PEPTIDES HAVING NOVEL POLAR N-TERMINAL GROUPS

Abstract: The present invention provides novel peptides having a non-cleavable transition state insert corresponding to the 10,11-position of the renin substrate (angiotensinogen) and having a novel polar group of formula (L1) (wherein X1 is H2N-, H2NC(CH3)2-, HO2C-, (H2N)(HO2C)CH-, or (HO)2P(O)O-) at the N-terminus of the peptide. These peptides are useful as renin inhibitors and as inhibitors of retroviral proteases. Renin inhibitors are useful for the diagnosis and control of renin-dependent hypertension, congestive heart failure, renin-dependent hyperaldosterism, other renin-dependent cardiovascular disorders and ocular disorders. Inhibitors of retroviral proteases, such as the HIV-I protease, are useful for treating diseases caused by retroviruses, such as human acquired immunodeficiency disease syndrome (AIDS).

Description: PEPTIDES HAVING NOVEL POLAR N-TERMINAL GROUPS DESCRIPTION BACKGROUND OF THE INVENTION The present invention provides novel compounds. More particu¬ larly, the present invention provides novel peptide analogs. Most particularly, the. present invention provides peptides containing a non-cleavable transition state insert corresponding to the 10,11- position of the renin substrate (angiotensinogen) and containing a novel polar group at the N-terminus of the peptide. These peptides are useful as renin inhibitors and as inhibitors of retroviral proteases. Renin inhibitors are useful for the diagnosis and control of renin-dependent hypertension, congestive heart failure, renin- dependent hyperaldosterism, and other renin-dependent cardiovascular disorders. Inhibitors of retroviral proteases, such as the HIV-I protease, are useful for treating diseases caused by retroviruses, such as human acquired immunodeficiency syndrome (AIDS) . Renin Is an endopeptidase which specifically cleaves a par- ticular peptide bond of its substrate (angiotensinogen) , of which the N- erminal sequence in equine substrate is for example: Renin Asp-Arg-Val-Tyr-Ile-His-Pro-Phe-His-Leu-Leu-Val-Tyr-Ser- IA 1 2 3 4 5 6 7 8 9 10 11 12 13 14 as found by L.T. Skeggs, et al. , J. Exper. Med. 106, 439 (1957). Human renin substrate has a different sequence as recently discovered by D.A. Tewkesbury, et al., Biochem. Biophys. Res. Comm. 99, 1311 (1981). It may be represented as follows: Renin i -Val-Ile-His- 11 12 13 IB and having the sequence to the left of the arrow (1) being as designated in formula IA above. Renin cleaves angiotensinogen to produce angiotensin I, which is converted to the potent pressor angiotensin II. A number of an- giotensin I converting enzyme inhibitors are known to be useful in the treatment of hypertension. Inhibitors of renin are also useful in the treatment of hypertension. A number of renin-inhibitory peptides have been disclosed. Thus, U.S. patent 4.424,207; European published applications 45,665; 104,041; and 156,322; and U.S. patent application, Serial No. 825,250, filed 3 February 1986; disclose certain peptides with the dipeptide at the 10,11-position containing an isostere bond. A number of statine derivatives stated to be renin inhibitors have been disclosed, see, e.g., European published applications 77,028; 81,783; 114,993; 156,319; and 156,321; and U.S. patents 4,478,826; 4,470,971; 4,479,941; and 4,485,099. Terminal disulfide cycles have also been disclosed in renin inhibiting peptides; see, e.g., U.S. patents 4,477,440 and 4,477,441. Aromatic and aliphatic amino acid residues at the 10,11 position of the renin substrate are disclosed in U.S. patents 4,478,827 and 4,455,303. C- erminal amide cycles are disclosed in U.S. patent 4,485,099 and European published applica¬ tions 156,320 and 156,318. Certain tetrapeptides are disclosed in European publications 111,266 and 77,027. Further, European pub- lished application No. 118,223 discloses certain renin inhibiting peptide analogs where the 10-11 peptide link is replaced by a one to four atom carbon or carbon-nitrogen link. Additionally, Holladay, et al., in "Synthesis of Hydroxyethylene and Ketomethylene Dipeptide Isosteres", Tetrahedron Letters, Vol. 24, No. 41, pp. 4401-4404, 1983 disclose various intermediates in a process to prepare stereo-di¬ rected "ketomethylene" and "hydroxyethylene" dipeptide isosteric functional groups disclosed in the above noted U.S. Patent No. 4,424,207. Additionally, published European Applications 45,161 and 53,017 disclose amide derivatives useful as inhibitors of angiotensin converting enzymes. " Certain dipeptide and tripeptides are disclosed in U.S. patents 4,514,332; 4,510,085; and 4,548,926 as well as in European published applications 128,762; 152,255; and 181,110. Pepstatin derived renin inhibitors have been disclosed in U.S. patent 4,481,192. Retro- inverso bond modifications at positions 10-11 have been disclosed in U.S. patent 4,560,505 and in European published applications 127,234 and 127,235. Derivatives of isosteric bond replacements at positions 10-11 have been disclosed in European published applications 143,746 and 144,209; and U.S. patent application, Serial No. 833,993, filed 27 February 1986. Isosteric bond modifications at positions 11-12 and 12-13 have been disclosed in European published application 179,352. Certain peptides containing 2-substituted statine analogues have been disclosed in European published application 157,409. Certain peptides containing 3-aminodeoxystatine have been disclosed in European published application 161,588. Certain peptides contain¬ ing l-amino-2-hydroxybutane derivatives at positions 10-11 have been disclosed in European published application 172,346. Certain peptides containing l-amino-2-hydroxypropane derivatives at positions 10-11 have been disclosed in European published application 172,347. Certain peptides containing N-terminal amide cycles have been disclosed in U.S. patent application, Serial No. 844,716, filed 27 March 1986. Certain peptides containing dihalostatine have been disclosed in PCT application, Serial No. 000,713, filed 7 April 1986. European published applications 156,322; 114,993; and 118,223; and U.S. patent application, Serial No. 798,459, filed 15 November 1985; U.S. patent application, Serial No. 825,250, filed 3 February 1986; U.S. patent application, Serial No. 833,993, filed 27 February 1986; and U.S. patent application, Serial No. 844,716, filed 27 March 1986; disclose hydroxamic acids or esters at the C-terminus. INFORMATION DISCLOSURE PCT Patent Application, Serial No. PCT/US89/00247, filed 27 January 1989, discloses renin inhibitory peptides having a variety of polar end groups at the N-terminus and/or the C-terminus. U.S. Patent 4,613,676 discloses certain substituted 5-amino-4- hydroxy valeryl derivatives, having 2 amino acid residues between the hydrogen or acyl N-terminus and the transition state moiety. A broad class of acyl substituents, including hydroxy-substituted alkyl and etherified sugar moieties, are disclosed. International Application PCT/EP87/00593 (International Publica¬ tion Number WO 88/02756 dated 21 April 1988) discloses the incorpora¬ tion of many types of sugars into peptides other than renin inhibi- tors. U.S. Patent 4,729,985 discloses renin inhibitors having a pro¬ tecting group with a molecular weight less than 500, including, e.g., a (tris-hydroxy)-(t-butyluriedo) . U.S. Patent 4,668,770 generically discloses renin inhibitory tripeptides having a poly-hydroxy group at the C-terminus. U.K. Patent Application GB 2200115-A (published 27 July 198S ' - discloses renin inhibitory peptides having a sugar moiety at the - terminus attached through an ether linkage. SUMMARY OF THE INVENTION The present invention particularly provides: A peptide having a non-cleavable transition state insert corresponding to the 10,11-position of a renin substrate (angiotensinogen) and having a moiety of the formula ~_ at the N- terminus 0 II Xl-(CH 2 ) n - c - L l wherein X^ is a) H 2 N-, b) H 2 NC(CH3) 2 -, c) H0 2 C- , d) (H 2 N)(H0 2 C)CH-, or e) (H0) 2 P(0)0-; wherein n is one to five, inclusive.2 These peptides are useful as renin inhibitors and as inhibitors of retroviral proteases. By "renin inhibitory peptide" is meant a compound capable of inhibiting the renin enzyme in mammalian metabolism and having three or more amino acid residues linked by peptidic or pseudo-peptidic bonds. By "a non-cleavable transition state insert" is meant a transi¬ tion state insert which is not cleavable by a hydrolytic enzyme in mammalian metabolism. A variety of such transition state inserts, corresponding to the 10,11-position of the renin substrate, are known in the art, including those disclosed in the following references, which are hereby incorporated by reference: U.S. Patent 4,424,207 (Szelke) ; European Patent 104041A (Szel- ke) ; European Patent Application 144.290A (Ciba Geigy AG) ; European Patent 0,156,322 (Merck); European Patent 161-588A (Merck); European Patent 0,172,347 (Abbott); European Patent 172-346-A (Abbott); European Patent 156-318 (Merck); European Patent 157-409 (Merck); European Patent 152-255 (Sankyo) ; and U.S. Patent 4,548,926 (Sankyo) ; and U.S. patent application, Serial No. 904,149, filed 5 September 1986; U.S. patent application, Serial No. 844,716, filed 27 March 1986; PCT application, Serial No. 000,713, filed 7 April 1986; U.S. patent application, Serial No. 945,340, filed 22 December 1986; and U.S. patent application, Serial No. 825,250, filed 3 February 1986; and A. Spaltenstein, P. Carpino, F. Miyake and P.B. Hyskins, Tetrahedron Letters, 27:2095 (1986); D.H. Rich and M.S. Bernatowicz, J. Med. Chem., 25:791 (1982); Roger, J. Med. Chem. , 28:1062 (1985); D.M. Glick, et al., Biochemistry, 21:3746 (1982); D.H. Rich, Biochem¬ istry, 24:3165 (1985); R.L. Johnson, J. Med. Chem., 25:605 (1982); R.L. Johnson and K. Verschovor, J. Med. Chem., 26:1457 (1983); R.L. Johnson, J. Med. Chem., 27:1351 (1984); P.A. Bartlett, et al. , J. Am. Chem. Soc, 106:4282 (1984); and Peptides: Synthesis, Structure and Function (V.J. Hruby; D.H. Rich, eds.) Proc. 8th American Peptide Sym. , Pierce Chemical Company, Rockford, 111., pp. 511-20; 587-590 (1983). By "polyhydroxy-substituted-alkyl moiety" is meant a cyclic or acyclic, branched or unbranched alkyl derivative having from three to nine carbon atoms and from two to eight hydroxyl substituents which are attached to the C-terminus of the renin inhibiting peptide by means of a bond or by amide, or ester linkages. These polyhydroxy- substituted-alkyl moieties include sugars and other linear or branched polyhydroxy-substituted-alkyl derivatives which are coupled to the C-terminal of the renin inhibitor peptide by means of an amino or a hydroxyl substituent on the polyhydroxy-substituted-alkyl moi¬ ety. The phrase "bonded directly through carbon or nitrogen" is meant to exclude the use of ether linkages between the polyhydroxy substituent and the peptide. Examples of suitable amino-substituted polyhydroxy-substituted-alkyl derivatives include the aminodesoxy- aldoses and the aminodesoxyketoses and their cyclic and reduced deriva ives, 2,3-dihydroxy-2-(hydroxymethyl) ropylamine, 2-hydroxy- 1,1-bis(hydroxymethyl)ethylamine, 3-hydroxy-2,2-bis(hydroxymethyl)- propylamine, 3-amino-l,2-propanediol, 2-amino-l,3-propanediol, 4- hydroxy-3,3-bis(hydroxymethy1)butylamine, and 2,3,4- rihydroxybutyl- amine. Examples of suitable carboxylic acid substituted polyhydroxy- substituted-alkyl derivatives include the onic and uronic acid sugars such as gluconic and glucuronic acids, glyceric acid, 3-hydroxy-2,2- bis(hydroxymethyl)propionic acid, 2-hydroxy-2,2-bis(hydroxymethyl)- acetic acid, 4-hydroxy-3,3-bis(hydroxymethyl)butyric acid, 2,3,4- trihydroxybutyric acid. Examples of suitable aldehyde or ketone sub- stituted sugars include the aldoses and ketoses which can be con¬ densed directly with the C-terminal of renin inhibitory peptides by means of an esterification. Examples of this and other reactions suitable for incorporating sugars onto peptides having a free amine are set forth in WO published PCT application 87/02756. By "derivatives" of amino acids is meant the well known amino acid derivatives commonly employed in renin inhibitors as set forth in the references above. Examples of the peptides of the present invention are represented by formula I. In formula I, the non-cleavable transition state insert, corresponding to the 10,11-position of the renin substrate, is designated E^Q-F ] _ ] _. The present invention provides novel peptides having polar functionalities at the N-terminus. The following N-terminal groups are preferred: 7-glutamic acid, j S-valine and phosphoric acid. These peptides have increased water solubility and improved ADME characteristics (for example, adsorption and excretion). As is apparent to those of ordinary skill in the art, the peptides of the present invention can occur in several diastereomeric forms, depending on the configuration around the asymmetric carbon atoms. All such diastereomeric forms are included within the scope of the present invention. Preferably, the stereochemistry of the amino acids corresponds to that of the naturally-occurring amino acids. Renin inhibitory peptides commonly have protecting groups at the C-terminus. These protecting groups are known in the polypeptide art. Examples of these protecting groups are given below. Any of these protecting groups are suitable for the peptides of the present invention. Examples of pharmaceutically acceptable acid addition salts include: acetate, adipate, alginate, aspartate, benzoate, ben- zenesulfonate, bisulfate, butyrate, citrate, camphorate, camphorsul- fonate, cyclopentanepropionate, digluconate, dodecylsulfate, ethane- sulfonate, fumarate, glucoheptanoate, glycerophosphate, hemisulfate, heptanoate, hexanoate, hydrochloride, hydrobromide, hydroiodide, 2- hydroxyethanesulfonate, lactate, maleate, methanesulfonate, 2- naphthalenesulfonate, nicotinate, oxalate, palmoate, pectinate, persulfate, 