N-[N'-(5-AMINO-4-HYDROXY-ACYLOYL)- alpha -AMINOACYLOYL] SUBSTITUTED HETEROCYCLES AND THEIR USE AS ANTIVIRAL AGENTS

Abstract: Compounds of formula (I) wherein R<1> is C1-C6 alkyl, C3-C8 cycloalkyl, aryl, heterocyclyl, or R<7>R<8>NCO; R<2> is C1-C6 alkyl, C3-C8 cycloalkyl(C1-C4)alkyl, aryl(C1-C4)alkyl, or heterocyclyl(C1-C4)alkyl; R<3> is C1-C6 alkyl, C3-C8 cycloalkyl, C3-C8 cycloalkyl(C1-C4)alkyl, aryl(C1-C4)alkyl, aryl(C2-C4)alkenyl, heterocyclyl(C1-C4)alkyl or heterocyclyl(C2-C4)alkenyl; R<4> is C1-C6 alkyl, C3-C8 cycloalkyl, aryl or heterocyclyl; R<5> and R<6> are each independently H, C1-C6 alkyl, C3-C7 cycloalkyl, or C1-C6 alkyl substituted by C1-C4 alkoxy, hydroxy or NR<7>R<8>; or R<5> and R<6> are linked to form, together with the nitrogen atom to which they are attached, a pyrrolidine, piperidine, morpholine, piperazine or N-(C1-C4 alkyl) piperazine group; each of R<7> and R<8> is independently H, C1-C6 alkyl or C3-C8 cycloalkyl or R<7> and R<8> may be joined together to form, with the nitrogen to which they are attached, a 4 to 8 membered nitrogen-containing heterocyclic group; each of R<9>, R<10>, R<11> and R<12> is independently H, C1-C6 alkyl or C3-C8 cycloalkyl; or R<9> and R<10>, or R<11> and R<12> may be joined together to form a 3 to 8 membered carbocyclic ring; X is a 4-10 membered mono- or bicyclic heterocyclic group containing carbon ring atoms and one ring nitrogen atom through which the group is attached to the adjacent carbonyl group; the group may be saturated or partially unsaturated and, in addition to the -(CR<11>R<12>)m -NR<5>R<6> substituent, it may be substituted by up to 4 further substituents each independently chosen from F, C1-C6 alkyl, C3-C8 cycloalkyl, OH, C1-C6 alkoxy or NR<7>R<8>; and n and m are each independently 0, 1 or 2; and wherein any alkyl or cycloalkyl group included in the aforementioned definitions may optionally be fully or partially substituted by fluorine; are inhibitors of retroviral proteases of utility in the treatment and prophylaxis of human retroviral infections.

Description: N-ΓN ' - ( 5-AMINO-4-HYDROXY-ACYLOYI 6( -AMINOACYLOYL] SUBSTITUTED HETEROCYCLES AND THEIR USE AS ANTIVIRAL AGENTS The present invention relates to certain peptide derivatives ∞nta-i-ning a heterocyclic group which are useful in the treatment or prophylaxis of human retroviral infections. The human i-mmunodeficiency virus (HIV) , a retrovirus, is the causative agent of a variety of clinical conditions, the most serious of which are ∞mmonly termed AIDS (Acquired Immunodeficiency Syndrome) , and ARC (AIDS-Related Complex) . Infection with HIV is characterised by progressive breakdown of the immune system and CNS dysfunction. Severely i-mmune deficient patients suffer from a wide range of opportunistic infections (e.g. pneuroocvstis carinii, human cyteimegalovirus, or Candida) , and cancers such as Kaposi's sarcoma. Loss of cells, particularly + . . . . . . CD4 lymphocytes, following infection with HIV is an l-nportant factor in the progressive impairment of -ϋπmune function. The infection of cells of raorκx-yte/macrophage lineage with HTV also contributes to the observed pathology. Unas, successful infection of CD4 cells by HIV is a key step in the disease process. HIV is a retrovirus; it encodes its genetic information in RNA, which is converted into DNA after the virus enters the host cell. An essential step in the retroviral replication cycle is the processing of an initial polypeptide precursor into mature structural and replicative proteins. This processing is carried out by a virus-coded protease and, in the absence of this enzyme activity, viral replication is blocked. We have discovered that certain peptide derivatives linked to a heterocyclic group are potent inhibitors of retroviral proteases, both in a cell-free assay and in infected cells and, in addition, show antiviral activity in tissue culture assays. This activity renders such ∞mpounds useful for the treatment and prophylaxis of retroviral infections, in particular, those caused by HIV. Thus, the invention provides cxfmpσunds of the formula :- (I) and pha-t-maceutically acceptable salts thereof and bicprecursors therefor, wherein R is C,-C 8 alkyl C_-C cycloalkyl, aryl, heterocyclyl or R 7 R 8 NCO; R 2 i .s C.-Cg alkyl, C.-Cg cycloalkyl (C.-C.) alkyl, aryl (C,^.) alkyl, or heterocyclyl (C-.-C.) alkyl; R is C,-C alkyl, C -C cycloalkyl, C -C cycloalkyl (C--C ) alkyl, aryl(C,-C,) alkyl, > aryl(C -C )- alkenyl, heterocyclyl (C,-C ) alkyl or heterocyclyl- (C 2 -C 4 )alkenyl; R is C,-C- alkyl, C_-C cycloalkyl, aryl or heterocyclyl; R 5 and R6 are each independently H, C,-C alkyl, C_-C_ cycloalkyl, or C,-C β alkyl substituted by C,-C, alkoxy, 78 5 6 1 4 hydroxy or NR R ; or R and R are linked to form, together with the nitrogen atom to which they are attached, a pyrrolidine, piperidine, morpholine, piperazine or N-(C,-C alkyl)piperazine group; 7 8 each of R and R is independently H, C,-C-- alkyl or C -C cycloalkyl or R 7 and R8 may be joined together to form, with the nitrogen to which they are attached, a 4 to 8 membered nitαx>gen-c»ntaining heterocyclic group; 9 10 11 12 . . each of R , R , R and 7. is independently H, C,-C Q Tf) π ip alkyl or C 3 -C 8 cycloal -,I or R and R , or R and R may be joined together co "orm a 3 to 8 membered carbocyclic ring; X is a 4-10 membered mono- or bicyclic heterocyclic group ∞ntaining carbon ring atoms and one ring nitrogen atom through which the group is attached to the adjacent carbonyl group; the group may be saturated or partially unsaturated and, in addition to the -(CR " TR ) -NR R 'm substituent, it may be substituted by up to 4 further substituents each independently chosen from F, C,-c, 78 alkyl, C -C cycloalkyl, OH, C,-C alkoxy or NR R ; and n and m are each independently 0, 1 or 2; and wherein any alkyl or cycloalkyl group included in the aforementioned definitions may optionally be fully or partially substituted by fluorine. In the above defi .ni.ti.on of R1, R2, R3 and R4, heterocyclyl means a 4 to 6 membered heterocyclic group containing as heteroatoms up to four nitrogen atoms, or an oxygen or sulphur atom optionally with one or two nitrogen atoms. The ring may be aromatic, or fully or partially saturated and may optionally be benzo-fused or substituted by C,-C-- alkyl, C-.-C-, cycloalkyl, C„-C.. I D -Ϊ O 2. > alkanoyl, C,-C alkoxy, halo, hydroxy, oxo or aryl. Preferred heterocyclyl groups are pyridyl, pyrimidinyl, thienyl, isoquinolyl and tetrazolyl. In the above defi .ni.ti.ons of R1, R2, R3 and R4, aryl means phenyl optionally substituted with from 1 to 3 substituents each independently selected from C,-C 6 alkyl, C -C 8 cycloalkyl, C,-C. alkoxy, C -C alkanoyl, hydroxy, halo, C,-C. alkyl fully or partially substituted by fluorine, C,-C. alkoxy fully or partially substituted by fluorine, phenyl, phenoxy, benzyl, benzoyl, 78 phenylSO -, pyridyl, tetrazolyl, phenyltetrazolyl, NR R or 7 8 7 8 CONR R ; wherein R and R are as previously defined. Halo means fluoro, chloro, bromo or iodo. Alkyl and alkoxy groups ∞ntøining 3 or more carbon atc-ms may be branched or straight-chain. Any alkyl, alkoxy or cycloalkyl group included in the above definitions may optionally be fully or partially substituted by fluorine. The term bioprecursor in the above definitionmeans a pharmaceutically acceptable biologically degradable derivative of the ccaopound of fo-ππula (I) which, upon administration to an animal or human being, is converted in the body to produce a c rpound of the foππula (I). Examples include ester derivatives formed between the free hydroxy group in the cxHπpound of formula (I) and, for example, an amino acid (such as L-valine). It will be appreciated that the compounds of fcramila (I) have a number of asymmetric carbon atoms and the invention includes all possible stereoisαmers whether separated or not. In one particular and preferred aspect of the invention there are provided cx-mpounds having the stereochemistry-: da) Iii the above formula heavy bonds are used to indicate that the group lies above the plane of the molecule while a broken bond is used to indicate that the group lies below. In the definition of R , aryl is preferably phenyl and heterocyclyl is preferably oxetan-3-yl or l,l-dioxothietan-3-yl. R is preferably t-butyl, isopropyl, oxetan-3-yl or l,l-dioxothietan-3-yl and (CR R ) is absent; or R is phenyl and (CR 9 R 10 ) is CH-.; or R 1 is H-.NCO-, CR-NHCO- or (CH ) NCO- and 9 lO n . . (CR R ) is CKL or CR(C-i-) . Particularly preferred are craπpounds wherein R is t-butyl, isopropyl or oxetan-3-yl and n is 0, most particularly where R (CR R ) - is t-butyl. In the definition of R , aryl is preferably phenyl and 2 heterocyclyl is for example pyridyl, pyrimidinyl or thienyl. R is preferably a-tγl(C,-C.)alkyl; benzyl is particularly preferred. . . . 4 In the definition of R , aryl is preferably phenyl and , . . , 4 heterocyclyl is preferably pyridyl, pyrimidinyl or thienyl. R is preferably C,-C 6 alkyl; particularly preferred are isopropyl and sec-butyl (valine or isoleucine derivatives) . The heterocyclic group X is preferably a 4-6 membered saturated or mor-ounsaturated group and is most preferably an azetidine, py-c-rolidine, tetrahydropyridine or piperi ine group; piperidine being particularly preferred. 7 8 R and R are preferably H and m is preferably O or 1. . . . 3 . . In the definition of R , aryl is phenyl, unsubstituted or sub-^ituted as defined in the term aryl above, and heterocyclyl is . . . . . 3 for example pyridyl, pyrimidinyl, lsoquinolyl or thienyl. R is 3 . preferably aryl(C,-C-)alkyl or aryl(C 2 -C 4 )alkenyl; R is most preferably benzyl optionally substituted in the phenyl ring fcy methyl, chloro, trifluoromethyl, trifluoromethoxy, pivaloyl, OH, CONMe , phenoxy, phenylsulphonyl or pyridyl or is 3-phenylpropyl or 3-phenyl-prop-2-enyl. Particular and preferred individual compounds include: 1-[N-((S)-5-t-butoxycarbonylamino-(S)-4-hydroxy-6-phenyl-(R)-2-(4- trifluoromethoxybenzyl)hexanoyl)-(S)-valyl]-4-metJιylamino- piperidine; 1-[N-((S)-5-t-l.xιtoxycarbonylamino-(S)-4-hydroxy-6-phenyl-(R)-2-(3- phenylprop-2-en-l-yl)hexanoyl-(S)-isoleucyl]-4-ethylamino- piperidine; and 1-[N-((R)-2-benzyl-(S)-5-t-butoj carbonylaπtino-(S)-4-hydroxy-6- phenylhexanoyl)-(S)-α-cyclohexylglycyl]-4-(2-methoxyethylamino)- piperidine. In a second aspect of the present invention, there is provided a compound of fo-απula (I) , or a p-narmaceutically acceptable salt thereof, for use as a medicament, especially for use in the treatment or prophylaxis of human retroviral infections, in particular HIV infections. The invention also includes the use of a ccαrpound of tiie formula (I) , or of a pharmaceutically acceptable salt thereof, for the manufacture of a medicament for use in the prophylaxis or treatment of retroviral infections. The invention further includes a pharmaceutical composition conprising a compound of the formula (I) , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable diluent or carrier. The antiviral activity of the compounds of general formula (I) is established using in vitro assay systems. For example, the coπrpounds of formula (I) are able to conpletely protect human T-cell line H9 for 7 days from the progressive ef ects of HIV infection. Untreated virus-infected cells display typical cytopathic effects such as formation of syncytia and cell death, m addition, virus particles produced from virus-infected cells treated with a cx-mpound of formula (I) are non-infectious. Examples of infections which may be treated or prevented fcy the coirpounds of formula (I) include those caused by human or animal refcroviruses, especially EHV-l. Clinical conditions which may therefore be treated or prevented include AIDS, ARC, and HEV related dementia. The coirpounds may also be used to block disease progression in symptαmless infected individuals. The ∞mpαunds of formula (I) can be prepared using the coupling and protection techniques which are familiar to those skilled in the art of peptide chemistry. The process is illustrated, by way of example, by the routes shown below for the preparation of coirpounds of formula (Ia) : The procedure outlined in Scheme A, starts with a protected lactone (H) . This is alkylated, using for example n-butyllithium and hex--fflethyldisilazane followed by addition of a cxar ound of 3 . . . . formula R Br and separation of the desired lsomer to give the product (HI) . The lactone ring is then opened by treatment with dilute alkali to give the corresponding hydroxy-acid and the hydroxy group is subsequently protected, for example as the t- butyldimetoylsilyl derivative by reaction with t-butyldimethyl- silyl chloride in N,N-dimethylformamide, followed by hydrolysis of the protected ester to give the intermediate (IV) . Synthesis of the other fragment required and the final coupling and deprotection step is illustrated in Scheme B, for the . . . . 5 6 . case where X is piperidine, m is 0, and neither R nor R is H. In this process the N-protected amino-acid (V) is coupled to 4-ketopiperidine and the coupled product (VI) is then subjected to reductive amination using, for example, sodium cγar3borohydride 56 . 5 6 and an amine of formula NHR R (wherein R and R are as previously defined other than H) . The N-protecting group is then removed and the amine product (VTII) is coupled to the intermediate (IV) and the hydros-protecting group X removed from the coupled product (IX) to give the final product of formula 1(a). In the case where one or both of R and R is H, the resulting amine ∞rre∑φonding to (VII) will require protection and thus is illustrated in Scheme C; the N and 0 protecting groups X and Y being removed in the final step of the process. In an alternative synthesis shown in scheme D the 4-ketopiperidine group is carried through to the coupling stage and the reductive animation conducted on the coupled, protected product (XII) to give the product (IX) which is then deprotected to give the final product as before. For coirpounds wherein R -(CR R ) - is other than t-butyl, the process can be performed with the appropriate group present in the starting material of formula (II) , or it can be performed using a coitpound of formula (IV) wherein R is t-butyl (BOC derivative) , and this is then removed after coupling to the intermediate (VIII) for exairple by treatment with t ifluoroacetic acid. The free amine is then reacylated, for exairple, in the case where R is oxetanyl and n is O, by reaction with 3-oxetanylojQr- carbonylo^-=nιccinimide, before final removal of the protecting groups. SCHEME A Protecting groups:- X: tButyldimethylsiIyl is preferred R CR'R 10 ),,: t-Butyl or benzyl are preferred SCHEME B (m=0, X=piperidine) 1. amide coupling reagent R 5 H- * , NaCNBH 3 R 6 Amide coupling reagent:- e.g., l-(3-dimethylaminopropyI)-3-ethylcarbodiimide. Protecting group X: t-butyldimethylsilyl is preferred. SCHEME C (R =H, m=0, X=piperidine) H H -N , NaCNBH 3 R 6 J amine protecting group R 2 1. acid 2. base R 1 -(CR 9 R 10 ) nv X JL -^ σv) OX R 3 R 4 amide coupling reagent H N γ — N (X) O R 2 R 4 Deprotect alcohol (xi) ox 6 3 o 2 2. Deprotect amine Amide coupling reagent:- e.g., l-(3-dimethyIaminopropyI)-3-ethylcarbodiimide Protecting groups:- X; t-butyldimethylsilyl is preferred. Y; Benzyloxycarbonyl is preferred. SCHEME D (m=0, X=piperidine) .R 5 HN R 6 , NaCNBH 3 Amide coupling reagent:- e.g., l-(3-dimethylaminopropyI)-3-ethylcarbodiimide Protecting group X; t-butyldimethylsilyl is preferred. The above sequences can be adapted as appropriate to be performed with any of the variants claimed for R 1 to R12 by appropriate selection of starting materials. Thus for example for ∞πrpounds where X is other than piperidine and n is 1 or 2, the synthesis is performed using the appropriate amine fragment of formula in place of (Vm) or (X). Again, if one of R and R is H appropriate N-protection will be required. I the above routes and specific Examples presented herein, certain hydroxy and aπdno-pratecting and (^rbo^-activating groups are required. It will be apparent to those -skilled in the art that the coupling and protection procedures described could be carried out by any standardmethod for peptide synthesis and these procedures are therefore included in the scope of the invention. The choice of a particular protecting group is dependent to a great extent upon the availability of the necessary reagent, its effect upon solubility of the protected compound, its ease of removal and the presence of other groups which might be affected by its use. For exairple, it is necessary in the above process to protect and deprotect particular amino groups in order to permit further reaction at the regenerated amino group and the choice of protecting group for a given amino group will depend upon the role of said amino group in the overall reaction scheme, Amino protecting groups having varying levels of lability can be used. Such groups are known in the art and attention is directed to the reviews by Bodansky et al., "Peptide Synthesis", 2nd Ed., John Wiley & Sons, N.Y. (1976); Greene, "Protective Groups in Organic Synthesis", John Wiley & Sons, N.Y. (1981); McQmie, "Protective Groups in Organic Chemistry", Plenum Press, N.Y. (1973); and to Sheppard in "Comprehensive Organic Chemistry, The Synthesis and Reactions of Organic Cc-mpounds", Pergamon Press, N.Y. (1979), edited by E. Haslam, Part 23.6, pages 321-339. A variety of conventional am-i-no-protecting groups are known to those skilled in the art. Representative amino-protecting groups include but are not limited to aryloxycarbonyl such as benzyloxycarbonyl; substituted or unsubstituted aralkyl such as benzyl, trityl, benzhydryl and 4-nitrobenzyl; benzylidene; arylthio such as phenylthio, nitrqphenylthio and trichloro- phenylthio; phosphoryl derivatives such as d-imethylfΛiosphoryl and 0,0-dibenzylphosphoryl; trialkylsilyl derivatives such as trimethylsilyl; and others as are described in U.S. Pat. No. 4,322,341. The preferred amino protecting group for use in the above sequence is t-butojycarbonyl. Procedures for substituting said group on a given amino group are well known. In general they comprise acylating the appropriate amino compound with the corresponding carbonyl chloride or anhydride in a reaction inert solvent, e.g. water, methylene chloride or tetrahydrofuran, in the presence of a base (acid acceptor) e.g. , sodium or potassium hydroxide when water is solvent; and, when an organic solvent is used, in the presence of a tertiary amine such as a triethylamine or pyridine. When an aqueous solvent system is used the pH of the reaction is typically held at about pH 8-10, and preferably at pH 9. The protected amino groups are converted to the unprotected amino groups by procedures known to those skilled in the art as appropriate to the particular group employed. The t-butoxy- carbonyl group is, for exairple, readily removed by treatment with dichloromethane saturated with hydrogen chloride gas. Various hydroxy-protecting groups are also known and are described in the literative sources already cited above. A preferred hydroxy protecting group is t-butyldimethylsilyl. This is introduced as previously described and is readily removed by treatment with tetra-n-tutylamnionium fluoride in tetrahydrofuran at room temperature. Activation of carboxy groups as a means of expediting a given acylation reaction is also methodology known to those skilled in the art. Especially useful in the herein described reaction sequence are the use of anhydrides and activated esters, particularly those esters derived from N-hydroxyphtoalimide, N-hvdroxy-ΞniccJ-nimide or 1-hydroxybenzotriazole, all of which are used in peptide syntheses. A dehydrative coupling agent is used to form the activated ester. Representative of such coupling agents are 1-cyclohexyl- 3-(2--morpholincethyl)carbodiimide, N,N'dicyclohejylcarbodiimide, N,N'-cartoπyldiimidazole, 1-(3-d-uπethylaιrrinσp-ropyl)-3- ethylt^arbodii ide, ethoxyacetylene, diphenylketene and N-ethyl- δ-pheiyl-isoxazol-iner-a'-sulfonate. The reaction conditions for using such coupling agents .are well described in the literature. In general they comprise