted with εubεtituents selected from amino, acetamido, chloro, fluoro, methoxy and nitro. 114. Compound of Claim 113 wherein the R4 aryl substituentε are in the para-poεition. 115. Compound of Claim 78 wherein R3 repreεentε heteroaralkyl radicals and R 4 iε a phenyl radical. 116. Compound of Claim 78 wherein R3 is a p-fluorobenzyl radical and R4 is a phenyl radical. 117. A pharmaceutical composition comprising a compound of Claim 78 and a pharmaceutically acceptable carrier. 118. Method of inhibiting a retroviral protease comprising adminiεtering a protease inhibiting amount of a composition of Claim 117. 119. Method of Claim 118 wherein the retroviral protease is HIV protease. 120. Method of treating a retroviral infection comprising administering an effective amount of a compoεition of Claim 117. 121. Method of Claim 120 wherein the retroviral infection iε an HIV infection. 122. Method for treating AIDS compriεing adminiεtering an effective amount of a composition of Claim 117. 123. A compound of Claim 1 which is: Propanamide, N- [2-hydroxy-3- [ (2- methylpropyl) (phenylsulfonyl)amino] -1- (phenylmethyl)propyl] -2-methyl-3- (methylεulfonyl) -, [1S- [1R*(R*),2S*]]-; Propanamide, N- [2-hydroxy-3- [ (3- methylbutyl) (phenylεulfonyl.)amino] -1- (phenylmethyl)propyl] -2-methyl-3- (methylεulfonyl) -, [1S- [1R*(R*) ,2S*]]-; Propanamide, N- [2-hydroxy-3- [ (propyl) (phenylεulfonyl)amino] -1- (phenylmethyl)propyl] - 2-methyl-3- (methylsulfonyl)-, [IS- [IR* (R*) ,2S*] ] -; Propanamide, N- [2-hydroxy-3- [ (butyl) (phenylsulfonyl)amino] -1- (phenylmethyl)propyl] -2- methy1-3-(methylsulfonyl)-, [1S-[1R*{R*) ,2S*] ]-; Propanamide, N- [2-hydroxy-3- [ (2-methylpropyl) (4-methoxyphenylsulfonyl)amino] -1- (phenylmethyl)propyl] - 2-methyl-3- (methylεulfonyl)-, [1S-[1R*(R*) ,2S*] ]-; Propanamide, N- [2-hydroxy-3-[ (butyl) (4-methoxyphenylεulfonyl)amino] -1- (phenylmethyl)propyl] - 2-methyl-3- (methylsulfonyl)-, [1S-[1R*(R*) ,2S*] ]-; Propanamide, N- [2-hydroxy-3- [ (propyl) (4-methoxyphenylεulfonyl)amino] -1- (phenylmethyl)propyl] - 2-methyl-3-(methylεuϊfonyl)-, [1S-[1R*(R*) ,2S*] ]-; Propanamide, N- [2-hydroxy-3- [ (2-methylpropyl) (4-acetamido)phenylεulfonyl)amino] -1- (phenylmethyl)propyl] -2-methyl-3- (methylsulfonyl) -, [1S- [1R*(R*),2S*]]-; Propanamide, N- [2-hydroxy-3- [ (3-methylbutyl) (4-amino)phenylsulfonyl)amino] -1- (phenylmethyl)propyl] -2- methy1-3-(methylsulfonyl)-, [1S-[1R*(R*) ,2S*] ]-; Propanamide, N- [2-hydroxy-3- [ (2-methylpropyl) (3 , 4-dimethoxy)phenylsulfonyl)amino] -1- (phenylmethyl)propyl] -2-methyl-3- (methylεulfonyl) -, [1S- [1R*(R*) ,2S*]]- ; or Preparation of Propanamide, . N- [2-hydroxy-3-[ (3- methylbutyl) (4-methoxyphenylεulfonyl)amino] -1- (phenylmethyl)propyl] -2-methyl-3- (methylεulfonyl) - [1S- [1R R*) ,2S*]]-.

Inventors: DECRESCENZO GARY A, FRESKOS JOHN N, GETMAN DANIEL, MUELLER RICHARD A, TALLEY JOHN J, VAZQUEZ MICHAEL L, DECRESCENZO, GARY, A., FRESKOS, JOHN, N., GETMAN, DANIEL, MUELLER, RICHARD, A., TALLEY, JOHN, J., VAZQUEZ, MICHAEL, L.
Applicants: DECRESCENZO GARY A, FRESKOS JOHN N, GETMAN DANIEL, MONSANTO CO, MUELLER RICHARD A, SEARLE & CO, TALLEY JOHN J, VAZQUEZ MICHAEL L, G.D. SEARLE & CO., THE MONSANTO COMPANY
Application year: 1993
Main classification: C07C317
IPC codes: A61K31, A61P31, C07C311, C07C317, C07C327, C07D307, C07D319