3-phenylpropionate, picrate, pivalate, propionate, succinate. tartrate, thiocyanate, tosylate, and undecanoate. The carbon atom content of various hydrocarbon-containing moieties is indicated by a prefix designating the minimum and maximum number of carbon atoms in the moiety, i.e., the prefix (C^-C ) indicates a moiety of the integer "i" to the integer "j" carbon atoms, inclusive. Thus (C -C4>alkyl refers to alkyl of one to 4 carbon atoms, inclusive, or methyl, ethyl, propyl, butyl, and isomeric forms thereof. C^-C cyclic amino indicates a monocyclic group containing one nitrogen and 4 to 7 carbon atoms. Examples of (C3-C ] _o)cycloalkyl, which include alkyl-substituted cycloalkyl containing a total of up to 10 total carbon atoms, are cyclopropyl, 2-methylcyclopropyl, 2,2-dimethylcyclopropyl, 2,3- diethylcyclopropyl, 2-butylcyclopropyl, cyclobutyl, 2-methyl- cyclobutyl, 3-propylcyclobutyl, cyclopentyl, 2,2-dimethylcyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, cyclononyl, cyclodecyl and isomeric forms thereof. Examples of aryl include phenyl, naphthyl, (o-, m- , or p-)tolyl, (o-, m- , or p-)ethylphenyl, 2-ethyl-tolyl, 4-ethyl-o-tolyl, 5- ethyl-m-tolyl, (o- , m- , or p-)propylphenyl, 2-propyl-(o- , m- , or p-)tolyl, 4-isopropyl-2,6-xylyl, 3-propyl-4-ethylphenyl, (2,3,4- 2,3,6-, or 2,4,5-)trimethylphenyl, (o-, m- , or p-)fluorophenyl, (o-, m- , or p-trifluoromethyl)phenyl, 4-fluoro-2,5-xylyl, (2,4-, 2,5-, 2,6-, 3,4-, or 3,5-)difluorophenyl, (o- , m- , or ρ-)chlorophenyl, 2- chloro-p-tolyl, (3-, 4-, 5- or 6-)chloro-o-tolyl, 4-chloro-2-propyl- phenyl, 2-isopropyl-4-chloroρhenyl, 4-chloro-3-fluorophenyl, (3- or 4-)chloro-2-fluorophenyl, (o-, m- , or p-)trifluoro-methylphenyl, (o-, m- , or p-)ethoxyphenyl, (4- or 5-)chloro-2-methoxy-phenyl, and 2,4- dichloro(5- or 6-)methylphenyl, and the like. Examples of -Het include: 2-, 3-, or 4-pyridyl, imidazolyl, indolyl, N lπ -formyl-indolyl, N in -C 1 -C 5 alkyl-C(0)-indolyl, 1,2,4- triazolyl, 2-, 4-, or 5-pyrimidinyl, 2- or 3-thienyl, piperidinyl, pyrryl, pyrrolinyl, pyrrolidinyl, pyrazolyl, pyrazolinyl, pyrazolidi- nyl, imidazolinyl, imidazolidinyl, pyrazinyl, piperazinyl, pyridazin- yl, oxazolyl, oxazolidinyl, isoxazolyl, isoxazolidinyl, morpholinyl, thiazolyl, thiazolidinyl, isothiazolyl, isothiazolidinyl, quinolinyl, isoquinolinyl, benzimidazolyl, benzothiazolyl, benzoxazolyl, furyl, thienyl, and benzothienyl. Each of these moieties may be substituted as noted above. As would be generally recognized by those skilled in the art of organic chemistry, a heterocycle as defined herein for -Het would not be bonded through oxygen or sulfur or through nitrogen which is within a ring and part of a double bond. Halo is halogen (fluoro, chloro, bromo, or iodo) or tri- fluoromethyl. Examples of pharmaceutically acceptable cations include: pharmacologically acceptable metal cations, ammonium, amine cations, or quaternary ammonium cations. Especially preferred metal cations are those derived from the alkali metals, e.g., lithium, sodium, and potassium, and from the alkaline earth metals, e.g., magnesium and calcium, although cationic forms of other metals, e.g., aluminum, zinc, and iron are also within the scope of this invention. Phar¬ macologically acceptable amine cations are those derived from primary, secondary, or tertiary amines. The novel peptides herein contain both natural and synthetic amino acid residues. These residues are depicted using standard amino acid abbreviations (see, e.g., IUPAC-IUB Joint Commission on Biochemical Nomenclature (JCBN) , "Nomenclature and Symbolism for Amino Acids and Peptides," Eur. J. Bioche . 138:9-37 (1984) unless otherwise indicated. The peptides of this invention are useful for treating any medical condition for which it is beneficial to reduce the levels of active circulating renin. Examples of such conditions include renin- dependent hypertension, hypertension, hypertension under treatment with another antihypertensive and/or a diuretic agent, congestive heart failure, renin-dependent hyperaldosterism, angina, post- myocardial infarction, other renin-dependent cardiovascular disorders and ocular disorders. The renin- ngiotension system may play a role in maintenance of intracellular homeostasis: see Clinical and Experimental Hypertension, 86, 1739-1742 (1984) at page 1740 under Discussion. The peptides of the present invention are preferably orally administered to humans to effect renin inhibition for the purpose of favorably affecting blood pressure. For this purpose, the compounds are administered from 0.1 mg to 100 mg per kg per dose, administered from 1 to 4 times daily. Equivalent dosages for other routes of administration are also employed. For example, renin-associated hypertension and hyperaldosteronism are effectively treated by the administration of from 0.5 to 50 milligrams of the compound per kilogram of body weight per day. The exact dose depends on the age, weight, and condition of the patient and on the frequency and route of administration. Such variations are within the skill of the practitioner or can readily be determined. The peptides of the present invention to effect renin inhibition may be in the form of pharmaceutically acceptable salts both those which can be produced from the free bases by methods well known in the art and those with which acids have pharmacologically acceptable conjugate bases. Conventional forms and means for administering renin-inhibiting compounds may be employed and are described, e.g., in U.S. Patent No. 4,424,207 which* is incorporated by reference herein. Likewise, the amounts disclosed in the U.S. Patent No. 4,424,207 are examples applicable to the compounds of the present invention. The peptides of the present invention to effect renin inhibition are preferably orally administered in the form of pharmacologically acceptable acid addition salts. Preferred pharmacologically acceptable salts for oral administration include the citrate and aspartate salts, although any pharmacologically acceptable salt is useful in this invention, including those listed above. These salts may be in hydrated or solvated form. For renin inhibition, the peptides of the present invention may be administered topically, parenterally, by inhalation spray, or rectally in dosage unit formulations containing conventional non- toxic pharmaceutically acceptable carriers, adjuvants and vehicles. The term parenteral as used herein includes subcutaneous injections, intravenous, intramuscular, intrasternal injection or infusion techniques. In addition to the treatment of warm-blooded animals such as mice, rats, horses, dogs, cats, etc., the compounds of the invention are effective in the treatment of humans. The pharmaceutical compositions of the peptides of the present invention for renin inhibition may be in the form of a sterile injectable preparation, for example as a sterile injectable aqueous or oleagenous suspension. This suspension may be formulated accord¬ ing to the known art using suitable dispersing or wetting agents and suspending agents. The sterile injectable preparation may also be a sterile injectable solution or suspension in a non-toxic parenteral¬ ly-acceptable diluent or solvent, for example as a solution in 1,3- butanediol. Among the acceptable vehicles and solvents that may be employed are water, Ringer's solution and isotonic sodium chloride solution. In addition, sterile, fixed oils are conventionally employed as a solvent or suspending medium. For this purpose any bland fixed oil may be employed including synthetic mono- or digly- cerides. In addition, fatty acids such as oleic acid find use in the preparation of injectables. The peptides of this invention for renin inhibition may also be administered in the form of suppositories for rectal administration of the drug. These compositions can be prepared by mixing the drug with a suitable non-irritating excipient which is solid at ordinary temperatures but liquid at the rectal temperature and will therefore melt in the rectum to release the drug. Such materials are cocoa butter and polyethylene glycols. The peptides of this invention may be administered in combination with other agents used in antihypertensive therapy such as diuretics, and/or ^-adrenergic blocking agents, CNS-acting agents, adrenergic neuron blocking agents, vasodilators, angiotensin I converting enzyme inhibitors, and the like as described for example in published European patent application 156,318. For example, the compounds of this invention can be given in combination with such compounds or salt or other derivative forms thereof as: Diuretics: acetazolamide; amiloride; bendroflumethiazide; benzthia- zide; bumetanide; chlorothiazide; chlorthalidone; cyclothiazide; ethacrynic acid; furosemide; hydrochlorothiazide; hydroflumethiazide; indacrinone (racemic mixture, or as either the (+) or (-) enantiomer alone, or a manipulated ratio, e.g., 9:1 of said enantiomers, respec¬ tively); metolazone; methyclothiazide; muzolimine; polythiazide; quinethazone; sodium ethacrynate; sodium nitroprusside; spironol- actone; ticrynaten; trimaterene; trichlormethiazide; α-Adrenergic Blocking Agents: dibenamine; phentolamine; phenoxyben- zamine; prazosin; tolazoline; β-Adrenergic Blocking Agents: atenolol; metoprolol; nadolol; propranolol; ti olol; ((±)-2-[3-(tert-butylamino) -2-hydroxypropoxy] -2-furananilide) (ancarolol) ; (2-acetyl-7-(2-hydroxy-3-isopropylaminopropoxy)benzofuran HC1) (befun- olol); ((±) -1- (isopropylamino)-3-(p-(2-cycloproρylmethoxyethyl)-phenoxy)-2- propranol HC1) (betaxolol) ; (1- [(3,4-dimethoxyphenethyl)amino] -3-(m-tolyloxy)-2-propanol HC1) (be- vantolol) ; (((±)-l-(4-((2-isopropoxyethoxy)methyl)phenoxy)-3-isopropylamino-2- propanol)fumarate) (bisoprolol) ; (4-(2-hydroxy-3- [4-(phenoxymethyl)-piperidino]-propoxy)-indole) ; (carbazolyl-4-oxy-5,2-(2-methoxyphenoxy)-ethylamino-2-propanol) ; (1-((1,1-dimethylethyl)amino)-3-((2-methyl Η-indol-4-yl)oxy)-2-pro- panol benzoate) (bopindolol) ; (1- (2-exobicyclo[2.2.1] -hept-2-ylphenoxy)-3- [(1-methylethyl)-amino] - 2-propanol HC1) (bornaprolol) ; (o- [2-hydroxy-3- [(2-indol-3-yl-1,1-dimethylethyl)-amino]propoxy]ben- zonitrile HC1) (bucindolol) ; (α- [ (tert.butylamino)methyl] -7-ethyl-2-benzofuranmethanol) (bufur- alol); (3- [3-acetyl-4- [3- (tert.butylamino) -2-hydroxypropyl]-phenyl] -1,1- diethylurea HC1) (celiprolol) ; ((±)-2-[2-[3-[(1,1-dimethylethyl)amino] -2-hydroxypropoxy]phenoxy] -N- methylacetamide HC1) (cetamolol) ; (2-benzimidazoly1-phenyl(2-isopropylaminopropanol)) ; ((±)-3'-acetyl-4'- (2-hydroxy-3-isopropylaminopropoxy)-acetanilide HC1) (diacetolol); (methyl-4- [2-hydroxy-3- [ (l-methylethyl)aminopropoxyl] ] -benzene- propanoate HC1) (esmolol) ; (erythro-DL-l-(7-methylindan-4-yloxy)-3-isopropylaminobutan-2-ol) ; (1-(tert.butylamino)-3- [0-(2-propynyloxy)phenoxy] -2-propanol (pargo- lol); (1- (tert.butylamino) -3- [o- (6-hydrazino-3-pyridazinyl)phenoxy] -2- propanol diHCl) (prizidilol) ; ((-) -2 -hydroxy- 5- [ (R) -1 -hydroxy- 2- [ (R) - (l-methyl-3-phenylpropyl) - amino] ethyl ]benzamide) ; (4-hydroxy-9- [2 -hydroxy- 3- ( i s op ropyl amino) -propoxy] -7-methyl-5H- furo[3,2-g] 1] -benzopyran-5-one) (iprocrolol) ; ( ( - ) - 5 - ( tert.butylamino) -2-hydroxypropoxy -3 ,4-dihydro-l- (2H) - naphthalenone HCl) (levobunolol) : (4- (2 -hydroxy- 3 - isopropylamino -propoxy) -1,2-benzisothiazole HCl) ; (4- [3- (tert.butylamino) -2-hydroxypropoxy] -N-methylisocarbostyril HCl); ((±)-N-2-[4- (2 -hydroxy- 3- isopropy la inopropoxy) phenyl] ethyl -N' - isopropylurea) (pafenolol) ; (3- [ [ (2- trifluoroaceta ido) ethyl] amino] -l-phenoxypropan-2-ol) ; (N-(3-(o-chlorophenoxy)-2-hydroxypropyl)-N'-(4' - chloro - 2 , 3 - dihydro - 3 - oxo-5-pyridazinyl)ethylenediamine) ; ((±)-N- [3-acetyl-4- [2-hydroxy-3- [ (l-methylethyl)amino]propoxyphenyl] - butanamide) (acebutolol) ; ((±) -4' - [3-(tert-butylamino) -2-hydroxypropoxy]spiro[cyclohexane-l,2' - indan] -1 ' -one) (spirendolol) ; (7- [3- [ [2-hydroxy-3- [ ( 2 -methylindol-4-yl)oxylpropyl] amino] butyl] thio- phylline) (teoprolol) ; ( (±) -1- tert.butylamino- 3- (thiochroman-8-yloxy) -2-propanol) (tertato- lol); ((±)-l-tert.butylamino-3-(2,3-xylyloxy)-2-propanol HCl) (xibenolol) ; (8-[3-(tert.butylamino)-2-hydroxypropoxy] -5-methylcouma in) (bucumo- lol); (2-(3-(tert.butylamino)-2-hydroxy-propoxy)benzonitrile HCl) (bunitro- lol); ((±)-2'-[3-(tert-butylamino)-2-hydroxypropoxy-5'-fluorobutyrophenone) (butofilolol) ; (l-(carbazol-4-yloxy)-3-(isopropylamino)-2-propanol) (carazolol) ; (5-(3-tert.butylamino-2-hydroxy)propoxy-3,4-dihydrocarbotyril HCl) (carteolol) ; (1-(tert.butylamino)-3-(2,5-dichlorophenoxy)-2-propanol) (clorano- lol); (l-(inden-4(or 7)-yloxy)-3-(isopropylamino)-2-propanol HCl) (indeno- lol); (l-isopropylamino-3- [(2-methylindol-4-yl)oxy]-2-propanol) (mepindo- lol); (1- (4-acetoxy-2 , 3 , 5-trimethylphenoxy)-3-isopropylaminopropan-2-ol) ( etipranolol) ; (1-(isopropylamino)-3-(o-methoxyphenoxy)-3- [(1-methylethyl)amino] -2- propanol) (moprolol) ; ( (1-tert.butylamino) -3- [ (5 , 6 ,7 , 8- etrahydro-cis-6 , 7-dihydroxy-l- naphthyl)oxy] -2-propanol) (nadolol) ; ((S)-1- (2-cyclopentylρhenoxy)-3- [(1,1-dimethylethyl)amino] -2-propanol sulfate (2:1)) (penbutolol) ; (4' - [l-hydroxy-2-(amino)ethyl]methanesulfonanilide) (sotalol) ; (2-methyl-3- [4- (2-hydroxy-3-tert.butylaminopropoxy)phenyl] -7-methoxy- isoquinolin-l-(2H)-one) ; (l-(4-(2- (4- fluorophenyloxy)ethoxy) phenoxy) -3- isopropylamino -2- propanol HCl) ; ((-)-p-[3-[(3,4-dimethoxyphenethyl)amino] -2-hydroxypropoxy] -β-methyl- cinnamonitrile) (pacrinolol) ; ((±) -2- (3 ' -tert.butylamino-2'-hydroxypropylthio)-4-(5'-carbamoyl-2'- thienyl)thiazole HCl) (arotinolol) ; ((±) -1- [p- [2-(cyclopropylmethoxy)ethoxy]phenoxy]-3-(isopropylamino)- 2-propanol) (cicloprolol) ; ( (±) -1- [ (3-chloro-2-methylindol-4-yl)oxy] -3- [ (2-phenoxyethyl)amino] - 2-propanol) (indopanolol) ; ((±)-6-[[2-[[3- (p-butoxyphenoxy) -2-hydroxypropyl]amino]ethyl]amino] - 1,3-dimethyluracil) (pirepolol) ; (4-(cyclohexylamino)-1-(1-naphtholenyloxy)-2-butanol) ; (l-phenyl-3- [2- [3-(2-cyanophenoxy)-2-hydroxypropyl]aminoethyl]hydan- toin