the use of a reaction inert solvent and te-riperatures ranging from ambient to 100°. The above-mentioned carbodiimide reagents are favoured since they permit use of ambient reaction temperature and afford satisfactory yields of the desired esters. Upon completion of the coupling reactions leading to the final products, the various protecting groups can be removed by the appropriate techniques previously discussed, and the compounds of the formula (I) isolated a d purified using conventional procedures such as recrystallisation or column dircimatography. The N-t-butoxycarbonyl (B0C-) derivatives of the naturally occurring amino acids used in the synthesis of the coirpounds of the formula (V) are commercially available as are their hvdrOxysuccini-n-ido esters. The corresponding -intermediates derived from unnatural amino acids can be prepared by standard procedures (see, for exairple, M. J. O'Donnell et. al., J. Amer. Chem. Soc., 1989, 111, 2353). The ∞πpσunds of formula (II) can be prepared from the corresponding t-l--utyloxy<-arbonyl-prot-ected amino-aldehydes (see D. H. Rich et. al., J. Qrr. Chem.. 1978, 43, 3624 and Y. Hamada et. al., Chem. Pharm. Bull.. 1982, 30(5), 1921) by reaction with ethyl propiolate (see A. H. Fray et. al., J. Qrcr. Chem., 1986, 51, 4828) , followed by reduction to give the 5-t-bu ylo-^carbonylaιrrino-4-hydrO^ Cyclization by refluxing in toluene then affords the lactones of formula (II) , as mixtures of diastereomers which can be separated by standard procedures. Compounds of formula (XIII) can be prepared fcy conventional synthetic methods, for example by coupling a N-protected amino acid with a N-substituted or N-protected 4-amincmethyl piperidine derivative. Thus, aαx>rding to a further aspect, the invention includes a process for preparing a compound of the formula (I) which comprises removing the protecting groups from a coπpαund of the formula: (XIV) wherein X is either H or a selectively removable hydrcxy- protecting group and Y is either R , or a selectively removable 1 6 nitrogen-protecting group and R to R are as previously defined with the proviso that at least one of -x and Y is a protecting group, and isolating the compound of formula (I) and optionally forming a pharmaceutically acceptable salt thereof. The preferred protecting group for X is t-butyldimethyl¬ silyl; this is removed by treatment with tetra-n-butγlammonium fluoride in an organic solvent, preferably tetrahydrofuran. The preferred protecting group for Y is benzyloxycarbonyl; this is remove ty catalytic hydrogenation. The novel -intermediates of fo-rmulae (IX) , (XI) , (XII) and (XIV) also form part of this invention. Examples of jiharmaceutically acceptable salts of the ccarpounds (I) are acid-addition salts, e.g. sulfates, bisulfates, phosphates, acetates, lactates, maleates, mesylates, fumarates, citrates, succinates and gluconates. In the treatment of patients having a retrovirus infection, especially MV, the compounds (I) will be administered by any suitable route, e.g. by the oral, parenteral (e.g. subcutaneous, intravenous, inta-amuscular, or intradermal) , rectal, nasal, topical (including buccal and sublingual) or vaginal routes. The formulations, which will contain an antiviral agent of the invention together with one or more pharmaceutically acceptable carriers and optionally other therapeutic agents, can be prepared according to conventional techniques well known in pharmacy. Oral dosage forms include in particular syrups, tablets and capsules which may contain flavouring agents in addition to an inert carrier. Tablets can be made by conventional compression or moulding techniques by compressing a powder of the appropriate ingredients, e.g. the antiviral agent in conjunction with a binder, diluent, lubricant and surface-active agent. Rectal formulations will be in suppository form, and vaginal formulations as, for exairple, tampons, creams or foams. Parenteral formulations will be in sterile form, e.g. as vials for injection containing aqueous or non-aqueous diluents, buffers and antioxidants so that the formulation will be isotonic with blood. In general, the appropriate dose of the anti-retroviral agents of the formula (I) will be from 1-50 mg/kg/day, preferably 1-25 mg/kg/day given in up to six divided doses per day. There may be of course instances where higher or lower dosages are merited acxx>rding to the age, weight, degree of illness and response of the patient, and appropriate therapy will be as determined by the medical practitioner. The cxmpounds of formula (I) may be used in combination with other drugs, same of which may potentiate their activity. Such drugs include the following:- (a) Reverse transcriptase inhibitors such as AZT, ddl, ddC, foscarnet, TTBO coirpounds, dipyridodiazepinones or 6-substituted acyclopyrimidine (HEPT) derivatives. (b) gpl20-CD4 blockers such as dextran sulphate and soluble CD4, including its combination with toxic agents such as pseudomonas toxin. (c) tat antagonists, such as I penicillamine; and (d) biological response modifiers including interferons, interleukins or colony sti-mulating factors, e.g. GM-CSF. The compounds of the invention were evaluated for antiviral activity by dissolving the test compound in 50 μl of DMSO and diluting in REMI 1640, a complex salts solution with a pH of 7.2, to 1 mg/ml. Testing was performed at 0.001, 0.01, 0.1, 1 and 10 as μg/ml against HIV 1 (strain IIIB) in a human T-cell line (H9) . Untreated control infections were initiated at the same time. Seven days post infection, tissue culture supernatants were titrated for the presence of infectious virus on C8166 cells (human T-cell line) . On days 3, 5, and 7 cultures were examined for appearance of syncytia. Control infections, untreated with drug, show typical viral cytopathic effects, including formation of syncytia and cell death. The IC, 00 quoted is the lowest test concentration affording coirplete protection to the culture. Using this test method, the compounds had an IC, nn values in the range 0.1 to 10.0 μg/ml. The preparation of certain starting materials and of the cσπpounds of formula (I) will now be more particularly illustrated by reference to the following experimental Examples. The purity of compounds was routinely monitored by thin layer chσmatography using Merck Kieselgel 60 F ?t .. plates. " Η-Nuclear magnetic reasonance spectra were recorded using either a Nicolet QE-300 or a Bruker AC-300 spectrometer and were all in cases consistent with the proposed structures. Chemical shifts are given in parts-per-million downfield from tetramethylsilane using conventional abbreviations for designation of major peaks: s, singlet; d, doublet; t, triplet; m, multiplet and b, broad. All temperatures are in degrees celsius. PREPARATION OF STARTING MATERIALS Tbt l' RMEDIATE PREPARATION 1 -butyrolactone a^ Ethyl C4S..5S) - and (4R,5Sl -5-t-butoxyc^rtonyla]iunc>-4-hvdroxy-6- bhenv---hex-2-γnoate A solution of diisop-α-pylairrine (6.4 ml) in dry tetxahydrofuran (25 ml) was stirred under nitrogen at -25°C and a 1.6 molar solution of n-butyllithium in hexane (24.4 ml) was added over 5 minutes, keeping tiie te-perature below -20°. After a further 15 minutes at -20° the solution was cooled to -70° and ethyl propiolate (3.8 g) was added dropwise over 10 minutes, keeping the temperature below -65°. The resulting yellow suspension was stirred at -70° for a further 20 minutes and then treated dropwise, over 10 minutes, with a solution of N-t-butoxy- carbonyl--L phenylalaninal (6.5 g, see J. R. Luly et al, J. Qrcr. Chem.. 1987, 52, 1487) in dry tetrahydrofuran (15 ml), again keeping the teπperature below -65°. The clear yellow solution was stirred at -70° for 2 hours then treated with acetic acid (4 ml) . The cooling bath was removed and the mixture was allowed to warm to -30° at which point water (100 ml) and ethyl acetate (100 ml) were added with vigorous stirring. Separation of the organic layer, followed by successive washing with 1 molar hydrochloric acid (50 ml) , saturated aqueous sodium bicarbonate (50 ml) and saturated brine (50 ml) , gave the crude product as an oil after drying (Na SO ) and evaporation of the solvent. The oil was purified by silica gel chroiratography using ethyl acetate-hexane (1:4) as the eluent. Evaporation of the product-ccnteining fractions gave an oil which solidified on standing overnight. Recrystallisation from ether-hexane afforded the title coirpounds as an approximately 2:1 mixture (4S,5S:4R,5S) of diastereomers, (4.3 g), m.p. 98-99°. Found: C,65.62; H,7.42; N,4.33. C lg H 25 N0 5 requires C,65.70; H,7.20; N,4.03%. N.M.R. (CDC1 3 ) 5 = 1.30-1.39 (m, 3H) ; 1.43 (s, 9H) ; 2.90-3.11 (m, 2H); 3.37-3.38 and 4.16-4.19 (2x brm, IH) ; 3.93-4.04 (m, IH) ; 4.22-4.33 (m, 2H) ; 4.51-4.56 ( , IH) ; 4.77-4.79 and 4.87-4.90 (2 x boa, IH); 7.24-7.35 (m, 5H) . b) Ethyl (4S.5S)- and t4R,5S) -5-t-butoxycarbonylamino-4-hvdroxy-6- phenylhexanoate The above product (1.17 g) was dissolved in ethanol (50 mg) and 5% Pd-BaSO catalyst was added. The mixture was then hydrogenated at 50 psi (344.7 kPa) for 2 hours. Filtration, followed by evaporation of the solvent under vacuum, gave the title coirpounds (approximately 2:1 mixture of diastereo-mers) as a white solid, (1.18 g) , m.p. 125-126°. Found: C,64.91; H,8.40; N,3.98, C lg I^ 9 N0 5 requires C,64.95; H,8.26; N,3.98%. N.M.R. (COCl 3 ) δ = 1.24-1.33 (m, 3H) ; 1.39 and 1.42 (2 x s, 9H) ; 1.72-1.95 (m, 2H); 2.38-2.62 (m,2H); 2.77-2.98 (m,2H) ; 3.02-3.04 and 3.40-3.42 (2 X m, IH exch. D 2 0) ; 3.59-3.91 (m, 2H) ; 4.08-4.21 (m, 2H); 4.58-4.61 and 4.86-4.89 (2 X m, IH) ; 7.22-7.37 (m, 5H) . cl (S)-5-r (S.-l-t-Butoxycartonylamino-2-phenylethyl1 cramma- butyrolactone The ga-crrrra-hydroxyester from (b) above was dissolved in 2.5% acetic acid-toluene (35 ml) and the solution was heated at reflux for 2 hours. After cooling and evaporation to dryness under vacuum, the residue was purified by silica gel chromatography, eluting with diethyl ether-hexane (40:60), to afford the title coirpound (0.4 g) , m.p. 98-99°. Found: C,66.77; H,7.78 requires: C,66.88; H,7.54; N,4.59%. m/e = 306 N.M.R. (CDC1 3 ) δ = 1.42 (s, 9H) ; 2.11-2.19 ( , 2H) ; 2.51-2.58 ( , 2H); 2.87-3.02 (m, 2H) ; 4.00-4.07 (m, IH) ; 4.47-4.52 (m, IH) ; 4.63 (d, J = 10, NH); 7.26-7.36 (m, 5H) . 25 [α] -22.6° (c = 1, MeOH). I. R. (KBr) 1775, 1690, 1525 cm "1 . INTERMEDIATE PRE ARATTON 2 (S . -5-t-Butoxycartonylamino- (S) 4- ft-l ityld-unethylsilyloxy) - ( RI -2- berιzyl-6-j-faenylhexanoic acid beι zyl-cf-- rma^-butv-tx>lactone. A cold (-10°) solution of hexamethyldisilazane (7.9 ml) in tetrahydrofuran (15 ml) was treated over 3 minutes with 1.6M n-butyllithium in hexane (23 ml) , keeping the teirrperature below 0°. After a further 5 minutes at 0° the solution was cooled to -70° and a solution of (S) -5-[ (S) -1-t- buto^carborylaπ-ino-2-phenylethyl] -gairrma-butyrolactone (5 g) in tetrahydrofuran (38 ml) was added, keeping the te-rperature below -65° . The solution was stirred at -70° for 15 minutes before benzyl bromide (1.95 ml) in tet-r-ahvdrOfuran (12.5 ml) was added over 1 minute and the solution stirred at -70° for an additional 10 minutes before being treated with acetic acid (6.5 ml) and the cooling bath removed. Water (50 ml) and ethyl acetate (50 ml) was added and the mixture allowed to warm to room teπperature. Separation of the organic layer, followed by drying (MgSO ) and evaporation of the solvent under vacuum gave the crude product as an oil. Chrcmatography on silica-gel, eluting with diethyl ether-hexane (50:50) , gave the title compound as a clear oil (3.52 g) . Found: C, 73.22; H, 7.50; N, 3.50. C ILJ0 4 requires C, 72.91; H, 7.34; N, 3.54%. [α] D -14° (c = 0.1%, MeOH) N.M.R. (CDC1 3 ) δ = 1.37 (s,9H) ; 1.95-2.30 (m,2H) ; 2.79- 3.20(m,5H) ; 3.92-4.01(m,lH) ; 4.21-4.25 (m, IH) ; 4.52-4.56(m,lH) ; 7.21-7.36(m,10H) . b) f S)-5-t-Butoxycarfconylamino-fS)-4-ft- I rtyldimethylsilyloxy.-fR.-2-benzyl-6-yιhenylhexanoic acid. A suspension of the product from (a) (17.63 g> in dioxan (120 ml) and water (60 ml) was treated with sodium hydroxide (IN, 53.5 ml) at room temperature. The reaction was stirred for 3 hours before being acidified to pH 5 by the addition of acetic acid. After standing for a further 30 minutes the precipitate was filtered off and washed with water. This solid was dissolved in ethyl acetate, dried (MgSO ) and evaporated under vacuum to a white solid which was triturated with hexane, filtered and dried to give the intermediate hydroxy acid (17.85 g) . A solution of this hydroxy acid in N,N-dimethylformamide was treated with imidazole (29.38 g) and t-butyldimethylsilyl chloride (32.53 g) at room temperature. After stirring for 18 hours, the solvent was evaporated under vacuum, the residue treated with ice/water, 10% citric acid to pH 4, and extracted using 2 x 400 ml portions of ethyl acetate. The combined extracts were dried (MgSO.) and evaporated under vacuum to a pale oil (29.2 g) . A solution of this oil in tetxahydrofuran (240 ml) was treated with acetic acid (240 ml) and water (80 ml) at room temperature. After stirring for 2 hours at room teirperature and 18 hours at 4°C the solution was evaporated under vacuum and the residue partitioned between water (400 ml) and ethyl acetate (400 ml) . The separated organic layer was washed with water (2 x 400 ml) , saturated brine (100 ml) , dried (MgSO ) and evaporated under vacuum to a pale oil. Chrσniatography on silica-gel, eluting with diethyl ether-hexane (70:30) gave the title cσirpound as a white glass (22.4 g) . m/e 528 (MH) + N.M.R. (OtSO-dg) 5 = 0.10(s,6H); 0.95(s,9H); 1.30(m,10H); 1.35(m,lH); 1.95(m,lH); 2.40(m,lH); 2.72(m,2H); 2.85(m,lH); 3.60(m,lH); 3.75 (m,lH) ; 6.88(d,lH); 7.22(m,10H). a) 1- fN-t-Butoxycarbonyl- f S) -valyl) -4-ketopiperidine. A solution of N-t-butoxycarbonyl-(S)-valine (3.64 g) , l-(3- dimethylaιrιincpropyl)-3-etoylcarbodiimide hydrochloride (3.86 g) , 1-hydroxybenzotriazole hydrate (3.40 g) and N,N- dii-∞propylethylamine (4.39 ml) in N,N-dimethylfo-πramide (20 ml) was treated with a solution of 4-ketopiperidine hydrochloride hydrate (3.87 g) and N,N-di-i^oprx ylethylamine (5.00 ml) in N,N-cUmethylfo-αr-amide (15 ml) at room temperature. After stirring for 18 hours the solvent was evaporated under vacuum and the residual oil was dissolved in water (50 ml) and ethyl acetate (50 ml) . The separated organic layer was washed with saturated aqueous sodium bicarbonate (2 x 100 ml) , dried (MgSO.) and evaporated under vacuum to an oil. Purification by silica-gel chrcmatography, eluting with ethyl acetate-hexane (60:40) , gave the title compound as a pale yellow oil (3.72 g) . m/e = 299 (MH) + N.M.R. (D-MSO-d o δ = 0.75(d,6H) ; 1.3 (s,9H) ; 1.85(m,lH) ; 2.25(m,3H) ; 3.5 (m,lH) ; 3.7(m,lH) ; 3.85(m,3H) ; 4.2 (t,lH) ; 6.9(d,lH) . b) 1-fN-t-Butoxycarboπyl-fS)-valyl)-4-dimethylaminopiperidine A solution of the product from (a) (1.5 g) in methanol (5 ml) was cooled in ice-water and treated with a solution of da-met-hylamine (1.08 g) in methanol (10 ml) . The pH of the solution was lowered to 6 by the careful addition of acetic acid before sodium cyanoborohydride (0.30 g) was added portioπwise and the solution stirred for 18 hours. The solvent was evaporated under vacuum and the residual oil dissolved in ethyl acetate (50 ml) , washed with aqueous sodium hydroxide (IN, 2 x 50 ml) and saturated brine (50 ml) , dried (MgSO.) and evaporated under vacuum to a solid. Recrystallisation from hexane afforded the title cσπpound (0.70 g) . Found: C,62.35; H,10.26; N,12.56. C^^^^ requires C, 62.35; H,10.16; N,12.83%. m/e = 322 (MH) + . N.M.R. (DMSO-d 6 ) δ = 0.89(2x s,6H) ; 1.0-1.3(m,2H) ; 1.3(s,9H); 1.6-1.8(m,2H); 1.8-1.9(m,lH) ; 2.1(s,6H) ; * 2.2(m,lH) ; 2.5-2.6(m,IH) ; 3.0(m,lH); 4.0(m,lH); 4.15(m,lH); 4.3(m,lH); 6.7(dd,lH). -l-NTERMEDIATE PREPARATION 4 a) 1- fN-t-Butoxycarbonyl- f S . -valyl) -4-methylam---nopiperidine The title compound was prepared by the same procedure as described for intermediate (3b) by reductive amination of intermediate (3a) with metiiylamine. Purification by c±-rcmatograrAiy on silica-gel, eluting with methylene chloride- meth-..nol-c»ncentrated aqueous ammonia (90:10:1) gave the title cx(rrpound as a colourless oil. N.M.R. (DMSO-d D δ = 0.7 (m,6H) ; 0.8-1.2 (m,2H) ; 1.3 (s,9H) ; 1.6- 1.7(m,2H); 1.8(m,3H); 2.2(s,3H); 2.6-3.0(m,3H) ; 3.8(m,lH); 4.0(m,lH); 4.1(m,lH); 6.6(dd,2H). b) 1-fN-t-Butoxycarbonyl-fS)-valyl)-4-fN-benzyloxycarbonyl-N- methylamino.piperidine A solution of the product from a) (4.0 g) in methylene chloride (300 ml) was treated with N-(benzyloxycarbonyloxy) succi-nimide (3.83 g) at room teπperature and the solution stirred for 72 hours. The reaction mixture was washed with saturated aqueous sodium bicarbonate (150 ml) , water (150 ml) , dried (MgSO ) and evaporated under vacuum to give an oil. Purification by chromatography on silica-gel, eluting with diethyl ether-hexane (80:20) gave the title coπpound as a colourless foam (5.4 g) . N.M.R. (DMSO-d,.) .5 = 0.7(m,6H); 1.3(s,9H); 1.3-1.7(m,4H) ; b 1.8(m,lH); 2.4-3.0(m,4H); 3.1 (m,3H); 4.l(m,lH); 4.4 (m,lH); 5.0(s,2H); 6.7(dd,lH); 7.3(m,5H). INTERMEDIATE PREPARATION 5 a) 1-fN-t-Butoxycarbonyl-fS)-isoleucyl)-4-ketopiperidine The title ∞rrpound was prepared as a colourless oil by the same procedure as described for intermediate (3a) reacting 4- ketopiperidine hydrochloride hydrate with N-t-butoxycarbonyl- (S)-isoleucine. m/e 313 (MH) + [α] D 25 -16° (c = 0.34%,MeOH) N.M.R. (CDC1 3 ) δ = 0.9(m,6H); 1.2(m,lH); 1.4(S,9H); 1.6(m,lH); 1.75(m,lH); 2.5(m,4H); 3.7(m,2H); 4.15(m,2H); 4.55(m,lH); 5.2(d,lH). b) 1- ΓN- f f R. -2-Benzyl- f S . -5-butoxycartonylamino- f S . -4-t-butyl- dimethylsilyloxy-6-τ^er-v-Lhexanoyl . - f S) -isoleucyll -4-keto¬ piperidine A solution of the product from (a) (3 g) in methylene chloride (100 ml) was saturated with hydrogen chloride at 0° and kept at this teπperature for a further 1 hour. Evaporation to dryness under vacuum gave the amine hydrochloride as a white foam. This was added to an active ester solution previously prepared by stirring together tiie product from --Jitermediate Preparation (2b) (2.92 g), 1-hydrαxybenzotriazole hydrate (1.12 g) , l-(3- dimetjiylamir-opropyl) -3-etJιylc-arbcdi-imide hydrochloride (1.33 g) and N,N-d- L-=κ- rcpyletiιyl^mine (2.40 ml) in methylene chloride (500 ml) for 10 minutes. After stirring for a further 24 hours the solvent was evaporated under vacuum, the residue dissolved in ethyl acetate (250 ml) , washed with water (2 x 200 ml) , dried (MgSO.) and evaporated under vacuum to give a white foam. Purification by chrctmatcgraphy on silica-gel, eluting with ethyl acetate-hexane (50:50) gave the title compound as a white foam (3.39 g). Found: C, 67.28; H, 8.58; N, 5.62. C^H-^N OgSi. 0.5 EtQAc requires C, 67.58; H, 8.87; N, 5.43%. m/e 722 (MH) + [α] D 25 -14° (c = 0.1%, MeOH) N.M.R. (EMSO-d δ = 0.05(d,6H); 0.78(t,6H); 0.85(s,9H); 1.15(m,4H); 1.26(s,9H); 1.5(m,lH); 1.77 (m,lH); 1.9(m,lH); 2.3(m,4H); 2.5(m,lH); 2.65(d,lH); 2.8(m,2H); 3.5(m,2H); 3.65(m,2H); 3.8(m,2H); 4.5(t,lH); 6.8(d,lH); 7.1(m,10H); 8.2(dd,lH). 