HCl) ; (3 ,4-dihydro-8- (2 -hydroxy- 3-isopropylaminopropoxy)-3-nitroxy-2H-l- benzopyran) (nipradolol) ; Angiotensin I Converting Enzyme Inhibitors: 1- (3-mercapto-2-methyl-l-oxopropyl) -L-proline (captopril) ; (1- (4-ethoxycarbonyl-2 ,4(R,R) - dime thylbutanoyl)indoline-2(S) -car - boxylic acid) ; (2- [2- [ (1- (ethoxycarbonyl) -3-phenyl-propyl]amino] -1-oxopropyl] - l,2,3,4-tetrahydro-3-isoquinoline carboxylic acid); ((S)-l-[2- [(1- (ethoxycarbonyl) -3 -phenylpropyl] amino] -l-oxopropyl]oc- tahydro-lH-indole-2-carboxylic acid HCl); (N-cyclopentyl-N-(3- (2,2-dimethyl-l-oxopropyl)thiol-2-methyl-l-oxo- propyl)glycine) (pivalopril) ; ((2R,4R) -2-(2-hydroxyphenyl)-3-(3-mercaρtopropionyl)-4-thiazolidine- carboxylic acid) ; ( 1- (N- [l(S)-ethoxycarbonyl-3-phenylpropyl]-(S)-alanyl)-cis,syn-octa- hydroindol-2(S)-carboxylic acid HCl); ((-)-(S)-l-[(S)-3-mercap o-2-methyl-1-oxopropyl]indoline-2-carboxylic acid) ; ([l(S),4S]-l-[3- (benzoylthio)-2-methyl-1-oxopropyl] -4-phenylthio-L- proline; (3-([1-ethoxycarbonyl-3-phenyl-(IS)-propyl]amino)-2,3,4,5-tetrahydro- 2-oxo-l-(3S)-benzazepine-1-acetic acid HCl) ; (N- (2-benzyl-3-mercaptopropanoyl)-S-ethyl-L-cysteine) and the S- methyl analogue; (N- (1(S)-ethoxycarbonyl-3-phenylpropyl)-L-alanyl-L-proline maleate) (enalapril) ; N- [l-(S)-carboxy-3-phenylpropyl]-L-alanyl-1-proline; N^- [l-(S)-carboxy-3-phenylpropyl] -L-lysyl-L-proline (lysinopril) ; Other Antihypertensive Agents: aminophylline; cr ptenamine acetates and tannates; deserpidine; meremethoxylline procaine; pargyline; tri- methaphan camsylate; and the like, as well as admixtures and combina- tions thereof. Typically, the individual daily dosages for these combinations can range from about one-fifth of the minimally recommended clinical dosages to the maximum recommended levels for the entities when they are given singly. Coadministration is most readily accomplished by combining the active ingredients into a suitable unit dosage form containing the proper dosages of each. Other methods of coad¬ ministration are, of course, possible. Thus, the novel peptides of the present invention possess an excellent degree of activity in treating renin-associated hypertension and hyperaldosteronism. Renin inhibitors have also been disclosed to control the rise in intraocular pressure associated with the use of steroidal anti- infla matory drugs as described in International Application PCT/- US86/02291 (International Publication Number WO 87/02581 dated 7 May 1987). The peptides of the present invention are also useful as novel human retroviral protease inhibitory peptide analogs. Therefore, the peptides of the present inventions inhibit retroviral proteases and thus inhibit the replication of the virus. They are useful for treating human patients infected with a human retrovirus, such as human immunodeficiency virus (HIV) which results in acquired immunodeficiency syndrome (AIDS) and related diseases. The capsid and nonstructural proteins of recroviruses are trans¬ lated from the viral genes gag and pol as polyproteins that are fur¬ ther processed by the viral protease (PR) to the mature proteins found in the viral capsid and necessary for viral functions and rep¬ lication. If the PR is absent or nonfunctional, the virus cannot replicate. The retroviral PR, such as HIV-1 PR, has been found to be an aspartic protease with active site characteristics similar to those exhibited by the more complex aspartic protease, renin. The term human retrovirus (HRV) includes human immunodeficiency « virus type I, human immunodeficiency virus type II, or strains there- of, as well as human T cell leukemia virus 1 and 2 (HTLV-1 and HTLV- 2) or strains apparent to one skilled in the art, which belong to the same or related viral families and which create similar physiological effects in humans as various human retroviruses. Patients to be treated would be those individuals: 1) infected with one or more strains of a human retrovirus as determined by the presence of either measurable viral antibody or antigen in the serum and 2) having either a symptomatic AIDS defining infection such as i) disseminated histoplasmosis, ii) isopsoriasis, iii) bronchial and pulmonary candidiasis including pneumocystic pneumonia iv) non- Hodgkin's lymphoma or v) Kaposi's sarcoma and being less than sixty years old; or having an absolute CD4 lymphocyte count of less than 200/m 3 in the peripheral blood. Treatment would consist of maintain¬ ing an inhibitory level of the peptide used according to this inven¬ tion in the patient at all times and would continue until the occur- rence of a second symptomatic AIDS defining infection indicates alternate therapy is needed. More specifically, an example of one such human retrovirus is the human immunodeficiency virus (HIV, also known as HTLV-III or LAV) which has been recognized as the causative agent in human acquired immunodeficiency disease syndrome (AIDS), P. Duesberg, Proc. Natl. Acad. Sci. USA, 86:755 (1989). HIV contains a retro viral encoded protease, HIV-I protease, that cleaves the fusion polypeptides into the functional proteins of the mature virus particle, E.P. Lillehoj , et al., J. Virology, 62:3053 (1988); C. Debuck, et al. , Proc. Natl. Acad. Sci., 84:8903 (1987). This enzyme, HIV-I protease, has been classified as an aspartyl protease and has a demonstrated homology to other aspartyl proteases such as renin, L.H. Pearl, et al., Nature 328:351 (1987); I. Katoh, et al., Nature 329:654 (1987). Inhibition of HIV-I protease blocks the replication of HIV and thus is useful in the treatment of human AIDS, E.D. Clerq, J.Med. Chem. 29:1561 (1986). Inhibitors of HIV-I protease are useful in the treatment of AIDS. Pepstatin A, a general inhibitor of aspartyl proteases, has been disclosed as an inhibitor of HIV-I protease, S. Seelmeier, et al., Proc. Natl. Acad. Sci. USA, 85:6612 (1986). Other substrate derived inhibitors containing reduced bond isosteres or statine at the scissle position have also been disclosed, M.L. Moore, et al., Biochem. Biophys, Res. Commun. 159:420 (1989); S. Billich, et al. , J. Biol. Chem. 263:17905 (1988); Sandoz, D.E. 3812-576-A. Thus, the peptides of the present invention are useful for treating diseases caused by retroviruses, such as human acquired immunodeficiency disease syndrome (AIDS), using dosages, forms and modes of adminstration equivalent to those described above for renin inhibition. Exact dosages, forms and mode of administration would be apparent to one of ordinary skill in the art such as a physician or pharmacologist. The compounds of the present invention are prepared as depicted in the charts and as described more fully in the Preparations and Examples. In these charts, the variables are as defined above. CHART A Chart A describes the preparation of renin inhibitory peptides having 7-glutamic acid as the polar N-terminal group. De-BOC'd BOC-Pro-Phe-N-MeHis-LVA-Ile-AMP, i.e., Pro-Phe-N-MeHis- LVA-Ile-AMP, of formula A-l is coupled with N(a)-BOC-α-benzyl-L-glut- amic acid, which is commercially available, using diethylcyano- phosphonate to afford peptide of formula A-2. The preparation of BOC-Pro-Phe-N-MeHis-LVA-Ile-AMP is described in U.S. patent applica¬ tion, Serial No. 147,073, filed 20 January 1988, and in published European patent application 0173481, published 5 March 1986, which are hereby incorporated by reference. Removal of the benzyl ester is accomplished under transfer hydrogenolytic conditions with ammonium formate and palladium catalyst in dimethylformamide, giving the peptide of formula A-3. The BOC group in formula A-3 is removed with trifluoroacetic acid to provide the final compound of formula A-5. This product is isolated by simply dripping the reaction mixture into ether-hexane. The precipitated product is centrifuged down, washed with ether-hexane, and dried under vacuum. Oxidation of the peptide of formula A-3 with m-chloroperbenzoic acid affords the N-oxide of formula A-4. Trifluoroacetic acid treat¬ ment of this, as described above, provides the final peptide of form¬ ula A-6. Other peptides of the present invention having γ-glutamic acid as the polar N-terminal group are prepared in an analogous manner to the procedures described above. CHART B The renin inhibitory peptides of the present invention having β- Val as the polar N-terminal group are prepared and assembled using standard procedures known in the peptide art similar to that described in Chart A. The synthesis of BOC-^-valine from ethyl 3,3- dimethylacrylate is described in Chart F below. The peptides of the present invention which contain Cha-Val alcohol as the transition state insert, are prepared in a fashion exactly analogous to their LVA counterparts. The synthesis of Cha-Val alcohol is described in PCT Patent Application, Serial No. PCT/US89/00247, filed 27 January 1989, which is hereby incorporated by reference. Chart B illustrates the preparation of renin inhibitory peptides having β-Val as the polar N-terminal group. The peptide of formula B-l wherein R g is Ile-AMP, is prepared as described in U.S. patent application, Serial No. 147,073, filed 20 January 1988, and in published European patent application 0173481, published 5 March 1986, which are hereby incorporated by reference. The peptide of formula B-l wherein R Q is Mba is prepared by proce¬ dures analogous to those described in U.S. patent application, Serial No. 07/147,073, filed 20 January 1988, and in published European pat¬ ent application 0173481, published 5 March 1986, which are hereby incorporated by reference. The appropriate peptide is coupled with BOC-^-Valine to give the compound of formula B-2 and then deprotected to give the compound of formula B-3, using standard procedures known in the art. Treatment of the compound of formula B-3 with trifluoro¬ acetic acid (TFA) effects removal of the BOC group to give the final peptide of formula B-4. Treatment of the compound of formula B-2 with two equivalents of m-chloroperbenzoic acid (MCPBA) in dichloromethane affords the N- oxide of formula B-5. Removal of the tosyl protecting group in form- ula B-5 follows standard protocol (1-hydroxybenzotriazole monohydrate in methanol) to provide the compound of formula B-6. Final deprotec- tion to the final peptide of formula B-7 is accomplished under stand¬ ard conditions for BOC group removal (trifluoroacetic acid, dichloro¬ methane) . The reaction mixture is dripped directly into vigorously stirred 1:1 ether-hexane, which precipitates the product as a floccu- lent solid. This is isolated by centrifuging, washed twice with ether-hexane, and dried under high vacuum to provide the final peptide as the trifluoroacetate salt. The synthesis of the Cha-Val alcohol congener of the peptide of formula B-7 is accomplished in an analogous manner; however, in its synthesis, histidine detosylation precedes MCPBA oxidation of the pyridine. Final deprotection and product isolation are carried out as described above for the LVA analog. Other peptides of the present invention having -Val as the polar N-terminal group are prepared in an analogous manner to the procedures described above. CHART C The synthesis of a phosphoric acid residue, in a form suitably protected for attachment to peptides, is outlined in Chart C. Benzyl glyoxylate of formula C-2 is prepared by diisopropylcarbodiimide (DIC) esterification of glyoxylic acid of formula C-l, which is commercially available. Treatment of the hydroxyester with di-tert- butyl N,N-diethylphosphoramidite, according to the procedure of J.W. Perich and R.B. Johns, Synthesis, 1988, 142-144, initially gives the mixed phosphite. This species is not isolated but is oxidized in situ with MCPBA to give the phosphate ester of formula C-3. Hydro- genolytic removal of the benzyl ester provides the acid of formula C- 4, suitable for coupling to peptide substrates. CHART D The synthesis of a four carbon homologue of the phosphoric acid residue prepared in Chart C is described in Chart D. The starting material for this synthesis is the vinylacetic acid of formula D-l, which is commercially available. The acid is converted to its benzyl ester of formula D-2, then the olefin of the benzyl ester of formula D-2 is hydroborated to give the compound of formula D-3 by the procedure of H.C. Brown, Organic Synthesis via Boranes, 1975, 51-52. Attachment of the phosphate acid piece proceeds as described above in Chart C to give the phosphate ester of formula D-4, which is con¬ verted to the acid of formula D-5 via hydrogenolysis. CHART E Standard methods are utilized to incorporate the phosphate acid residues prepared in Charts C and D into peptides. The acids of formula C-4 and D-5 are coupled with a variety of amines, using either diethylcyanophosphonate (DEPC) or diisopropylcarbodiimide (DIC) as the coupling reagent. Chart E illustrates the assembly of a renin inhibitory peptide having a phosphoric acid residue as the polar N-terminal group. The peptide of formula E-l (A-l) is coupled with the acid of formula C-4, prepared as described in Chart C, using DEPC or DIC to provide the product of formula E-2. m-Chloroperbenzoic acid (MCPBA) oxidation proceeds smoothly at the pyridine nitrogen to afford the N-oxide of formula E-3. Final deprotection of the peptide of formula E-2 to the final peptide of formula E-4 and of the peptide of formula E-3 to the final peptide of formula E-5 is initially carried out in 1:1 tetrahydro- furan-water which is 4M hydrochloric acid. 4M aqueous hydrochloric acid alone can be used; the peptides dissolve as they react. After about an hour at room temperature, the reaction mixtures are pumped to dryness (via a potassium hydroxide tower), redissolved in water, and lyophilized, yielding the desired peptides. Other peptides of the present invention having a phosphoric acid residue as the polar N-terminal group are prepared in an analogous manner to the procedures desdribed above. CHART F Chart F describes the