3-NTΞMED3-ATE PR-iPARATTONS 6-12 Cvclol^toxycarbonyloxysuccinimide B-i^-(t ichloromethyl)carbonate (3.5 mmole, 1.04 g) was dissolved in dichloromethane (25 ml) under an atmosphere of nitrogen. The solution was cooled to -20°C using a solid carbon dioxide/acetone bath. Cyclobutanσl (10 mmole, 0.72 g) and diisopropylet±iylaπtine (21 mmole, 2.71 g) were dissolved in dichloromethane (20 ml) and this solution was added dropwise to the above solution over 10 minutes. The mixture was then stirred at -20°C for 15 minutes and N-hydro-^-^cxanimide (10 mmole, 1.15 g) added in one lot. The solution was allowed to warm to room teπperature over 1.5 hours then poured into saturated aqueous sodium hydrogen carbonate solution and extracted with dichloromethane (2 x 50 ml) . The combined organic extracts were dried over MgSO , filtered and evaporated under vacuum. The residue was further purified by column chromatography on silica eluting with hexane:ethyl acetate 7:3. Evaporation of the product conteining fractions and recrystallisation from hexane gave the title σcarpound (515 mg) , m.p. 88-90°C. Found: C,50.94; H,5.17; N,6.54%. C g H l;L 0 5 requires C,50.71; H,5.20; N,6.57%. The following su∞inimide esters were prepared from the appropriate alcohol using the method described above. EXAMPLE 1 1- TN- f f R) -2-Benzyl- f S) -5-t-butoxycarbonylamino- (S) -4-t-butyl- dimethylsiloxy-6-phenylhexanoyl) - f S) -valyll -4- aimethylamino- piperidine A solution of l-(N-t-buto^carbonyl-(S)-valyl)-4-ά-imetoylaιrιino- piperidine (0.46 g) in methylene chloride (20 ml) was saturated with hydrogen chloride at 0° and kept at this temperature for a further 1 hour. Evaporation to dryness under vacuum gave the bis-amine di-hydrochloride as a white solid. A solution of this product and N,N-diisopropylethylamine (0.3 ml) in N,N-<ii-methylfon-<5mide (5 ml) was added to an active ester solution previously prepared by stirring together the product from intermediate preparation (2b) (0.5 g) , 1-hyά-roxybenzotriazole (0.19 g) , l-(3-<iimetlιylaιrιi-r ropyl hydrochloride (0.22 g) and N,N-c iscpropylet±ιylamine (0.25 ml) in N,N-<iiπethylfo-αi3amide (10 ml) for 10 minutes. After stirring for a further 24 hours, water was added and the product extracted into ethyl acetate (2 x 100 ml) . The combined organic layers were washed with saturated aqueous sodium bicarbonate (2 x 100 ml) , dried (MgSO.) and evaporated under vacuum to give a yellow oil. Purification by ciϊrcπatography on silica-gel, eluting with methylene chloride-methanol (90:10) , gave the title ∞πpσund as a white glass (0.51 g) . N.M.R. (DMS0-d 6 ) δ = 0.05 (s,6H) ; 0.8 (s,9H) ; 1.1-1.9 (m,6H) ; 1.2 (S,9H) ; 2.05(S,6H) ; 2.4-2.8 (m,8H) ; 3.0-4.0 (m, 4H) ; 4.2 (m,lH) ; 6.7 (m,lH) ; 7.1 ( , 10H) ; 7.8 (d,lH) . EXAMPLE 2 1-TN-ffR.-2-Benzyl-fSI-5-t-butoxycarbonylamino-fS)-4-hydroxy-6- phenylhexanoyl)-fS.-valyll-4-d-urrethylam-ύτopiperidine The product from Exairple 1 (0.51 g) in tetrahydrofuran (15 ml) was treated with 1M tetxa-n-butγlammonium fluoride in tetrahydrofuran (2.03 ml) at room teπperature. After stirring for a further 48 hours the solvent was evaporated under vacuum and the residue dissolved in ethyl acetate (100 ml) , washed with saturated aqueous sodium bicarbonate (2 x 100 ml) , water (2 x 100 ml) , dried (MgSO.) and evaporated under vacuum. The crude product thus obtained was purified by chrcm-atography on silica-gel eluting with methylene chloride-methanol (85:15) . After evaporation of the product fractions, the residue was crystallised from diethyl ether/hexane to afford the title compound (0.08 g) m.p. 176-178°. Found: C, 69.41; H, 8.47; N, 8.93. C j gHg^O,. requires C, 69.42; H, 8.74; N, 9.00%. m/e 623 (MH) + [α] D 25 -9° (c = 0.1%, MeOH) N.M.R. (DMSO-d o 5 = 0.7(d,6H) ; l.l-1.4(m,3H) ; 1.3 (s,9H) ; 1.6- 1.8(m,3H) ; 2.15(S,6H) ; 2.25(m,lH) ; 2.5(m r 4H) ; 2.8 (m,4H) ; 3.0(m,lH) ; 3.4(m,lH) ; 3.6(m,lH) ; 4.0(m,lH) ; 4.3 (m,lH) ; 4.5(m,IH) ; 6.4(d,lH) ; 7.2(m,10H) ; 7.8 (d,lH) . EXAMPLE 3 1- ΓN- f f R. -2-Benzyl- (S\ -5-t-butoxycarbonγlamino- f S . -4-t-butγl- d-i τ-ethylsilyloxy-6-pheπylhexanoyl) -(S) -valyll -4- f N-benzyloxy- (-arbonyl-N-met-hylamino . piperidine A solution of 4-(N-berιzyoxycarbαnyl-N-methylam carbonyl- (S) -valy) piperidine (5.4 g) in methylene chloride (200 ml) was saturated with hydrogen chloride at 0° and kept at this teπperature for a further 1 hour. The solvent was evaporated under vacuum and the residue dissolved in methylene chloride (400 ml) and extracted with saturated aqueous sodium bicarbonate (300 ml) . The organic phase was washed with saturated brine (100 ml) , dried (MgSO.) and evaporated under vacuum to give the amine free-base (3.1 g) . A solution of this product (1.18 g) in methylene chloride (70 ml) was added to an active ester solution previously prepared by stirring together the product from intermediate preparation (2b) (1.5 g) , 1-hydroxy-benzotriazole (0.575 g) , l-(3-dimethyl- aιιύnopropyl)-3-et±ιyl-carbcdi-uι-ide hydrochloride (0.65 g) and N,N-diisopropylet±ylaιι-ine (0.59 ml) in methylene chloride (150 ml) for 20 minutes. After stirring for a further 24 hours, the solution was washed with IN hydrochloric acid (200 ml) , saturated aqueous sodium bicarbonate (200 ml) , saturated brine (100 ml) , dried (MgSO ) and evaporated under vacuum. The residue was purified by chromatography on silica-gel, eluting with diethyl ether-hexane (20:80) , to give the title compound as a white foam (1.8 g). N.M.R. (DMSO-d S = 0.05(S,6H); 0.8(m,6H); 0.9(s,9H); 1.25(s,9H); o 1.2-1.6(m,6H); 1.9(m,2H); 2.4-3.1( ,9H) ; 3.6(m,lH); 3.7(m,3H); 4.0(m,2H); 4.45(m,2H); 5.05(s,2H); 6.85(d,lH); 7.2(m,10H); 7.3(m,5H); 7.85 & 7.95(2x d,lH). Xa PT.?! 4 1-fN-ffRI-2-Benzyl-fS)-5-t-butoxy(^rbonylamino-f S)-4-hvdrOxy-6- phenylhexanoyl.-f S)-valyll-4-fN-benzyloxycarbonyl-N-methylamino)- piperidine The product from Exairple 3 (1.75 g) in tetrahydrofuran (150 ml) was treated with 1M tet a-n-butylammonium fluoride in tetrahydrafrjran (6.12 ml) at room temperature. After sti-rring for a further 24 hours the solvent was evaporated under vacuum and the residue dissolved in ethyl acetate (300 ml) and washed with saturated aqueous sodium bicarbonate (200 ml) , IN hydrochloric acid (200 ml) , water (to pH 7) , dried (MgSO.) and evaporated under vacuum to give the title coirpound as a white foam (1.61 g) . m/e 742 (MH) + N.M.R. (DMSO-d 6 ) δ = 0.0 & 0.05(silyl residues); 0.75(m 6H) ; 0.8(silyl residue); " 1.2-1.7(m,6H); 1.25(s,9H); 1.85(m,lH); 2.4-3.0(m,10H); 3.4(m,lH); 3.55(m,lH); 4.0(m,2H); 4.45(m,3H); 5.05(m,2H); 6.35(d,lH); 7.2(m,10H); 7.3(m,5H); 7.3 & 7.4(2X d,lH). EXAMPT.T.5 1-TN-f(R,-2-Benzyl-fS)-5-t-butoxycarbonylamino-fSI-4-hvdroxy-6- phenylhexanoyl)-fS)-valyll-4-methylaminopiperidine A solution of the product from Exairple 4 (1.5 g) in absolute ethanol (60 ml) was treated with 10% palladium on charcoal (200 mg) . The mixture was stirred at room teirperature under hydrogen at a pressure of 30 psi for 3 hours. The catalyst was filtered and the solvent evaporated under vacuum to give a colourless oil which was purified by chromatography on silica-gel, eluting with methylene ciiloride-methanol-concentrated aqueous ammonia. After evaporation of the product fractions, the residue was crystallised from ethyl acetate/hexane to afford the title cxfπpound (0.765 g) m.p. 170-171°. Found: C, 69.10; H, 8.47; N, 9.14. C 35 H 52 N 4 0 5 requires C, 69.04; H, 8.60; N, 9.20%. m/e 609 (MH) + [α] D 25 -19° (c = 0.1%, MeOH) N.M.R. (DMSO-d.) δ = 0.7(d,6H); 1.0(m,2H); 1.25(s,9H); o 1.25(m,lH); 1.5-2.0(m,4H); 2.25(S,3H); 2.4-3.1(m,8H) ; 3.4(m,lH); 3.5(m,lH); 3.8(t,lH); 4.05(m,lH); 4.45(m,lH); 4.5(t,lH); 6.4(m,lH); 7.1-7.3(m,10H), 7.75(d,lH). EXAMPLE 6 1-ΓN-ffR.-2-Benzyl- (S)-5-butoxycarbonylamino-fS)-4-hvdroxy-6- T--henylhexanoγl)-fS.-isoleucyll-4-ketopiperidine A solution of the product from intermediate preparation (5b) (3.35 g) was treated with 1M fluoride in (13.9 ml) at room temperature. After stirring for a -further 48 hours the solvent was evaporated under vacuum, the residue dissolved in ethyl acetate (300 ml) and washed with saturated aqueous sodium bicarbonate (200 ml) , IN hydrochloric acid (200 ml) , water (to pH 7) , dried (MgSO.) and evaporated under vacuum to give a yellow foam. Purification by chromatography on silica-gel, eluting with ethyl acetate- hexane (50:50) gave the title cσπpound as a white foam (0.848 g). m/e 508 (M-100)H + N.M.R. (DMSO-d..) δ = 0.75(m,6H) ; 1.0-1.8(m,8H) ; 1.3(s,9H); o 2.3(m,2H); 2.6(m,2H); 2.8(m,3H); 3.4-3.7(m,3H) ; 3.8(m,2H); 4.55(m,2H); 6.4(m,lH); 7.1-7.3(m,10H) ; 7.85 & 8.0(2x d,IH) . EXAMPLE 7 1-ΓN- f f R-2-Benzyl- ( S . -5-t-butoxycarbonylaιιιir-o— f S) -4-hvdroxy-6- phenylhexanoyl. -fS) -isoleucyll -4-methylaπrir 3piperidine A solution of the product from Example 6 (0.385 g) in methanol (20 ml) was added to a 33% solution of metoylamine in ethanol (0.5 ml) diluted with methanol (15 ml) and acidified to pH 5-6 with acetic acid. Sodium cyanoborohydride (28 mg) was added and the reaction stirred for a further 18 hours. The solution was diluted with ethyl acetate (100 ml) and washed with aqueous sodium hydroxide (IN, 2 x 50 ml) , dried (MgSO ) and evaporated under vacuum. Purification by chrσrratography on silica-gel, eluting with methylene chloride-irøthar-ol-concentrated aqueous ammonia followed by recrystallisation from ethyl acetate/hexane afforded the title ∞mpound (0.195 g) m.p. 159-161°. Found: C, 68.93; H, 8.80; N, requires C,68.93; H, 8.76; N, 8.93%. [α] D 25 -15° (c = 0.1%, MeOH) N.M.R (EMSO-d-) δ = 0.7(m,6H); 0.9-1.4(m,5H) ; 1.2(S,9H); 1.5- 1.8(m,4H); 2.25(s,3H); 2.4-3.0(m,8H); 3.4(m,lH); 3.5(m,lH); 3.85(m,lH); 4.1(m,lH); 4.5(m,2H); 6.4(m,lH); 7.1(m,10H); 7.8(m,lH). EXfiMPLE 8 1- TN- f (R) -2-Benzyl- f S) -5-t-butoxycartonylamino- f S) -4-hvdroxy-6- phenylhexanoyl) - f S) -isoleucyll -4-aminopiperidine The title compound was prepared by the same procedure as described for Example 7 by reacting the product from Exairple 6 with ammonium acetate, m.p.161°. Found: C,68.32; N,8.59; N,9.03. C 5 H 52 N 4 0 5 . 1 / 4 iy> requires C, 68.55; H,8.55: N,9.14%. m/e 609 (MH) + [α] D 25 -1° (c = 0.1%, MeOH) N.M.R. (DMSO-d,,) δ = 0.7 (m, 6H) ; 0.9-1.4 (m,5H) ; 1.25(s,9H) ; 1.5- 1.85(m,4H) ; 2.7-2.9 (m,8H) ; 3.0(t,lH) ; 3.5(m, lH) ; 3.8 (t,lH) ; 4.1(m,lH) ; 4.5(m,2H) ; 6.4 (d,lH) ; 7.1(m,10H) ; 7.8(m,lH) . EXAMPLE 9 1-rN-ffR)-2-Benzyl-fS.-5-t-butoxy(^rbonylamino-fS)-4-t-butyl- dimethylsilyloxy-6-phenylhexanoyl.-(S)-valyll-4-(pyrrolidin-1-yl.- piperidine The title cxmpound was prepared by the same procedure as described for Exairple 1 by reacting the amine derived from l-(N-t- buto-xycarbonyl)-(S)-valyl-4-(pyrrolidin-l-yl)piperidine with an active ester derived from the product from intermediate preparation (2b) . m/e 763 (MH) + N.M.R. (DMSO-d,) δ = 0.1(s,6H); 0.8(m,6H); 0.9(s,9H); 1.15(m,5H) ; 1.25(s,9H) ; 1.65(m,3H) ; 1.8 (m,lH) ; 1.9(m,lH) ; 2.2(m,lH) ,* 2.3-3.1(m,12H) ; 3.55 (m, IH) ; 3.65(m,lH) ; 3.8(m,lH) ; 4.15(m,lH) ; 4.5(m,lH) ; 6.8 (d,lH) ; 7.2 (m, 10H) ; 7.8 & 7.9(2x d,lH) . EXAMPLE 10 1- ΓN- f f R) -2-Benzyl- f S) -5-t-huto-xycartonylamino- f S -4-hydroxy-6- pheπylhexanoyl) - f S) -valyll -4- f pyrrolidin-1-yl) piperidine The title c-xstpound was prepared from the product of Example 9 by the same procedure as described for Example 2, m.p. 187-188° . Found: C,69.31; H,8.76; N,8.64. C^H^^. 3 /^ 0 requires C,69.37; H,8.73; N,8.51%. m/e 649 (MH) + [α] D 25 -17° (c = 0.1%, M20H) . N.M.R. (EMSO-dg) 5 = 0.65(d,6H) ; 1.1-1.3 (m,4H) ; 1.2(s,9H) ; 1.5-1.8(m,6H) ; 2.1(m,lH) ; 2.2-3.0(m,12H) ; 3.3(m,lH) ; 3.45(m, H) ; 3.8(m,lH) ; 4.0(m,lH) ; 4.4(m,lH) ; 4.5(m,lH) ; 6.35(m,lH) ; 7.0-7.2 (m r 10H) ; 7.7(m,lH) . EXAMPLE 11 4-Amino-l-fN-t-butoxycarbonyl)-fS)-valylpiperidine The title compound was prepared by the same procedure as described for intermediate 3b) by reductive amination of intermediate 3a) with ammonium acetate, m/e 300 (MH) + N.M.R (DMSO-dg) 5 = 0.8(m,6H); l.l(m,2H) ; 1.3(s,9H); 1.7(m,2H); 1.9(m,lH); 2.7-2.9(m,2H) ; 3.1(m,lH); 3.9(m,lH); 4.2(m,2H); 6.7(m,lH). EXAMPLE 12 1-rfN-t-Butoxycarbonyl- (S)-valyll-4-fN-benz-yloxycartonylamino)- piperidine The title cxsrpound was prepared from the product of Example 11 by the same procedure as described for intermediate (4b) . m/e 434 (MH) + N.M.R (DMS0-d 6 ) δ = 0.8(m,6H) ; 1.15(m,lH); 1.3(m,lH); 1.35(s,9H); 1.7(m,2H); 1.9(m r lH); 2.7(m,lH); 3.1(m,lH); 3.55(S,1H); 3.9(m,lH); 4.2(m,2H); 5.0(s,2H); 6.7(m,lH); 7.35 (m, 6H) . EXftMPLE 13 1-fN-f (R)-2-Benzyl-fS,-5-t-butoxycartonylamino- (S)-4-t-butyl- dimethylsilyloxy-6-phenylhexanoyl)-fS,-valyll-4-benzyloxycarbonyl- aminopiperidine The title compound was prepared by the same procedure as described for Exairple 3 by reacting the amine derived from the product of Example 12 with an active ester derived from the product from intermediate preparation (2b) . m/e 843 (MH) + N.M.R (DMSO-d 6 ) δ = 0.1(s,6H); 0.8(m,6H); 0.9(s,9H); 1.1- 2.0(m,7H); 1.3(s,9H); 2.4-2.9(m,6H) ; 3.1(m,lH); 3.5(m,lH); 3.7(m,lH); 4.0(m,lH); 4.2(m,lH); 4.5(m,lH); 5.0(s,2H); 6.75(m,lH); 7.1-7.5(m,16H) ; 7.85(d,lH). EXftMPLE 14 1-fN-ffR.-2-Benzyl-fS)-5-t-butoxycarbonylamino-fS)-4-hydroxy-6- phenylhexanoyl)-fS.-valyll-4-benzyloxycarbonylaminopiperidine The title compound was prepared from the product of Example 13 by the same procedure as described for Example 4, m.p. 185-187°. Found: C,69.51; H,7.72; N,7.67. C H 56 N.O requires C,69.2; H,7.74; N,7.69%. m/e 729 (MH) + N.M.R (DMSO-d..) δ = 0.75(m,6H); 1.3(s,12H); 1.6(m,2H); o 1.7(m,lH); 1.85(m,lH); 2.5(m,2H); 2.7-2.9(m,4H) ; 3.1(m,lH); 3.4(m,lH); 3.5(m,2H); 3.85(m,lH); 4.15(m,IH) ; 4.5(m,lH); 4.55(m,lH); 5.0(s,2H); 6.4(t,lH); 7.0-7.5(m,16H) ; 7.75(d,lH). EXftMPLE 15 4-Amino-l-TN-ffR)-2-benzyl-fS)-5-t-butoxy(ar--x.nylaιιύnc>- (S)-4- hvdroχy-6-phenylhexanoyll-fS)-valyllpiperidine The title compound was prepared from the product of Example 14 by the same procedure as described for Example 5. Found: C,68.42; H,8.37; N,9.29. C^H^N^ requires C,68.60; H,8.47; N,9.42%. m/e 595 (MH) + N.M.R. (πiSO-d δ = 0.7(m,6H); 1.0(m,2H); 1.3(s,10H); 1.6(m,lH); 1.7(m,2H); 1.85(m,lH); 2.5-3.05(m,8H) ; 3.4(m,lH); 3.55(m,lH); 3.8(m,lH); 4.1(m,lH); 4.45(m,lH); 4.5(m,lH); 6.4(d,lH); 7.2(m,12H); 7.75(d,lH). EXftMPLE 16 1-fN-t-Butoxycarbonyl)-fS)-valyl-4-ethylaminopiperidine The title compound was prepared by the same procedure as described for intermediate 3b) by reductive amination of intermediate 3a) with ethylamine. N.M.R. (DMSO-dg) δ = 0.8(m,6H) ; 1.0(t,3H); 1.2(m,2H); 1.4(s,9H); 1.8(m,2H); 1.9(m,lH); 2.5(q,2H); 2.6-2.8(m,2H) ; 3.0(m,lH); 3.9(m,lH); 4.2(m,2H); 6.7(dd,lH). EXAMPLE 17 4- f N-Benzyloxycartonyl-N-ethylamino) -1-f N-t-butoxycarbonyl) - (S) - valylpiperidine The title compound was prepared from the product of Example 16 by the same procedure as described for intermediate (4b) . N.M.R. (EMS0-d 6 ) δ = 0.8(m,6H); 1.0(t,3H); 1.35(s,9H); 1.4- 1.8(m,4H); 1.9(m,lH); 2.5(m,2H); 3.0-3.2 (m,2H) ; 3.9-4.3 (m,3H) ; 4.5(m,lH); 5.1(s,2H); 6.7 & 6.9(2 d,lH); 7.4(m,5H). EXftMPLE 18 1-N- f f R. -2-Benzyl- f S) -5-t-butoxycarbonylamino- f S) -4-t-butyl- d-uτ-et-hylsilyloxy-6-phenylhexanoyl) - f S) -valyll -4- f N-benzyloxy- carbonyl-N-ethylamino) piperidine The title cxtπpound was prepared by the same procedure as described for Example 3 by reacting the amine derived from the product of Example 17 with an active ester derived from the product from intermediate preparation (2b) . Found: C,68.34; H,8.38; N,6.43. C^K^N^Si.- 1 /^ 11 -, 0 requires C,68.16; H,8.52; N,6.36%. m/e 871 (MH) + [α] 25 -13° (C = 0.12%, MeOH) N.M.R. (DMS0-d 6 ) ^ = 0.1(s,6H); 0.8(m,6H); 0.9(s,9H); 1.0(m,3H); 1.2(s,9H); 1.2-1.7 (m,6H) ; 2.0(m,2H): 2.4-3.0 (m, 6H) ; 3.0-3.2(m,2H); 3.6(m,lH); 3.7(m,lH); 3.8-4.1(m,2H) ; 4.45(m,2H); 5.1(s,2H); 6.75(d,lH); 7.2(m,10H); 7.4(m,5H); 7.8 & 7.9 (2X d, lH) . EXftMPLE 19 1-TN-ffR)-2-Benzyl-fS)-5-t-butoxycarbonylamino-fS)-4-hvdroxy-6- phenylhexanoyl)- (S)-valyll-4-fN-ben- loxycarbonyl-N-ethylamino)- piperidine The title ∞rrpound was prepared from the product of Example 18 by the same procedure as described for Example 4. Found: C,69.59; H,7.85; N,7.43. C^HggN j O-, requires C,69.81; H,7.99; N,7.43%. m/e 757 (MH) + [α] D 25 -10° (c = 0.1%, MeOH) N.M.R. (DMSO-d δ = 0.75(m,6H) ; 1.0(m,3H); 1.25(s,9H); 1.2- 1.7(m,6H); 1.9(m,lH); 2.4-2.6(m,4H) ; 2.6-2.9( ,3H) ; 3.0- 3.2(m,2H); 3.4(m,lH); 3.55(m,lH); 3.8-4.1(m,2H) ; 4.4-4.6(m,3H) ,* 5.1(m,2H); 6.4(m,lH); 7.1-7.3(m,10H) ; 7.4(m,5H); 7.8 & 7.9(2x d,lH). EXAMPLE 20 1-TN-ffR)-2-Benzyl-fS)-5-t-butowcarbonylamino-fS)-4-hvdroχy-6- phenylhexanoyl)-fS)-valyll-4-^thylaminopiperidine The title α-mpound was prepared from the product of Example 19 by the same procedure as described for Example 5. Found: C,69.34; H,9.06; N,9.27. C 3 gH 54 N 4 0 5 requires C,69.42; H,8.74; N,9.00%. m/e 623 (MH) + [α] 25 -10° (c = 0.11%, MeOH) N.M.R. (DMSC-d 6 ) * = 0.7(d,6H); 0.95(t,3H) ; 1.0-l.l(m,2H) ; 1.2(s,9H); 1.4-1.9(m,5H); 2.4-3.0(m,10H); 3.4(m,lH); 3.55(m,lH); 3.8(m,lH); 4.1(m,lH); 4.45(t,lH); 4.5(t,lH); 6.4(m,lH); 7.1-7.3(m,10H); 7.8(m,lH). EXAMPLE 21 (S)-5-ffS)-l-t-Butoxycarbonylamino-2-phenethyl,-fR)-3-f3- phenylprop-2-enyl)-qamma-butyrolactone. The title compound was prepared by the same procedure as described for Intermediate Preparation (2a) by alkylation of the lactone with l-bromo-3-phenylprop-2-ene. Found: C,73.95; H,7.22; N,3.29. C- 6 H 31 0 4 requires C,74.08; H,7.41; N, 3.32%. m/e 421 (MH + ) [α] 25 +1° (c = 0.1%, MeOH) D N.M.R. (DMSO-d δ = 1.24(s,9H) ; 2.05(m,lH) ; 2.31(m,2H) ; o 2.6(m,lH) ; 2.76 (m,3H) ; 3.81(m, lH) ; 4.5 (m,lH) ; 6.23 (m,lH) ; 6.45(d,lH) ; 7.07 (d,lH) ; 7.32 (m,10H) . EXAMPLE 22 fS)-5-t-Butoxycarbαnylamino-fS)-4-ft-butyldimethylsilyloxy)- (R.-2-f3-phenylprop-2-enyl)-6-phenylhexanoic acid. The title compound was prepared from the product from Example 21 by the same procedure as described for Intermediate Preparation (2b). Found: C,69.53; H,8.59; N,2.52. C 32 H 47 0 5 Si requires C,69.40; H,8.55; N,2.53%. m/e 452 (M + -101) [α] 25 -28° (c = 0.1%, IfeOH) D N.M.R. (DMSO-d,) 5 = 0.1(d,6H); 0.9l(s,9H) ; 1.27(s,9H); o 1.38(m,lH); 1.94(m,lH); 2.41(m,3H); 2.58(m,lH); 2.72(d,lH); 3.62(b,lH); 3.75(b,lH); 6.2(m,lH); 6.43(d,lH); 6.86(d,lH); 7.25(m,10H) ; 12.13(b,IH) . EXftMPLE 23 1-ΓN-ffS)-5-t-Butoxyoarbonylaitr-i.no-fS)-4-t-butyldimethylsilyloχy-6- phenyl-fS)-2-f3-phenylprop-2-en-l-yl))hexanoyl-fS)-valyll-4-keto¬ piperidine The title cxmpαund was prepared from the product from Example 22 and the product from Ihte-cmediate Preparation (3a) by the same procedure as described for Intermediate Preparation (5b) . Found: C,68.63; H r 8.80; N,5.71. C^H^ j OgSi requires C,68.72; H,8.65; N,5.72%. m/e 734 (MH + ) [α] 25 +5° (c = 0.1%, MeOH) D N.M.R. (CDC j ) δ = 0.13(d,6H); 0.92(m,6H); 1.0(s,9H); 1.37(s,9H); 1.72(m,lH); 1.85(m,lH); 2.0-2.45(m,7H) ; 2.52(m,lH); 2.72(m,2H); 3.52(m,lH); 3.77(m,4H); 4.0(m,lH); 4.72(m,2H) ; 6.1(m,lH); 6.25(d,lH); 6.33(d,lH); 7.3(m,10H). EXftMPLE 24 1-fN-f fS) -5-t-Butoxycartonylamino-f S) -4-t-butyldimethylsilyloxy-6- phenyl- f S) -2- f 3-phenylprop-2-en-l-yl) hexanoyl) - f S) -valyll -4- methylairiinopiperidine The title compound was prepared by the same procedure as described for Example 7 fcy reacting the product from Exairple 23 with etiiylamine. N.M.R. (DMSO-d 6 ) δ = 0.13(s,6H); 0.71(m,6H); 0.9(s,9H); 1.15(b,2H); 1.27(s,10H); 1.72(m,2H); 1.98(m,2H); 2.21(s,3H); 2.32(b,2H); 2.5(b,2H); 2.67(m,lH); 2.73-3.95 (m, 2H) ; 4.14(m,lH); 3.58(b,lH); 3.7(b,lH); 3.92(m,lH); 4.10(m,lH); 4.53(m,lH); 6.13(m,lH); 6.35(m,lH); 6.79(m,lH); 7.22(m,10H); 7.93(m,lH). EXftMPLE 25 1- f N- ( f S) -5-t-Butoxycartonylamino- f S) -4-hvdroxy-6-phenyl- f S) -2- f 3-phenylprop-2-en-l-yl) hexanoyl) - (S) -valyll -4-ιrethylamino- piperidine The title compound was prepared from the product from Example 24 by the same procedure as described for Example 2, m.p. 149-151°. Found: C, 69.98; H,8.53; N,8.66. C. ^ H 4 N.0 5 requires C, 70.00 ; H,8.57; N,8.82%. [α] 25 + 16° (c = 0.1%, MeOH) D N.M.R. (DMSO-dg) δ = 0.76(d,6H) ; 0.92(m,lH); 1.07(m,lH); 1.27(s,9H); 1.33(m,lH); 1.65(m,3H); 1.9(m,lH); 2.18(s,3H); 2.3(m,2H); 2.43(m,2H); 2.58(m,lH); 2.76(m,2.5H) ; 3.08(t,0.5H) ; 3.41(m,lH); 3.55(m,lH); 3.73(m,lH); 4.04(m,lH); 4.52(m,lH); 4.6(d,lH); 6.08(m,lH); 6.31(m,-lH) ; 6.42(d,lH); 7.24(m,10H); 7.85(m,lH). EXAMPLE 26 4-Amino-l-fN-ffS)-5-t-butoχycarbonylaιτtino-fS)-4-t-butyldimethyl- silyloxy-6-phenyl-fS)-2-f3-phenylprop-2-en-l-yl)hexanoyl-fS)- valyl1piperidine The title compound was prepared by the same procedure as described for Example 7 by reacting the product from Example 23 with ammonium acetate. m/e 735 (MH + ) N.M.R. (DMSO-dg) δ = 0.17(s,6H); 0.85(m,6H); 0.93 (s,9H); 1.22(b,2H); 1.31(s,10H); 1.68(b,2H); 2.0(b,2H); 2.34(m,2H); 2.46(b,lH); 2.54(1H); 2.65-2.95(m,3.5H) ; 3.13(m,0.5H) ; 3.62(b,lH); 3.71(b,lH); 3.93(b,lH); 4.17(b,lH); 4.58(m,lH); 6.l9(m,lH); 6.38(1H); 6.81(m,lH); 7.3(m,10H); 7.93(t,lH). EXAMPLE 27 4-Amino-l- fN- f f S) -5-t-buto-xycartonylamir-o- f S) -4-hvdroχy-6-pheπyl- f S) -2- f 3-phenylprop-2-en-l-yl) hexanoyl) - f S) -valyll piperidine The title compound was prepared by the same procedure as described for Exairple 26, m.p. 111-112°. Found: C,69.44; H,8.53; requires C,69.64; H,8.44; N,9.02%. [α] 25 + 18° (c = 0.1% MeOH) D N.M.R. (EMSO-dg) δ = 1.27(d,6H); 1.05(m,2H); 1.23(s,9H); 1.33(m,lH); 1.64 (b,3H); 1.9(m,lH); 2.l8(m,lH); 2.35(m,2H); 2.58(m,lH); 2.72(m,3.5); 3.05(m,0.5); 3.41(b,lH); 3.55(b,lH); 3.85(m,lH); 4.1(m,lH); 4.52(m,lH); 4.6(d,lH); 6.09(m,lH); 6.32(m,lH); 6.42(d,lH); 7.26(m,10H); 7.85(d,lH). EXftMPLE 28 1-rN-ffS)-5-t-Butoxycartonylamino-fS)-4-hvdroχy-6-phenyl-fS)-2-f3- phenylprop-1-yl)hexanoyl)-fS)-valyll-4-methylaιrι-i-r3piperidine A solution of the product from Example 25 (0.25 g) in absolute ethanol was treated with 10% palladium on charcoal (25 mg) . The mixture was stirred at room temperature under hydrogen at a pressure of 30 psi (2 bar) for 4 hours. The catalyst was filtered and the solvent evaporated under vacuum to give a foam which was purified by chrϋmatography on silica-gel, eluting with methylene chloride-methanol-c»ncentrated aqueous ammonia. After evaporation of the product fractions the residue was recrystallised from ethyl acetate/hexane to afford the title ∞mpσund m.p. 101-105°. Found: C,68.89; H,8.79; N,8.68. C 37 H 5 g 4 0 5 . 