synthesis of the B0C- -Valine residue from ethyl 3,3-dimethylacrylate. When ethyl 2,2-dimethylacrylate of form¬ ula F-l is heated in a saturated ethanolic solution of ammonia, the amino ester of formula F-2 is formed by Michael addition of ammonia. Although this reaction is slow (half life of about 10 hours at 80°C) , no aminolysis of the ester is observed. A BOC group is added to give the compound of formula F-3, and hydrolysis of the ester provides the acid of formula F-4. CHART G As does Chart B above, Chart G further illustrates the prepara¬ tion of renin inhibitory peptides having £-Val as the polar N- terminal group. The peptide of formula G-l wherein R30 is Ile-AMP, is prepared as described in PCT patent application, Serial No. PCT/US88/03436, filed 11 October 1988, which is hereby incorporated by reference. The peptide of formula G-l wherein R30 is Mba is prepared by procedures analogous to those described in PCT patent application, Serial No. PCT/US88/03436, filed 11 October 1988. The appropriate peptide is coupled with B0C-3-Valine to give the compound of formula G-2 and then deprotected to give the compound of formula G-3, using standard procedures known in the art. Treatment of the compound of formula G-3 with trifluoroacetic acid (TFA) effects removal of the BOC group to give the final peptide of formula G-4. Generally, the renin inhibiting polypeptides may be prepared by solution phase peptide synthetic procedures analogous to those described hereinafter or to those methods known in the art. Ap¬ propriate protecting groups, reagents, and solvents for the solution phase method can be found in "The Peptides: Analysis, Synthesis, and Biology," Vols. 1-5, eds. E. Gross and T. Meienhofer, Academic Press, NY, 1979-1983; "The Practice of Peptide Synthesis", M. Bodansky and A. Bodansky, Springer-Verlag, New York, 1984; "The Principles of Peptide Synthesis", M. Bodansky, Springer-Verlag, New York, 1984. Thus, for example, the carboxylic moiety of N α -t-butyloxycarbonyl (BOC)-substituted amino acid derivatives having suitable side chain protecting groups, if necessary, may be condensed with the amino functionality of a suitably protected amino acid or peptide using a conventional coupling protocol such as dicyclohexylcarbodiimide (DCC) and 1-hydroxybenzotriazole (HOBT) or diethylphosphoryl cyanide (DEPC) and triethylamine Et3 ) in methylene chloride or dimethylformamide. Following coupling reaction completion, the Ϊ^-BOC moiety may be selectively removed with 50% trifluoroacetic acid with or without 2% anisole (v/v) in methylene chloride. Neutralization of the resultant trifluoroacetate salt may be accomplished with 10% diisopropylethyl- amine or sodium bicarbonate in methylene chloride. Variations in the above description for starting materials, reactants, reaction conditions and required protecting groups to obtain other such N-alkylated compounds are known to an ordinarily skilled chemist or are readily available in the literature. The compounds of the present invention may be in either free form or in protected form at one or more of the remaining (not previously protected) peptide, carboxyl, amino, hydroxy, or other reactive groups. The protecting groups may be any of those known ir. the polypeptide art. Examples of nitrogen and oxygen protection groups are set forth in T.W. Greene, Protecting Groups in Organic Synthesis, Wiley, New York, (1981); J.F.W. McOmie, ed. Protective Groups in Organic Chemistry, Plenum Press (1973); and J. Fuhrhop and G. Benzlin, Organic Synthesis, Verlag Chemie (1983). Included among the nitrogen protective groups are t-butoxycarbonyl (BOC) , ben- zyloxycarbonyl, acetyl, allyl, phthalyl, benzyl, benzoyl, trityl and the like. The following compounds of the present invention are preferred: -Val-Phe-N-MeHis-LVA-MBA or L-histidinamide, N-(3-amino-3- methyl-1-oxobutyl) -L-phenylalanyl-N- [2-hydroxy-5-methyl-4- [ [ (2- methylbutyl)amino]carbonyl] -1-(2-methylpropyl)hexyl] -Nα-methyl-, [1S- [1R*,2R*,4R*(R*)]]-, bis(trifluoroacetate) (salt); /9-Val-Phe-N-MeHis-CVA-MBA or L-Histidinamide, N-(3-amino-3- methyl-1-oxobutyl) -L-phenylalanyl-N- [1- (cyclohexylmethyl)-2-hydr¬ oxy-5-methyl-4- [ [ (2-methylbutyl)amino]carbonyl]hexyl] -Nα-methyl- , [1S-[1R*,2R*,4R*(R*)]]-, bis(trifluoroacetate) (salt); 7-Glu-Phe-N-MeHis-CVA-MBA or L-Histidinamide, L-7-glutamyl-L- phenylalanyl-N- [1-(cyclohexylmethyl)-2-hydroxy-5-methyl-4-[ [(2-me h- ylbutyl)amino]carbonyl]hexyl] -Nα-methyl- , [IS- [IR*,2R*,4R*(R*)] ] - , bis(trifluoroacetate) (salt); 7-Glu-Phe-N-MeHis-CVA-Ile-AMP-NO or L-Histidinamide, L-7-glutam- yl-L-phenylalanyl-N-[l-(cyclohexylmethyl)-2-hydroxy-5-methyl-4-[ [ [2- methyl-1- [ [ (2-pyridinylmethyl)amino]carbonyl]butyl]amino]carbonyl] - hexyl]-Nα-methyl-, N-oxide, [IS-[1R*,2R*,4R*(1R*,2R*)]] - , tris(tri- fluoroacetate) (salt); 7-Glu-Pro-(0CH 3 )Tyr-His-CVG or L-Histidinamide, L-7-glutamyl-L- prolyl-O-methyl-L-tyrosyl-N- [1- (cyclohexylmethyl) -2,3-dihydroxy- 5-methylhexyl]-, [1R*,2S*,3R*)]- , bis (trifluoroacetate) (salt); 7-Glu-Pro-Phe-N-MeHis-CVG or L-Histidinamide, L-7-glutamyl-L- prolyl-L- phenylalanyl-N- [1-(cyclohexylmethyl)-2,3-dihydroxy-5-meth- ylhexyl] -Nα-methyl-, [IS-(1R*,2S*,3R*) bis(trifluoroacetate) (salt); 7-Glu-Pro-Phe-N-MeHis-CVA-MBA or L-Histidinamide, L-7-glutam- yl-L-prolyl-L-phenylalanyl-N-cyclohexylmethyl)-2-hydroxy-5-methyl-4- [[(2-methylbutyl)aminoicarbonyl]hexyl] -Nα-methyl- , [IS- [1R*.2R*,4R*- (R*)]]-. bis(trifluoroacetate) (salt;; 7-Glu-Pro-Pne-N-MeHis-LVA-MBA or L-Histidinamide, L-7-glutam- vl-L-prolyl-L-phenylalanyl-N- [2-yάroxy-5-methyl-4- [ [2-methylbutyl)- amino]carbonyl] -1-(2-methylpropyl)hexyl-Nα-methyl- , [IS- [1R*,2R*,4R*- (R*)]]-. bis(trifluoroacetate) (salt); 7-Glu-Pro-Phe-N-MeHis-LVA-Ile-NH(CH 2 ) 4 CH(C00H)(NH 2 ) or L-Lysine, N6- [N-(5- [ [N- [N- (l-D-7-glutamyl-L-prolyl)-L-phenylalanyl] -N-methyl-L- histidyl]amino] -4-hydroxy-7-methyl-2-(l-methylethyl)-1-oxooctyl] -L- isoleucyl]-, [2S-(2R*,4R*,5R*)] - , tris(trifluoroacetate) (salt); 7-Glu-Pro-Phe-N-MeHis-CVA-NH(CH 2 ) CH(C00H)(NH 2 ) or L-Histidin¬ amide, L-7-glutamyl-L-ρrolyl-L-phenylalanyl-N- [4- [ [ (5-amino-5-carb- oxypentyl)amino] carbonyl] -1- (cyclohexylmethyl)-2-hydroxy-5-methyl- hexyl]-Nα-methyl- , [IS-[1R*,2R*,4R*(R*)]]- , tris(trifluoroacetate) (salt); (H0) 2 P(0)0CH 2 C(0)-Pro-Phe-N-MeHis-LVA-Ile-AMP or L-Histidin¬ amide, N-[N-[1- [(phosphonooxy)acetyl] -L-prolyl]-L-phenylalanyl] -N-[2- hydroxy-5-methyl-1- (2-methylpropyl)-4- [ [ [2-methyl-l- [ [ (2-pyridinyl- methyl)amino]carbonyl]butyl]amino]carbonyl]hexyl] -Nα-methyl- , di- hydrochloride, [IS- [1R*,2R*,4R*(2R*,2R*) ] ] - ; (H0) 2 P(0)0(CH 2 ) 3 C(0)-Pro-Phe-N-MeHis-LVA-Ile-AMP or L-Histidin¬ amide, N-[[1- [l-oxo-4-(phosphonooxy)butyl]-3-pyrrolidinyl]carbonyl] - L-phenylalanyl-N- [2-hydroxy-5-methyl-l-(2-methylpropyl)-4- [ [ [2-meth¬ yl-l- [ [ (2-2-pyridinylmethyl)amino]carbonyl]butyl]amino]carbonyl]hex- yl]-Nα-methyl-, dihydrochloride, [IS-[1R*(S*) ,2R*,4R*(1R*)] ] - ; The following compounds of the present invention are more preferred: 0-Val-Phe-N-MeHis-LVA-Ile-AMP or L-histidinamide, N-(3-amino-3- methyl-1-oxobutyl)-L-phenylalanyl-N- [2-hydroxy-5-methyl' i -l-(2-methylp- ropyl)-4- [ [ [2-methyl-l- [ [ (2-pyridinylmethyl)amino]carbonyl]butyl]- amino]carbonyl]hexyl] -Nα-methyl- , [IS-[1R*,2R*, R*(1R*,2R*) ] ] - , tris- (trifluoroacetate) (salt) ; /3-Val-Phe-N-MeHis-CVA-Ile-AMP or L-Histidinamide, N-(3-amino-3- methyl-1-oxobutyl)-L-phenylalanyl-N- [1-(cyclohexylmethyl)-2-hydroxy- 5-methyl-4- [ [ [2-methyl-l- [ [ (2-pyridinylmethyl)amino]carbonyl]but¬ yl]amino]carbonyl]hexyl] -Nα-methyl- , [1S-[1R*,2R*,4R*(1R*,2R*)]]-, tris(trifluoroacetate) (salt); 7-Glu-Pro-Phe-N-MeHis-LVA-Ile-AMP or L-Histidinamide, L-7- glutamyl-L-prolyl- -phenylalanyl-N- [2-hydroxy-5-methyl-1-(2-methyl- propyl) -4- [ [ [2-methyl-1- [ (2-pyridinylmethyl)amino]carbonyl]butyl- ;amino]carbonyl]hexyl] -Nα-methyl- , [IS- [1R*,2R*,4R*(1R*,2R*)] ] -, tris(trifluoroacetate) (salt); 7-Glu-Pro-Phe-N-MeHis-CVA-Ile-AMP or L-Histidinamide, L-7- glutamyl-L-prolyl-L-phenylalanyl-N- [1-(cyclohexylmethyl)-2-hydroxy- 5-methyl-4-[ [ [2-methyl-l- [ [ (2-pyridinylme hyl)amino]carbonyl]butyl]- amino]carbonyl]hexyl] -Nα-methyl-, [1S-[1R*, ,2R*,4R*(1R*,2R*)] ] - , tris(trifluoroacetate) (salt); 3-Val-Phe-NC(CH3)His-CVA-Ile-NH(CH 2 ) 4 CH(C00H)(NH 2 ) or L-Lysine, N6- [N- [5-[ [N- [N- (3-amino-3-methyl-1-oxobutyl)-L-phenylalanyl]-N-meth¬ yl-L-histidyl]amino]-6-cyclohexyl-4-hydroxy-2-(l-me hylethyl)-1-oxo- hexyl]-L-isoleucyl] - , [2S-(2R*,4R*,5R*)] - , tris(trifluoroacetate) (salt); 7-Glu-Pro-Phe-N-MeHis-CVA-Ile-NH(CH 2 ) CH(C0OH)(NH 2 ) or L-Lysine, N6- [N- [6-cyclohexyl-5- [ [N[ (l-L-7-glutamyl-L-prolyl)-L-phenylalanyl] - N-methyl-L-histidyl]amino] -4-hydroxy-2-(l-methylethyl)-l-oxohexyl]-L- isoleucyl], [2S- (2R*,4R*,5R*)] - , tris(trifluoroacetate) (salt); (H0) 2 P(0)0CH 2 C(0)-Pro-Phe-N-MeHis-LVA-Ile-AMP-N0 or L-His¬ tidinamide, 1- [(phosphonooxy)acetyl] -L-prolyl-L-phenylalanyl-N- [2- hydroxy-5-methyl-l-(2-methylpropyl)-4-[ [ [2-methyl-l- [ [(2-pyridinyl- methyl)amino]carbonyl]butyl]amino]carbonyl]hexyl] -Nα-methyl- , N- oxide, dihydrochloride, [IS- [1R*,2R*,4R*(1R*,2R*)] ]-; (H0) 2 P(0)0(CH 2 ) 3 C(0)-Pro-Phe-N-MeHis-LVA-Ile-AMP-N0 or L-Hist¬ idinamide, N-[[1- [l-oxo-4-(phosphonooxy)butyl] -3-pyrrolidinyl] - carbonyl] -L-phenylalanyl-N- [2-hydroxy-5-methyl-1-(2-me hylpropyl)-4- [ [ [2-methyl-l- [ [ (2-2-pyridinylmethyl)amino]carbonyl]butyl]amino] - carbonyl]hexyl] -Nα-methyl-, N-oxide, monohydrochloride, [1S-[1R*- (S*) ,2R*, R*(1R*,2R*)]]- . The following compounds of the present invention are most pre¬ ferred: -Val-Phe-N-MeHis-LVA-Ile-AMP-NO or L-Histidinamide, N-(3- amino-3-methyl-1-oxobutyl)-L-phenylalanyl-N- [2-hydroxy-5-methyl-1-(2- methylpropyl)-4- [ [ [2-methyl-l- [[(2-pyridinylmethyl)amino]carbonyl] - butyl]amino]carbonyl]hexyl]-Nα-methyl- , N-oxide, [IS- [1R*,2R*, R*- (1R*,2R*)]]-, tris(trifluoroacetate) (salt); /3-Val-Phe-N-MeHis-CVA-Ile-AMP-NO or L-Histidinamide, N-(3- amino-3-methyl-1-oxobutyl)-L-phenylalanyl-N- [1-(cyclohexylmethyl)-2- hydroxy-5-methyl-4- [ [ [2-methyl-l- [ [(2-pyridinylmethyl)amino]carbon- yl]butyl]amino]carbonyl]hexyl] -Nα-methyl- , N-oxide, [IS- [1R*,2R*, - 4R*(1R*,2R*)]]-, tris(trifluoroacetate) (salt); 7-Glu-Pro-Phe-N-MeHis-LVA-Ile-AMP-NO or L-Histidinamide, L-7-glutamyl-L-prolyl-L-phenylalanyl-N- [2-hydroxy-5-methyl-1-(2-meth- ylpropyl)-4- [ [ (2-methyl-l- [ [ (2-pyridinylmethyl)amino]carbonyllbut¬ yl]amino]carbonyl]hexyl]-Nα-methyl- , N-oxide, [IS[1R*,2R*,4R*(1R*, - 2R*)]]-, tris(trifluoroacetate) (salt) ; 7-Glu-Pro-Phe-N-MeHis-CVA-Ile-AMP-NO or L-Histidinamide, L-7- glutamyl-L-propyl-L-phenylalanyl-N- [1-(cyclohexylmethyl)-2-hydroxy-5- methyl-4-[ [ [2-methyl-l- [ [ (2-pyridinylmethyl)amino]carbonyl]butyl]- amino]carbonyl]hexyl] -Nα-methyl-, N-oxide, [IS-[1R*,2R*,4R*(1R*, - 2R*)]]-, tris(trifluoroacetate) (salt); (HO) 2 P(0)OCH 2 C(0)-Pro-Phe-N-MeHis-CVG or L-Histidinamide, 1- [ (phosphonooxy)acetyl] -L-prolyl-L-phenylalanyl-N- [1-(cyclohexyl¬ methyl)-2,3-dihydroxy-5-methylhexyl]-Nα-methyl- , monohydrochloride, [1S-(1R*,2S*,3R*)]-. DESCRIPTION OF THE PREFERRED EMBODIMENTS The following Preparations and Examples illustrate the present invention. In the Preparations and Examples below and throughout this document: ^H-NMR is nuclear magnetic resonance AMP is 2-(aminomethyl)pyridinyl AMP-NO is (2-pyridylmethyl)amino, pyridine N-oxide Ampip is 4-(aminomethyl)piperidine 3-Asp is ?-asparagine BOC is t-butoxycarbonyl Bz is benzyl C is centigrade Cbz is benzyloxycarbonyl CDCI3 is deuteriochloroform Celite is a filter aid CVA is Cha*[CH(0H)CH 2 ]Val CVG is 2S-amino-l-cyclohexyl-3R,4S-dihydroxy-6-methylheptane DCC is dicyclohexylcarbodiimide DEPC is diethylphosphoryl cyanide EtOAc is ethyl acetate FTrp is N in" formyl-Trp g is grams 7 -Glu is 7 -glutamic acid His is histidine N-MeHis is Nα-methyl histidine HOBT is 1-hydroxybenzotriazole HPLC is high performance liquid chromatography Iba is isobutylamine lie is isoleucine IR is infrared spectra LVA is Leu^(CH(0H)CH 2 )Val with the S configuration at C4 (the hydroxyl-bearing carbon atom) . M or mol is mole MBA is 2-methylbutylamino (racemic or optically active) Me is methyl min is minute ml is milliliter MPLC is medium pressure liquid chromatography MS is mass spectroscopy Ph is phenyl Phe is phenylalanine Pro is proline RIP means a compound having the formula H-Pro-His-Phe-His-Phe- Phe-Val-Tyr-Lys-0H.2(CH 3 C(0)0H) .XH 2 0 which is a known renin-inhibit¬ ing peptide. Sta is statine TBS is tert-butyldimethylsilyl TEA is triethylamine TFA is trifluoroacetic acid THF is tetrahydrofuran TLC is thin layer chromatography Tos is p-toluenesulfonyl TsOH is p-toluenesulfonic acid Tyr is tyrosine (0CH3)Tyr is O-methyl tyrosine /3-Val is jS-Valine. The wedge-shape line indicates a bond which extends above the plane of the paper relative to the plane of the compound thereon. The dotted line indicates a bond which extends below the plane of the paper relative to the plane of the compound thereon. In the examples below. HPLC is high pressure liquid chromatog¬ raphy and k' is the partition ratio obtained. The solvent system used is indicated in parentheses after the partition ratio: A is 50% methanol, 50% aqueous phosphate pH 3 buffer; B is 55% methanol, 45% aqueous phosphate pH 3 buffer; C is 60% methanol, 40% aqueous phos¬ phate pH 3 buffer; and D is 65% methanol, 35% aqueous phosphate pH 3 buffer. The flow rates were at 1.5 ml/min. The detector was set at 225 or 254 nm. In the examples below, the renin inhibitory activity of the peptides of the present invention (IC5Q'S) are determined using the in vitro test described in U.S. patent application, Serial No. 07/07/147,073, filed 20 January 1988, and in published European patent application 0173481, published 5 March 1986, pages 103-105, which are hereby incorporated by reference. The in vitro &C50 is measured in nanomolars. Compounds of the present invention have also exhibited renin-inhibitory activity during in vivo testing. Preparation 1 BOC- Υ -Glu(α-0Bn) -Pro-Phe-(N-Me)His-LVA-Ile-AMP (Formula A-2) Refer to Chart A. To a stirred solution of 125 mg of the peptide of formula A-l and 61 mg of BOC-7-glu-α-OBn in 1 ml of dichloromethane is added 31 μL of diisopropylethylamine, followed by 28 μL of diethylcyanophos- phonate. The mixture is stirred overnight, then chromatographed on silica gel with 4-10% methanol in dichloromethane to afford 167 mg of the title product as a white solid. Physical characteristics are as follows: λ E NMR and FAB HRMS (m+H) : 1149.668. Preparation 2 BOC-7-Glu-Pro-Phe-(N-Me)His-LVA-lie-AMP (Formula A-3) Refer to Chart A. A mixture of 163 mg of the title product of Preparation 1, 137 mg of ammonium formate, and 90 mg of 5% Pd/C in 1.4 ml of dry dimethylformamide is stirred under argon for 18 hours, then filtered through Celite and concentrated under high vacuum. The residue is chromatographed on silica gel with 5-20% methanol in dichloromethane to afford 137.5 mg of the title product. Physical characteristics are as follows: l NMR and FAB HRMS (m+H) : 1097.578. Preparation 3 BOC-7-Glu-Pro-Phe- (N-Me)His-LVA-Ile-AMP N-oxide (Formula A-4) Refer to Chart A. A solution of 53 mg of the title product of Preparation 2 and 11.5 mg of m-chloroperbenzoic acid in a small amount of dichlorometh¬ ane is stirred at room temperature for five hours, then chromato¬ graphed directly on silica gel with 10-25% methanol in dichlorometh- ane. The title product is obtained as 33.3 mg of a white solid. Physical characteristics are as follows: l U NMR and FAB HRMS (m+H): 1113.5. Example 1 7-Glu-Pro-Phe-(N-Me)His-LVA-Ile-AMP tris trifluoro¬ acetate (Formula A-5) Refer to Chart A. A solution of 31.5 mg of the title product of Preparation 2 in a few drops of 1:1 trifluoroacetic acid-dichloromethane is allowed to stand for 1 hour, then is dripped slowly into 7 ml of 1:1 ether- hexane. The mixture is stirred for 15 minutes, then spun down in a centrifuge tube. The solid is washed twice with 1:1 ether-hexane by slurrying and re-centrifuging, and is dried under vacuum to afford 36 mg of the title product as a white solid. Physical characteristics are as follows: FAB HRMS (m+H): 959.5707. IC 50 (nM): 0.35. Example 2 7-Glu-Pro-Phe-(N-Me)His-LVA-Ile-AMP N-oxide tris trifluoroacetate (Formula A-6) Refer to Chart A. A solution of 32.8 mg of the title product of Preparation 3 in a few drops of 1:1 trifluoroacetic acid-dichloromethane is allowed to stand for 1 hour, then is dripped slowly into 10 ml of 1:2 ether- hexane. The mixture is stirred for 15 minutes, then spun down in a centrifuge tube. The solid is washed twice with 1:2 ether-hexane by slurrying and re-centrifuging, and is dried under vacuum to afford 40 mg of the title product as a white solid. Physical characteristics are as follows: FAB HRMS (m+H): 975.5655. IC 50 (nM): 1.0. Preparation 4 B0C-(N-Me)His(Ts)-CVG To a stirred solution of 360 mg of 2(S)-amino-1-cyclohexyl- 3(R) ,4(S)-dihydroxy-6-methylheptane and 800 mg of BOC-(N-Me)His(Ts) , prepared as described in U.S. patent application, Serial No. 234,413, filed 19 August 1988, in 5 ml of dichloromethane is added 420 μL of diisopropylethylamine, followed by 290 μL of diethylcyanophosphonate. The reaction mixture is stirred overnight, then chromatographed on silica gel with 30-40% ethyl acetate in dichloromethane to afford 518 mg of the title product. Preparation 5„ BOC-Phe-(N-Me)His(Ts)-CVG The title product of Preparation 4 is de-BOC'd with trifluoro- acetic acid under standard conditions. To a stirred solution of 0.8 mol of this amine and 320 mg of BOC-Phe in 3 ml of dichloromethane is added 270 μL of diisopropyl¬ ethylamine, followed by 190 μL of diethylcyanophosphonate. The reaction mixture is stirred overnight, then chromatographed on silica gel with 30-50% ethyl acetate in dichloromethane to afford the title product. Preparation 6- BOC-Pro-Phe-(N-Me)His(Ts)-CVG The title product of Preparation 5 is de-BOC'd with trifluoro¬ acetic acid under standard conditions. To a stirred solution of 325 mg of this amine and 130 mg of BOC- Pro in 3 ml of dichloromethane is added 150 μL of diisopropylethyl¬ amine, followed by 100 μL of diethylcyanophosphonate. The reaction mixture is stirred overnight, then chromatographed on silica gel with 30-50% ethyl acetate in dichloromethane to afford 345 mg of the title product. Preparation 7 BOC-7-Glu(α-0Bn)-Pro-Phe-(N-Me)His(Ts)-CVG The title product of Preparation 6 is de-BOC'd with trifluoro¬ acetic acid under standard conditions. To a stirred solution of 50 mg of this amine and 25.5 mg of BOC- Glu(α-OBn) in 0.5 ml of dichloromethane is added 13 μL of diisoprop¬ ylethylamine, followed by 12 μL of diethylcyanophosphonate. The reaction mixture is stirred overnight, then chromatographed on silica gel with 3% methanol in dichloromethane to afford 75.6 mg of the title product. Physical characteristics are as follows: ^ • H NMR and FAB HRMS (m+H): 1112.574. Preparation 8 BOC-7-Glu(α-0Bn)-Pro-Phe-(N-Me)His-CVG A solution of 74.8 mg of the title product of Preparation 7 and 34 mg of 1-hydroxybenzotriazole in a small amount of methanol is allowed to stand overnight, then is concentrated under reduced pres¬ sure. Silica gel chromatography of the residue with 2-4% methanol (saturated with ammonia) in dichloromethane affords 55.0 mg of the title product. Physical characteristics are as follows: X H NMR and FAB HRMS (m+H): 958.5629. Preparation 9 BOC-7-Glu-Pro-Phe-(N-Me)His-CVG A mixture of 53.7 mg of the title product of Preparation 8, 53 mg of ammonium formate, and 40 mg of 5% Pd/C in 0.5 ml of dry dimeth- ylformamide is stirred overnight under argon, then filtered through Celite and concentrated under high vacuum. The residue is chromato¬ graphed on silica gel with 5-20% methanol (saturated with ammonia) in dichloromethane to afford 43.8 mg of the title product as a white solid. Physical characteristics are as follows: 1 H NMR and FAB HRMS (m+H): 906.4732. Example 3 7-Glu-Pro-Phe-(N-Me)His-CVG bis trifluoroacetate A solution/ of 42.8 mg of the title product of Preparation 9 in 0.3 ml of 1:1 trifluoroacetic acid-dichloromethane is allowed to stand for 1 hour, then added to 10 ml of rapidly stirred 1:2 ether- hexane. The precipitated solid is spun down, washed well with 1:2 ether-hexane, and dried under vacuum to afford the product as a white solid. Physical characteristics are as follows: FAB HRMS (m+H): 768.4677. HPLC (90/10 methanol/aqueous phosphate buffer containing 5.22 g NaH P0 4 monohydrate and 0.76 ml of 85% phosphoric acid in 4 1 of Burdick & Jackson water, 225 nm) k' : 11.3. IC 50 (nM): 0.41. Preparation 10 BOC-His(Ts)-CVG To a stirred solution of 230 mg of 2(S)-amino-l-cyclohexyl-3(R) , 4(S)-dihydroxy-6-methylheptane, and 500 ml of BOC-His(Ts), prepared as described in U.S. patent application, Serial No. 234,413, filed 19 August 1988, in 5 ml of dichloromethane is added 270 μL of diisopro- pylethylamine, followed by 190 μL of diethylcyanophosphonate. The reaction mixture is stirred overnight, then chromatographed on silica gel with 30-40% ethyl acetate in dichloromethane to afford 322 mg of the title product. Preparation 11 BOC-(OMe)Tyr-His(Ts)-CVG The the title product of Preparation 10 is de-BOC'd with trisfluoroacetic acid under standard conditions. To a stirred solution of 0.5 mmol of this amine and 228 mg of B0C(0Me)Tyr in 3 ml of dichloromethane is added 170 μL of diisopro- pylethylamine, followed by 120 μL of diethylcyanophosphonate. The reaction mixture is stirred overnight, then chromatographed on silica gel with 3-5% methanol in dichloromethane to afford the title prod- uct. Preparation 12 B0C-Pro-(0Me)Tyr-His(Ts)-CVG The title product of Preparation 11 is de-BOC'd with trifluoroa¬ cetic acid under standard conditions. To a stirred solution of 354 mg of this amine and 140 mg of BOC- Pro in 3 ml of dichloromethane is added 200 μL of diisopropylethyl- amine, followed by 110 μL of diethylcyanophosphonate. The reaction mixture is stirred overnight, then chromatographed on silica gel with 30-50% ethyl acetate in dichloromethane to afford 374 mg of the title product. Preparation 13 BOC-7-Glu(α-0Bn)-Pro-(OMe)Tyr-His(Ts)-CVG The title product of Preparation 12 is de-BOC'd with trifluoroa¬ cetic acid under standard conditions. To a stirred solution of 50 mg of this amine and 25 mg of BOC- Glu(α-OBn) in 0.5 ml of dichloromethane is added 13 μL of diisoprop- ylethylamine, followed by 12 μL of diethylcyanophosphonate. The reaction mixture is stirred overnight, then chromatographed on silica gel with 3% methanol in dichloromethane to afford 67.5 mg of the title product. Physical characteristics are as follows: l NMR and FAB HRMS (m+H): 1128.567. Preparation 14 B0C-7-Glu(α-0Bn)-Pro-(OMe)Tyr-His-CVG A solution of 66.8 mg of the title product of Preparation 13 and 32 mg of 1-hydroxybenzotriazole in a small amount of methanol is allowed to stand overnight, then is concentrated under reduced pres- sure. Silica gel chromatography of the residue with 2-4% methanol (saturated with ammonia) in dichloromethane provides 52.1 mg of the title product. Physical characteristics are as follows: -Η NMR and FAB HRMS (m+H): 974.5599. Preparation 15 BOC-7-Glu-Pro-(OMe)Tyr-His-CVG A mixture of 51.0 mg of the title product of Preparation 14, 50 mg of ammonium formate, and 40 mg of 5% palladium on carbon in 0.5 ml of dry dimethylformamide is stirred overnight under argon, then filtered through Celite and concentrated under vacuum. Chromatogra¬ phy of the residue on silica gel with 5-10% methanol in dichlorometh¬ ane affords 42.4 mg of the title product. Physical characteristics are as follows: X H NMR and FAB HRMS (m+H): 884.5117. Example 4 7 -Glu-Pro-(OMe)Tyr-His-CVG bis trifluoroacetate A solution of 41.8 mg of the title product of Preparation 15 in 0.3 ml of 1:1 trifluoroacetic acid-dichloromethane is allowed to stand for 1 hour, then dripped slowly into 10 ml of rapidly stirred 1:2 ether-hexane. The precipitated solid is spun down, washed well with ether-hexane, and dried under high vacuum to afford 46 mg of the title product as a white solid. Physical characteristics are as follows: FAB HRMS (m+H): 784.4582. IC 50 (tiM): 0.19. Preparation 16 B0C-/3-Val-Phe-(N-Me)His(Ts)-LVA-Ile-AMP N-oxide (Formula B-5) Refer to Chart B. A solution/suspension of 101 mg of the peptide of formula B-2 and 38 mg of m-chloroperbenzoic acid in 1 ml of dichloromethane Is stirred overnight, then quenched with a few drops of saturated aqueous sodium sulfite. The solvents are carefully pumped off and the residue chromatographed on silica gel with 4-10% methanol in dichloromethane to afford 53.2 mg of the title product as a yellow solid. Physical characteristics are as follows: l l. NMR and FAB HRMS (m+H): 1102.600. Preparation 17 B0C- -Val-Phe-(N-Me)His-LVA-Ile-AMP N-oxide (Formula B-6) Refer to Chart B. A solution of 52.1 mg of the title product of Preparation 16 and 26 mg of 1-hydroxybenzotriazole in a small amount of methanol is allowed to stand overnight and is then concentrated under reduced pressure. Chromatography of the residue on silica gel with 4 to 6 to 7% methanol (saturated with ammonia) in dichloromethane affords 20.7 mg of the title product. Physical characteristics are as follows: X H NMR and FAB HRMS (m+H): 948.5913. HPLC (90/1C methanol/aqueous phosphate buffer containing 5.22 g NaH P0 4 monohydrate and 0.76 ml of 85% phosphoric acid in 4 1 of Burdick & Jackson water, 254 n ) k': 8.0. Example 5 /3-Val-Phe-(N-Me)His-LVA-Ile-AMP N-oxide tris tri¬ fluoroacetate (Formula B-7) Refer to Chart B. A solution of 20.2 mg of the title product of Preparation 17 in 0.3 ml of 1:1 trifluoroacetic acid-dichloromethane is allowed to stand for one hour, and is then added dropwise to 10 ml of rapidly- stirred 1:1 ether-hexane. The mixture is stirred for 15 minutes, then transferred to a centrifuge tube and spun down. The solid is « washed three times by slurrying in ether-hexane and re-centrifuging, and is then dried under vacuum to provide 22 mg of the title product as a white solid. Physical characteristics are as follows: ^ ■ H NMR and FAB HRMS (m+H): 848.5401. IC 50 (τiM): 2.3. HPLC (90/10 methanol/aqueous phosphate buffer containing 5.22 g NaH 2 P0 4 monohydrate and 0.76 ml of 85% phosphoric acid in 4 1 of Burdick & Jackson water, 254 nm) k' : >40. Preparation 18 H-CVA-Mba hydrochloride To a stirred solution of 1.5 g of BOC-CVA(OTBS)-0H, prepared as described in PCT patent application, Serial No. PCT/US89/00247, filed 27 January 1989, and 0.45 ml of 2(S)-methylbutylamine in 12 ml of dichloromethane at 0 β is added 0.8 ml of diisopropylethylamine, followed by 0.5 ml of diethylcyanophosphonate. The reaction mixture is stirred overnight, then chromatographed on silica gel with 10-20% ethyl acetate in hexane to afford the coupled product. This material, in 20 ml of ether, is saturated with gaseous hydrogen chloride; volatiles are then removed under a stream of nitrogen and the residue is dried in vacuo to give 1.2 g of the title produc . Preparation 19 BOC-(N-Me)His(Ts)-CVA-Mba To a stirred solution of 75.4 mg of the title product of Prepar¬ ation 18 and 102 mg of BOC-(N-Me)His(Ts) in 1.5 ml of dichloromethane is added 80 μL of diisopropylethylamine, followed by 37 μL of diethylcyanophosphonate. The reaction mixture is stirred overnight, then flash chromatographed on silica gel with 70-80% ethyl acetate in hexane to afford 106 mg of the title product. Physical characteristics are as follows: X H NMR and FAB HRMS (m+H): 746.4527. Preparation 20 BOC-Phe-(N-Me)His(Ts)-CVA-Mba The title product of Preparation 19 is de-BOC'd with trifluoro¬ acetic acid in dichloromethane according to standard procedure. To a stirred solution of 80 mg of this amine and 50 mg of BOC- Phe in 1 ml of dichloromethane is added 32 μL of diisopropylethyl¬ amine, followed by 28 μL of diethylcyanophosphonate. The reaction mixture is stirred overnight, then flash chromatographed on silica gel with 70% ethyl acetate in dichloromethane to afford 87 mg of the title product. Physical