0.4 EtoAC requires C,68.97; N,8.87; N,8.33%. m/e 637 (MH + ) [α] 25 - 5° (c = 0.1%, MeOH) N.M.R. (EMSO-d 0.75(d,6H); 1.04(m,2H); 1.26(s,llH); 1.4(m,3H); o 1.59(m,lH); 1.74(m,2H); 1.92(m,lH); 2.24(d f ^H); 2.5(b,6H); 2.75(m,2H); 3.05(m,lH); 3.37(m,lH); 3.55(κ.lH); 3.91(m,lH); 4.12(m,lH); 4.56(m,2H); 6.42(d,lH); 7.17(m,10H); 7.83(d,lH). EXftMPLE 29 fS)-5-ffS)-l-t-Butoxycarbonylamino-2-phenylethyl)-fR)-3-f4- methylbenzyl)-αamma-butyrolactone. The title compound was prepared by the same procedure as described for Intermediate Preparation (2a) by alkylation of the lactone with 4-methylbenzyl bromide. Found: C,73.28; H,7.65; N,3.40. C 25 H_ 1 N0 4 requires C,73.32; H,7.63; N,3.42%. [α] - 20° (c = 0.1% MeOH) . D N.M.R. (CDC1 3 ) δ = 1.36(s,9H); 1.97(m,lH); 2.22( ,IH) ; 2.32(s,3H); 2.76(m,lH); 2.75(m,2H); 2.94(m,lH); 3.07(d,d,lH) ; 3.95(m,lH); 4.24(t,lH); 4.53(d,lH); 7.l3(d,d,lH) ; 7.26(m,5H). EXAMPLE 30 f S) -5-t-Butoxycarbonyla nino- f S) -4- f t-butyldimethylsilyloxy) - fR)-2-f4-methylbenzyl)-6-t-henylhexanoic acid. The title compound was prepared from the product from Example 29 by the same procedure as described for Intermediate Preparation (2b) . Found: C,68.94; H,8.69; N,2.55. C 31 H 47 N0 5 Si requires C,68.72; H,8.74; N,2.58%. m/e 542 (MH + ) N.M.R. (DMSO-dg) , <5 = 0.11(m, 6H) ; 0.95(s,9H) ; 1.31(d,9H) ; 1.62 (m,lH) ; 2.0(m,lH) ; 2.33 (d,3H) ; 2.45-3.13 (m, 5H) ; 3.68-4.02 (m,2H) ; 4.75(m, 0.5H) ; 6.3 (m,0.5H) ; 7.0-7.4 (m, 9H) ; 9.4-10.0 (broad, IH) . EXftMPLE 31 1-TN-ffS)-5-t-Butoxyc^rbonylamino-fS)-4-t-butyldimethylsilyloxy- fR)-2-f4-methylbenzyl)-6-phenylhexanoyl)-fS)-valyll-4-keto¬ piperidine The title campound was prepared from the product from Example 30 and the product from -Intermediate Preparation (3a) by the same procedure as described for Intermediate Preparation (5b) . m/e 722 (MH + ) N.M.R. (DMSO-dg) δ = 0.13(s,6H) ; 0.83(d,6H); 0.9(s,9H); 1.25(s,llH); 1.95(m,2H); 2.2(s,3H,); 2.25(m,3H); 2.44(m,2H); 2.55(m,lH); 2.79(m,2H); 3.55(m,2H); 3.71(m,2H); 3.84(m,2H); 4.51(t,lH); 6.77 (d,lH); 7.03(dd,4H); 7.2(m,5H); 8.0(d,lH). EXAMPLE 32 1-ΓN-ffS)-5-t-Butoxytarboπylamino-fS)-4-hvdroxy-fR)-2-f4-methyl- benzyl)-6-rhenylhexanoyl)-fS)-valyll-4-ketopiperidine The title compound was prepared from the product from -Example 31 by the same procedure as described for Exairple 6. m/e 608 (MH + ) N.M.R. (CDC1 3 ) δ = 0.87(d,d,6H); 1.41(s,9H) ; 1.73(b,2H); 1.98(m,lH); 2.26(s,3H); 2.4(m,4H); 2.64(m,lH); 2.87(m,4H); 3.65(m,4H); 3.88(m,lH); 4.00(m,lH); 4.72(t,lH); 4.88(d,lH); 6.38(d,lH); 6.93(q,4H); 7.27(m,5H). EXftMPLE 33 benzyl) -6-ffienyhexanoyl) -f S) -valyll -4-methylaminσpiperidine The title compound was prepared from the product from Example 32 by the same procedure as described for Exairple 7, m.p. 182-184°. Found: C,69.40; H,8.66; N,9.0l. C 3 gH 54 N 4 0 5 requires C,69.42; H,8.74; N,8.99%. m/e 623 (MH + ) [α] 25 - 20° (c = 0.1%, MeOH) D N.M.R. (DMSO-dg) δ = 0.72(d,6H); 1.06(m,2H); 1.29(s,10H); 1.01(m,lH); 1.73(m,2H); 1.88(m,lH); 2.24(d,6H); 2.45(m,lH); 2.52(m,lH); 2.72(m,5H); 3.04(m,lH); 3.42(m,lH); 3.53(b,lH); 3.8(m,lH); 4.08(m,lH); 4.5(m,2H); 6.37(m,lH); 6.98(s,4H); 7.2(m,5H); 7.74(d,lH). EXftMPLE 34 4-Amino-l- ΓN- f f S) -5-t-butoxycartonylamino- f S) -4-hvdroxy- f R) -2- f 4- methylbenzyl) -6-phenylhexanoyl) -f S) -valyll piperidine The title compound was prepared from the product from Exairple 32 by the same procedure as described for Example 8, m.p.167-168 c Found: C,68.87; H,8.37; N,8.96. C^H N 0 requires C, 69.04 ; H,8.61; N,9.20%. m/e 609 (MH + ) [α] 25 -2° (c = 0.1%, MeOH) D N.M.R. (DMSO - d δ = 0.72(d,6H); 1.02(m,2H); 1.25 (b,10H); 1.63(b,5H); 1.86(m,lH); 2.23(s,3H); 2.56(m,1.5H) ; 2.73(b,4.5H) ; 3.02(m,0.5); 3.4(b,lH); 3.52(b,lH); 3.89(m,0.5H) ; 4.1(d,lH); 4.47(m,2H); 6.4(m,lH); 6.97(m,5H); 7.17(m,6H); 7.74(d,lH). EXAMPLE 35 f S) -5- f f S) -l-t-Butoxycartonylamino-2-phenylethyl) - fR) -3- f 3- methylbenzyl ) -qamma-butyrolactone . The title cxampound was prepared by the same procedure as described for Intermediate Preparation (2a) by alkylation of the lactone with 3-methylbenzyl bromide. N.M.R. (CDC1 3 ) δ = 1.36(S,9H); 1.96(m,lH); 2.23(m,lH); 2.30(s,3H); 2.73(dd,lH); 2.88(m,2H); 2.96(m,lH); 3.10(dd,lH); 3.95(q,lH); 4.26(m,lH); 4.53(d,lH); 7.0(m,3H); 7.26(m,6H). EXAMPLE 36 fS)-5-t-Butoxycartonylamino-fS)-4-ft-butyldimethylsilyloxy)- fR)-2-f3-methylbenzyl)-6-phenylhexanoic acid. The title conpound was prepared from the product from Exairple 35 by the same procedure as described for -Intermediate preparation (2b). Found: C,68.60; H,9.11; N,2.63. C_ H 47 N0 5 Si requires.. C,68.72; H,8.74; N,2.58%. m/e 542 (MH + ) [α] 25 -53° (c = 0.1%, MeOH) D N.M.R. (DMSO-dg) δ = 0.1(d,6H); 0.9(s,9H); 1.3(s,9H); 1.3(m,lH); 1.91(m,lH); 2.24(s,3H); 2.55-2.91(complex 5H,) ; 3.56(b,lH); 3.72(b,lH); 6.85(d,lH); 6.98(m,3H); 7.2(6H,m). EXAMPLE 37 1-ΓN-ffS)-5-t-Butoxycarbonylamino-fS)-4-t-butyldimethylsilyloxy- fR)-2-f3-methylbenzyl)-6-phenyhexanoyl)-fS)-valyl -4- ketopiperidine The title compound was prepared from the product from Example 36 and the product from Intermediate Preparation (3a) by the same procedure as described for Intermediate Preparation (5b) . Found: C,67.86; H,8.97; N,5.70. C 41 Hg 3 N 3 0gSi requires C,68.19; H,8.79; N,5.82%. m/e 722 (MH + ) [α] 25 - 16° (c = 0.1%, MeOH) D N.M.R. (EMSO-d,-) δ = 0.08(d,6H); 0.83(broad based singlet 17H); D 1.21(ε,10H); 1.93(m,2H); 2.17(s,3H); 2.25(b,2H); 2.42(m,2H); 2.63(d,lH,); 2.82(m,2H); 3.53(b,2H); 3.65(b,2H); 3.81(b,2H) ; 4.47(t,lH); 6.73(d,lH); 6.9-7.26(m,9H) ; 8.04(d,lH). EXAMPLE 38 1-ΓN- f f S) -5-Butoxycarbonylamino- f S) -4-t-butyldimethylsilyloxy-fR) - 2- f 3-methylbenzyl) -6-pheπylhexanoyl ) - f S) -valyl 1 -4-ιrethylamino- piperidine The title compound was prepared from the product from Example 37 by the same procedure as described for Example 24. Found: C,67.70; H,9.37; N,7.49 C^HggN^Si 0.5 H.,0 -requires C,67.60; H,9.32; N,7.50%. m/e 737 (MH + ) [α] 25 - 10° (c = 0.1% MeOH) D N.M.R. (DMSO-d δ = ~ 0.05(m,6H); 0.78(m,6H) ; 0.83 (s,9H); σ 1.05(m,2H); 1.2(s,10H,); 1.7(m,2H); 1.91(m,2H); 2.22(d,6H); 2.38(b,2H); 2.48(m,lH); 2.6-2.85 (complex 4.5H) ; 3.05(m,0.5H) ; 3.5(b,lH); 3.62(m,lH); 3.8l(m,lH); 4.05(m,lH); 4.43(m,lH); 6.67(d,lH); 7.06(m,10H); 7.85(dd,lH) . EXftMPLE 39 1-TN-ffS)-5-t-Butoχycarbonylamino-fS)-4-hvdroxy-fR)-2-f3-methyl- benzyl)-6-phenylhexanoyl)-fS)-valyll-4-methylaminopiperidine The title ccmpound was prepared from the product from Example 38 by the same procedure as described for Exairple 2, m.p. 174-176°. Found: C,69.73; H,8.73; N,8.93. C -H H 0 5 requires C,69.42; H,8.74; N,8.99%. m/e 622 (MH + ) [α] 25 +1.0 (c = 0.1% MeOH) N.M.R. (DMSO-dg) <S = 0.73 (d,6H) ; 1.05(m,2H) ; 1.29 (s, 10H) ; 1.61(b,lH) ; 1.71(m,2H) ; 1.85(m,lH) ; 2.24 (s,6H) ; 2.43 (m,2H) ; 2.62 (m,2H) ; 2.76(m,3.5) ; 3.05(m,0.5H) ; 3.42 (b, lH) ; 3.53 (b, lH) ; 3.78 (m,lH) ; 4.07 (m,lH) ; 4.5(m,2H) ; 6.48 (m,lH) ; 6.9 (m,3H) ; 7.15(m,6H) ; 7.77(m,lH) . EXAMPLE 40 1-fN- f f S) -5-t-Butoxycarbonylamino- f S) -4-t-butyldimethylsilyloχy-6- pheπyl- fR) -2- f 3-phenylprop-2-en-l-yl) hexanoyl) - f S) -valyll -4-ethyl- amtinopiperidine The title compound was prepared by the same procedure as described for Exairple 7 by reacting the product from Example 23 with ethylamine. Found: C,68.01; H,9.23; N,7.34. C 4 H_ 0 N,O 5 Si. 0.2 C3LC1 requires C,68.04; H,9.09; N,7.18%. m/e 763 (MH + ) [α] 25 + 12° (c = 0.1 MeOH) D N.M.R. (DMSO-dg) 5 = 0.1(s,6H); 0.72(m,6H); 0.9(s,9H); l.θ(m,5H); 1.27(s,10H); 1.7(m,2H); 1.98(m,2H); 2.31(m,2H) ; 2.5(m,5H); 2.64(m,lH); 2.8-3.05(complex, IH) ; 3.57(m,lH); 3.68(m,lH); 3.92(m,lH); 4.10(m,lH); 4.62(m,lH); 6.14(m,lH); 6.34(m,lH); 6.79(m,lH); 7.25(complex; 10H) ; 7.92(m,lH). EXftMPLE 41 1-TN-ffS)-5-t-Butoxycarbonylamino-fS)-4-hvdroxy-6-rhenyl-fR)-2-f3- phenylprop-2-en-l-yl)hexanoyl)-fS)-valyl " )-4-ethylaminopjperidine The title compound was prepared from the product from Example 40 fcy the same procedure as described for Example 2, m.p. 152-154°. Found: C,70.60; H,8.91; N,8.60. C 3g H 5 gN 4 0 5 requires C,70.33; H,8.69; N,8.63%. m/e 649 (MH + ) [α] + 19° (c = 0.1% MeOH) N.M.R. (DMSO-dg) δ = 0.73(d,6H); 0.96(m,3H); 1.09(m,2H); 1.26(s,9H); 1.47(m,lH); 1.66(m,3H); 1.92(m,lH); 2.19(m,lH); 2.38(m,2H) ; 2.55-3.15(complex 7H) ; 3.42(m, H) ; 3.57(m, IH) ; 3.87(m,lH); 4.10(m,lH); 4.5(m,lH); 4.62(d,lH); 6.1(m,lH); 6.37(m,2H); 7.24(m,10H); 7.88(d,lH). EXftMPLE 42 1- ΓN- f f S) -5-t-Butoxycartonylam-ino- f S) -4-t-butyldimethylsilyloxy- 6-phenyl- f R) -2- f 3-rhenylprop-2-en-l-γl) hexanoyl) - f S) -isoleucyll - 4-ketopiperidine The title compound was prepared from the product from Exairple 22 and the product from Intermediate Preparation (5a) by the same procedure as described for Intermediate Preparation (5b) . Found: C,68.70; H,9.00; N,5.62. C^Hg^OgSi requires C,69.03; H,8.76; N,5.62%. m/e 748 (MH + ) [α] 25 = +22° (c = 0.1% MeOH) D N.M.R. 0.13(s,6H); 0.81(m,6H); 0.92(s,9H); 1.2(m,3H); 1.29(s,9H); 1.55(m,lH); 1.72(m,lH); 2.05(m,2H); 2.3(m,3H); 2.45(m r 2H); 2.67(b,lH); 2.8(m,lH); 3.5-3.8(m,5H) ; 3.9(m,lH); 4.6(m,lH); 6.17(m,lH); 6.33(m,lH); 6.78(d,lH); 7.23(m,10H); 8.l2(d,lH). EXftMPLE 43 1-fN-f fS) -5-t-Butoχycartoπylamino—fS) -4-t-butylά methylsilyloxy- 6-phenyl- f R) -2- f 3-phenylprop-2-en-l-yl) hexanoyl) - f S) -isoleucyll - 4-methyla- nopiperidine The title ccmpound was prepared by the same procedure as described for Example 7 by reacting the product from Example 42 with methylamine. Found: C,68.04, H,9.09; N,7.18. C 44 H 70 N 4 O-.Si. 1/5 CH-C1 requires C, 67.76; H,9.09; N,7.19%. m/e 763 (MH + ) [o.] 25 + 4° (c = 0.1% MeOH) N.M.R. (DMSO-d δ = 0.l2(s,6H) ; 0.78(m,6H); 0.9(s,9H); 0.95-1.15(m,4H); 1.29(s,9H); 1.49(b,lH); 1.73(m,3H); 2.01(b,lH); 2.22(s,3H); 2.31(m,3H); 2.5(m,2H); 2.65(b,lH); 2.82(m,lH); 2.93 + 3.12(m,lH); 3.63(m,2H); 3.85-4.2 (m,2H) ; 4.55(m,lH); 6.l3(m,lH); 6.33(dd,lH); 6.27(m,lH); 7.25(m,10H); 7.97(dd,lH). EXftMPLE 44 1-fN- f f S) -5-t---^toxycarbonylaπrino-4-hvdroxy-6--^ enyl- fR) -2 f 3- phenylprop-2-en-l-yl) hexanoyl) - f S) -isoleucyll -4-met-hylamir.o- piperidine The title compound was prepared from the product from Exairple 42 by the same procedure as described for Exairple 2, m.p. 145-147° . Found: C,67.39; H,8.63; N,8.25. O. H-. JJ^ 3/2 1^0 requires C,67.52; H,8.79; N,8.29. m/e 649 (MH + ) [α] 25 = +6° (c = 0.1% MeOH) D N.M.R. (DMSO-d..) δ = 0.73(m,6H); 0.82-1.17(m,3H) ; 1.26(s,10H); b 1.38(b,lH); 1.7(m,4H); 2.2(s,4H); 2.3(m,lH); 2.43(m,3H); 2.52-2.82(m,3H); 2.86(m,0.5); 3.10(m,0.5); 3.4(b,lH); 3.57(m,lH); 3.8-4.l6(m,2H); 4.58(m,2H); 6.08(m,lH); 6.32(m,lH); 6.43(d,lH); 7.22(m,10H) ; 7.88(t,IH) . EXAMPLE 45 1-fN-ffS)-5-t-Butoxycarbonylamino-fS)-4-t-butyldimethylsilyloxy- 6-phenyl-fR)-2-f3-phenylprop-2-en-l-yl)hexanoyl)-fS)-isoleucyll- 4-ethylaminopiperidine The title compound was prepared by the same procedure as described for Example 7 by reacting the product from Exairple 42 with ethylamine. Found: C,68.46; H,9.22; N,7.24. C JL N 0-.Si 0.2 CH 2 C1 2 requires C,68.36; H,9.18; N,7.05%. m/e 777 (MH + ) ?5 [α] + 6° (c = 0.1% MeOH) D N.M.R. (DMSO-d..) δ = 0.11(s,6H) ; 0.78(m,6H); 0.91(s,9H); o 0.97(m,5H); 1.12(m,lH); 1.24(s,10H); 1.46(b,lH); 1.71(m,3H); 2.02(m,lH); 2.3(m,2H); 2.50(m,5H); 2.62(b,lH); 2.78(m,lH); 2.85-3.15(m,lH); 3.64(m,2H); 3.85-4.2(m,2H) ; 4.56(m,lH); 6.12(m,lH); 6.32(m,lH); 6.75(m,lH); 7.24(m,10H); 7.9(dd,lH). EXftMPLE 46 1-ΓN-ffS)-5-t-Butoxyc^rbonylamino-fS)-4-hvdroxy-6-tAιenyl-fR)-2- f3-phenylprop-2-en-l-yl)hexanoyl-fS)-isoleucyl-4-el±ylamιino- piperidine The title c-ompound was prepared from the product from Example 45 by the same procedure as described for Example 2, m.p. 150-151°. Found: C,69.85; H,8.70; N,8.34. C^H^N^ 0.51^0 requires C69.71; H,8.85; N,8.34%. m/e 663 (MH + ) [α] 25 + 14° (c = 0.1% MeOH) D N.M.R. (DMSO-dg) δ = 0.75(m,6H); 0.97(m,5H); 1.03(m,lH); 1.25(s,9H); 1.35(m,2H); 1.69(m,4H); 2.18(m,lH); 2.33(m,lH); 2.4-2.84(m,7H); 2.85(m,0.5); 3.l8(m,0.5); 3.4(m,lH); 3.55(m,lH); 3.8-4.15(m,2H); 4.59(m,2H); 6.09(m,lH); 6.32(m,lH); 6.42(d,lH); 7.23(m,10H) ; 7.37(t,IH) . EXAMPLE 47 4-Acetamidσπethylpyridine An ice-cooled solution of 4-aπtincHretftylpyridine (25 g) and triethylamine (34.8 g) in methylene chloride (100 ml) was treated with a solution of acetic anhydride (30.5 g) in methylene chloride (50 ml) over 15 minutes. The reaction was allowed to warm to room temperature where it was stirred overnight before being washed with saturated brine (25 ml) , dried (MgSO ) and evaporated under vacuum to provide a dark brown semi-solid (45 g, still contains triethylamine) which was used directly for the next stage. EXAMPLE 48 l-t-Butoxycartonyl-4-ac^tamidoιrethylpiperidine A solution of the product from Example 47 (45 g) in acetic acid (300 ml) was treated with platinum oxide (0.5 g) and was stirred under an atmosphere of hydrogen at 60 psi (4.1 bar) and 60°C for 24 hours before the solvent was removed by evaporation under vacuum. A solution of the residue in methylene chloride (300 ml) was treated at room teiiperature with di-tert-butyl dicarbonate (50.2 g) and stirred for a further 18 hours. The reaction was diluted with methylene chloride (150 ml) and washed with water (3 x 150 ml) , dried (MgSO ) and evaporated under vacuum to give a light brown solid which was triturated with hexane, filtered and dried under vacuum to provide the title compound, (24.1 g) , m.p. 90-92°. Found: C,60.89; H,9.32; N,10.81. requires C, 60.94; H,9.40; N, 10.94%. m/e 256 M + N.M.R (DMSO-d-) δ = 0.95 (m,2H) ; 1.4 (s,9H) ; 1.45-1.6 (m, 3H) ; 1.8 (S, 3H) ; 2.65 (m,2H) ; 2.9 (t,2H) ; 3.9 (m,2H) ; 7.85 (t, lH) . EXftMPLE 49 l-t-B^toxycartonyl-4-aιr nomethylpiperidine A solution of the product from Example 48 (21 g) and sodium hydroxide (9 g) in methanol (100 ml) and water (20 ml) was heated under reflux for 72 hours. The reaction was allowed to cool and the solution extracted with ethyl acetate (5 x 100 ml) . The ccmb-Lned organic layers were dried (MgSO ) and evaporated under vacuum to provide the title compound as a colourless oil, (12.2 g). m/e 214 M + N.M.R. (EMSC-dg) * = 1.0(m,2H); 1.4(s,9H); 1.7(m,3H); 2.4(d,2H); 2.65(m,2H); 4.0(m,2H). EXftMPLE 50 4-Ben-wloxycar--X3nylaιrunoιre^ A solution of the product from Example 49 (12.2 g) in methylene chloride (150 ml) at room temperature was treated with N-(ben-^lo^carbonylo^)su(^inimide (17.05 g) and the reaction stirred for an additional 4 hours. The solution was diluted with methylene chloride (150 ml) , washed with water (3 x 100 ml) , dried (MgSO and evaporated under vacuum to give a solid residue. Recrystallisation from ethyl acetate/hexane provided the product as a white solid (13.6 g) , m.p. 106-107°. Found: C,64.02; H,8.03; N,7.93. °' 5 H 2° rθ 3 uires C,63.78; H,8.11; N,7.83%. m/e 348.9 (MH) + N.M.R. (EMSO-d 5 = 0.9(m,2H); 1.4(s,9H); 1.6(m,3H); D 2.65(m,2H); 2.9(t,2H); 3.9(m,2H); 5.0(s,2H); 7.4(m,6H). EXftMPLE 51 4-Ben- loxyc^rbonylaιrd-rιomethylpiperidine A solution of the product from Example 50 (5.0 g) in methylene chloride (40 ml) was saturated with hydrogen chloride at 0° and kept at this teπperature for a further 1 hour. The solvent was evaporated under vacuum to give a colourless foam which was dissolved in distilled water (40 ml) and lyophilised to provide the title conpound, 3.77 g. Found: C,57.80; H,7.13; N,9.42. C i jj N 2 0 2 .HC1. 1 / 3 H 2 0 requires C,57.77; H,7.10; N,9.65%. m/e 249.03 (MH) + N.M.R. (DMSO-d,-) δ = 1.2-1.4(m,2H); 1.6-1.8(m,3H) ; 2.8(m,2H); 2.9(t,2H); 3.25(d,2H); 5.0(s,2H); 7.3-7.5(m,6H) ; 8.8(brs,lH) ; 9.2(brs,lH). EXftMPLE 52 4-Benzyloxycz-rbonylamincmethyl-l-fN-t-butoxycartoπ^ - f S) - valylpiperidine A active ester solution previously prepared by stirring together N-t-butoi-ycarbonyl valine (1.91 g) , l- hydrate (1.31 g) , l-(3- cu^net.hylaιι-incprcpyl)-3-ethylcarbα hyό±cchloride (2.2 g) and N,N-diisopπ^ylethylamine (7.7 ml) in methylene chloride (100 ml) for 30 minutes was treated with the product from Example 51 (1.91 g) at room temperature and the reaction stirred for 18 hours at this teπperature. The solvent was evaporated under vacuum and the residue partitioned between ethyl acetate (100 ml) and water (100 ml) . The organic layer was separated, dried (MgSO ) and evaporated under vacuum to give a foam. Purification by chraratography on silica-gel, eluting with ethyl acetate-hexane (80:20) , gave the title compound (3.3 g) . Found: C,63.44; H,8.15; N,9.71. C^H j -^O... 0.5 1^0 requires C,63.32; H,8.31; N f 9.23%. m/e 448.25 (MH) + N.M.R. (DMSO-dg) 5 = 0.8(m,6H) ; 1.0(m,2H) ; 1.35(s,9H) ; 1.65(m,3H) ; 1.9 (m,lH) ; 2.5(m,lH) ; 2.85-3.05 (m, 3H) ; 4.0(m,lH) ; 4.2 (m, H) ; 4.35(m,lH) ; 5.0(s,2H) ; 6.15 & 6.2 (2xd,lH) ; 7.3-7.4 (m,6H) . EXftMPLE 53 1-fN- f fR) -2-Benzyl- f S) -5-t--- rtoxycarbonylamino- f S) -4-t-butyl- d--j^thylsilyloxy-6- henylhexanoyl) -f S) -valyll -4- f N-benzyloxy- carbonylam-inσmethyl) piperidine The title cxj-rpσund was prepared as a colourless foam by reacting the amine derived from the product of Example 52 with the active ester derived from the product of Intermediate Preparation 2b, using the same procedure as described for Exairple 3. Found: C,67.80; H,8.56; N,6.39. C^H-^N^Si. 0.5 H^O requires C,67.88; H,8.42; N,6.46%. m/e 856.93 (MH) + N.M.R. (DMSO-d δ = 0.05(2xs,6H); 0.75-0.9(m,8H) ; 0.85(S,9H); o 1.15(m,lH); 1.2(s,9H); 1.55(m,3H); 1.9(m,2H); 2.4-3.0(m,9H); 3.55(m,lH); 3.65(m,lH); 3.85(m,lH); 4.8(m,lH); 4.95(m,IH) ; 5.0(s,2H); 6.75(t,lH); 7.1-7.4(m,16H) ; 7.8(m,lH). EXftMPLE 54 1-fN-ffR)-2-Benzyl-fS)-5-t--t ttoxy(^arbonylam rιo-4-hydroxy-6-τAιeπyl- hexanoyl)-fS)-valyl-4-fN-ben2^loxyc-arbonylaminomethyl)piperidine The title compound was prepared from the product of Exairple 53 using the procedure described for Exairple 4, m.p. 187-188°. Found: C,69.53; H,7.78; N,7.74. C^H^N^ requires C,69.52; H,7.87; N,7.54%. m/e 742.89 (MH) + [α] D 25 -15° (c = 0.11%, MeOH) N.M.R. (EMSO-d D δ = 0.75(d,6H); 0.7-1.0(m,2H) ; 1.3(s,9H); 1.3(m,lH); 1.6(m,4H); 1.85(m,lH); 2.4-3.0(m,9H) ; 3.4(m,lH); 3.55(m,lH); 3.9(m,lH); 4.3(m,lH); 4.45(m,lH); 4.6(m,lH); 5.0(d,2H); 6.4(d,lH); 7.1-7.35(m,16H); 7.75(m,lH). EXAMPLE 55 1-rN-ffR)-2-Benzyl-fS)-5-t-butoxycartonylamino-fS)-4-hvdroxy-6- phenylhexanoyl)-fS)-valyl-4-methylaminopiperidine The title compound was prepared from the product of Example 54 using the procedure described for Example 5. Found: C,67.91; H,8.51; N,9.12. C 3f -H 52 N 4 0 5 requires C,68.01; H,8.59; N,9.07%. m/e 609.57 (MH) + [α] D +1-8° (C = 0.11%, MeOH) N.M.R. (DMSO-dg) δ - 0.75(d,6H); 0.87(m,4H); 1.25(s,9H); 1.4(m,lH); 1.5-1.8(m,4H); 1.85(m,lH); 2.4(t,2H); 2.45-3.0(m,7H) ; 3.12-3.50(m,2H); 3.6(m, H); 4.35(m,lH); 4.4(m,lH); 4.55(m,lH); 6.4(d,lH); 7.1-7.3(m,10H); 7.8(d,lH). EXftMPLE 56 4-Methylamd-nemethylpyridine A solution of 4-pyridinecarboxaldehyde (30 g) in absolute ethanol (180 ml) was treated with a 33% solution of methylamine in ethanol (180 ml) and 10% palladium on charcoal and was stirred under an atmosphere of hydrogen for 8 hours at room temperature. The catalyst was filtered and the solvent evaporated under vacuum to give a brown oil. Distillation under vacuum provided the title co-rpound as a colourless oil, (23 g) , b.p. 96-98°, ll-mraHg. N.M.R. (CDCL j ) δ = 1.3(brs,lH); 2.4(s,3H); 3.75(s,2H); 7.2(d,2H); 8.5(d,2H). EXAMPLE 57 4-fN-Acetyl-N-met-hylamu-ncgiethyl)pyridine An ice-cooled solution of the product from Exairple 56 (23 g) and triethylamine (29.3 g) in methylene chloride (150 ml) was treated with acetic anhydride (25.5 g) over 30 