characteristics are as follows: X H NMR and FAB HRMS (m+H): 893.5207. Preparation 21 BOC-0-Val-Phe-(N-Me)His(Ts)-CVA-Mba The title product of Preparation 20 is de-BOC'd with trifluoro¬ acetic acid in dichloromethane according to standard procedure. To a stirred solution of 0.10 mmol of this amine and 25.4 mg of BOC-jS-Val in 0.8 ml of dichloromethane is added 20 μL of diisoprop¬ ylethylamine, followed by 18 μL of diethylcyanophosphonate. The reaction mixture is stirred overnight, then flash chromatographed on silica gel with 80% ethyl acetate in dichloromethane to afford 93.1 mg of the title product. Physical characteristics are as follows: X H NMR and FAB HRMS (m+H): 992.5881. Preparation 22 BOC-0-Val-Phe-(N-Me)His-CVA-Mba A solution of 91.6 mg of the title product of Preparation 21 and 50 mg of 1-hydroxybenzotriazole in a small amount of methanol is allowed to stand overnight, then is concentrated under reduced pressure. Silica gel chromatography of the residue on silica gel with 5% methanol (saturated with ammonia) in dichloromethane provides 68 mg of the title product as a white solid. Physical characteristics are as follows: 1 H NMR and FAB HRMS (m+H): 838.5792. Example 6 /3-Val-Phe-(N-Me)His-CVA-Mba trifluoroacetate A solution of the title product of Preparation 22 (64.7 mg) in 0.4 ml of 1:1 trifluoroacetic acid -dichloromethane is allowed to stand for 1 hour, then is dripped slowly into 15 ml of rapidly- stirred 1:4 ether-hexane. The solid is isolated by centrifuging and washed by first re-slurrying in 1:4 ether-hexane and then spinning down. After drying of the product under high vacuum, 65 mg of the title product is obtained. This product is soluble in water, crashes out upon addition of aqueous sodium bicarbonate, but redissolves on addition of pH 7 phosphate buffer. Physical characteristics are as follows: FAB HRMS (m+H): 738.5247. IC 50 (nM): 0.41. Preparation 23 BOC-Phe-(N-Me)His(Ts)-CVA-Ile-AMP To a stirred solution of 0.98 mmol of H-(N-Me)His(Ts)-CVA-Ile- AMP, prepared as described in PCT patent application, Serial No. PCT/US89/00247, filed 27 January 1989, and 392 mg of BOC-Phe in 4.9 ml of dichloromethane is added 260 μL of diisopropylethylamine, followed by 230 μL of diethylcyanophosphonate. The reaction mixture is stirred overnight, then chromatographed on silica gel with 3-6% methanol in dichloromethane to afford 587 mg of the title product. Further elution of the column provides 301 mg of recovered amine. The proposed structure of the title compound is supported by ^H NMR. Preparation 24 BOC-0-Val-Phe-(N-Me)His(Ts)-CVA-Ile-AMP The title product of of Preparation 23 is de-BOC'd with tri¬ fluoroacetic acid in dichloromethane according to standard procedure. To a stirred solution of 90.4 mg of this amine and 26 mg of BOC- / δ-Val in 0.75 ml of dichloromethane is added 20 μL of diisopropyl¬ ethylamine and 18 μL of diethylcyanophosphonate. The mixture is stirred overnight, then chromatographed on silica gel with 3-5% methanol in dichloromethane to afford 117 mg of the title product. Physical characteristics are as follows: l H NMR and FAB HRMS (πri-H) : 1126.638. Preparation 25 BOC-3- al-Phe-(N-Me)His-CVA-Ile-AMP A solution of 0.10 mmol of the title product of Preparation 24 and 53 mg of 1-hydroxybenzotriazole in a small amount of methanol is allowed to stand overnight, then is concentrated under reduced pressure. Silica gel chromatography of the residue on silica gel with 2-5% methanol (saturated with ammonia) in dichloromethane affords 74.7 mg of the title product. Physical characteristics are as follows: X H NMR and FAB HRMS (m+H): 972.6314. Example 7 5-Val-Phe-(N-Me)His(Ts) -CVA-Ile-AMP tris trifluoro¬ acetate A solution of 23.0 mg of the title product of Preparation 25 in a few drops of 1:1 trifluoroacetic acid-dichloromethane is allowed to stand for 1 hour and is then dripped slowly into 10 ml of rapidly- stirred 1:2 ether-hexane. The precipitated solid is spun down, washed twice with 1:2 ether-hexane, and dried under high vacuum to afford 26 mg of the title product as a white solid. The solid is soluble in water and in pH 7 phosphate buffer. Physical characteristics are as follows: FAB HRMS (m+H): 872.5787. IC 50 (*nM): 0.29. Preparation 26 BOC- -Val-Phe-(N-Me)His-CVA-Ile-AMP N-oxide A solution of 49.5 mg of the title product of Preparation 25 and 11.8 mg of m-chloroperbenzoic acid in a small amount of dichlorometh¬ ane is stirred at room temperature for 3 hours, then chromatographed directly on silica gel with 4-7% methanol (saturated with ammonia) in dichloromethane to provide 37.3 mg of the title product as a white solid. Physical characteristics are as follows: --E NMR and FAB HRMS (m+H): 988.6219. HPLC (90/10 methanol/aqueous phosphate buffer containing 5.22 g NaH P0 4 monohydrate and 0.76 ml of 85% phosphoric acid in 4 1 of Burdick & Jackson water, 254 nm) k': 9.6. Example 8 -Val-Phe-(N-Me)His-CVA-Ile-AMP N-oxide tris tri¬ fluoroacetate A solution of 35.9 mg of the title product of Preparation 26 in a small amount of 1:1 trifluoroacetic acid-dichloromethane is allowed to stand for 1 hour and is then dripped slowly into 10 ml of rapidly- stirred 1:2 ether-hexane. The precipitated solid is spun down, washed twice with 1:2 ether-hexane, and dried under high vacuum to afford 39 mg of the title product as a white solid. The solid is soluble in water and in pH 7 phosphate buffer. Physical characteristics are as follows: FAB HRMS (m+H): 888.5736. IC 50 (nM): 0.43. Preparation 27 Benzyl glyoxylate (Formula C-2) Refer to Chart C. Glycolic acid (761 mg) of formula C-l is dissolved, with the aid of heat, in 3 ml of acetonitrile. The solution is diluted with 10 ml of dichloromethane, and to this is added 122 mg of 4-dimethylamino pyridine, 3.1 ml of benzyl alcohol, and 1.72 ml of diisopropylcarb¬ odiimide. The mixture is stirred over the weekend, then solvents are removed under a stream of nitrogen. The residue is slurried in ether and filtered, and the filtrate washed with small amounts of dilute hydrochloric acid and brine, and dried (magnesium sulfate) . Removal of the solvent under reduced pressure and flash chromatography of the residue on silica gel with 60% ether-hexane provides 1.57 g of the product, slightly contaminated with benzyl alcohol, as a colorless oil. Physical characteristics are as follows: X H NMR 8 : 2.48, 4.21, 5.24, 7.4. Preparation 28 (Benzyloxycarbonyl)methyl di-tert-butyl phosphate (Formula C-3) Refer to Chart C. To a solution/suspension of 500 mg of the title product of Preparation 27 and 422 mg of IH-tetrazole in 3 ml of dry tetrahydro- furan under argon is added 0.84 ml of phosphoramidite reagent. Heat is generated, and the tetrazole soon dissolves. After 2 hours, a solution of 570 mg of m-chloroperbenzoic acid in 4 ml of dichloromet¬ hane is added slowly, with ice cooling near the end of addition to moderate the exothermic reaction. The reaction mixture is given an aqueous workup, with sodium bisulfite washes, and the material is flashed on silica gel with 8% acetone-dichloromethane to afford 978 mg of the title product as a colorless oil. Physical characteristics are as follows: X H NMR 8 : 1.48, 4.55, 5.23, 7.4. FAB HRMS (m+H): 359.1652. Preparation 29 Carboxy ethyl di-tert-butyl phosphate (Formula C-4) Refer to Chart C. A solution of 575 mg of the title product of Preparation 28 in 5 ml of ethanol is shaken with 5% palladium on carbon under 60 psi hydrogen overnight, then filtered through Celite. Concentration of the filtrate under reduced pressure provides 293 mg of the title product as a colorless oil. Physical characteristics are as follows: NMR 8 : 1.49, 1.51, 4.54, 8.6. Preparation 30 Benzyl vinylacetate (Formula D-2) Refer to Chart D. To a stirred solution of 5 ml of vinylacetic acid, 5.7 ml of benzyl alcohol, and 0.61 g of 4-dimethylamino pyridine in 50 ml of dichloromethane is added, via addition funnel over about 45 minutes. 8.2 ml of dacarbazine. The addition causes gentle boiling of the solution. After 18 hours, the mixture is filtered from diisopropyl urea and the filtrate concentrated under reduced pressure. Ether- hexane is added to the residue, and this mixture filtered again. The filtrate is washed with dilute acid and base, dried (magnesium sulf- ate) , and concentrated under reduced pressure to a yellow oil. Dis¬ tillation under high vacuum through a short column (b.p. 80-82°/ca 0.1 mmHg) provides 8.94 g of the title product as a colorless liquid. Physical characteristics are as follows: X H NMR 8 : 3.14, 5.14, 5.16-6.20, 5.88-5.99, 7.4. Preparation 31 Benzyl 4-hydroxybutanoate (Formula D-3) Refer to Chart D. Into a flame-dried 100 ml flask capped with a rubber septum, under argon, is syringed 25 ml of borane-tetrahydrofuran (nominally 1 M) . The stirred solution is cooled in ice-brine, and to it is added, via cannula, a solution of 3.53 g of 2-methyl-2-butene in 8 ml of dry tetrahydrofuran over a period of about 15 minutes. Following the addition, the clear solution is warmed to 0° and held there through completion of quenching. After 90 minutes, 4.41 g of the title prod¬ uct of Preparation 30 (neat) is added over a period of 20 minutes, and the mixture is stirred at 0°C for another 30 minutes. Water (1 ml) is then added cautiously, followed by a mixture of 8.3 ml of 30% hydrogen peroxide and 8.3 ml of 3N sodium hydroxide. The mixture is extracted three times with ether; the organic phase is washed with dilute base and sodium sulfite dried (magnesium sulfate) , and concentrated under reduced pressure. Flash chromatography of the residue on silica gel with 50-100% ether-pentane affords 2.21 g of the title product as a colorless oil. Physical characteristics are as follows: λ R NMR 8 : 1.67, 1.91, 2.50, 3.69, 5.13, 7.4. Preparation 32 3-(Benzyloxycarbonyl)propyl di-tert-butyl phosphate (Formula D-4) Refer to Chart D. To a solution/suspension of 777 mg of the title product of Preparation 31 and 560 mg of IH-tetrazole in 4 ml of dry tetrahydro- furan under argon is added 1.15 ml of phosphoramidite reagent. Heat is generated, and the tetrazole soon dissolves. After 18 hours, a solution of 812 mg of m-chloroperbenzoic acid in 6 ml of dichloro¬ methane is added slowly, with ice cooling near the end of addition to moderate the exothermic reaction. The reaction mixture is given an aqueous workup, with sodium bisulfite washes, and the material is flashed on silica gel with 5-10% acetone-dichloromethane to afford 1.46 g of the title product as a colorless oil. Physical characteristics are as follows: l R NMR 8 : 1.47, 1.51, 2.0, 2.51, 4.0, 5.12, 7.4. FAB HRMS (m+H): 387.1944. Preparation 33 3-Carboxypropyl di-tert-butyl phosphate (Formula D-5) Refer to Chart D. A solution of 155 mg of the title product of of Preparation 32 in 2 ml of ethanol is shaken with 5% palladium on carbon under 60 psi hydrogen overnight, then filtered through Celite. Concentration of the filtrate under reduced pressure provides 100 mg of the title compound as a colorless oil. Physical characteristics are as follows: X H NMR 8 : 1.47, 1.53, 2.0, 2.5, 4.0, 7.3. Preparation 34 (t-Bu0) 2 P(0)0CH 2 C0-Pro-Phe-(N-Me)His-LVA-Ile-AMP (Formula E-2) Refer to Chart E. To a solution of 83 mg of the peptide of formula E-l and 54 mg of the acid of formula C-4 of Preparation 29 in 0.6 ml of dichloro¬ methane is added 19 μL of diisopropylcarbodiimide. After 18 hours the reaction mixture is chromatographed directly on silica gel with 4-6% methanol (saturated with ammonia) in dichloromethane to provide 55.3 mg of the title compound as a white solid. Physical characteristics are as follows: X H NMR and FAB HRMS (m+H) : 1080.622. Preparation 35 (t-Bu0) 2 P(0)0CH 2 C0-Pro-Phe-(N-Me)His-LVA-Ile-AMP N-oxide (Formula E-3) Refer to Chart E. A solution of 48.1 mg of the title product of Preparation 34 and 10 mg of m-chloroperbenzoic acid is stirred for 2 hours, then quenched with a few drops of aqueous sodium sulfite. The solvents are pumped off and the residue chromatographed on silica gel with 4- 6% methanol (saturated with ammonia) in dichloromethane to afford 31.7 mg of the title product as a white solid. Physical characteristics are as follows: 1 H NMR and FAB HRMS (m+H): 1096.621. Example 9 (H0) P(0)0CH 2 C0-Pro-Phe-(N-Me)His-LVA-Ile-AMP bis hydrochloride (Formula E-4) Refer to Chart E. A solution of 20.2 mg of the title product of Preparation 34 in 0.5 mi of 4 M aqueous hydrochloric acid is allowed to stand for one h, then the solvent is pumped off under high vacuum via a potassium hydroxide trap. The residue is dissolved in absolute ethanol, which is then carefully pumped off, and this treatment is repeated once. The residue is then dissolved in water and the solution lyophilized to provide 18.5 mg of the title product as a fluffy white solid. Physical characteristics are as follows: FAB HRMS (m+H): 965.5042. HPLC (90/10 methanol/aqueous phosphate buffer containing 5.22 g NaH 2 P0 monohydrate and 0.76 ml of 85% phosphoric acid in 4 1 of Burdick and Jackson water, 254 nm) k' : 1.7. IC 50 (nM): 1.6. Example 10 (H0) 2 P(0)0CH 2 C0-Pro-Phe-(N-Me)His-LVA-Ile-AMP N-oxide bis hydrochloride (Formula E-5) Refer to Chart E. A solution of 47 mg of the title product of Preparation 35 in 1 ml of 4 M aqueous hydrochloric acid is allowed to stand for one h, then the solvent is pumped off under high vacuum via a potassium hydroxide trap. The residue is dissolved in absolute ethanol, which is then carefully pumped off, and this treatment is repeated once. The residue is then dissolved in water and the solution lyophilized to provide 41 mg of the title product as a fluffy white solid. Physical characteristics are as follows: FAB HRMS (m+H): 984.4945. HPLC (90/10 methanol/aqueous phosphate buffer containing 5.22 g NaH 2 P0 4 monohydrate and 0.76 ml of 85% phosphoric acid in 4 1 of Burdick and Jackson water, 254 nm) k' : 1.7. IC 50 (nM): 2.5. Preparation 36 (t-Bu0) 2 P(0)0(CH 2 ) 3 C0-Pro-Phe-His(Ts)-LVA-Ile-AMP To a stirred solution of 98.4 mg of Pro-Phe-His(Ts)-LVA-Ile-AMP, tosyl-protecting group analog of the peptide of formula A-l, prepared as described in U.S. patent application, Serial No. 07/147,073, filed 20 January 1988, and in published European patent application 0173481, published 5 March 1986, and about 0.3 mmol of acid of form¬ ula D-5 of Preparation 33 in 1 ml of dichloromethane is added 35 μL of diisopropylethylamine, followed by 20 μL of diethylcyanophosphon¬ ate. The reaction mixture is stirred overnight, then chromatographed on silica gel with 4-7% methanol in dichloromethane to afford 106 mg of the title compound as a tan foam. Physical characteristics are as follows: l R NMR and FAB HRMS (m+H): 1262. Preparation 37 (t-BuO) 2 P(0)0(CH 2 ) 3 CO-Pro-Phe-His-LVA-Ile-AMP A solution of 31.6 mg of the title product of Preparation 36 and 11 mg of 1-hydroxybenzotriazole in a small amount of methanol is allowed to stand overnight, then is concentrated under reduced pressure. Silica gel chromatography of the residue on silica gel with 5-7% methanol (saturated with ammonia) in dichloromethane affords 32.1 mg of a product which appears to be a mixture of the desired compound along with some unidentified silicon-derived contaminant. Re-chromatography separates the product from the contaminant but gives only a 15.8 mg recovery. Physical characteristics are as follows: X H NMR and FAB HRMS (πH-H) : 1108.654. Example 11 (H0) 2 P(0)0(CH 2 ) 3 C0-Pro-Phe-His-LVA-Ile-AMP bis hydrochloride To a solution of 15.5 mg of the title product of Preparation 37 in 0.25 ml of tetrahydrofuran is added 0.25 ml of 8 M aqueous hydro¬ chloric acid. After 1 hour, the solvent is pumped off under high vacuum, via a potassium hydroxide trap, and the residue is dissolved in water and lyophilized to give 14.8 mg of the title product as a white solid. Physical characteristics are as follows: FAB HRMS (m+H): 996.5354. IC 50 (nM): 0.45. Preparation 38 (t-Bu0) 2 P(0)0(CH 2 ) 3 C0-Pro-Phe-His(Ts)-LVA-Ile-AMP N-oxide A solution of 38.1 mg of the title product of Preparation 36 and 12 mg of m-chloroperbenzoic acid in 0.3 ml of dichloromethane is allowed to stand for 2 hours, then quenched with solid sodium sulfite. Chromatography of the mixture on silica gel with 3-7% methanol in dichloromethane affords 27.8 mg of the title compound as a white solid. Physical characteristics are as follows: l ϋ NMR and FAB HRMS (m+H): 1278. Preparation 39 (t-Bu0) 2 P(0)0(CH 2 ) 3 C0-Pro-Phe-His-LVA-Ile-AMP N- oxide A solution of 25.7 mg of the title product of Preparation 38 and 11 mg of 1-hydroxybenzotriazole in a small amount of methanol is allowed to stand overnight, then is concentrated under reduced pressure. Silica gel chromatography of the residue on silica gel with 5-8% methanol (saturated with ammonia) in dichloromethane affords 16.0 mg of the title compound. Physical characteristics are as follows: l R NMR and FAB HRMS (m+H): 1124.652. Example 12 (H0) 2 P(0)0(CH 2 ) 3 C0-Pro-Phe-His-LVA-Ile-AMP N-oxide bis hydrochloride To a solution of 14.9 mg of the title product of Preparation 39 in 0.25 ml of tetrahydrofuran is added 0.25 ml of 8 M aqueous hydro- chloric acid. After 1 hour, the solvent is pumped off under high vacuum, via a potassium hydroxide trap, and the residue is dissolved in water and lyophilized to give 11.0 mg of the title product as a white solid. Physical characteristics are as follows: FAB HRMS (m+H): 1012.534. IC 50 (nM): 1.9. Preparation 40 (t-Bu0) 2 P(0)0CH 2 C0-Phe-(N-Me)His(Ts)-LVA-Ile-AMP To a stirred solution of 124 mg of H-Phe-(N-Me)His(Ts)-LVA-Ile- AMP, prepared as described in U.S. patent application, Serial No. 07/147,073, filed 20 January 1988, and in published European patent application 0173481, published 5 March 1986, and ca. 0.25 mmol of the acid of formula C-4 of Preparation 29 in 1 ml of dichloromethane is added 49 μL of diisopropylethylamine, followed by 26 μL of diethyl¬ cyanophosphonate. The reaction mixture is stirred overnight, then chromatographed on silica gel with 3-6% methanol in dichloromethane to afford 129 mg of the title compound. Physical characteristics are as follows: X H NMR and FAB HRMS (m+H): 1137.581. Preparation 41 (t-BuO) 2 P(0)OCH 2 CO-Phe-(N-Me)His-LVA-Ile-AMP A solution of 36.1 mg of the title product of Preparation 40 and 13 mg of 1-hydroxybenzotriazole in a small amount of methanol is allowed to stand overnight, then is concentrated under reduced pres- sure. Silica gel chromatography of the residue on silica gel with 5- 7% methanol (saturated with ammonia) in dichloromethane provides 13.2 mg of the title compound as a white solid. Physical characteristics are as follows: X H NMR and FAB HRMS (m+H): 983.5724. Example 13 (H0) 2 P(0)0CH 2 C0-Phe- (N-Me)His-LVA-Ile-AMP bis hydro¬ chloride A solution of 13 mg of the title product of of Preparation 41 in 0.5 ml of 4 M aqueous hydrochloric acid is allowed to stand for 90 minutes, then evaporated to dryness under nitrogen. The residue is dissolved in water and this solution lyophilized to give 12.5 mg of the title product as a white solid. Physical characteristics are as follows: FAB HRMS (m+H): 871.83. IC 50 (nM): 15. Preparation 42 (t-Bu0) 2 P(0)0CH 2 C0-Phe- -Asp(α-0Bn)-LVA-Ile-AMP To a stirred solution of 117 mg of H-Phe-^-Asp(α-OBn)-LVA-Ile- AMP of formula G-l, prepared as described in PCT patent application, Serial No. PCT/US88/03436, filed 11 October 1988, and ca. 0.3 mmol of acid of formula C-4 of Preparation 29 in 0.5 ml of dichloromethane and 0.7 ml of dimethylformamide is added 31 μL of diisopropylethyl¬ amine, followed by 27 μL of diethylcyanophosphonate. The reaction mixture is stirred overnight, then chromatographed on silica gel with 3-8% methanol in dichloromethane to afford 78.0 mg of the title com¬ pound. Physical characteristics are as follows: X H NMR and FAB HRMS (m+H): 1037. Preparation 43 (t-Bu0) 2 P(0)0CH 2 C0-Phe- -Asp-LVA-Ile-AMP A mixture of 77 mg of the title product of Preparation 42, 50 mg of ammonium formate, and 40 mg of 5% palladium on charcoal in 1 ml of dimethylformamide is stirred under argon for two days, then filtered through Celite and concentrated under vacuum. The residue is chromatographed on silica gel with 5-15% methanol In dichloromethane to afford 33.3 mg of the title compound as a white solid. Physical characteristics are as follows: 1 H NMR and FAB HRMS (m+H) : 947. Example 14 (H0) 2 P(0)0CH 2 C0-Phe-S-Asp-LVA-Ile-AMP hydrochloride To a solution of 33.3 mg of the title product of Preparation 43 in 0.4 ml of te rahydrofuran is added 0.2 ml of concentrated hydro¬ chloric acid. After 45 minutes, volatiles are pumped off, and the residue redissolved in water and lyophilized to afford 25.8 mg of the title product. Physical characteristics are as follows: FAB HRMS (m+H): 873.3556. IC 50 (iiM): 29. Preparation 44 (t-Bu0) 2 P(0)0CH 2 C0-Pro-Phe-(N-Me)His(Ts)-CVG To a stirred solution of 50 mg of H-Pro-Phe-(N-Me)His(Ts)-CVG, prepared as described in U.S. patent application, Serial No. 234,413, filed 19 August 1988, and ca. 0.2 mmol of the acid of formula C-4 of Preparation 29 in 0.2 ml of dichloromethane is added 13 μL of diiso¬ propylcarbodiimide. After 24 hours, the mixture is chromatographed on silica gel with 3-5% methanol-dichloromethane to afford 37.1 mg of the title compound as a white foam. Physical characteristics are as follows: X H NMR and FAB HRMS (m+H): 1043.525. Preparation 45 (t-Bu0) 2 P(0)0CH 2 C0-Pro-Phe-(N-Me)His-CVG A solution of 37 mg of the title product of Preparation 44 and 20 mg of 1-hydroxybenzotriazole in a small amount of methanol is allowed to stand overnight, then is concentrated under reduced pressure. Silica gel chromatography of the residue on silica gel with 4-6% methanol (saturated with ammonia) in dichloromethane provides 19.4 mg of the title compound as a white solid. Physical characteristics are as follows: X H NMR and FAB MS (m+H): 889. Example 15 (H0) 2 P(0)0CH 2 C0-Pro-Phe-(N-Me)His-CVG hydrochloride A solution of 19.2 mg of the title product of Preparation 45 in a small amount of 4 M aqueous hydrochloric acid is allowed to stand for 75 minutes, then the solvent is pumped off. The residue is dissolved in a small amount of absolute ethanol, which is carefully pumped off; this treatment is repeated once. The residue is dis¬ solved in water and the solution lyophilized to afford 16.9 mg of the title product as a fluffy white solid. Physical characteristics are as follows: FAB HRMS (m+H): 777.3956. IC 50 (nM): 3.4. Preparation 45 Ethyl 3-amino-3,3-dimethylpropanoate (Formula F-2) Refer to Chart F. Ethyl dimethylaerylate (641 mg) is dissolved in 10 ml of a saturated ethanolic solution of ammonia. The solution is contained in a thick-walled glass vessel which is sealable by means of a Teflon Ace-thread plug. The solution Is cooled to -15° in an ice-salt bath and re-saturated with ammonia from a lecture bottle. The tube is sealed and heated behind a safety shield to 80. After 22 hours, the tube is cooled, and the bulk of the ammonia purged out with nitrogen. Removal of the remaining solvent under reduced pressure affords 645 mg of the title product, which is contaminated with a small amount of starting material. Physical characteristics are as follows: H NMR 1.23; 1.30; 1.65; 2.39; 4.15. Preparation 46 Ethyl 3-butyloxycarbonylamino-3,3-dimethylprop- anoate (Formula F-3) Refer to Chart F. To a solution of 645 mg of the title product of Preparation 45 in 10 ml of dichloromethane is added 970 mg of BOC anhydride. After 3 days the solution is concentrated, and the residue chromatographed on silica with 10% ethyl acetate in hexane to afford 880 mg of the title product as a colorless oil. Physical characteristics are as follows: 1H NMR 1.26; 1.38; 1.44; 2.67; 4.13; 4.9. Preparation 47 3-Butyloxycarbonylamino-3,3-dimethylpropanoic acid (Formula F-4) Refer to Chart F. To a solution of 491 mg (2.00 mmol) of the title product of Preparation 46 in 4 ml of tetrahydrofuran is added 2.2 ml of IM potassium hydroxide. The mixture is stirred vigorously overnight, then tetrahydrofuran is removed under nitrogen. The remaining aqueous phase is washed once with dichloromethane and then acidified. The white precipitate is extracted with three portions of dichloro- methane, and the combined organic phases dried magnesium sulfate and concentrated under reduced pressure to afford 358 mg of the title product as a colorless oil. Physical characteristics are as follows: X H NMR 1.41; 1.46; 2.75. Preparation 48 3-Butyloxycarbonylamino-3 , 3-dimethylpropanoyl- Phe-Asp(a-OBn)-LVA-Mba (Formula G-2: R30 is Mba) Refer to Chart G. - To a stirred suspension of 12.2 mg of the title product of Preparation 47 and 28.1 mε of H-Phe-Asp(OBn)-LVA-Mba of formula G-l wherein R 0 is Mba in 0.4 ml of dichloromethane is added 10 μl of diisopropylethylamine and 9 μl of diethylphosphoryl. After 18 hours the mixture is chromatographed on silica with 2-3% methanol in dichloromethane to afford 40.9 mg of the title product as a yellowish solid. Physical characteristics are as follows: X H NMR 0.7-0.9, 1.0-1.6, 2.38, 2.5-3.7, 4.7, 5.0, 7.1-7.3. FAB MS (m+H)-853. Preparation 49 3-Butyloxycarbonylamino-3 , 3-dimethylpropanoyl- Phe-Asp(a-OBn)-LVA-Ile-AMP (Formula G-2: R30 is He-AMP) Refer to Chart G. To a stirred suspension of 28 mg of the title product of Prepar¬ ation 47 and 78.7 mg of H-Phe-Asp(OBn)-LVA-Ile-AMP in 0.7 ml of dichloromethane and 0.5 ml of dimethylformamide is added 21 μl of diisopropylethylamine and 18 μl of diethylphosphoryl. After 18 hours the mixture is chromatographed on silica with 4-6% methanol in dichloromethane to afford 82.5 mg of the title product as a white solid. Physical characteristics are as follows: T-H NMR 0.7-0.9, 1.10, 1.15, 1.2-1.8, 2.39, 2.5-2.8, 4.3-4.5, 5.1, 7.0-7.5, 8.36. FAB MS (m+H)-987. Preparation 50 3-Butyloxycarbonylamino-3 , 3-dimethylpropanoyl- Phe-(N-Me)His(Ts)-LVA-Mba (Formula B-2: R 20 is Mba) Refer to Chart B. To a stirred suspension of 31.5 mg of the title product of Preparation 47 and 0.12 mmol of H-Phe-(N-Me)His(Ts)-LVA-Mba of formula B-l wherein R 2 Q is Mba in 1.0 ml of dichloromethane is added 25 μl of diisopropylethylamine and 23 μl of diethylphosphoryl. After 18 hours the mixture is flash chromatographed on silica with ethyl acetate to afford 114 mg of the title product as a yellowish oil. Physical characteristics are as follows: l R NMR 0.5-1.6. 