minutes. The reaction was allowed to warm to room temperature where it was stirred overnight before the solvent was evaporated under vacuum , the residue dissolved in methylene chloride (250 ml) and washed with aqueous sodium hydroxide solution (IN, 100 ml) . The organic layer was dried (Na p 00_) and evaporated under vacuum to give the title compound as a brown oil which solidified on standing. N.M.R. (CDC1 3 ) δ = 2.1 & 2.15(2xs,3H) ; 2.9(2xs,3H); 4.5 & 4.55(2XS,2H) ; 7.1(m,2H); 8.5-8.6(m,2H). EXAMPLE 58 4-fN-AcetylfN-methylam-inomethyl)-1-t-butoxycarbonylpiperidine A solution of the product from Example 57 (17.5 g) in acetic acid (250 ml) was treated with platinum oxide (1.0 g) and was stirred under an atmosphere of hydrogen at 60 psi and 60°C for 48 hours before tiie catalyst was filtered and the solvent removed ty evaporation under vacuum. The residue was partitioned between methylene chloride (200 ml) and water (200 ml) which was treated with aqueous sodium hydroxide solution to pH 10 and then saturated with sodium chloride. The organic layer was separated and the aqueous extracted with methylene chloride (3 x 150 ml) . The combined organic extracts were dried (MgSO ) and evaporated under vacuum to provide the title conpound as a yellow oil which solidified on standing, (13.1 g) . A suspension of this product (16.3 g) in dioxan (120 ml) was treated with di-tert-butyl dicarbonate (24 g) at room teirperature and the reaction stirred for 60 hours. The solvent was evaporated under vacuum and the residue partitioned between methylene chloride (150 ml) and water (150 ml) . The organic layer was washed with aqueous citric acid solution (5%, 100 ml) , dried (MgSO ) and evaporated under vacuum to give a yellow oil. Purification by chrcmatography on silica-gel, eluting with ethyl acetate-methanol (9:1) gave the title compound as a colourless oil which crystallised on standing to a low melting point solid, (19.6 g) . m/e 271.04 (MH) + N.M.R (CDC1 3 ) δ = 1.2(m,2H); 1.4(s,9H); 1.6(m,2H) ; 1.8(m,lH); 2.1(s,3H); 2.65(t,2H); 2.9 & 3.0(2xs,3H); 3.1-3.3(m,2H) ; 4.1(m,2H). EXftMPLE 59 l-t-Butoxycarbonyl-4- f N-irethylaminσmethyl) piperidine The title compound was prepared from the product of Example 58 by the same procedure as described for Example 49. m/e 456.90 (MH) + N.M.R. (CDCl ) δ = 1.15(m,2H) ; 1.4 (s,9H) ; 1.5-1.75 (m,4H) ; 2.45(s,3H) ; 2.5(m,2H) ; 2.7 (t,2H) ; 4.1(m,2H) . EXftMPLE 60 4-fN-Benzyloxycar-.x3nyl-N-πethyla-rιinomethyl -1-t-butoxycarbonyl- pjperidine The title compound was prepared from the product of Exairple 59 by the same procedure as described for Exairple 50. Purification fcy chromatography on silica-gel, eluting with hexane-ethyl acetate (3:2) gave the title compound as a colourless oil. m/e 352.91 (MH) + N.M.R (CDC1 3 ) δ = 1.25(m,2H); 1.4(s,9H); 1.6(m,2H); 1.8(m,lH); 2.65(m,2H); 2.95(s,3H); 3.2(m,2H); 4.1(m,2H) ; 5.1(s,2H); 7.4(m,5H). EXftMPLE 61 4- f N-Benzyloxycarbonyl-N-ιre1^ylaιrιincιmethyl) piperidine The title ccatpound was prepared from the product of Example 60 by the same procedure as described for Exairple 51, m.p. 193-196°. Found: C,59.54; H,7.60; N,9.41. ^--H-^N^.l.lHCl requires C,59.57; H,7.64; N,9.27%. m/e 262 M + N.M.R. (EMSO-d fc_>) δ = 1.3-1.5(m,2H) , 1.7(m,2H) ; 1.9(m,lH) ; 2.7- 3.0(m,5H) ; 3.1-3.3 (m,4H) ; 5.05(s,2H) ; 7.35(m,5H) ; 8.8 (brs,lH) ; 9.2 (brs,lH) . EXAMPLE 62 4-f N-Benzyloxycartonyl-N-iτethylairi-inoirethyl) -1- f N-t-butoxy- carbonyl) - f S) -valylpiperidine A solution of the product of exairple 61 (1.62 g) in N,N- diiϊeidιy--io namide (35 ml) was treated at room teπperature with N-t-buto-xycarborψl-(S)-valine N-hydroxysu∞inimide ester (1.7 g) and N,N-di:Lscpr 3ylethylamine (4.7 ml) and the reaction stirred for 18 hours. The solvent was evaporated under vacuum and the residue partitioned between ethyl acetate (75 ml) and water (75 ml) . The organic layer was separated, washed with aqueous citric acid solution (5%, 50 ml) , saturated brine (50 ml) , dried (MgSO . ) and evaporated under vacuum to a colourless foam. Purification by c±roiratography on silica-gel, eluting with hexane-ethyl acetate (2:1) gave the title cxmpound, (1.96 g) . m/e 462.11 (MH) + N.M.R. (DMSO-d o δ = 0.8(m,6H) ; 0.8-1.2 (m,2H) ; 1.35(s,9H) ; 1.5-1.7(m,2H) ; 1.8-2.0(m,2H) ; 2.55(m,lH) ; 2.85-3.2(m,6H) ; 4.0(m,lH) ; 4.2 (m,lH) ; 4.3 (m,lH) ; 5.05(s,2H) ; 6.7 & 6.8(2xm,lH) ; 7.4(m,5H) . EXftMPLE 63 1-fN- f fR) -2-Benzyl- f S) -5-t-butoxycartonylamino- f S) -4-butyl- d-ijethylsilyloxy-6-rhenylhexanoyl) - f S) -valyl] -4- f N-benzyloxy- cartonyl-N-ιrethylaιr\inoιιethyl) piperidine The title compound was prepared as a colourless foam by reacting the amine derived from the product of Exairple 62 with the active ester derived from the product of Intermediate Preparation 2b, using the same procedure as described for Exairple 3. m/e 871.21 (MH) + N.M.R. (DMSO-d δ = 0.15(S,6H); 0.8-1.15(m,8H) ; 0.9(s,9H); 1.3(s,9H); 1.5(m,lH); 1.55(m,2H); 1.8-2.l(m,3H) ; 2.5- 3.0(m,10H); 3.l(m,2H); 3.6(m,lH); 3.7(m,lH); 3.8-4.1(m,lH); 4.35(m,lH); 4.5(m,lH); 5.1(s,2H); 6.8-8.0(m,17H) . EXftMPLE 64 phenylhexanoyl) - f S) -valyll -4- f N-ben-^loxycarbonyl-N-irethylamino- methyl) piperidine The title compound was prepared as a colourless foam from the product of Exairple 63 using the procedure described for Exairple 4. Found: C,70.05; H,8.07; N,7.34. C..H g0 N O requires C,69.81; H,7.99; N,7.40%. m/e 757.06 (MH) + [α] D 25 -8° (c = 0.1%, MeOH) N.M.R. (DMSO-dg) d = 0.75(m,6H) ; 0.8-1.0(m,2H) ; 1.3(s,9H); 1.3(m,lH); 1.5-1.7(m,3H); 1.85(m,2H); 2.4-2.6 (m, 4H) ; 2.7- 2.9(m,6H); 3.1(m,2H); 3.45(m,lH); 3.55(m,lH); 3.9(m,lH); 4.8(m,lH); 4.4-4.6(m,2H); 5.1(m,2H); 6.4(d,lH); 7.1- 7.4(m,15H); 7.75(m,lH). EXftMPLE 65 1- fN- f f R) -2-Benzyl- f S) -5-butoχycarbonylamino-4-hydroxy-6-tAιenyl- hexanoyl) - f S) -valyl " ) -4-ιrethylaminomethylpiperidine The title compound was prepared as a colourless f c from the product of Example 64 using the procedure describe, ior Exairple 5. Found: C,69.26; H,8.43; N,8.88. CJ1 NO. require;. C,69.45; H,8.68; N,9.00%. m/e 623.11 (MH) + [α] 25 -1° (c = 0.1%, MeOH) N.M.R. (DMSO-dg) δ = 0.8(d,6H); 0.8-1.0^,2^; 1.3 (m, IH) ; 1.3(S,9H); 1.6-1.8(m,4H); 1.85(m,lH); 2.25(S,3H); 2.8(t,2H); 2.4-3.1(m,7H); 3.45(m,lH); 3.55(m,lH); 3.9(m,lH); 4.3(m,lH); 4.5(m,lH) ; 4.6(m,lH) ; 6.4(d,lH) ; 7.05-7.29 (m,10H) ; 7.73 (d,lH) . EXftMPLE 66 fS)-5-t-Butoxycartonylamino-fS)-4-ft-butyldimethylsilyloxy)- fR)-2-r4-f2-pheπyl-2H-tetrazol-5-yl)benzyl!-6-pheπylhexanoic acid. The title cσampound was prepared by the same procedure as descri-tβd for Intermediate Preparation 2 using 5-(4-brσmιobenzyl)-2-phenyl- 2H-tetrazole. N.M.R. (EMSC-dg) S = 0.12(d,6H); 0.91(s,9H) ; 1.30(s,9H); 1.42(t,lH); 1.97(t,lH); 2.50(m,2H) ; 2.72-3.04(m,4H) ; 3.61(t,lH); 3.76(d,lH); 6.88(d,lH); 7.10-7.28(m,5H) ; 7.42(d,2H); 7.61-7.73(m,3H); 8.11(d,2H) ; 8.17(d,2H). EXftMPLE 67 4-fN-Benzyloxycarbonyl-N-ιrethylamino) -1-rN-f f S) -5-t-butoχy- carboπylamino-f S) -4-t-butyldi-methylsilyloxy-6-phenyl-fR) -2-r4- f 2- phenyl-2H-tetrazol-5-yl) benzvπhexanoyl) -f S) -valyl'l .pe . i τ*=> The title compound was prepared from the product of Example 66 and the product from Intermediate Preparation (4b) by the same procedure as described for Example 3. m.p. 103-106° . Found: C,67.35; H,7.75; N,11.09. C 5 gH 7 gN g 0 7 Si requires C,67.11; H,8.06; N,11.18%. m/e 108 (M + NH 4 ) + N.M.R. (DMSO-dg) δ = 0.15(d,6H); 0.82-0.91(m,6H) ; 0.93(s,0H); 1.4(d,9H); 1.5 (broads 3H); 1.90-2.10(broad 2H) ; 2.52(s,7H); 2.56-2.78(m,6H) ; 2.85-3.10(m,2H) ; 3.58(broad s,IH) ; 3.73(broad,IH); 3.80-4.14(m,2H) ; 4.35-4.58(m,2H) ; 5.03(s,2H); 6.70(t,lH); 7.11-7.46(m,l2H); 7.58-7.69(m,3H) ; 7.94(dd,lH); 8.04(d,2H); 8.13(d,2H). EXftMPLE 68 4-fN-Benzyloxycartonyl-N-mel±ιylamino-1-fS)-5-t-butoxycarboπyl- amino-fS)-4-hvdroxy-6-ι^enyl-fR)-2-r4-f2-phenyl-2H-tetrazol-5-yl)- benzyllhexanoyl1-fS)-valylpiperidine The title compound was prepared from the product of Example 67 by the same procedure as described for Example 4. Found: C,67.80; H,6.84; N,12.70. C 5() Hg 2 N 8 0 7 requires C,67.70; H,7.04; N,12.63%. m/e 887 (MH + ) N.M.R. (DMSO-dg) δ = 0.77 (d, 6H) ; 1.30 (S,9H) ; 1.38-1.55 (m,3H) ; 1.70 (t, lH) ; 1.88 (m,lH) ; 2.52 (s, 3H) ; 2.35-2.80 (m,2H) ; 2.61 (S,2H) ; 2.68(s,2H) ; 2.87-3.07(m,2H) ; 3.46 (broad, IH) ; 3.59 (broad, IH) ; 3.90-4.11(m,2H) ; 4.31-4.57(m,3H) ; 4.60(d,lH) ; 5.03(s,2H) ; 6.44 (d,lH) ; 7.l2-7.39(m,l2H) ; 7.59-7.72 (m, 3H) ; 7.88 (dd,lH) ; 8.03 (d, 2H) ; 8.16 (dd, 2H) . EXftMPLE 69 1-ΓN-ffS)-5-t-&αtoxy(-arbonylaιtuno-4-hvdrOχy-6-τAιenyl-fR)-2-r4-f2- pheπyl-2H-tetrazol-5-yl)benzyl1hexanoyl-fS)-valyll-4-ιretoylamino- piperidine The title compound was prepared from the product of Example 68 by the same procedure as described for Exairple 5. Found: C,66.89; H,7.27; N,14.97. C^HggNgO.. requires C,67.00; H,7.50; N,14.88%. N.M.R. (DMSO-dg) δ = 0.73(d,6H); 0.85-1.08(m,2H) ; 1.31(s,9H); 1.54-1.74(m,2H); 1.78-1.89(m,lH); 2.l3(d,3H); 3.73(dd,lH); 3.98(t,lH); 4.47(dt,lH); 4.64(dd,lH) ; 6.47(dd,lH); 7.l2-7.26(m,5H); 7.37(d,2H); 7.61-7.74(m,3H) ; 7.80(t,lH); 8.04(m,2H) ; 8.18(d,2H) . m/e 753 (MH) + EXftMPLE 70 fS)-5-TfS)-l-t-Butoxycarbonylamιi-no-2-phenylethyll-fR)-3-f3- chlorobenzyl)-cramma-but-yrolactone. The title conpound was prepared ty the same procedure as described for Intermediate Preparation (2a) by alkylation of the lactone with 3-chlorobenzyl bromide. Found: C,66.78; H,6.73; N,3.17. C H_ C1NO requires C,67.05; H,6.56; N,3.17%. [α] D 25 -7.4° (c = 0.1%, MeOH) m/e 447.43, 449.50 (MNH 4 ) + N.M.R. (CDC1 3 ) δ = 1.4(s,9H); 2.0(m,lH); 2.3(m,lH); 2.75(dd,lH); 2.9-3.1(m,3H); 3.15(dd,IH) ; 4.0(q,lH); 4.3(t,lH); 4.55(d,lH); 7.0-7.4(m,9H). EXftMPLE 71 f S) -5-t-Butoχycarbonylamino- f S) -4-t-butyldimethylsilyloxy- fR) - 2-f3-chlorobenzyl) -6-phenylhexanoic acid. The title compound was prepared from the product from Exairple 70 by the same procedure as described for Intermediate Preparation (2b) , m.p. 65-67° (glass) . Found: C,63.90; H,7.50; N,2.40. C 3() H 44 Cl 0 5 Si -requires C,64.00; H,7.90; N,2.50%. m/e 562.09, 563.92 [α] D 25 -24° (C = 0.1%, IfeOH) N.M.R. (CDC1 3 ) δ = 0.05(d,3H) ; 0.15(d,3H) ; 0.95(s,9H) ; 1.4(s,9H) ; 1.6(m,2H) ; 2.4-3.1(m,5H) , 3.85(d,lH) ; 4.0(dd,lH) ; 4.8 (d, IH) ; 6.9-7.4 (m, 9H) . EXftMPLE 72 1-rN-f f S) -5-t-Butoxycartoπylaπ-ino-fS) -4-t-butyl iτrathylsilyloxy- f R) -2- f 3-chlorobenzyl) -6-pheπy hexanoyl) - f S) -isoleucyll -4-keto¬ piperidine. The title compound was prepared from the product of Example 71 and the product from Intermediate Preparation (5a) by the procedure described for Intermediate (5b) . Found: C,65.00; H,8.30; N,5.70. C^H^CM j OgSi -requires C,65.10; H,8.30; N,5.60%. m/e 756.21 (MH) + [α] D 25 +4.4° (c = 0.1%, MΞOH) N.M.R. (EMSO-d o-) «5 = 0.15(s,6H) ; 0.85(m,6H) ; 0.9(s,9H) ; 1.15(m,2H) ; 1.3 (s,9H) ; 1.55(m,lH) ; 1.8(m,lH) ; 2.0(m,lH) ; 2.2- 2.95(m,9H) ; 3.55(m,2H) ; 3.65(m,lH) ; 3.75(m,lH) ; 3.9(m,2H) 4.55(m,lH) ; 6.75(d,lH) ; 7.1-7.4(m,9H) ; 8.2(d,lH) . EXftMPLE 73 1-ΓN- f f S) -5-t-Butoxycartonylamino- fS) -4-t-butyldimethylsilyloxy- fR) -2- f 3-chlorobenzyl) -6-phenylhexanoyl) - f S) -isoleucyll -4- f 2- methoxyethylamino) piperidine . The title compound was prepared by the same procedure as described for Example 7 by reacting the product of Example 72 with 2-ιretoo.xyethylamine. Found: 0,64.60; H,8.90; N,6.70. C^Hy j CU^OgSi requires C,64.80; H,8.80; N,6.90%. m/e 815.02 (MH) + [α] D 25 -7.0° (c = 0.1%, MeOH) N.M.R. (DMSO-dg) δ = 0.1(s,6H) ; 0.8(m,6H) ; 0.9(s,9H) ; 0.95- 1.25(m,3H) ; 1.3 (s,9H) ; 1.6(m,2H) ; 1.75(m,3H) ; 1.95(m,lH) ; 2.4- 2.95-3.1(m,10H) ; 3.2 (s,3H) ; 3.35(t,2H) ; 3.45-3.7 (m,2H) ; 3.9 (m, lH) ; 4.15 (m, IH) ; 4.55 (m, lH) ; 6.75 (m, lH) ; 7.05-7.35 (m, 9H) ; 7.95 & 8.05 (2xd, lH) . EXftMPLE 74 1-fN-ffS)-5-t-Butoxycartonyla-nύno-fR)-2-f3-chlorobenzyl)-fS)- 4-hvdroχy-6-phenylhexanoyl)-fS)-isoleucyl1-4-f2- methoxyethylamino)piperidine. The title compound was prepared from the product of Example 73 by the same procedure as described for Example 2. Found: C,65.00; H,8.40; N,8.00. C H^ C1N 0 requires C,65.10; H,8.20; N,8.00%. m/e 700.95 (MH) + [α] D 25 +7.5° (c = 0.1%, MeOH) N.M.R. (EMSO-dg) <5 = 0.75(m,6H) ; 1.0(m,4H); 1.3(s,9H); 1.2- 1.8(m,5H); 2.5-3.05(m,10H); 3.2(s,3H); 3.35(t,2H); 3.45( ,IH) ; 3.55(m,lH); 3.8(m,lH); 4.1(m,lH); 4.55(m,2H); 6.4(m,lH); 7.0- 7.25(m,9H); 7.85(m,lH). EXftMPLE 75 1-TN-ffS)-5-t-Butoxycar--x3nylamino-fS)-4-t---aιtyldimethylsilyloxy- fR)-2-f3-chlorobenzyl)-6-phenylhexanoyl)-fS)-valyll-4-fN-benzyl- oxyc^rbonyl-N-methylamino)piperidine. The title conpound was prepared from the product of Example 71 and the product from -Intermediate Preparation (3b) by the same procedure as described for Exairple 3, m.p. 80-90°(glass) . Found: C,66.00; H.7.80; N,6.20. C 4g H 71 ClN 4 0,-Si requires C,66.00; H,8.00; N,6.30%. m/e 891.07, 892.56 [ ] D 25 -14° (c = 0.1%, MeOH) N.M.R. (CDC1 3 ) δ = 0.15(d,6H); 0.85(dd,6H) ; 0.95(s,9H); 1.3(m,2H); 1.4(s,9H); 1.5-2.1(m,5H) ; 2.35-3.05(m,11H) ; 3.75(m,lH); 4.0(m,lH); 4.25(m,lH); 4.5-4.8(m,3H) ; 5.15(s,2H); 6.15 & 6.4(2xd,lH); 6.8-7.5(m,14H) . EXftMPLE 76 1-TN- S)-5-t--.^toxyc r.-X3nylamino- R)-2-(3-chlorobenzyl)-fS)- 4-hvdroxy-6-phenylhexanoyl)-fS)-valyl1-4-fN-benzyloxycarbonyl- N-methylamino)piperidine. The title ∞πpound was prepared from the product of Exairple 75 by the same procedure as described for Example 4. m.p. 95- 100° (glass). Found: C,66.50; H,7.40; N,7.20. C^H^CIN^ requires C,66.40; H,7.40; N,7.20%. m/e 676.9 (MH-^ΕOC) " * " [α] D 25 0.0° (σ = 0.1%, MeOH) N.M.R. (CDC1 3 ) «5 =0.8(d,3H); 0.9(d,3H); 1.4(s,9H) ; 1.55(m,2H); 1.65-1.85(m,4H); 1.9(m,lH); 2.5-3.2(m,i:iH); 3.6-3.9(m,3H) ; 4.05(d,lH); 4.5-4.8(m,2H); 4.95(m r lH); 5.15(S,2H); 6.4 & 6.6 (2xd,lH) ; 6.8-7.5 (m, 14H) . EXftMPLE 77 1- FN- ( f S) -5-t-Butoxyc.ar-∞πylaιrιino- f R) -2- f 3-chlorobenzyl) - f S) - 4-hvdroχy-6-phenylhexanoyl) - f S) -valvπ -4-methylamιinopiperidine. The title compound was prepared from the product of Example 76 by the same procedure as described for Example 5, m.p. 164-166°. m/e 642.98, 644.00 (M + ) N.M.R. (CDC1 3 ) «S = 0.8(d,3H); 0.9(m,3H); 1.3(m,2H); 1.4(s,9H); 1.5-2.0(m,5H); 2.55-3.1(m,llH); 3.55-3.85(m,2H); 3.9(d,lH) ~ ; 4.35(d,lH); 4.7(m,lH); 4.9(m,lH); 6.45 & 6.55(2xd,lH); 6.8- 7.5(m,9H). _ EXAMPLE 78 f S) -5- f f S) -l-t-Buto.gycartonylamino-2-τ^er-ylethyll - f R) -3- f 4- trif luorσ ethoxybenzyl) -gamrma-butyrolactone. The title compound was prepared by the same procedure as described for Intermediate Preparation (2a) by alkylation of the lactone with 4-trif luorαiiet-hoxybenzyl bromide, m/e 479.9 (MH) + [α] D 25 -8° (c = 0.1%, MeOH) N.M.R. (CDC1 3 ) δ = 1.4(s,9H); 1.95(m,lH); 2.3(m,lH); 2.75- 3.05(m,4H); 3.15(dd,lH); 4.0(dd,lH); 4.3(dd,lH); 4.55(d,lH); 7.1-7.35(m,9H). EXAMPLE 79 fS)-5-t-Butoxycarbonylamino-fS)-4-ft-butyldimethylsilyloxy)-6- phenyl-fR)-2-f4-trifluoromethoxybenzyl)hexanoic acid. The title c-ompound was prepared from the product from Example 78 by the same procedure as described for Intermediate Preparation (2b) , m.p. 65-75° (glass) . Found: C,61.20; H,7.30; N,2.30. C 31 H 44 F 3 N °6 Si rec ϊ uires C,60.90; H,7.30; N,2.30%. m/e 612.41 (MH) + [α] D 25 -25° (c = 0.1%, MeOH) N.M.R. (CDC1 3 ) 5 = 0.1(d,6H) ; 1.0(s,9H) ; 1.4 (s,9H) ; 1.6(m,2H) ; 2.6(dd,lH) ; 2.75(m,2H) ; 2.95(dd,lH) : 3.1(m,lH) ; 3.7(dd,lH) : 3.95(dd,lH) ; 4.8(d,lH) ; 7.0(m,9H) . EXAMPLE 80 1- TN- f f S) -5-t-Butoxycarbonylamino- f S) -4-t-butyldimethylsilyloχy-6- phenyl- f R) -2- f 4-trif luoromethoxybenzyl) hexanoyl) - f S) -valyll -4- f N- ber-zyloxycartonyl-N-irethylamino) piperidine . The title compound was prepared from the product of Exairple 79 and the product from Intermediate Preparation (4b) by the sane procedure as described for Exairple 3, m.p. 80-90° (glass) . Found: C,63.90; H,7.50; N,5.90. C^H-.F.-N.OgSi requires C,63.80; H,7.60; N,5.90%. m/e 941.08 (MH) + [α] D 25 -3° (c = 0.1%, MeOH) N.M.R. (CDC1 3 ) δ = 0.05(d,6H) ; 0.85(m,6H) ; 0.95 (s,9H) ; 1.3- 1.8 (m,7H) ; 1.4 (s,9H) ; 2.4-3.0 (m, 11H) ; 3.75(m, lH) ; 4.0(m,2H) ; 4.6(m,3H) ; 5.15(s,2H) ; 6.2 & 6.4 (2xd,lH) ; 7.0-7.4 (m, 14H) . EXAMPLE 81 1-[N-ffS)-5-t-Butoxyc^bonylaιrιino-fS)-4-hvdroχy-6-phenyl-fR)- 2-f4-trifluoromethoxybenzyl)hexanoyl)-fS)-valyll-4-fN- benzyloxycarbonyl-N-nethylamino)piperidine. The title compound was prepared from the product of Exairple 80 by the same procedure as described for Example 4, m.p. 188-190°. Found: C,64.20; H,7.00; N,6.80. C^H^F^Og requires C,63.90; H,7.00; N,6.80%. m/e 826.86 (MH) + [α] D 25 -6.3° (c = 0.1%, MeOH) N.M.R. (CDC1 3 ) δ - 0.8(t,3H); 0.9(m,3H); 1.4(s,9H); 1.4- 2.0(m,7H); 2.5-3.2(m,llH); 3.5-3.85(m,3H) ; 4.0(d,lH); 4.7(m,2H); 4.9(m,lH); 5.15(s,2H); 6.4 & 6.55(2xd,lH) ; 7.0-7.4(m,14H) . EXAMPLE 82 1- fN- f f S) -5-t-Butoχy(^rbonylamino- f S) -4-hvdrc-xy-6-phenyl- f R) - 2- f 4-trif luoroπeldioxybenzyl) hexanoyl) -f S) -valyll -4- .methylamtinopiperidine. The title compound was prepared from the product of Example 81 by the same procedure as described for Example 5, m.p.186-188°. Found: C,62.30; H,7.40; N,8.00. C^A^N.Og requires C,62.40; H,7.40; N,8.10%. m/e 692.9 (MH) + [or] D 25 -2.9° (c = 0.1%, MeOH) N.M.R. (CDC-L j ) δ = 0.8(s,3H) ; 0.9(s,3H) ; 1.2-1.5 (m,lH) ; 1.4(s,9H) ; 1.6-2.1(m,6H) ; 2.5(s,3H) ; 2.6-3. l(m,8H) ; 3.5- 4.0(m,4H) ; 4.45(m,lH) ; 4.7(m,lH) ; 4.9(d,lH) ; 6.55(m,lH) ; 7.0- 7.4(m,9H) EXftMPLE 83 1- ΓN- f f S) -5-t-Butoχycarbonylamino- f S) -4-t-hutyldimetftylsilyloχy-6- phenyl-fR) -2- f 4-trif luoromethoxybenzyl) hexanoyl) -f S) -isoleucvπ-4- ketopiperidine. The title compound was prepared from the product of Example 79 and the product from Intermediate Preparation (5a) by the procedure as described for Intermediate (5b) . Found: C,62.50; H,8.00; N,5.20. C 42 H 62 F 3 N 3°7 Si re 3 uires C,62.60; H,7.80; N,5.20%. m/e 806.54 (MH) + [α] D 25 -5.3° (C = 0.1%, ϊfeOH) N.M.R. (DMSO-dg) S = 0.1(s,6H) ; 0.85(m,6H) ; 0.9 (s,9H) ; 1.15(m,2H) ; 1.3 (s,9H) ; 1.55(m,lH) ; 1.8(m,lH) ; 2.0(m,lH) ; 2.2- 2.95(m,9H) ; 3.6(m,3H) ; 3.85(m,3H) ; 4.55(m,lH) ; 6.75(d,lH) ; 7.1-7.3 (m,9H) ; 8.15(d,lH) . EXftMPLE 84 1-fN-f fS) -5-t-Butoxyc irtonylaι-ιino-fS) -4-t-butyld-urethylsilyloχy-6- phenyl- f R) -2- f 4-trif luoromethoxybenzyl) hexanoyl) - f S) -isoleucyll -4- ethylamdnopiperidine. The title compound was prepared by the same procedure as described for Example 7 by reacting the product of Example 83 with ethylamine. Found: C,63.50; H,8.45; N,6.70. C Hg g F N 4 0gSi requires C63.30; H,8.30; N,6.70%. m/e 835.16 (MH) + tα] D 25 -24° (c = 0.1%, MeOH) N.M.R. (DMSO-d δ = 0.1(S,6H); 0.8(m,6H); 0.9(s,9H); b 1.0(m,3H); 1.05-1.25(m,4H); 1.3(s,9H); 1.45(m,lH); 1.75(m,3H); 1.95(m,lH); 2.4-3.1(m,10H); 3.5-3.7(m,2H); 3.9(m,lH); 4.15(m,lH); 4.55(m,lH); 6.75(m,lH); 7.1-7.3(m,9H) ; 7.9 & 8.0(2xd,lH). EXftMPLE 85 1-TN-ffS)-5-t-Butoxycarbonylamino-fS)-4-hvdroχy-6-phenyl-fR)- 2-f4-trifluoromethoxybenzyl)hexanoyl)-fS)-isoleucyll-4- ethylaminopiperidine. The title ccarpound was prepared from the product of Example 84 by the same procedure as described for Example 2, m.p. 172-174°. Found: C,63.00; H,7.90; N,7.70. C 38 H-- 5 F 3 N 4 0g requires C,63.30; H,7.70; N,7.80%. [α] D 25 -4° (c = 0.1%, MeOH) m/e 721.57 (MH + ) N.M.R. (DMSO-dg) δ = 0.7(d,3H); 0.8(d,3H); 1.0(m,3H); 1.0- 1.45(m,5H); 1.25(s,9H); 1.7(m,4H); 2.4-3.05(m,10H) ; 3.4(m,lH); 3.55(m,lH); 3.9(m,lH); 4.l(d,lH); 4.55(m,2H); 6.4(d,lH); 7.1- 7.3(m,9H); 7.85(m,lH). EXftMPLE 86 N-t-Butoxycarbonyl-α-cyclohexylqlvcine A suspension of (S)-α-cyclohexylglycine (J. Chem. Soc., 1957, 2076) (5.6 g) and potassium carbonate (4.92 g) in dioxan (120 ml) and water (30 ml) was treated with a solution of di-t-butyl dicarbonate (8.56 g) in dioxan (40 ml) and water (10 ml) . The reaction was stirred at room teirperature for 18 hours before the solvent was evaporated under vacuum, the residue dissolved in water (100 ml) and then washed with ether. The aqueous layer was treated with acetic acid to pH 3.5 and extracted with ethyl acetate (3 x 50 ml) . The combined organic extracts were dried (MgS04) , and evaporated under vacuum to give the title compound (9.59 g). m/e 257.99 (MH) + [α]-. 25 +8° (c = 0.1%, MeOH) N.M.R. (DMSO-d o δ = 1.05(m,5H) ; 1.3 (s,9H) ; 1.6(m,6H) ; 3.73 (t,lH) ; 6.9(d,lH) . -EXAMPLE 87 1- f N-t-Butoxycarbonyl-f S) -α-cvclohexylqlvcyl) -4-ketopiperidine. The title cxmpαund was prepared from the product of Example 86 and 4-ketopiperidine hydrochloride hydrate by the same procedure as described for -D termediate Preparation (3a) . Found: C, 63.80; H,8.85; N,8.24. inquires C,63.89; H,8.94; N,8.28% m/e 339.11 (MH) + [α] D 25 0° (c = 0.1%, MeOH) N.M.R. (DMSO-d o.) δ = l.l(m,5H) ; 1.35(s,9H) ; 1.7(m,6H) ; 2.33(m,3H) ; 2.45(m,lH) ; 3.55(m,lH) ; 3.75(m,lH) ; 4.9(m,2H) ; 4.3 (t,lH) ; 6.95(d,lH) . EXAMPLE 88 1-fN- f- f R) -2-Benzyl- f S) -5-t-butoxycartoπylamino- f S) -4-t-butyl- d-imethylsilyloχy-6-pheπylhexanoyl) - f S) -θ!-cyclohexylqlvcyll -4- ketopiperidine. The title compound was prepared from the product of Example 87 and the product from -Ditermediate Preparation (2b) by the same procedure as described for Intermediate (5b) . Found: C, 69.04; H,8.76; N,5.62. C^Hg^OgSi requires C,69.24; H,8.23; N,5.71 m/e 748 (MH) + [α] D 25 -9° (c = 0.1%, MeOH) N.M.R. (DMSO-dg) δ = 0.05(s,6H) ; 0.85(s,9H) ; 0.8-1.3(m,6H) ; 1.25(s,9H) ; 1.4-2.0(m, 7H) ; 2.1-2.9 (m, 9H) ; 3.5(m,2H) ; 3.65(m,2H) ; 3.85(m,2H) ; 4.5(m,lH) ; 6.75(d,lH) ; 7.0- 7.25 (m, 10H) ; 8.0 (m, IH) . EXftMPLE 89 1-rN-f fR) -2-Benzyl-fS) -5-t-butoxycartonylamino-fS) -4-t- butyldimethylsilyloxy-6-rhenylhexanoyl) - f S) -α-cvclohexylqlvcvπ -4- methylaminopiperidine. The title conpound was prepared from the product of Exairple 88 by the same procedure as described for Example 7. Found: C, 68.47; H,9.10; N,7.29. C^H^^O-.Si.- 1 /^ 0 requires C,68.45; H,9.27; N,7.26 m/e 762.97 (MH) + [α] D 25 -6° (c = 0.1%, MeOH) N.M.R. (DMSO-d <5 = 0.1(s,6H); 0.85(s,9H); 0.9-1.3(m,7H) ; o 1.25(s,9H); 1.5-1.85(m,9H); 1.95(m,lH); 2.25(s,3H); 2.4- 3.1(m,8H); 3.55(m,lH); 3.6(m,lH); 3.85(m,lH); 4.1(m,lH); 4.55(m,lH); 6.75(d,lH); 7.1-7.3(m,10H); 7.85(2xd,lH). EXAMPLE 90 1-TN-f-fR)-2-Benzyl-fS)-5-t-butoxycarbonylamino-fS)-4-hydrOxy- 6-phenylhexanoyl)-fS)-ce-cvclohexylqlycyl]-4-methylaιrιinopiperidine♦ The title compound was prepared from the product of Example 89 by the procedure as described for Exairple 2, m.p. 132-136°. Found: C, 70.74; H,8.51; N,8.59. C^HggN^g requires 0,70.34; H,8.70; N,8.63 m/e 648.98 (MH) + [α] D 25 -7° (c = 0.1%, MeOH) N.M.R. (DMSO-dg) δ = 0.8-1.4(m,7H); 1.3(s,9H); 1.4-1.8(m,10H) ; 2.25(s,3H); 2.4-3.1(m,8H); 3.5(m,lH); 3.6(m,lH); 3.85(m,lH); 4.1(m,lH); 4.55(m,2H); 6.4(d,lH); 7.1-7.3(m,10H) ; 7.75(m,lH). EXftMPLE 91 1- fN- ( (R) -2-Benzyl- f S) -5-t-butoxycartonylamdno- f S) -4-t- butyld.i-methylsilyloxy-6-phenylhexanoyl) - f S) -a- cvclohexylqlycyl ] -4- f 2-methoxyethylamino) piperidine. The title compound was prepared by the same pi icedure as described for Example 7 by reacting the product of Exairple 88 with 2-.metho-xyethylamine. Found: C, 68.11; H,9.31; N,6.89. C i N O Si requires 0,68.45; H,9.24; N,6.94 m/e 806.97 (MH) + 25 [C-] D -9° (C = 0.1%, MeOH) N.M.R. (DMSO-dg) δ = 0.1(s,6H) ; 0.9(s,9H) ; 0.9-1.3 (m,7H) ; 1.3 (s,9H) ; 1.45-1.9 (m,9H) ; 1.95(m,lH) ; 2.4-3.1 (m, 10H) ; 3.2(s,3H) ; 3.4(t,2H) ; 3.6(m,lH) ; 3.65(m,lH) ; 3.9(m,lH) ; 4.15(m,lH) ; 4.55(m,lH) ; 6.75(m,lH) ; 7.1-7.3 (m,10H) ; 7.82 (2xd,lH) . EXftMPLE 92 1-rN-f fR) -2-Benzyl- fS) -5-t-butoxycarbonylamιino- f S) -4-hydroxy- 6-phenylhexanoyl) -f S) -α-cyclohexylqlycyl] -4- f 2- methoxyethylamino) piperidine . The title co-rpound was prepared from the product of Example 91 by the same procedure as described for Example 2, m.p. 118-122°. Found: C,68.73, H,8.56, N,7.93. C^Hg^Og. 3 /^ 0 requires C,68.45; H,8.76; N 7.98 m/e 692.98 (MH) + [α] D 25 -1° (c = 0.1%, MeOH) N.M.R. (DMSO-dg) δ = 0.8-1.4 (m,8H) ; 1.3 (s,9H) ; 1.4-1.85 (m,9H) ; 2.4-3.1(m,10H) ; 3.2(s,3H) ; 3.35(t,2H) ; 3.45(m,lH) ; 3.55(m,lH) ; 3.85(m,lH) ; 4.1(m,lH) ; 4.55(m,2H) ; 6.4(d,lH) ; 7.2 (m,10H) ; 7.75(m,lH) . EXAMPLE 93 f S) -5- r f S) -l-t-Butoxycarboπylamino-2-phenyleth.yll - fR) -3- f 4- N.N-d-jjetAylcarbaπ Jylbenzyl) -qanma-butyrolactone. A solution of the active ester prepared from (S)-5-[ (S)-l-t- butoxycartorιyla-minc-2-phenylethyl] - (R) -3- (4-carboxybenzyl) - gaπrima-butyrolactone (2.5 g) in N,N-di-methylformamide (20 ml) was treated with 1-hydroxybenzotriazole hydrate (1.15 g) , l-(3- d-lmetoylam--nopropyl)-3-ethylcarbt>ai-^ hydrochloride (1.36 g) and N,N-<iiiscprcpyletftylamine (2.47 ml) was treated with d-ύmetoylamine hydrochloride (0.55 g) and the reaction stirred for 3 hours at room temperature. The mixture was partitioned between water (150 ml) and ethyl acetate (2 x 100 ml) . The combined organics were washed with IN hydrochloric acid (100 ml) , saturated aqueous sodium bicarbonate (100 ml) , saturated brine (100 ml) , dried (MgSO ) and evaporated under vacuum. The resulting white foam was purified by chrcamatography on silica- gel, eluting with hexane-ethyl acetate (20:80) to give the title compound, (1.96 g) . Found: C,69.44; H,7.28; N,6.05. -=~ ~ C 2r jB 3 ^ 2 0 5 requires C,69.50; H,7.34; N,6.00%. m/e 467 (MH + ) EXftMPLE 94 fS)-5-t-Butoxycartonylaιtιino-fS)-4-t-butyldimethylsilyloxy-fR)- 2-f4-N-N-diπethylcarbamoylbenzyl)-6-t-henylhexanoic acid. The title compound was prepared from the product from Example 93 by the same procedure as described for Intermediate (2b) . m/e 599 (MH + ) N.M.R. (DMSO-d..) δ = 0.09(d,6H); 0.87(s,9H); 1.26(s,9H); 1.35(m,lH); 1.92(m,lH); 2.4(m,lH); 2.64-3.00( ,10H) ; 3.48(m,lH); 3.72(m,lH); 6.86(d,lH); 7.2(m,9H). EXftMPLE 95 1-TN-ffS)-5-t-Butoxycarbonyl--nrιino-fS)-4-t-butyldimethylsilyloxy- fR)-2-f4-N,N-d-ύrrethylcarbamoy-U-)enzyl)-6-rheπylhexanoyl)-fS)- isoleucyl1-4-ketopiperidine. The title compound was prepared from the product from Example 94 and the product from Intermediate Preparation (5a) by the procedure as described for Intermediate Preparation (5b) . Found: C,66.80; H,8.41; N,7.02. C^HggN^Si requires C,66.63; H,8.64; N,7.06%. [α] 25 -6° (c = 0.1% MeOH) 589 N.M.R. (DMSO-dg) 5 = 0.1(s,6H); 0.81(m,6H); 0.89(s,9H); 1.16(m,2H); 1.26(s,9H); 1.52(m,lH); 1.79(m,lH); 1.96(m,lH); 2.17-2.74(complex 6H) ; 2.9(broad,9H) ; 3.5-3.95(complex 6H) ; 4.55(m,lH); 6.77(d,lH); 7.2(m,9H); 8.l5(d,lH). EXftMPLE 96 1-TN-( S)-5-t-Butoxycarbonylamino-fS)-4-t-butyldimethylsilyloxy- fR)-2-f4-N.N-d-urethylcarbamoylbenzyl)-6-phenylhexanoyl)-fS)- isoleucyl]-4-f2-methoχyethylamino)piperidine. The title compound was prepared from the product from Example 95 by the procedure as described for Exairple 73. Found: C,64.86; H,9.03; N,8.18. C^^^i^Si, 0.25 CH- j Cl^ requires C,64.97; H,8.94; N,8.01% m/e 852 (MH + ) [α] 25 -5° (c = 0.1% MΞOH) 589 N.M.R. (DMSO-dg) 5 = 0.1(s,6H); 0.28(m,6H); 0.35(s,9H); 0.95-1.33 (complex, 13H) ; 1.47(m,lH); 1.8(m,3H); 2.45(m,lH); 2.4-3.1 (complex, 16H) ; 3.23(s,3H); 3.37(m,2H); 3.55(b,lH); 3.67(m,lH); 3.95(m,lH); 4.17(m,lH); 4.54(m,lH); 6.74(d,lH); 7.2(m,9H); 7.95(m,lH). EXftMPLE 97 dimethylcarbamov-l±enzyl) - f S) -4-hydroxy-6-pheπylhexanσyl) - f S) - isoleuc^ll-4-f2-πethoxyethylam--no)piperidine. The title compound was prepared from the product from Example 96 fcy the procedure as described for Example 2. m/e 738 (MH + ) r ..25 -5° (c = 0.1% MeOH) WsB9 N.M.R. (EMSO-dg) δ = 0.73(m,6H); 1.03(m,2H); 1.26(s,9H); 1.3-1.43 (m, 3H) ; 1.58-1.86 (m, 4H) ; 2.5-3.07 (complex, 16H) ; 3.23(s,3H); 3.4(m,3H); 3.57(m,lH); 3.9(m,lH); 4.1(m,lH); 4.55(m,2H); 6.4(d,lH); 7.17(m,9H); 7.80(m,lH). EXftMPLE 98 f S) -5- r f S) -l-t-Butoxycartonylamino-2-phenylethyll - f R) -3- f 4-N- iscprc^3yl(.arb--g--ov-ll-enzyl) -qamma-butyrolactone. The title ∞mpound was prepared from (S)-5-[(S)-l-t- butojψcarbonylam-ino-2-pheπylethyl] - (R) -3- (4-carboxybenzyl) - gamma-butyrolactone (Example 1, PLC 546) and isopropylamine by the procedure as described for Example 93. Found: C,68.91; H,7.59; N,5.65. C 2 gH 3 gN 2 0 5 ; 0.5 CH j CO j C^H^ requires C,69.29; H,7.62; N,5.57%. m/e 481 (MH + ) [α] 25 -7° (c = 0.1% MeOH) 589 N.M.R. (DMSO-dg) δ = 1.15(d,6H); 1.21(s,9H); 2.05(m,2H); 2.7(m,3H); 2.9l(m,lH); 3.05(dd,lH); 3.75(m,lH); 4.08(m,lH); 4.38(m,lH); 7.03(d,lH); 7.24(m,7H); 7.77(d,2H); 8.l3(d,lH). EXAMPLE 99 fS)-5-t-Butoxycarbonylamino-fS)-4-t-butyld-i-methylsilyloxy-fR)- 2-f4-N-isopropylcarbamoyl)benzyl-6-phenylhexanoic acid. The title compound was prepared from the product from Exairple 98 by the same procedure as described for Intermediate (2b) . Found: C,66.32; H,8.53; N,4.45. C 34 H 52 N 2°6 re£ 3 uires C,66.63; H,8.55; N,4.57%. m/e 613 (MH + ) [α] 25 -33° (C = 0.1% MeOH) 589 N.M.R. (DMSO-d c ) δ = ~ 0.1(d,6H); 0.9(s,9H); 1.15(d,6H); 1.24(s,9H); b 1.37(m,lH); 1.93(m,lH); 2.4(m,lH); 2.75(m,3H); 2.9(m,lH); 3.6(m,lH); 3.72(m,lH); 4.07(m,lH); 6.86(d,lH); 7.2(m,7H); 7.74(d,2H); 8.11(d,lH); 12.15(S,1H). EXAMPLE 100 1-fN-ffS)-5-t-Butoxycarbonylamino-fS)-4-t-butyldimethylsilyloxy- fR)-2-f4-N-isopropylcarbamoyl)benzyl-6-tAιenylhexanσyl)-fS)- isoleucyl1-4-ketopiperidine. The title compound was prepared from the product from Example 99 and the product from Intermediate Preparation (5a) by the procedure as described for Intermediate Preparation (5b) . Found: 0,67.22; H,8.90; N,6.81. C 45 H 7() N 4 0 7 Si requires C,66.96; H,8.74; N,6.94%. ?5 [α] -8° (c = 0.1% MeOH) 589 N.M.R. (DMSO-dg) <5 = 0.05(d,6H); 0.76(m,6H); 0.83(s,9H); l.l(m,8H); 1.21(s,9H); 1.49(m,lH); 1.75(m,lH); 1.92(m,lH); 2.1-2.92(complex, 9H) ; 3.5(m,2H); 3.6-3.9(m,4H) ; 4.05(m,lH); 4.52(m,lH); 6.72(d,lH); 7.l4(m,7H); 7.68(d,2H); 8.03(m,2H). EXAMPLE 101 1-fN-ffS)-5-t-Butoxycarbonylamino-fS)-4-t-butyldimethylsilyloxy- fR)-2-f4-N-isopropylcarbamoyl)benzyl-6-τAιenylhexanoyl)-fS)- isoleucyl1-4-ethylaminopiperidine. The title compound was prepared by the same procedure as described for Exairple 7 by reacting the product of Example 100 with ethyla ine. Found: 0,66.70; H,9.14; N,8.30. C 47 H 77 N 5 0gSi; 0.2 CH- j C^ requires C,66.96; H,9.21; N,8.29%. m/e 836 (MH + ) [α] 25 -14° (c = 0.1% MeOH) 589 N.M.R. (DMSO-d δ = 0.1(s,6H); 0.76(m,6H); 0.87(s,9H); o 0.95(m A 3H); 1.03-1.22(m,10H); 1.28(s,9H); 1.46(m,lH); 1.7(m,3H); 1.95(m,lH); 2.4-3.1(complex, 10H); 3.48-4.2(m,5H) ; 4.5(m,lH); 6.78(d,lH); 7.19(m,7H); 7.72(d,2H); 7.8(d,0.5H); 7.8,7.95(2xd,lH) ; 8.1(d,lH). EXAMPLE 102 1- ΓN- f f S) -5-t-Butoxycartonylaιrvino- f S) -4-hydroχy- f R) -2- f 4-N- isopropylcarbamoyl) benzyl-6-t)henylhexanoyl) - f S) -isoleucyll -4- ethylaπiinopiperidine . The title compound was prepared from the product -ran Example 101 by the procedure as described for Exairple 2. Found: C,68.08; H,8.59 N,9.64. C^Hg^Og requires C,68.20; H,8.79; N,9 ^ 70%. m/e 722 (MH + ) [α] 25 + 3° (c = 0.1% IfeOH) 589 N.M.R. (DMSO-d δ = 0.73(m,6H) ; 0.85-1.5(complex; 23H) ; b 1.67(m,4H); 2.5-3.05(coπplex 10H) ; 3.41(m,lH); 3.56(m,lH); 3.67-3.91(complex, IH); 4.05(m,2H); 4.55(m,2H); 6.4(t,lH); 7.19(m,7H); 7.72(d,2H); 7.8(m,lH); 8.08(d,lH). EXAMPLE 103 f S) -5-r f S) -l-t-Butoxycartonylair nc>-2-phenylethyll - fR) -3- f4- benzyloxybenzyl) -qa mna-butyrolactone. The title conpound was prepared by the sane procedure as described for Intermediate Preparation (2a) by alkylation of the lactone with 4-benzyloxybenzyl bromide. m/e 523.9 (MNa) + N.M.R. (EMSO-d o £ = 1.2(s,9H) ; 2.0(m,2H) ; 2.6(m,3H) ; 2.85(m,2H) ; 3.7(m,lH) ; 4.3 (m,lH) ; 5.0(s,2H) ; 7.2 (m,14H) . EXftMPLE 104 fR)-2-f4-Benzyloxybenzyl)-fS)-5-t-butoxycartonylamino-fS)-4-t- butyldimethylsilyloxy-6-ι-)henylhexanoic acid. The title conpound was prepared from the product from Example 103 by the sane procedure as described for Intermediate (2b) . Found: C,69.99; H,7.90; N,2.40. C 37 H 5 NO g Si requires C,70.11; H,8.11; N,2.21%. m/e 633.96 (MH) + N.M.R. (DMSO-dg) δ = 0.06(d,6H); 0.85(S,9H); 1.15(t,lH); 1.2(s,9H); 1.85(t,lH); 2.4(m,lH); 2.7(m,4H); 3.55(m,IH) ; 3.7(m,lH); 5.0(S,2H)-; 6.85-7.4(m,15H). EXftMPLE 105 1-rN-ffR)-2-f4-Benzyloxybenzyl)-fS)-5-t-butoxyc.artonylaπtino- fS)-4-t--^ityld-i-methylsilyloxy-6-phenylhexanoyl)-fS)- isoleucyl1-4-ketopiperidine. The title compound was prepared from the product from Example 104 and the product from Interπediate Preparation (5a) by the procedure as described for Intermediate Preparation (5b) . Found: 0,68.64; H,8.22; N,5.02. C^HggN^Si.^I^O requires C,68.86; H,8.43; N,5.02%. [α] 25 -5° (c = 0.15, MeOH) m/e 935.94 (M+thio)H + N.M.R. (DMSO-dg) <5 = 0.03(s,6H); 0.8(m,6H); 0.85(s,9H) 1.15(m,3H); 1.25(s,9H); 1.5(m,lH); 1.65(m,lH); 1.9(m,lH); 2.25(m,4H); 2.7(m,4H); 3.5(m,2H); 3.65(m,2H); 3.9(m,2H); 4.5(m,lH); 5.0(s,2H); 7.2(m,15H); 8.05(d,lH). EXftMPLE 106 1-fN- f fR) -2- f 4-Benzyloxybenzyl) - f S) -S-t-fcutoxycarbonylamino- f S) -4-t-butyldimethylsilyloxy-6-phenylhexanoyl) - f S) - isoleucyl 1 -4-nethylaminopiperidine . The title compound was prepared by the same procedure as described for Example 7 by reacting the product of Exairple 105 with methylamine. m/e 842.88 (MH) + N.M.R. (DMSCH- b 5 = 0.1(S,6H) ; 0.8 (m,6H) ; 0.9 (s,9H) ; l.l(m,6H) ; 1.25(s,8H) ; 1.5(m,lH) ; 1.75(m,3H) ; 1.95 (m, IH) ; 2.3 (s,3H) ; 2.53(m,4H) ; 2.75(m,4H) ; 3.6(m,2H) ; 3.95(m,lH) ; 4.15(m,lH) ; 4.55(m,lH) ; 5.0(s,2H) ; 6.75(d,lH) ; 6.9- 7.45(m,14H) ; 7.9(2xd,lH) . EXAMPLE 107 1-fN-f fR) -2- f4-Benzyloxybenzyl) - f S) -5-t-butoxycartonylamino- fS) -4-hvdroxy-6-rhenylhexanoyl) -fS) -isoleucyll -4- methylaminopiperidine. The title ccmpαund was prepared from the product from Example 106 by the procedure as described for Example 2, m.p. 157-159°. Found: C,70.46; H,8.25; N,7.59. C^Hg^Og -requires C,70.85; H,8.30; N,7.69%. [α] D 25 +33° (c = 0.1%, MeOH) m/e 728.96 (MH) + N.M.R. (DMSO-d δ = 0.75(m,6H) ; 0.9-1.2(m,3H) ; 1.3(s,9H); b 1.3-1.5(m,2H) ; 1.55-1.85(m,4H); 2.3(s,3H); 2.5-2.85(m,8H) ; 3.4(m,lH); 3.55(m,lH); 3.9(m,lH); 4.1(m,lH); 4.55(m,2H); 5.05(s,2H); 6.4(m,lH); 6.85(m,2H) ; 7.0(d,2H); 7.1-7.25(m,5H) ; 7.3-7.45(m,5H) ; 7.8(t,lH). EXftMPLE 108 1-rN-ffS)-5-t-Butoxycartonylamino-fS)-4-hvdroxy-fR)-2-f4- hvdroxybenzyl)-6-phenylhexanoyl)-fS)-isoleucyll-4- iretAylaminopiperidine. A solution of the product from Exairple 107 (0.3 g) in πethanol (60 ml) was treated with 10% palladium on charcoal (0.25 g) and was stirred under an atmosphere of hydrogen at 30 p.s.i. (2.0 bar) for one hour at room teπperature. The catalyst was filtered off and the solvent evaporated under vacuum to give a white foam. Purification by chromatography on silica-gel, eluting with methylene chloride-irethanol-concentrated aqueous ammonia (90:10:1) gave the title conpound which was recrystallised from ethyl acetate/hexane to give a white powder, (0.117 g) , m.p. 201-203°. Found: C,65.77; H,8.24; N,8.44. C^^N^g^O requires C,65.83; H,8.59; N,8.53%. [α] 25 3n -12° (c = 0.1%, MeOH) m/e 638.99 (MH) N.M.R. (DMSO-d..) δ = 0.75(m,6H) ; 0.9-1.15(m,2H) ; 1.2(s,lH); b 1.3(S,8H); 1.3-1.45(m,2H); 1.55-1.8(m,4H) ; 2.25(s,3H); 2.5- 3.1(m,9H); 3.4(m,lH); 3.55(m,lH); 3.85(m,lH); 4.1(m,lH); 4.5(m,2H); 6.4(d,lH); 6.55(m,2H); 6.85(d,2H); 7.1-7.25(m,5H) , 7.75(d,lH). EXAMPLE 109 4-f2-t-Butyl-l.3-dioxolan-2-yl)benzyl bromide A solution of 4-(2-t-butyl-l,3-dioxolan-2-yl) toluene [D.E. 3,235,589] (0.22 g) in carbon tetrachloride (8 ml) was treated with sodium hydrogen carbonate (84 mg) and N-bα nιo-=nιccinimide (0.18 g) and the mixture refluxed for 15 minutes in the presence of a 60W light. The reaction was cooled, diluted with hexane (8 ml) , filtered and evaporated under vacuum to give the product as an oil which crystallised on standing (0.256 g). N.M.R. (CDC1 3 ) δ = 0.95(s,9H); 3.7(m,2H); 4.0(m,2H); 4.5(s,2H); 7.35-7.5(m,4H). EXftMPLE 110 fS)-5-TfS)-l-t-Butoχyc^rbonylamino-2-phenylethyll-fR)-3- r 4-f2- t-butyl-1.3-dioxolan-2-yl)benzyl]-cfam-τa-butyrolactone. The title compound was prepared by the same procedure as described for Intermediate Preparation (2a) ty alkylation of the lactone with the product of Example 109. [α] D 25 -12° (c = 0.1%, MeOH) m/e 541.13 (MNH 4 ) + N.M.R. (CDC1 3 ) c5 = 1.0(S,9H); 1.45(s,9H); 2.0(m,-lH); 2.25(m,lH); 2.75(dd,lH); 2.9(d,2H); 3.0(m,lH) ; 3.15(dd,IH) ; 3.7(m,2H); 4.0(m,3H); 4.35(m,lH); 4.5(m,lH); 7.0-7.4(m,9H) . EXftMPLE 111 f S) -5-t-Butoxycartonylamino- f S) -4-t-butylolinethylsilyloxy- f R) - 2- T4- f 2-t-butyl-l .3-dioxolan-2-yl) benzyl] -6-phenylhexanoic acid. The title compound was prepared from the product from Example 110 by the same procedure as described for Intermediate Preparation (2b) . Found: C,67.25; H,8.60; N,2.61. CJL.rø-.Si reqtαires C,67.75; H,8.76; N,2.14%. m/e 656.33 (MH) + [α] D 25 -27° (c = 0.1%, MeOH) N.M.R. (CDC1 ) δ = 0.10(m,6H) ; 0.90(s,9H) ; 0.95(s,9H) ; 1.35(s,9H) ; 1.6(m,lH) ; 1.9(m,lH) ; 2.5-3.1(m,5H) , 3.70(m,3H) ; 3.9 (m,3H) 4.75(d,lH) ; 7.0-7.4 (m,9H) . EXAMPLE 112 1-ΓN-ffS)-5-t-Butoxycarboπylamino-fS)-4-t- butyldimethylsilyloxy-fR)-2-r4-f2-t-butyl-l.3-dioxolan-2- yl)benzyll-6-phenylhexanoyl)-fS)-valyll-4-ketopiperidine. The title compound was prepared from the product of Example 111 and the product from Intermediate Preparation (5a) by the procedure as described for Intermediate (5b) . Found: 0,67.18; H,8.52; N,4.94. C ^^OgSi requires C,67.51; H r 8.80; N,5.03%. m/e 836.64 (MH) + [α] D 25 +5° (c = 0.1%, MeOH) N.M.R. (CDC1 3 ) δ = 0.1(s,6H); 0.9(m,24H); 1.3-1.4(m,2H) ; 1.35(s,9H); 1.65(m,lH); 1.8(m,lH); 2.0(m,lH); 2.4-2.75(m,8H) ; 2.9(m,lH); 3.6-3.8(m,4H); 3.8-4.0(m,4H) ; 4.7(m,2H); 6.4(d,lH); 6.95(d,2H); 7.2-7.35(m,7H) . EXAMPLE 113 1-rN-ffS)-5-t-Butoxycarbonylaπrino-fS)-4-t- butyldimethylsilyloxy-fR)-2-f4-f2-t-butyl-l,3-dioxolan-2- yl)benzyl]-6-phenv-lhexanoyl)-fS)-valyll-4- i-ethylaminopiperidine The title conpound was prepared by the same procedure as described for Example 7 by reacting the product of Example 112 with methylamine. Found: 0, 67.31; H,8.84; N, 6.52. C, IL N 0._Si requires C, 67.73 ; H, 9.24; N, 6.58%. m/e 851.07 (MH) + [α] +6.0° (c = 0.1%, MeOH) N.M.R. (CDC1 3 ) 0.1(s, 6H) ; 0.85 (t,6H) ; 0.95 (s, 18H) ; 1.35 (s, 9H) ; 1.6-1.8 (m,4H) ; 1.85-2.0(m,3H) ; 2.4 (s,3H) ; 2.45-3.2 (m,8H) ; 3.7 (m,3H) ; 3.9-4.1(m,4H) ; 4.4 (ι-., -lH) ; 4.7-4.85 (m, 2H) ; 6.4 (m,lH) ; 6.95 (m,2H) ; 7.25 (m,2H) ; 7.3 (m,5H) . EXAMPLE 114 1-fN-(fS)-5-t-Butoχycarbonylamino-fR)-2-[4- 2-t-butyl-l.3- dioxolan-2-yl)benzyll-fS)-4-hydroχy-6-phenylhexanoyl)-fS)- valyll-4-nethylaminopiperidine A solution of the product from Exairple 113 in methylene chloride was cooled to -78°C and saturated with hydrogen chloride for 30 minutes. The excess hydrogen chloride was blown off with nitrogen and the solvent was evaporated under vacuum and the residue partitioned between IN aqueous sodium hydroxide and ethyl acetate. The organic layer was dried (MgSO and evaporated to give the crude product. A solution of this product in acetonitrile (0.5 ml) was treated with 10 drops of 40% aqueous hydrogen fluoride and the reaction stirred for 10 minutes. The solvent was evaporated and the residue again partitioned between ethyl acetate and IN aqueous sodium hydroxide. The organic layer was dried (MgSO ) and evaporated under vacuum. The residue was purified by chrαπatography on silica-gel using methylene chloride- methanol-concentrated aqueous ammonia (93:7:1). The clean fractions were combined, evaporated under vacuum and the solid residue recrystallised from ether to give the title c mpound as a white solid (0.13 g) , m.p. 123-125°. Found: 0,68.48; H,8.59; N,7.97. C 4() Hg 0 N Og. 1 / 2 H 2° requires 0,68.44; H,8.76; N,7.98%. m/e 693.04 (MH) [α] 25 +2.0° (c = 0.1%, MeOH) N.M.R. (CDC1 3 ) 0.8(d,3H); 0.9(d,3H); 1.2(m,lH); 1.3 (s,9H) ; 1.35(s,9H); 1.4-1.8(m,3H); 1.9(m,3H); 2.45(2xs,3H); 2.6-3.1(m,8H); 3.6(m,lH); 3.75(m,2H); 3.85(m,lH); 4.3(m,lH); 4.7(m,lH); 4.85(m,lH); 6.4 & 6.5(2xd,lH); 7.0(d,2H); 7.25(m,5H); 7.55(d,2H) . EXftMPLE 115 f R) -3- f 4-Benzenesulphonylbenzyl) - f S) -5- r f S) — 1-t-butoxycarboπyl- amir_c^2-τ enylethyl-qamma-^^ The title compound was prepared by the same procedure as described for Intermediate Preparation (2a) , by the alkylation of the lactone with 4-benzenesulphonylbenzyl bromide. Found: C,67.16; H ,.6.24; N,2.85. C^H^ OgS requires C,67.29; H,6.17; N,2.62%. m/e 536 (MH + ) N.M.R. (CDC1 3 ) δ = 1.37 (s,9H) ; 1.86-1.98 (m,lH) ; 2.25-2.36 (m, IH) ; 2.28-3.23 (m,5H) ; 3.95-4.03 (m, IH) ; 4.32-4.37(m,lH) ; 4.49 (d,lH) ; 7.19-7.96(m,l4H) . EXAMPLE 116 fR) -2- f 4-Benzenesulrhonylbenzyl) - f S) -5- ft-butoxycartonylairiino) - fS) -4- ft-tautyl rlimethylsilyloxy) -6-phenylhexanoic acid The title compound was prepared from the product of Example 115 by the same procedure as described for -Ditermediate Preparation (2b) . Found: C,63.56; H,7.44; N,1.92. C 3 gH 4g N0 7 SSi: 1/5 O^CO^ requires C,63.51; H,7.22; N,2.04%. m/e 568 (MH-Boc) + [α] 25 -32° (c = 0.1%, MeOH) D N.M.R. (DMSO-dg) δ = 0.03 (s,3H) ; 0.08 (s,3H) ; 0.84(s,9H) ; 1.23 (s,9H) ; 1.85-1.94(m,lH) ; 2.32-2.46 (m, IH) ; 2.61-2.95(m,5H) ; 3.50-3.58 (brm,lH) ; 3.64-3.69 (m, IH) ; 6.82 (d,lH) ; 7.11-7.95 (m, 14H) . EXAMPLE 117 1- ΓN- f f R) -2- f 4-Benzenesul^ony -benzyl) - f S) -5-t-butoxycarbonyl- f S) - 4-butyldiι-ethylsilyloxy-6-phenylhexanoyl) - f S) -valyll -4-keto¬ piperidine The title compound was prepared from the product of Example 116 and the product from Interirediate Preparation (3a) by the procedure described for Intermediate (5b) . Found: C, 63.25; H,7.61; N,4.73. C^gHg^OgSSi: 2/5 CH- j Cl-, requires C,63.13; H,7.46; N,4.76%. m/e 749 (MH-Boc) + N.M.R. (DMSO-dg) δ - 0.07 (s,6H) ; 0.83-0.89 (m,15H) ; 1.27(s,9H) ; 1.91-2.95(m,l2H) ; 3.49-3.62 (m, 3H) ; 3.72-3.79 (m,3H) ; 4.48-4.54(m, IH) ; 6.76(d,lH) ; 7.11-7.94 (m, 14H) ; 8.16 (d,lH) . EXAMPLE 118 1- TN- f fR) -2- f 4-Benzenesulphonylbenzyl) - f S) -5-t-butoxycarbonyl- a ino- f S) -4-t-butyldimethylsilvoloxy-6-^ enylhexanoyl- f S) -valyll - 4-^thylaminopiperidine The title conpound was prepared by the same proicedure as described for Exairple 7 by reaction of the product of Example 117 with ethylamine. N.M.R. (DMSO-dg) <S = 0.08-0.10 (m,6H) ; 0.79-0.86 (m, 15H) ; 0.97-1.21 (m,6H) ; 1.25(s,9H) ; 1.74-1.98 (m,4H) ; 2.29-3.13 (m, 10H) ; 3.51-3.66 (m,2H) ; 3.84-3.97 (m,lH) ; 4.05-4.22 (m,lH) ; 4.41-4.54 (m,lH) ; 6.71 (d, IH) ; 7.13-8.04 (m, 15H) . EXftMPLE 119 1-TN-ffR)-2-f4-Benzenesulphonylbenzyl)-fS)-5-t-butoxycarbonyl- a ino-fS)-4-hvdroxy-6-phenylhexanoyl)-fS)-valyl]-4-methylamino- piperidine The title cx pound was prepared from the product of Example 118 by the same procedure as described for Example 2. Found: C,65.30; H,7.68; N,7.42. C^H^N j O j Si. 1/5 CH-,C1 2 requires C,65.00; H,7.45; N,7.08%. m/e 763 (MH + ) [α] + 13° (c = 0.1%, MeOH) D N.M.R. (DMSO-dg) δ = 0.71-0.76(m,6H) ; 0.92-1.41(m,l4H) ; 1.59-1.88(m,5H); 2.52-3.55(m,12H) ; 3.76-3.89(m,lH) ; 4.02-4.09(m, H) ; 4.40-4.58(m,2H) ; 6.37-6.41(m,IH) ; 7.11-7.93(m,15H). EXAMPLE 120 fS)-5-TfS)-l-t-Butoxycarbonylamino-2-phenylethyl1-fR)-3-f4- phenoxybenzyl)- fairrma-butyrolactone The title compound was prepared by the same procedure as described for -Intermediate Preparation (2a) , by alkylation of the lactone with 4-phenoxybenzyl bromide. Found: C,74.09; H,6.67; N,2.98. C 3Q H 33 0 5 requires C,73.92; H,6.77; N,2.87%. m/e 488 (MH + ) [α] 25 -3° (c = 0.1%, MeOH) D N.M.R. (CDC1 3 ) δ = 1.38 (s,9H) ; 1.96-2.08 (m, IH) ; 2.24-2.33 (m, IH) ; 2.74-3.16(m,5H) ; 3.95-4.03 (m,lH) ; 4.28-4.33 (m,lH) ; 4.54 (d,lH) ; 6.93-7.40(m,14H) . EXAMPLE 121 fS) -5-Butoxycartonylamino-fS) -4-ft-hutyldimethylsilyloxy) -fR) -2- f 4-phenoxybenzyl) -6-phenylhexanoic acid The title compound was prepared from the product of Example 120 by the same procedure as described for Intermediate Preparation (2b) . Found: C,69.78; H,8.10; N,2.3l. C 3 gH 4g NOgSi requires C, 69.79 ; H,7.92; N,2.26%. m/e 619 (MH + ) N.M.R. (DMSO-dg) δ = 0.06(2, 3H) ; 0.08 (s,3H) ; 0.85 (S,9H) ; 1.18-1.40(m,10H) ; 1.84-1.95 (m,lH) ; 2.31-2.45 (m,lH) ; 2.65-2.89 (m,5H) ; 3.54-3.62 (m,lH) ; 3.66-3.73 (m, IH) ; 6.34 (d,lH) ; 6.39-7.35(m,14H) . EXAMPLE 122 1- ΓN- f f S) -5-t-Butoxyc--trbonylamino- f S) -4-t-butyldimethylsilyloxy- f R) -2- f 4-thenoxybenzyl) -6-phenylhexanoyl) - f S) -valyl] -4- f N-benzyl- oxycarbonyl-N-methyl) aminopiperidine The title cxmpcund was prepared from the product of Example 121 and the product from --nte-nmediate Preparation (3b) by the same procedure as described for Exairple 3. Found: C,69.23; H,8.30; N,6.28. C 55 K-,gN OgSi requires C, 69.54; H,8.00; N,5.90%. m/e 850 (MH-Boc) N.M.R. (DMSO-d δ = 0.15(s,6H) ; 0.85-0.97 (m, 15H) ; b 1.20-1.71(m,l4H) ; 1.91-2.05 (m,2H) ; 2.38-3.15(m,10H) ; 3.57-3.64 (m, IH) ; 3.69-3.75 (m, IH) ; 4.07-4.18 (m, 2H) ; 4.45-4.58 (m,2H) ; 5.08 (s,2H) ; 6.73-7.39 (m,20H) ; 7.83-7.90 (m, IH) . EXAMPLE 123 1-fN-f fS) -5-t-Butoxycartoπylamino-f S) -4-hvdroxy- fR) -2-f 4-rhenoxy- benzyl) -6-rheπylhexanoyl) - f S) -valyll -4- f N-benzyloxycarbonyl-N- methyl) aminopiperidine The title compound was prepared from the product of Exairple 122 by the sane procedure as described for Example 4. Found: C,69.12; H,7.46; N,6.36. C^Hg^Og: 1^0 requires C,69.0l; H,7.51; N,6.57%. m/e 835 (MH + ) N.M.R. (DMSO-dg δ = 0.74-0.79(m,6H); 1.22-1.93(m,16H) ; 2.42-3.20(m,10H) ; 3.41-3.62(m,2H) ; 4.03-4.11(m,2H) ; 4.39-4.62(m,3H); 5.07(s,2H); 6.44(d,lH); 6.83-7.39(m,19H) ; 7.78(d,lH). EXAMPLE 124 1-fN-ffS)-5-t---fotoxycarbonylamino-fS)-4-hydroxy-fR)-2-f4-phenoxy- benzyl)-6-phenylhexanoyl)-fS)-valyll-4-ιretoylanιiιopiperidine The title conpound was prepared from the product of Example 123 by the same procedure as described for Example 5. m.p. 101-108°. Found: C,69.09; H,7.89; N,7.85. C 41 H 5 gN 4 0g: 1/21^0 requires 0,69.39; H,8.04; N,7.9%. m/e 701 (MH + ) [α] 25 + 19° (c = 0.1%, MeOH) D N.M.R. (DMSO-dg) δ = 0.73-0.76(m,6H) ; 0.91-1.15(m,2H) ; 1.21-1.39(m,10H); 1.61-1.88(m,4H) ; 2.25(d,3H); 2.45-3.58(m,llH) ; 3.82-3.92(m,lH); 4.05-4.11(m,IH) ; 4.44-4.51(m,2H) ; 6.43(d,lH); 6.81-7.39(m,14H) ; 7.69-7.75(m,IH) . EXAMPLE 125 1-fN-t-Butoxycarbonyl)-fS)-valyl-4-hvdroχyazetidine A solution of N-t-butojQcarbonyl-(S)-valine * (5.87 g) , l-(3-di-methylaminopropyl)-3-etoylcar--x)di-i-ιr de hydrochloride (6.21 g) , 1-hydroxybenzotriazole hydrate (4.01 g) and N,N-diisopropyl- ethyla ine (9 ml) in N,N-d--methylform--mιide (75 ml) was treated with a solution of 3-hydroxyazetidine hydrochloride (3.8 g) and N,N-diisopropylethylamine (9 ml) in N,N-^diιrethylfo-πnaιrάde (25 ml) at room temperature. After stirring for 18 hours the solvent was evaporated under vacuum and the residual oil dissolved in ethyl acetate (100 ml) and water (100 ml) . The separated organic layer was washed with saturated aqueous sodium bicarbonate (2 x 100 ml) , dried (MgSO ) and evaporated under vacuum to an oil. Purification by silica gel chromatography eluting with methylene chloride- -αaeth-mol-∞ncentrated aqueous ammonia gave the title conpound as a colourless foam (4.5 g) . Found 0,57.70; H,8.95; N,10.34. C I^ 4 N 2 0 4 requires 0,57.33; H,8.88; N,10.29%. m/e 273 (MH + ) N.M.R. (EMSO-dg) £ = 0.82 (m,6H) ; 1.38(s,9H) ; 1.87 (m,lH) ; 3.49-3.75(m,2H) ; 3.82-4.12 (m, 2H) ; 4.31(m,lH) ; 4.45(m,lH) ; 5.73 (m,lH) ; 6.86(m,lH) . EXAMPLE 126 1-fN-t-Butoxycarbonyl)-fS)-valyl-4-ketoazetidine A solution of the product from Example 125 (4.5 g) in methylene chloride (25 ml) and triethylamine (11.4 ml) was added to a previously prepared solution of dimethylsulphoxide (4.68 ml) and oxalylchloride (2.9 ml) in methylene chloride (50 ml), cooled to -78°C. After stirring for 1 hour the reaction was allowed to warm to room teπperature. The solution was washed with aqueous citric acid (10%, 2 x 50 ml) followed by saturated aqueous sodium chloride (2 x 50 ml) , dried (MgSO ) and evaporated under vacuum to give a yellow oil. Purification by chromatography on silica-gel, eluting with ethyl acetate hexane (30:70) gave the title ∞πpound as a colourless foam (2.1 g) . Found: C,57.87; H,7.88; N,10.45. C 13 H 22 N 2°4 re 3 uires C,57.76; H,8.20; N,10.36%. m/e 271 (MH) + N.M.R. (DMSO-d ) δ = 0.88(m,6H) ; 1.38(s,9H); 1.96(m,lH); 3.87(t,lH); 4.59-5.11(m,4H) ; 7.01(d,lH) . EXftMPLE 127 1-TN-ffR)-2-Benzyl-fS)-5-t-butoxycarbonylamino-fS)-4-t-butyl- d.iιeth.ylsilyloxy-6-phenylhexanoyl)-fS)-valyll-4-ketoazetidine The title compound was prepared from the product of Exairple 126 and the product from Intermediate Preparation (2b) by the same procedure as described for Intermediate Preparation (5b) to give a colourless foam (1.95 g) . Found: 0,66.16; H,8.24; N,6.20. C 38 H^ 7 N 3 0gSi. 1/21^0 requires 0,66.18; H,8.42; N,6.10%. m/e 680 (MH + ) [α] 25 -6° (c = 0.17%, MeOH) D N.M.R. (DMSO-d, b.) <5 = 0.09 (d,6H) ; 0.87 (s,9H) ; 0.90 (m,6H) ; 1.17-1.25(m,lH) ; 1.29(S,9H) ; 1.96(m,2H) ; 2.38-2.77 (m, 3H) ; 2.81-2.95(m,2H) ; 3.56(m,lH) ; 3.70(m,lH) ; 4.08 (m, lH) ; 4.58-4.97 (m,4H) ; 6.l3 (d,lH) ; 7.18 (m,10H) ; 8.12 (d,lH) . EXftMPLE 128 1- TN- f f R) -2-Benzyl- f S) -5-t-butoxycarbonylamino- f S) -4-t-butyl- dimethylsilylσxy-6-tAιenylhexanoyl) -f S) -valyl]-4-ethylamino- azetidine The title compound was prepared by the same procedure as described for Example 7 by reaction of the product of Exairple 127 with ethylamine. Found: 0,66.34; H,9.10; N,7.69. C 4 Hg N 0--Si. H O requires 0,66.11; H,9.09; N,7.71%. m/e 710 (MH + ) [α] 25 -4° (c = 0.12%, MeOH) . N.M.R. (DMSO-dg) δ = 0.11(s,6H); 0.82(m,6H); 0.89(s,9H); 0.99(t,3H); 1.13-1.25(m,lH); 1.28(s,9H); 1.79-2.01(m,2H) ; 2.14-2.34(m,IH) ; 2.36-2.48(m,2H) ; 2.51-2.75(m,3H) ; 2.78-2.96(m,2H) ; 3.36-3.61(m,3H) ; 3.63-3.77(m,2H) ; 3.79-4.09(m,2H) ; 4.13-4.26(m,IH) ; 6.75(m,IH) ; 7.08-7.29(m,10H) ; 7.93(m,lH). EXftMPLE 129 1-fN-fR)-2-Benzyl-fS)-5-t-butoxycarbonylaιrιino-fS)-4-hvdroxy-0- phenylhexanoyl)-fS)-valyll-4-ethylamιinoazetidine The title compound was prepared from the product of Example 128 by the same procedure as described for Example 2 to give the product as a colourless foam. Found: 0,67.03; H,8.13; N,9.08. C 34 H 5() N 4 0 5 . 2/3 H 2 0 requires 0,67.32; H,8.41; N,9.24%. m/e 595(MH + ) [α] 25 -13° (c = 0.1%, MeOH) D N.M.R. (DMSO-dg) t5 = 0.74(m,6H); 0.98(t,3H); 1^18-1.46^,^) ; 1.29(s,9H); 1.61(m,lH); 1.70(m,lH) ; 2.34-2.61(m,5H) ; 2.66-2.90(m,4H) ; 3.36-3.59(m,4H) ; 3.67-4.18(m,3H) ; 4.51(d,IH) ; 6.38(m,lH); 7.05-7.29(m,10H) ; 7.77(m,lH). EXAMPLE 130 f S) -5- r f S) -l-t-Butoxycartonylaιrιino-2--Aιenylethyl] - f R) -3- f 4-iodo- benzyl) -gamma-butyrolactone The title conpound was prepared by the same procedure as described for -Ditermediate Preparation (2a) by alkylation of the lactone with 4-idobenzyl bromide. Found: 0,55.55; H,5.42; N,2.65. C 24 ∑^gIN0 4 requires 0,55.28; H,5.41; N,2.68% m/e 522.7 (MH + ) [α] 25 0° (c = 0.1%, MeOH) D N.M.R. (DMSO-d,.) δ = 1.25(s,9H); 2.05(m,2H); 2.65(m,3H); b 2.85(m,lH); 3.0(dd,lH); 3.75(m,lH); 4.4(m,lH); 7.05(d,2H); 7.2(m,6H); 7.65(d,2H). EXftMPLE 131 pyridyl)benzyl)-<rammabutyrolactone A heterogeneous solution of 4-boroπ-qpyridine hy-3rochloride (1.95 g) in water (30 ml) and diethyl ether (30 ml) was cooled in an ice bath and treated with solid sodium bicarbonate until the pH of the aqueous layer reached >7.0. The ether layer was separated, dried (MgSO.) and evaporated under vacuum at 0°C to provide a colourless oil. A solution of the oil in tet ahydrofuran (30 ml) was cooled to -100°C and treated with t-butyllithium (1.7M in pentane, 11.8 ml) dropwise over 20 minutes keeping the temperature below -95°C. After an additional 10 minutes at -100°, a solution of zinc chloride in diethyl ether (1.0 M, 12 ml) was added over 10 minutes and the reaction allowed to warm to room teπperature. Tetrald≤(triphenylphosphine)palladium (0.1 g) and a solution of the product from Example 130 (1.05 g) in tet-rahydrofuran (10 ml) were added and the reaction stirred at room teπperature 1.5 hours. A solution of ammonium chloride (2 g in water (10 ml) was added and the resulting mixture poured into a solution of ethylenediamine tetraacetic acid (9.5 g) in water (100 ml) and the pH adjusted to pH 8 with solid sodium bicarbonate. The solution was extracted with methylene chloride (3 x 100 ml) and the combined organic extracts washed with saturated brine (200 ml) , dried (MgSO .) and evaporated under vac--uum. The residue was purified by chromatography on silica-gel with a gradient elution of ethyl acetate-hexane (1:9) through to neat ethyl acetate, to provide the title c mpound as a colourless foam, (0.59 g) . Found: 0,73.3; H,6.78; N,5.84. C I^L N- j O. requires 0,73.71; H,6.83; N,5.93%. m/e 473.08 (MH + ) [α] 25 -2° (c = 0.1%, MeOH) D N.M.R. (DMSO-dg) δ = 1.25(s,9H) ; 2.1(m,2H); 2.7(m,3H); 2.95(m,lH) ; 3.1(dd,lH); 3.8(m,lH); 4.4(m,lH); 7.05(d,lH); 7.2(m,5H); 7.4(d,2H); 7.7(d,2H); 7.75(d,2H); 8.6(d,2H). EXftMPLE 132 fS)-5-t-Butoχyc^rtonylaπrino-fS)-4-t-butyld-uιethylsilyloxy-6- phenyl-fR)-2-f4-f4-pyridyl)benzyl)hexanoic acid The title compound was prepared from the product of Exairple 131 by the same prOcedure as described for Intermediate Preparation (2b) . Found: 0,69.0; H,7.70; N,4.53. C 3 _H 4 gN 2 0 5 Si requires C,69.5; H,8.00; N,4.63%. m/e 605.38 (MH + ) [α] 25 -45° (c = 1%, MeOH) D N.M.R. (DMSO-dg) 5 = 0.1(d,6H); 0.9(s,9H); 1.25(s,9H); 1.4(m,lH); 1.95(m,lH); 2.45(m,lH); 2.8(m,3H); 2.95(m,lH); 3.6(m,lH); 3.75(bd,lH); 6.9(s,lH); 7.2(m,5H); 7.3(d,2H); 7.7(d,2H); 7.75(d,2H); 8.6(d,2H);l2.2(6s,lH). EXftMPLE 133 1-[N-ffS)-5-t-Butoxycarbonylaπrino-fS)-4-t-butyldimethvsilyloχy-6- phenyl-fR)-2-f4-f4-pyridyl)benzyl)hexanoyl)-fS)-valyl]-4-keto¬ piperidine The title compound was prepared from the product of Example 132 and the product from Intermediate Preparation (3a) by the same procedure as described for Intermediate Preparation (5b) . Found: 0,68.6; H,8.2; N,6.8. C 4 _Hg N 4 O g Si requires 0,68.8; H,8.22; N,7.14%. m/e 785.08 (MH + ) [α] 25 +12° (c = 0.1%, MeOH) D N.M.R. (DMSO-d δ = 0.1(d,6H); 0.85(dd,6H); 0.9(s,9H); b 1.25(m,lH); 1.27(s,9H); 2.0(m,2H); 2.3(m,5H); 2.7(m,2H); 2.9(m,2H); 3.55(m,2H); 3.8(m,4H); 4.55(t,lH); 6.8(d,lH); 7.2(m,5H); 7.35(d,2H); 7.65(m,4H); 8.1(d,lH); 8.6(d,2H). EXftMPLE 134 1-rN-ffS)-5-t-Butoxycartonylaιrιino—fS)-4-t-butyldimethylsilyloxy-6- phenyl-fR)-2-f4-f4-pyridyl)benzyl)hexanoyl)-fS)-valyll-4-methyl- aminopiperidine The title compound was prepared by the same procedure as described for Example 7 by the reaction of the product of Example 133 with methylamine. m/e 800.15 (MH + ) [α] 25 +16° (c = 0.1%, MeOH) D N.M.R. (DMSO-d δ = 0.15(dd,6H); 0.85(dd,6H); 0.9(s,9H); b 1.0-1.3(m,3H); 1.25(s,9H); 1.75-2.05(m,4H); 2.35(d,3H); 2.6-2.95(m,7H); 3.1(t,lH); 3.55(m,lH); 3.7(m,lH); 3.9(bd,lH); 4.05(bd,lH); 4.2(bt,lH); 4.5(dt,lH); 6.75(m,lH); 7.1-7.35(m,7H) ; 7.65(d,4H); 7.95(dd,lH); 8.7(d,2H) . EXftMPLE 135 1-fN-ffS)-5-t-Butoxycartonylamino-fS)-4-hvdroxy-6-phenyl-fR)-2-f4- f4-pyridyl)benzyl)hexanoyl)-fS)-valyll-4-ιrethylaminopiperidine The title compound was prepared from the product of Example 134 by the same procedure as described for Example 2 and was obtained as an amorphous solid. Found: C,69.74; H,8.09; N,10.15. C H-.--N O requires C,70.04; H,8.08; N,10.21%. m/e 685.95 (MH + ) [α] 25 +33° (c = 0.1%, MeOH) D N.M.R. (DMSO-dg) S = 0.8(d,3H); 0.9(d,3H); 1.25(m,3H); 1.4(s,9H); 1.8(m,4H); 2.4(d,3H); 2.9(m,8H); 3.6(m,lH); 3.75(m,lH); 3.9(bd,lH); 4.25(bd,lH); (4.75(q,lH); 4.9(d,lH); 6.5(dd,lH); 7.1(d,2H); 7.25(m,7H); 7.5(m,4H); 8.65(d,2H). EXftMPLE 136 1-fN-fR)-2-Benzyl-fS)-5-cyclol.xιtoxycarbonylamino-fS)-4-hydroxy-6- phenylhexanoyl)- S)-valyll-4-methylaminopiperidine hydrate a) The product from Example 4 (371 mg) was dissolved in dichloromethane (10 ml) and the solution was cooled in an ice bath. Trifluoroacetic acid (2 ml) was added dropwise over 1 minute and the solution stirred at 0°C for 45 minutes. The solvent was evaporated under vacuum and the residue basified with saturated aqueous sodium bicarbonate solution, then extracted with dic oro ethane (3 x 50 ml) . The c tmbined organic extracts were dried over MgS0 4 , filtered and evaporated under vacuum to give 1- [N-((S)-5-amino-(R)-2-benzyl-(S)-4-hydro-xy-6-phenylhexanoyl)-(S)- valyl]-4-(N-benzyloxycarbonyl-N-metoylamino)piperidine hemihydrate as a white foam (315 mg) . Found: 0,69.84; H,8.00; N,8.42. C 3 gH 5() N 4 0 5 . 0.51^0 requires 0,70.02; H;7.89; N,8.60%. b) The above product (0.45 mmole, 290 mg) was dissolved in dichloromethane (20 ml) and cyclobutoxycarbonyloxysucc-in-i de (0.5 mmole, 107 mg) added. The mixture was stirred at room te-rrperature for 4 hours and the solvent removed under vacuum. The residue was redissolved in ethyl acetate (100 ml) and the solution was washed with dilute hydrochloric acid (0.2 M, 50 ml), saturated aqueous sodium bicarbonate (50 ml) brine (10 ml) and then dried over sodium sulphate, filtered and the filtrate evaporated to dryness. The residue was purified by column chroiratcgraphy on silica, eluting with dichlo-rcmethane:methanol (98:2), and crystallised from diethyl ether to give 1-[N-((R)-2-benzyl-(S)-5-cyclobutoxy- c-artonylamino-(S)-4-hydroxy-6-phenylhexanoyl)-(S)-valyl]-4-(N- benzyloj^carbonyl-N-irethylan no)piperidine (262 mg) , m.p. 162-164°C. Found: 0,69.52; H,7.73; N,7.41. C^HggN 0 requires 0,69.71; H,7.62; N,7.56%. [α] 25 -14° (c = 0.1, MeOH). 589 c) A solution of the above product (0.31 mmol, 227 mg) in methanol (25 ml) was treated with 10% palladium on charcoal (60 mg) . The mixture was stirred at room temperature under hydrogen at a pressure of 2.76 bar (40 p.s.i.) for 2 hours. The catalyst was removed by filtration and the solvent evaporated under vacuum to give an oil which was purified by column chromatography on silica-gel eluting with dichlorcHre1.h-=uie:irethanol:880 ammonia (93:6:1) . After evaporation of the product fractions the residue crystallised on trituration with diethylether to af f ord the title cxmpσund (162 mg) , m.p. 168-170°C. Found: 0,68.47; H,8.16; N,9.04; C ς ^ Q N^Og. 0.4 1^0 requires 0,68.47; H,8.34; N,9.13%. m/e [MH] + 607 [α] 25 -13° (c = 0.1 MeOH) 589 N.M.R. (DMSO-d b δ = 0.75(d,6H) ; 1.08(m,2H) ; 1.30(m,lH) ; 1.50(q,lH) ; 1.64(m,2H) ; 1.72-1.90 (m,6H) ; 2.15(m,2H) ; 2.32 (s,3H) ; 2.50-2.90(m,8H) ; 3.42 (m,lH) ; 3.55(m,lH) ; 3.84(m,lH) ; 4.l3 (m,lH) ; 4.47(dt,lH) ; 4.65(m,2H) ; 6.68(m,lH) ; 7.05-7.30(m,10H) ; 7.75(d,lH) . EXftMPLE 137 1- TN- f f S) -5-AmirιocartonyImethoxycarbonyla^ f R) -2-benzyl- ( S) -4- hydroxy-6-tAιeπylhexanoyl) - f S) -valyl] -4- f N-methylamino) piperidine hemihydrate a) To a solution of l-[N-( (S)-5-amino-(R) -2-benzyl- (S) -4- hydroxy-6-phenylhexanoyl) - (S) -valyl] -4- (N-benzoyloxycarboπyl-N- methylamino) piperidine, (from Exairple 136(a) , 0.5 mmole, 321 mg) in dichlorcmethane (20 ml) was added methoiiycarbonylmethoxy- cartonylsucc-inimide (0.6 mmol, 139 mg) and the resulting solution stirred at room teirperature for 18 hours. The solvent was removed under vacuum and the residue was redissolved in ethyl acetate (100 ml) . The solution was washed with 0.2N hydrochloric acid (50 ml) , saturated aqueous sodium bicarbonate (25 ml) and brine (10 ml) . The organic phase was then dried over magnesium sulphate, filtered and evaporated to dryness. The residue was purified by column chromatography on silica gel eluting with dichlorcmethane-irethanol (98:2) . Evaporation of the product containing fractions gave l-[N-( (R) -2-benzyl-(S) -4-hydroxy-(S) -5-ιrethoxycartonylπethoxy- cartonylaιrιinσ-6-phenyhexanoyl- (S) N-methylamino) piperidine as a white foam (374 mg) , m/e [MH ] 759. b) A solution of the above product (0.43 mmole, 330 mg) was dissolved in methanolic ammonia (10 ml) at 0°C. After 40 ir-inutes the solvent was removed under vacuum and the residue pjurif ied by column ch-ranatography on silica-gel eluting ethyl ac-etate:methanol (98:2) . Evaporation of the product containing fractions gave 1- [N- ( (S) -5-aιrιinocarbony-ljmetooxycarbonyla-mir-o- (R) -2-benzyl- (S) -4- hydroxy-6-phenylhexanoyl) - (S) -valyl) ] -4- (N-benzyloxycarbonyl-N- netoylamino) piperidine as a white foam. (155 mg) , m/e [MH] 744. c) Catalytic hydrogenation of the above product over palladium on charcoal as described for Example 136 step (c) gave the title compound, m.p. 130-135°C dec. Found: 0,63.98; H,7.82; N,11.02; C 33 H 4 7 N 5°6* °* 5 ^2° re£ 3 uires C,64.06; H,7.82; N,11.32%. [α] -16° (c = 0.1 MeOH) . 589 N.M.R. (DMSO-d, b.) δ = 0.74 (m, 6H) ; 0.83 (m,lH) ; 0.95-1.90 (m,7H) ; 2.12 (m,lH) ; 2.25(s,3H) ; 2.50-2.90 (m, 7H) ; 3.46 (m,lH) ; 3.53 (m,lH) ; 3.70(m,lH) ; 4.07 (m,lH) ; 4.2l(s,2H) ; 4.48 (m,lH) ; 4.78 (dbs,lH) ; 7.00(d, lH) ; 7.05-7.30 (m,l2H) ; 7.73 (d,lH) . EXftMPLE 138 1-fN-ffS)-5-f1-Aminocarbonylethoxy)t^arboπylamino-fR)-2-benzyl- fS)-4-hvdroxy-6-phenv-lhexanoyl)-S-valyll-4-fN-methylamino)- piperidine hydrochloride. a) The procedure of Example 137 step (a) was followed using 1-(methoxycarbonyl)ethoxyc-.arbonylo^suc^iri-uriide (2 mmole, 490 mg) and the -same amine (1 mmole, 642 mg) to give l-[N-((R)-2-benzyl- (S)-4-hydroxy-(S) carbonylamino-6- phenylhexanoyl)-S-valyl]-4-(N-benzylo^carbonyl-N-iretoylamino)- piperidine, (598 mg) m/e [MH] 773. b) The above product (0.74 mmole, 572 mg) was dissolved in 2,2- dimethoxypropane (5 ml) and p-toluenesulphonic acid (5 mg) was added. The solution was heated at 50°C for 2 hours and the solvent was then removed under vacuum. The residue was redissolved in ethyl acetate (100 ml) and washed with saturated aqueous sodium bicarbonate solution (25 ml) then brine (10 ml) . The organic layer was dried over magnesium sulphate, filtered and evaporated to dryness. The compound was further purified by column chromatography on silica-gel eluting with hexane:ethyl acetate (60:40) . Evaporation of the product ∞nteining fractions gave 1-[N-((S)-4-benzyl-2,2-dimethyl-3-(1-ιretooxyc^rbonyl-ethoxy)- carbonyloxazolidine-5-(S)-((R)-2-benzyl)-3-propanoyl)-(S) -valyl) ]-4-(N-benzyloxyc^rbonyl-N-irethylamino)-piperidine (408 mg). m/e [MH] + 813. c) The above product (230 mg) was dissolved in methanolic ammonia (10 ml) and the solution was stirred at roam temperature for 18 hours. The solvent was removed under vacuum and the residue was purified by column c-hroπatography on silica-gel, eluting with hexane: ethyl acetate (40:60) . The product containing fractions were evaporated to dryness to give l-[N-((3-(l-amino- carboiψlethcxy) carbonyl) -(S) -4-benzyl-2 , 2-dimethyloxazolidine-5- ( (S) - ( (R) -2-benzyl) -3-propanoyl) ) - (S) -valyl] -4- (N-benzyloxy- cartonyl~N-ιrethylamino) piperidine as a white foam (145 mg) . m/e [MH] + 798. d) The above product from step (c) (0.18 mmole, 145 mg) was dissolved in methanol (10 ml) and p-toluenesulphonic acid (0.05 mmole, 10 mg) was added. The solution was heated at reflux, under nitrogen, for 2.5 hours. The cooled solution was jpαured into ethyl acetate (100 ml) and washed with saturated aqueous sodium bicarbonate (25 ml) and brine (10 ml) . The organic layer was then dried over magnesium sulphate, filtered and evaporated to dryness. The residue was purified by column chroiiatography on silica-gel, eluting with ethyl acetete:methanol (19:1) . Evaporation of the product-conteining fractions gave 1- [N- ( (S) -5- (1-aminocarbonylethoxy) carbonylamino- (R) -2-benzyl- cartoιιyl-N-ιτe1-hylaιτι-i-no) piperidine (73 mg) . m/e [MH] 758. e) The above product from step (d) (70 mg, 0.09 mmole) was hydrogenated using the same conditions as described in Example 136(c) to give the title conpound (43 mg) . This was redissolved in ethyl ac^tate:methanol 2:1 (10 ml) and treated with ethereal hydrogen chloride to give the hydrochloride as a white crystalline solid (43 mg) , m.p. >142°C dec. Found C,58.98; H,7.42; N,9.45. C 34 H 49 N 5°6* HC1 ' 1 * 5 ^2°' °' 5 C 4 H 8°2 re£ 3 uires C,59.12; H,7.86; N,9.58%. m/e [MH] + 624 [α] 25 +1° (c = 0.1 MeOH) [α] +154° (c = 0.1 MeOH) 365 N.M.R. (DMSO-dg) δ = 0.75(m,6H) ; 1.13-1.70(m,8H) ; 1.62(m,lH); 1.87(m,IH) ; 2.02(broad IH) ; 2.44-2.88(m,10H) ; 3.43(m,IH) ; 3.52(m,lH); 4.42(m,3H); 4.66(m,2H); 6.90(m,lH); 7.05-7.30(m,12H) ; 7.84(m,lfl) ; 8.97(broad s,2H) . EXftMPLE 139 1- r N-ffS)-5-f1-Aminocarbonyl-l-πethylethoχy)carbonylamino-fR)- 2-benzyl-fS)-4-hydroχy-6-phenylhexanoyl)-fS)-valyll-4-fN-methyl- amino)piperidine hydrochloride a) The product from Example 136(a) (0.93 mmole, 594 mg) was dissolved in dichloromethane (20 ml) and the solution was treated with pyridine (1.5 mmole, 119 mg) and 1-methoxycarbonyl-l-nethyl- ethylchlorofornate (1.1 mmole, 199 mg) . The solution was stirred at room teπperature for 1 hour and the solvent was then removed under vacuum. The residue was redissolved in ethyl acetate (100 ml) and washed with 0.5 N hydrochloric acid (25 ml) , saturated aqueous sodium bicarbonate (25 ml) and brine (10 ml) . The organic layer was dried over magnesium sulphate, filtered and the filtrate was evaporated to dryness. The residue was further purified by column chromatography on silica-gel eluting with c chloro-nethane: methanol (98:2). The product containing fractions were evaporated to give 1-[N-((R)-2-benzyl-(S)-4-hydroxy-(S)-5-(1-methoxy- carbonyl-1-methylethoxy)cartonylaπιino-6-phenylhexanoyl)-(S)- valyl]-4-N-ben-^loxycartonyl-N-πethylaιrrino)piperidine, (554 mg) , m/e [MH] + 787. b) The above product from step (a) (540 mg) was dissolved in 2,2-di.rιethoxypropane following the procedure of Example 138 step (b) to give the oxazolidine derivative (483 mg) . c) The product from step (b) above (483 mg) was dissolved in dioxan (10 ml) and 1M sodium hydroxide solution (0.6 ml) was added. The solution was heated at 50°C for 24 hours and then poured into water (50 ml) and the mixture was then acidified with 1M hydrochloric acid (1.0 ml) and extracted with ethyl acetate (3 x 50 ml) . The combined organic extracts were dried over magnesium sulphate, filtered and evaporated to dryness. The residue was further purified by column chromatography on silica gel, eluting with ethyl acetate:glacial acetic acid (99:1). The product c»nteining fractions were evaporated to give l-[N-((S)-4-benzyl- 3-(1-carboxy-l-methylethoxy)carbonyl-2 ,2-dimethyloxazolidine-5- ((S)-((R)-2-benzyl)-3-propanoyl))-(S)-valyl]-4-(N-benzylox- carbonyl-N-irethylamdno)-piperidine as a white foam (183 mg) . m/e [MH] + 813 d) The product from step (c) above (175 mg, 0.22 mmole) was dissolved in dry dichloromethane (10 ml) and 1-hydroxybenzo- triazole (0.35 mmole, 47 mg) was added. l-(3-Diπetoylamino- propyl)-3-ethyl-carbodiimide hydrochloride (0.30 mmole, 58 mg) was then added and the solution stirred at room teirperature for 45 minutes. Methanolic ammonia (1 ml) was introduced and after a further 20 minutes at roam teπperature the solution was evaporated to dryness. The residue was redissolved in ethyl acetate (100 ml) and the solution was washed with hydrochloric acid (0.1 mmole, 50 mg) , saturated aqueous sodium bicarbonate (25 ml) and brine (10 ml) . The solution was dried over magnesium sulphate, filtered and the filtrate was evaporated to give l-[N-(3-(l-aminocarbonyl-l- irethylethαxy)carbonyl-(S)-4-benzyl-2,2-όiπethyl-oxazolid-ine-5- ((S)-((R)-2-benzyl)-3-propanoyl))-(S)-valyl]-4-(N-Icenzyloxy- cartoi l-N-methylamino)-piperidine. m/e [MH] 812. e) The product -from step (d) above was treated with p-toluene sulphonic acid in methanol and the product then hydrogenated following the procedures of Example 138 steps (d) and (e) to give the title compound (64 mg) m.p. >125°C dec. Found: C,60.23; H,7.85; N,9.51. C gU NgOg. HCl.^O. 0.25 C 4 Hg0 2 requires C,60.58; H,7.90; N,9.80%. m/e [MH] + 638 [α] 25 13° (c = 0.1 MeOH) 589 N.M.R. (DMSO-d δ = 0.75(m,6H) ; 1.21-1.45(m,llH) ; 1.56(m,lH) ; b 1.86(m,lH); 2.42-2.87(m,9H); 3.05-3.53(m,4H) ; 4.10(m,lH); 4.48(m,2H); 4.70(bs,lH); 6.86(t,lH); 7.17(m,12H); 7.88(dd,lH); 8.9(b,sH). EXftMPLE 140 1-rN-ffR)-2-Benzyl-fS)-4-hvdroxy-fS)-5-f1-ι-ethylaminocarbonyl- ethoxy)carbonylamιino-6-phenv-lhexanoyl) -(S)-valyll-4-fN-methyl- amino) iperidine- hydrochloride, hydrate. The procedure of Example 139 was followed but using πethylamine in step (d) instead of ammonia. Subsequent deprotection as described in Example 138 gave the title ccampound (258 mg) , m.p. 166-172°C dec. Found: 0,60.80; H,7.77; N,9.86. C ^ NgOg. HCl. IL0 requires C,60.72; H,7.86; N,10.12%. m/e [MH] + 638 ?5 [α] -12° (c = 0.1 MeOH) . 589 N.M.R. (DMSO-dg) 5 = 0.75(m,6H); 1.20-1.68 (m,7H) ; 1.88(m,lH); 2.05(m,2H); 2.40-2.90 (m, 13H) ; 3.17(m,lH); 3.43(m,lH); 3.52(m,lH); 4.07(m,lH); 4.45(m,2H); 4.70(m,2H) ; 6.88(m,lH); 7.07-7.30(m,10H) ; 7.82(m,2H); 8.98(bs,2H). EXftMPLE 141 1- TN- f f R) -2-Benzyl- f S) -4-hvdroxy- f S) -5-oxeton-3-oχycartonylamino- 6-phenylhexanoyl) - f S) -valyll -4- f N-methylamino) piperidine The product from Exairple 136 step (a) (642 mg, 1 mmole) was dissolved in dichloromethane (20 ml) and oxetan-3-oj.ycarboηyloxy- suc-cinimide (from Preparation 12, 221 mg, 1 mmole) added using the procedure outlined in Exairple 136 step (b) . Subsequent deprotection using the procedure of Example 136 step (c) gave the title compound (168 mg) m.p. 125-129°C dec. Found: 0,66.80; H,8.09; N,8.77. C 3 H 4g N 4 0g requires C,67.08; H,7.95; N,9.20%. m/e [MH] + 609. [α] -33° (c = 0.1 MeOH) 589 N.M.R. (DMSO-dg) 5 = 0.75 (m,6H) ; 1.00-1.94 (m,7H) ; 2.10-2.25(m,3H); 2.42-2.90(m,9H) ; 3.47(m,lH); 3.57(m,lH); 3.82(m,lH); 4.07(m,lH); 4.43(dq,2H); 4.50 (m,lH); 4.68(m,3H); 5.l2(p,lH); 7.09-7.27(m,llH) ; 7.77(m,lH). EXftMPLE 142 1-[N-ffR)-2-Benzyl-fS)-5-f1.l-dioxothiet.an-3-owc^rbonylamino)- fS)-4-hvdroxy-6-phenylhexanoyl)-fS)-valyll-4-fN-iτetoylaminol- piperidine a) The product from Exairple 136 step (a) (2.57 g, 4 mmole) was dissolved in dichloromethane (100 ml) and the product from Preparation 11 (1.04 g, 45 mmol) added using the procedure outlined in Example 136 step (b) . The product, l-[N-((R)-2- benzyl-(S)-4-hydroxy-(S)-6-phenyl-(S)-5-(thietan-3-oxycarbonyl- amino)hexanoyl)-(S)-valyl]-4-(N-benzyloxyi-^rbonyl-N-iretoylait no)- piperidine was obtained as a glass (2.42 g) . m/e [MH] 759. b) The product from step (a) above (1.60 g, 2.11 mmole) was dissolved in dichloromethane (100 ml) and the solution was cooled in an ice bath. 3-Chloroperbenzoic acid (85%, 430 mg, 2.11 mmole) was added portionwise over 1 minute and the solution stirred at 0°C for 20 minutes. The solvent was removed under vacuum and the residue redissolved in ethyl acetate (100 ml) and washed with saturated aqueous sodium bicarbonate solution (25 ml) and brine (10 ml) . The organic layer was then dried over magnesium sulphate, filtered and the filtrate was evaporated to dryness. Trituration of the residue with ether gave the 1-oxo-thietanyl derivative as a white solid (1.38 g), m.p. 125-129°C dec. m/e [MH] + 775. c) The product from step (b) above (700 mg, 0.9 mmole) was dissolved in dichloromethane (50 ml) and 3-chloroperbenzoic acid (85%, 183 mg, 0.9 mmole) was added portionwise over 1 minute. The solution was stirred at room temperature for 2 hours and the solvent -removed under vacuum. The residue was redissolved in ethyl acetate (50 ml) and washed with saturated aqueous sodium bicarbonate solution (20 ml) and brine (10 ml) . The organic extract was dried over magnesium sulphate, filtered and the filtrate evaporated to dryness to give the l,l,dioxo-thietanyl derivative as a white solid. (609 mg) . m.p. 203-205°C. m/e [MH] 791. d) The product from step (c) above (500 mg, 0.63 mmole) was hydrogenated by the method described in 136 step (c) using a 1:1 mixture of methanol:ethyl acetate as solvent to give the title product (202 mg), m.p. 189-191°C dec. Found: C,61.79; H,7.59; N,8.39. C 34 H 4 gN 4 0 7 S requires 0,62.17; H,7.37; N,8.53%. m/e [MH] + 657. [α] 25 -32° (c = 0.1 MeOH) 589 N.M.R. (DMSO-d δ = 0.75(m,6H) ; 1.05(m,lH); 1.30(m,lH); b 1.62-1.92(m,5H); 2.28(S,3H); 2.50-3.10(m,8H) ; 347(m,lH); 3.55(m,lH); 3.78-4.l5(m,4H) ; 4.44-4.72(m,4H) ; 5.04(m,lH); 7.05-7.34(m,12H) ; 7.81(d,IH) . EXftMPLE 143 1-rN-ffS)-4-Hvdroxy-fS)-5-ffS)-l-irethylaminocarbonylethoxy)- carbonylamino-6-rhenyl-fR)-2-f4-trifluoromethoxybenzyl)hexanoyl)- fS)-valyll-4-fN-ethylamino) iperidine. hydrochloride, hydrate a) (S)-5-t-Butoxycarbonylamino-(S)-4-(t-tfutyldήrethylsilyloxy)- 6-phenyl-(R)-2-(4-trifluoronethoxybenzyl)hexanoic acid (from Example 79, 5.0 g, 8.17 mmole) was reacted with 1-(N-t-butoxy- cartonyl-(S)-valyl-4-ketopiperidine (from Intermediate Preparation 3(a)) , following the procedure of Intermediate Preparation 5(b) to give 1-[N-((S)-5-t-tutoxycarbonylaιιιino-(S)-4-t-butyldimethyl- silyloxy-6-phenyl-(R)-2-(4-trifluoromethoxybenzyl)hexanoyl)-(S)- valyl]-4-ketopiperidine, (6.46 g) . m/e [MH] 793. b) Reaction of the product from step (a) above with ethylamine following the prcicedure described in Example 7 gave 1-[N-((S)-S-t-l-xαtoxycartonylairtino-(S)-4-t-tutyldiιtetftylsilyloxy- 6-phenyl-(R)-2-(4-trifluoromethoxybenzyl)hexanoyl)-(S)-valyl]-4- ethylaminopiperidine. m/e [MH] 822. c) The product from step (b) above (5.94 g, 7.24 mmole) was dissolved in dichloromethane and benzyloxycarboriylo-^sucxsinimide (1.87g, 7.50 mmole) was added. The solution was stirred at room teirperature for 2 hours and the solvent was then removed under vacuum. The residue was redissolved in ethyl acetate (100 ml) and washed with 0.25M hydrochloric acid (50 ml) , saturated aqueous sodium bicarbonate (25 ml) and brine. The organic layer was dried over magnesium sulphate, filtered and the filtrate evaporated to dryness. Further purification was carried out by column chroiratography on silica gel eluting with d chlorcmethane:methanol (98:2) . Evaporation of the product containing fractions gave 1-[N-((S)-5-t-butyloxycarbonylamino-(S)-4-t-fcutyldi-methyl- silyloxy-6-phenyl-(R)-2-(4-trifluoromethoxybenzyl)hexanoyl)-(S)- valyl]-4-[N-benzyloxycarbonyl-N-etoylamino)piperidine (6.30 g) . m/e [MH] + 955. d) The product from step (c) above was reacted with tetra-n- butylammonium fluoride as described in Example 2 to give 1-[N- ((S)-5-t-butyloxycarbonylamino-(S)-4-hydroxy-6-phenyl-(R)-2-(4- trifluoromethoxybenzyl)hexanoyl)-(S)-valyl]-4-[N-benzyloxy- cartonyl-N-ethylamino)piperidine, m.p. 164-167°C. Found: 0,63.98; H,7.36; N,6.41. C^HggF^Og requires C,64.27; H,7.07; N,6.66%. m/e [MH] + 841 e) The N-t-tutyloxycarbonyl group was removed by treatment with trifluoroacetic acid following the procedure of Exairple 136 step (a) to give l-[N-((S)-5-aπtino-(S)-4-hydroxy-6-phenyl-(R)-2-(4-tri- fluoromethoxybenzyl)hexanoyl)-(S)-valyl]-4-[N-benzyloxycarboπyl- N-ethylamino)piperidine, m/e [MH] 741. f) The product from step (e) above was reacted with (S)-(l- ιtetho.xycartonylethoxy)carbonyloxy^ (from -Ditermediate -P-reparation 9) following the procedure of Exairple 136 step (b) to give 1-[N- ( (S) -4-hydroxy- (S) -5- ( (S) -1-metho.xycarbonylethoxy) - cartonylamino-6-phenyl-2- (4-tr.i-f luoromethoxybenzyl) hexanoyl) - (S) - valyl]-4-(N-benzyloxyc»rtonyl-N-ethylaιιι-ino)piperidi-ne. m/e [MH] 871. g) Reaction of the product from step (f ) above with 2,2-diπethoxypropane as described in Example 138 step (b) gave the oxazolidine derivative which was reacted with methylamine and subsequently dep-rotected as described in Exaπple 140 to give the title coipound. m.p. 223-226°C. Found: C,56.68; H,7.00; N,8.53. C-^ H^. HCl. 1^0 requires 0,56.32; H,7.0l; N,8.86%. m/e MH] 736. [α] 25 + 6° (c = 0.1 MeOH) . 589 N.M.R. (DMSO-dg) δ = 0.75(m,6H) ; 1.15-1.68 (m, 12H) ; 1.85(m,lH) ; 2.55-3.13 (m,12H) ; 3.25(m,lH) ; 3.48(m,5H) ; 4.l3 (m,lH) ; 4.43 (m,2H) ; 4.71(m,lH) ; 6.88(t,lH) ; 7.22(m,9H) ; 7.75(d,lH) ; 7.90(t,lH) ; 8.95(bs 2H) ; EXftMPLE 144 l-[N-fS)-4-Hvdroxy-fS)-5-ffR)-1-ι-ethylaminocarbonylethoxy)- carbonylamino-6-phenyl-fR)-2-f4-trifluoromethoxybenzyl)hexanoyl)- fS)-valyll-4-fN-ethylamino)-piperidine, hydrochloride, hydrate The procedure described in Exaπple 143 was followed but using (R)-(1-ιιel-hoxycarboπylethoxy) from Intermediate Preparation 10 in step (f) . The product was obtained as a white solid, m.p. 198-200°C dec. Found: 0,55.89; H,7.06; N,8.78. C 37 H 52 F 3 N 5 0 . HCl. H 2 0 requires C,56.23; H,7.01; N,8.86%. m/e [MH] + 736. [α] 0° (c = 0.1 MeOH) 25 589 [α] +15° (c = 0.1 MeOH) . 365 N.M.R. (DMSO-dg) δ = 0.75(m,6H) ; 1.16-1.68(m,10H) ; 1.86(m,lH); 2.08(m,2H); 2.56-3.08(m,12H); 3.25(m,lH); 3.40(m,4H); 3.55(m,lH); 4.16(m,lH); 4.45(m,2H); 4.70(m,lfl); 6.90(t,lH); 7.18(m,9H); 7.80(d,lH); 7.91(t,lH); 8.83(bs,2H).

Claims: CLAIMS 1. A compound having the formula:- (I) or a pharmaceutically acceptable salt thereof or bioprecursor therefor, wherein: R is 0,-C-. alkyl, 0_-C o cycloalkyl,, aryl, heterocyclyl, or 7 R J o R'R°NCO; 2 R is C.-C 8 alkyl, C 3 -C 8 cycloalkyl(Cy-C.)alkyl, aryl(C,-C )alkyl, or heterocyclyl(C,-C.)alkyl; 3 . 4 R is C,-Cg alkyl, C 3 -C 8 cycloaUcyl, C 3 -C 8 cycloalkyl (C ^ ^JaU yl, aryl (C-.-C 4 ) alkyl, aryl(C 2 -C 4 )alkenyl, heterocyclyl (0,-C alkyl or heterocyclyl (C,-C ) alkenyl ; 4 <≤ 4 R _ is C A..--,C c b alkyl, 0_J-Co o cycloalkyl, aryl or heterocyclyl; R and R are each independently H, C.-C 8 alkyl, C -CL cycloalkyl, or 0,-C- alkyl substituted by C,-C. alkoxy, hydroxy or NR R ; or ~- t~ R and R are linked to form, together with the nitrogen atom to which they are attached, a pyrrolidine, piperidine, morpholine, piperazine or N-(C.-C alkyl) piperazine group; each of R 7 and R8 is independently H, C,-C- alkyl or C_-C_ 7 8 J O cycloalkyl; or R and R may be joined together to form, with the nitrogen to which they are attached, a 4 to 8 membered nitrcgen-containing heterocyclic group; each of R9, R10 , R11 and R12 is independently H, C.-C-. alkyl or C 3 ~C g cycloalkyl; or R 9 and R10, or R11 and R12 may be joined together to form a 3 to 8 -membered carbocyclic ring; X is a 4-10 membered mono- or bicyclic heterocyclic group ∞nraining carbon ring atoms and one ring nitrogen atom through which the group is attached to the adjacent carbonyl group; the group may be saturated or partially unsaturated and, in addition to the -(CR^R 12 )^ -NR 5 R 6 substitutent, it may be substituted by up to 4 further substitutents each independently chosen from F, 0,-Cg alkyl, C -Cg cycloalkyl, OH, C j - Cg alkoxy or NR 7 R 8 ; and n and m are each independently 0, 1 or 2; and wherein any alkyl or cycloalkyl group included in the aforementioned definitions may optionally be fully or partially substituted by fluorine. 2. A compound as claimed in claim 1 having the stereochemistry- : da) 1 6 9 12 wherein R toR , R toR , n, m and X are as previously defined in claim 1. 3. A compound as claimed in claim 1 or claim 2 wherein R is t-butyl, and n is O, or R -(CR R ) - is benzyl. 4. A cxmpound as claimed in claim 3 wherein R 2 is benzyl. 4 5. A cxmpound as claimed in claim 3 or claim 4 wherein R is isopropyl or sec-butyl. 3 6. A compound is claimed in any one of claims 3 to 5 wherein R is benzyl optionally substituted in the pAienyl ring by methyl, chloro, CF_, OCF 3 , pivaloyl, OH, OONMe , phenoxy, phenylsulphonyl or pyridyl or R is 3-phenylpropyl or 3-phenyl-prop-2-enyl. 7. A compound as claimed in any one of claims 3 to 6 wherein each of R 9 , R 10 , R 11 and R 12 is H. 8. A conpound as claimed in any one of claims 3 to 7 wherein X is piperidinyl. 9. A cxsnpound as claimed in claim 1 wherein said compound is: l-[N-( (S) -5-t-butoxycarbonylaιrιino- (S) -4-hydroxy-6-pheπyl- (R) -2- (4-trif luoromethoxybenzyl) hexanoyl) - (S) -valyl] -4-πethylamino- piperidine; 1- [N- ( (S) -5-t-butoxycarbonylaιrdno- (S) -4-hydroxy-6-phenyl- (R) -2- (3-phenylprop-2-en-l-yl) hexanoyl- (S) -isoleucyl] -4-ethylamino- piperidine; or 1- [N- ( (R) -2-benzyl- (S) -5-t-butoxycarbonylamino- (S) -4-hydroxy- 6-phenylhexanoyl) - (S) -α-cyclohexylglycyl] -4- (2-methoxyethyl- amino) iperidine . 10. A process for preparing a compound of the formula (I) as claimed in claim 1 which comprises removing the protecting groups from a compound of the formula: (XIV) wherein Λ is either H or a selectively removable hydroxy- protecting group and Y is either R , or a selectively removable nitrogen-protecting group and R 1 to R6 and R 9 to R 12 are as previously defined with the proviso that at least one of λ and Y is a protecting group, and isolating the compound of formula (I) and optionally forming a pharmaceutically acceptable salt thereof. 11. A pharmaceutical composition comprising a compound of the formula (I) or (Ia) or a pharmaceutically acceptable salt thereof, as claimed in any one of claims 1 to 9, together with a pharmaceutically acceptable diluent or carrier. 12. A conpound of the formula (I) , or (Ia) or a pha-t-maceutically acceptable salt thereof, as claimed in any one of claims 1 to 9 for use in medicine , in particular for use in the treatment or prophylaxis of human retroviral infections. 13. The use of a compound of the formula (I) or (Ia) as claimed in any one of claims 1 to 9, or a pharmaceutically acceptable salt thereof, for the manufacture of a medicament for use in the treatment or pjrophylaxis of human retroviral infections. 14. A method of treating human trσviral infections which comprises administering an effective amount of a compound of the formula (I) or (Ia) as claimed in any one of claims 1 to 9.

Inventors: GREENGRASS COLIN WILLIAM, GYMER GEOFFREY WILLIAM, HOOPLE DAVID WILLIAM THOMAS, STREET STEPHEN DEREK ALBERT, WHITTLE PETER JOHN, GREENGRASS, COLIN, WILLIAM, GYMER, GEOFFREY, WILLIAM, HOOPLE, DAVID, WILLIAM, THOMAS, STREET, STEPHEN, DEREK, ALBERT, WHITTLE, PETER, JOHN
Applicants: GREENGRASS COLIN WILLIAM, GYMER GEOFFREY WILLIAM, HOOPLE DAVID WILLIAM THOMAS, PFIZER, PFIZER LTD, STREET STEPHEN DEREK ALBERT, WHITTLE PETER JOHN, PFIZER INC., PFIZER LIMITED
Application year: 1993
Main classification: C07D205
IPC codes: A61K31, A61P31, A61P37, C07D205, C07D207, C07D211, C07D307, C07D401, C07D405, C07D407, C07D409, C07F7