1.83, 2.0, 2.20, 2.57, 2.9-3.0, 6.8-7.6. FAB HRMS (m+H)-952.5593. Preparation 51 3-Butyloxycarbonylamino-3 , 3-dimethylpropanoyl- Phe-(N-Me)His(Ts)-LVA-Ile-AMP (Formula B-2: R 20 is Ile-AMP) Refer to Chart B. To a stirred solution of 24 mg of the title product of Prepara¬ tion 47 and 91.2 μmol of H-Phe-(N-Me)His(Ts)-LVA-Ile-AMP of formula B-l wherein R 2 Q is Ile-AMP in 0.9 ml of dichloromethane is added 19 μl of diisopropylethylamine and 17 μl of diethylphosphoryl. After 18 hours the mixture is chromatographed on silica with 3-5% methanol in dichloromethane to afford 84 mg of the title product as a white solid. Physical characteristics are as follows: - ■ R NMR 0.6-1.8, 1.8-3.6, 2.38, 2.76, 4.4-4.6, 7.0-7.9, 8.49. FAB HRMS (m+H)- 1086.616. Preparation 52 3-Butyloxycarbonylamino-3 , 3-dimethylpropanoyl- Phe-Asp-LVA-Mba (Formula G-3: R30 is Mba) Refer to Chart G. A solution of 43 μmol of the title product of Preparation 48 in a small amount of methanol is shaken with ca. 30 mg of 5% Pd/C under 60 psi H 2 for 18 hours, then filtered through Celite. The filtrate is concentrated under reduced pressure and the residue chromato¬ graphed on silica with 4-14% methanol in dichloromethane to afford 28.9 mg of the title product as a white solid. Physical characteristics are as follows: FAB HRMS (m+H)-800.4571. HPLC (70/30 methanol/aqueous phosphate buffer containing 5.22 g NaH 2 P0 4 monohydrate and 0.76 ml of 85% phosphoric acid in 4 1 of Burdick & Jackson water); 225 nm) k'-10.6. Preparation 53 3-Butyloxycarbonylamino-3, 3-dimethylpropanoyl- Phe-Asp-LVA-Ile-AMP (Formula G-3:R 30 is Ile-AMP) Refer to Chart G. A mixture of 82 mg of the title product of Preparation 49, 53 mg of ammonium formate, and 50 mg of 5% Pd/C in 0.8 ml of dimethylform- amide is stirred under argon overnight. At this point, the mixture is solid, so enough methanol is added to regain fluidity, and the mixture is stirred for 4 more days. The mixture is filtered through Celite and the filtrate concentrated under reduced pressure. Chroma- tography of the residue on silica with 5-15% methanol in dichloro¬ methane affords 69.4 mg of the title product as a white solid. Physical characteristics are as follows: λ R NMR 0.6-0.9, 1.02, 1.08, 1.31, 1.6-1.9, 2.2-2.8, 4.2-4.6, 7.0-7.2, 7.5, 8.34. FAB HRMS (m+H)-896.5484. HPLC (70/30 methanol/aqueous phosphate buffer containing 5.22 g NaH 2 P0 4 monohydrate and 0.76 ml of 85% phosphoric acid in 4 1 of Burdick & Jackson water), 254 nm) k'-6.6. Preparation 54 3-Butyloxycarbonylamino-3 , 3-dimethylpropanoyl- Phe-(N-Me)His-LVA-Mba (Formula B-3: R 20 is Mba) Refer to Chart B. A solution of 112 mg of the title product of Preparation 50 and 50 mg of 1-hydroxybenzotriazole in 1 ml of methanol is allowed to stand for 18 hours, then concentrated under reduced pressure. Chrom¬ atography of the residue on silica with 2.5-5% methanol (saturated with ammonia) in dichloromethane affords 69.8 mg of the title product as a white solid. Physical characteristics are as follows: λ NMR 0.7-0.9, 1.1-1.8, 2.0, 2.4, 2.77, 3.0-3.6, 7.1-7.6. FAB HRMS (m+H)-798.5487. HPLC (90/10 methanol/aqueous phosphate buffer containing 5.22 g NaH 2 P0 4 monohydrate and 0.76 ml of 85% phosphoric acid in 4 1 of Burdick & Jackson water); 225 nm) k'-6.7. Preparation 55 3-Butyloxycarbonylamino-3 , 3-dimethylpropanoyl- Phe-(N-Me)His-LVA-Ile-AMP (Formula B-3: R 20 is Ile-AMP) Refer to Chart B. A solution of 83.9 mg of the title product of Preparation 51 and 35 mg of 1-hydroxybenzotriazole in 1 ml of methanol Is allowed to stand for 18 hours, then concentrated under reduced pressure. Chrom¬ atography of the residue on silica with 3-5% methanol (saturated with ammonia) in dichloromethane affords 65.9 mg of the title product as a white solid. Physical characteristics are as follows: X H NMR 0.4-0.6, 0.7-1.8, 2.0-2.4, 2.9, 3.3, 4.4-4.7, 7.1-7.7, 8.48. FAB HRMS (m+H)-932.5984. HPLC (90/10 methanol/aqueous phosphate buffer containing 5.22 g NaH P0 4 monohydrate and 0.76 ml of 85% phosphoric acid in 4 1 of Burdick & Jackson water); 254 nm) k'-7.3. Example 16 3-Amino-3,3-dimethylpropanoyl-Phe-B-Asp-LVA-Mba trifluoroacetate (Formula G-4: R30 is Mba) Refer to Chart G. To 17.3 mg of the title product of Preparation 52 is added ca. 0.5 ml of 1:1 TFA-dichloromethane. The solution is allowed to stand for 2 hours, and then is added to 10 ml of rapidly stirred 1:1 ether- hexane. The product is filtered off through a fritted disc (fine porosity), washed well with 1:1 ether-hexane, and dried to constant weight under hivac to afford 13 mg of the title product as a white solid. Physical characteristics are as follows: *FAB HRMS (m+H)-662.4494. Example 17 3-Amino-3,3-dimethylpropanoyl-Phe-B-Asp-LVA-Ile-AMP trifluoroacetate (Formula G-4: R30 is Ile-AMP) Refer to Chart G. To 57.2 mg of the title product of Preparation 53 is added ca. 0.5 ml of 1:1 trifluoroacetate-dichloromethane. The solution is allowed to stand for 1 hour, and then is added to 15 ml of rapidly stirred 1:1 ether-hexane. The product is filtered off through a fritted disc (fine porosity), washed well with 1:1 ether-hexane, and dried to constant weight under hivac to afford 69 mg of the title product as a white solid. This material has a solubility greater than 5 mg/ml in 0.9% aqueous sodium chloride. Physical characteristics are as follows: FAB MS (m+H)-796. HPLC (70/30 methanol/aqueous phosphate buffer containing 5.22 g NaH P0 4 monohydrate and 0.76 ml of 85% phosphoric acid in 4 1 of Burdick & Jackson water); 254 nm) k'-6.2. Example 18 3-AmIno-3,3-dimethylpropanoyl-Phe-(N-Me)His-LVA-Mba trifluoroacetate (Formula B-4: R g is Mba) Refer to Chart B. To 58.6 mg of the title product of Preparation 54 is added ca. 0.5 ml of 1:1 trifluoroacetate-dichloromethane. The solution is allowed to stand for 1 hour, and then is added to 15 ml of rapidly stirred 1:1 ether-hexane. The product is filtered off through a fritted disc (fine porosity), washed well with 1:1 ether-hexane, and dried to constant weight under hivac to afford 53 mg of the title product as a white solid. This material has a solubility greater than 5 mg/ml in 0.9% aqueous sodium chloride. Physical characteristics are as follows: FAB HRMS (m+H)=698.4949. Example 19 3-A ino-3 , 3-dime hylpropanoyl-Phe-(N-Me)His-LVA-Ile- AMP trifluoroacetate (Formula B-4: R Q is Ile-AMP) Refer to Chart B. To 52.5 mg of the title product of Preparation 55 is added ca. 0.5 ml of 1:1 trifluoroacetate-dichloromethane. The solution is allowed to stand for 1 hour, and then is added to 15 ml of rapidly stirred 1:1 ether-hexane. The product is filtered off through a fritted disc (fine porosity), washed well with 1:1 ether-hexane, and dried to constant weight under hivac to afford 59 mg of the title product as a white solid. This material is readily soluble in water and pH 7 buffer. Physical characteristics are as follows: FAB HRMS (m+H)-832.5480. Examples 20-37 Following chemical processes and procedures analogous to those described above and using starting materials and reactants which are commercially available or readily prepared by methods known in the art, the following compounds of the present invention, having the indicated physical characteristics, are prepared: (20) 7-Glu-Pro-Phe-N-MeHis-LVA-Ile-NH(CH 2 ) CH(C00H)(NH 2 ) or L-Lysine, N6-[N-(5-[ [N-[N-(l-D-7-glutamyl-L-prolyl)-L-phenylalanyl] - N-methyl-L-histidyl] amino] -4-hydroxy-7-methyl-2-(l-methylethyl)-1- oxooctyl] -L-isoleucyl] - , [2S-(2R*,4R*,5R*) ] - , tris(trifluoroacetate) (salt). IC 50 : 3.9 x 10" 9 M. FAB-HRMS: (m + H) + at 997.6095. (21) 7-Glu-Pro-Phe-N-MeHis -CVA- Ile-NH(CH 2 ) 4 CH(C00H) (NH 2 ) or L-Lysine , N6 - [N- [ 6 -cyclohexyl-5 - [ [N[ (l-L-7-glutamyl-L-prolyl) -L- phenylalanyl ] - N -methyl -L-his tidyl ] amino ] -4 -hydroxy- 2 - ( 1 -me thyl - ethyl) -1-oxohexyl] -L-isoleucyl] , [ 2S- (2R* , 4R* , 5R*) ] - , tris (tri¬ fluoroacetate) (salt) . IC 50 : 2.5 x lO" 9 M. FAB-HRMS : (m + H) + at 1037 . 642. (22) 7-Glu-Pro-Phe-N-MeHis-CVA-NH(CH 2 ) 4 CH(C0OH)(NH 2 ) or L-His¬ tidinamide, L-7-glutamyl-L-prolyl-L-phenylalanyl-N- [4- [ [ (5-amino- 5-carboxypentyl)amino carbonyl] -1- (cyclohexylmethyl) -2-hydroxy- 5 -me thylhexyl] -Nα-methyl-, [IS- [1R*,2R*,4R*(R*) ] ] - , tris(trifluoro- acetate) (salt) . IC 50 : 1.9 x 10 "9 M. FAB-HRMS: (m + H) + at 924.5560. (23) 7-Glu-Pro-Phe-N-MeHis-CVA-MBA or L-Histidinamide, L-7- glut amyl -L-prolyl- L-phenylalanyl-N -cyclohexylmethyl) -2 -hydroxy - 5-methyl-4- [ [ (2-methylbutyl)amino]carbonyl]hexyl] -Nα-methyl- , [1S- [1R*,2R*,4R*(R*)]]-, bis (trifluoroacetate) (salt). IC 50 : 2.8 x 10 *10 M. FAB-HRMS: (m + H) + at 865.5506. (24) 7-Glu-Pro-Phe-N-MeHis-CVA-Ile-AMP or L-Histidinamide, L-7- glutamyl-L-prolyl-L-phenylalanyl-N- [1- (cyclohexylmethyl) -2-hydroxy- 5-methyl-4- [ [ [2-methyl-l- [ [ (2 -pyridinylme thyl) amino] carbonyl] butyl] - amino] carbonyl] hexyl] -Nα-methyl- , [IS- [1R*, ,2R*,4R*(1R*,2R*) ] ] - , tris (trifluoroacetate) (salt). IC 50 : 2.9 x lO "10 M. FAB-HRMS: (m + H) + at 999 (only low resolution mass spectra). (25) 7-Glu-Pro-Phe-N-MeHis-CVA-Ile-AMP-NO or [COUSIN does not list a name for this compound] . IC 50 : 3.2 x 10 "10 M. FAB-HRMS: (m + H) + at 1015 (only low resolution mass spectra). (26) 7-Glu-Pro-Phe-N-MeHis-LVA-MBA or L-Histidinamide, L-7-glut- amyl-L-prolyl-L-phenylalanyl-N- [2-ydroxy-5-methyl-4- [ [2-methylbutyl)- amino]carbonyl] -1-(2-methylpropyl)hexyl-Nα-methyl- , [IS- [1R*,2R*,4R*- (R*)]]-, bis(trifluoroacetate) (salt). IC 50 : 5.5 x lO" 10 M. FAB-HRMS: (m + H) + at 825.5245. (27) 7-Glu-Phe-^-Asp-LVA-MBA or L-Asparagine, N2-(N-L-7-glutam- yl-L-phenylalanyl) -N- [2-hydroxy-5-methyl-4-[ [(2-methylbutyl)amino] - carbonyl]-l-(2-methylpropyl)hexyl] , [IS- [1R*,2R*,4R*(R*)] ] - , mono- (trifluoroacetate) (salt) . IC 50 : 6.0 x 10" 7 M. FAB-HRMS: (m + H) + at 692.4249. (28) 7-Glu-Phe-N-MeHis-LVA-Ile-AMP or L-Histidinamide, L-7-glut- amyl-L-phenylalanyl-N- [2-hydroxy-5-methyl-l-(2-methylpropyl)-4- [ [ [2- methyl-] - [ [2-pyridinylmethyl)amino]carbonyl]butyl]amino]carbonyl]hex- yl] -Nα-methyl-, [IS- [1R*,2R*,4R*(1R*,2R*)] ] - , tris(trifluoroacetate) (salt) . IC 50 : 1.0 x 10 -8 M. FAB-HRMS: (m + H) + at 862.5193. (29) 7-Glu-Phe-N-MeHis-LVA-MBA or L-Histidinamide, L-7-glut- amyl-L-phenylalanyl-N- [2-hydroxy-5-methyl-4- [ [(2-methylbutyl)amino] - carbonyl] -1-(2-me hylpropyl)hexyl] -Nα-methyl- , [IS- [1R*,2R*,4R*(R*) ] , bis(trifluoroacetate) (salt). FAB-HRMS: (m + H) + at 728.4733. (30) 7-Glu-Phe-N-MeHis-CVA-MBA or L-Histidinamide, L-7-glutam- yl-L-phenylalanyl-N- [1-(cyclohexylmethyl)-2-hydroxy-5-methyl-4- [ [(2- methylbutyl)amino]carbonyl]hexyl] -Nα-methyl-, [IS- [1R*,2R*,4R*(R*)] ] , bis(trifluoroacetate) (salt). IC 50 : 2.3 x lO "9 M. FAB-HRMS: (m + H) + at 768.5020. (31) 7-Glu-Phe-N-MeHis-LVA-Ile-AMP-NO or L-Histidinamide, L-7- glutamyl-L-phenylalanyl-N- [2-hydroxy-5-methyl-l-(2-methylpropyl)-4- [ [ [2-methyl-l- [ [2-pyridinylmethyl)amino]carbonyl] -2-methylbutyl] - amino]carbonyl]hexyl]-Nα-methyl- , N-oxide, [IS- [1R*,2R*,4R*(1R*, - 2R*)]]-, tris(trifluoroacetate) (salt). IC 50 : 2.3 x 10" 8 M. FAB-HRMS: (m + H) + at 878 (only low resolution mass spectra). (32) 7-Glu-Phe-N-MeHis-CVA-Ile-AMP-NO or L-Histidinamide, L-7- glutamyl-L-phenylalanyl-N- [1-(cyclohexylmethyl)-2-hydroxy-5-methyl-4- [ [ [2-methyl-l- [ [ (2-pyridinylmethyl)amino]carbonyl]butyl]amino]carb- onyl]hexyl] -Nα-methyl-, N-oxide, [IS- [1R*,2R*,4R*(1R*,2R*)] ] - , tris- (trifluoroacetate) (salt) . IC 50 : 9.1 x lO" 10 M. FAB-HRMS: (m + H) + at 918.5465. (33) -Val-Phe-NC(CH 3 )His-LVA-Ile-NH(CH 2 ) 4 CH(COOH) (NH 2 ) or L-Lysine , N6- [N- [5- [ [N- [N- (3-amino-3-methyl-l-oxobutyl) -L-phenyl¬ alanyl ] -N-methyl -L-histidyl ] amino] -4-hydroxy-7-methyl-2- (l-methyl- ethyl) -1-oxooctyl] -L-isoleucyl] - , [2S- (2R*,4R* , 5R*) ] , tris(tri- fluoroacetate) (salt) . IC 50 : 3.2 x 10" 8 M. FAB-HRMS : (m + H) + at 870.5806. (34) -Val-Phe-NC(CH 3 )His-CVA-Ile-NH(CH 2 ) 4 CH(COOH) (NH 2 ) or L-Lysine , N6- [N- [ 5- [ [N- [N- (3-amino-3-methyl-l-oxobutyl) -L-phenyl¬ alanyl ] -N-methyl -L-histidyl ] amino ] - 6 - cyclohexyl - 4-hydroxy- 2 - (1- methylethyl) -l-oxohexyl ] -L-isoleucyl] - , [2S- (2R* , 4R* , 5R*) j - , tris- (trifluoroacetate) (salt) . IC 50 : 2.5 x 10 *s M. FAB-HRMS: (m + H) + at 910.6108. (35) -Val-Phe-NC(CH 3 )His-CVA-NH(CH 2 ) CH(COOH)(NH 2 ) or L-His¬ tidinamide, N-(3-amino-3-methyl-l-oxobutyl)-L-phenylalanyl-N- [4- [ [ (5- amino-5-carboxypentyl)amino]carbonyl] -1-(cyclohexylmethyl)-2-hydrox- y-5-methylhexyl] -Nα-methyl- , [IS- [1R*,2R*,4R*(R*) ] ] - , tris(trifluoro¬ acetate) (salt) . IC 50 : 2.5 x 10 "8 M. FAB-HRMS: (m + H) + at 797.5260. (36) 0-Val-Phe-NC(CH 3 )His-LVA-Ile-Ampip or L-Histidinamide, N- (3-amino-3-methyl-l-oxobutyl)-L-phenylalanyl-N-[2-hydroxy-5-methyl-1- (2-methylpropyl) -4- [ [ [2-methyl-l- [ [(4-piperidylmethyl)amino]carbon- yl]butyl]amino]carbonyl]hexyl] -Nα-methyl-, [IS-[1R*,2R*,4R*(1R*, - 2R*)]]-, tris(trifluoroacetate) (salt). IC 50 : 3.1 x 10 "8 M. FAB-HRMS: (m + H) + at 838.5900. (37) 5-Val-Phe-NC(CH 3 )His-LVA-NH-CH((CH 2 ) 4 NH 2 )C(0)-Ampip or L- His idinamide, N-(3-amino-3-methyl-1-oxobutyl)-L-phenylalanyl-N- [2- hydroxy-5-methyl-1- (4-aminobutyl) -4- [ [ [2-methyl-l- [ [ (4-piperidyl- methyl)amino]carbonyl]butyl]amino]carbonyl]hexyl] -Nα-methyl- , [1S- [1R*,2R*,4R*(1R*,2R*)]]-, tetrabis(trifluoroacetate) salt). IC 50 : 3.4 x 10 *7 M. FAB-HRMS: ( + H) + at 853.6047. FORMULA CHART A — B 7 D — E ιo — F ιr '13 0 II X 1 -(CH 2 ) n -C- Ll R ι \ ^ CH 0 I II L 3 -0 — CH C R ι H CH 0 I II H — N CH C I Ri CO H 0 I II - Vl — CH — (CH 2 ) m — C L 5 FORMULA CHART (continued) I 3 CH 2 Y R 4 0 •NH-CH — CH-CH 2 -CH-C- I 3 CH? R 4 0 I I II ■ NH-CH— CH 2 -NH-CH-C- L 8 I 3 CH? 0 0 I II II ■ NH-CH C-CF 2 -C- L 9 I 3 CH? OH OH R 4 0 ■ NH-C IH— CIH-C IH-C iH-nC- L 10 I 3 CH OH OH I I I ■ NH-CH — CH— CH-CH 2 -Pχ L n CHART A Pro-Phe-N-MeHis-LVA-Ile-Amp A-l Boc-τGlu(OBn)-Pro-Phe-N-MeHis-LVA-Ile-Amp A-2 Boc-7Glu-Pro-Phe-N-MeHis-LVA-Ile-Amρ A-3 -LVA-Ile-Amp- Glu-Pro-Phe-N-MeH 7Glu-Pro-Phe-N-MeHis-LVA-Ile-Amp— »0 A-6 CHART B Phe-N-MeHis(Ts)-LVA-R 20 B-l BOC-^-Val-Phe-N-MeHis(Ts)-LVA-R 20 B-2 BOC-^-Val-Phe-N-MeHis(Ts) -LVA-Ile-AMP — ►O B-5 -LVA-Ile-AMP- 3TFA-/9-Val-Phe-N-MeHis-LVA-R 20 B-4 2TFA-0-Val-Phe-N-MeHis-LVA-Ile-AMP— *0 B-7 CHART C C-l HO C0 2 Bzl C-2 (Bu t O) 2 P(0)0CH 2 C0 2 Bzl C-3 (Bu t 0) 2 P(0)0CH 2 C0 2 H C-4 CHART D ^^ r ∞ 2 R D-l ,C0 2 Bzl D-2 D-3 (Bu c O) 2 P(0)0(CH 2 ) 3 C0 2 Bzl D-4 (Bu c O) 2 P(0)0(CH 2 )3C0 2 H D-5 CHART E Pro-Phe-N-MeHis-LVA-He-Amp E-l (A-l) (Bu c ) 2 -P(0)0CH 2 C0-Pro-Phe-N-MeHis-LVA-Ile-Amp E-2 -Ile-Amp- 0 HCI- (H0) 2 P(0)0CH 2HC1- (HO) P(0)0CH 2 C0-Pro-Phe-N-MeHis -LVA- He-Amp →O E-5 CHART F C0 2 Et F-l F-2 H F-3 H F-4 CHART G Phe-^-Asp(OBn) -LVA-R 3C G-l BOCN H G-2 G-3 TFA-H 2 N ,> A ' Phe-0-Asp-LVA-R 3O G-4

Claims: CLAIMS 1. A peptide having a non-cleavable transition state insert corresponding to the 10,11-position of a renin substrate (angiotensinogen) and having a moiety of the formula U j _ at the N- terminus 0 x (CH 2 ) n -C- wherein XX is a) H 2 N- , b) H 2 NC(CH 3 ) 2 - , c) H0 2 C- , d) (H 2 N) (H0 2 C) CH or e) (H0) 2 P (0)0- ; wherein n is one to five, inclusive. 2. In a peptide having a non-cleavable transition state insert corresponding to the 10,11-position of a renin substrate (angiotensinogen) , the improvement which comprises inclusion in the peptide of a moiety of the formula L at the N-terminus 0 X 1 -(CH 2 ) n -C- L X wherein X is a) H 2 N- , b) H 2 NC(CH 3 ) 2 -, c) H0 2 C- , d) (H 2 N)(H0 2 C)CH-, or e) (H0) 2 P(0)0-; wherein n is one to five, inclusive. 3. The peptide of claim 1 of the formula I A 6- B 7- C 8- D 9- E 10- F ll- G 12- H 13 τ wherein Ag is a monovalent moiety of the formula L-_ ; X 1 -(CH 2 ) n -C- Ll wherein B7 is absent or a divalent moiety of the formula L 2 ; wherein Cg is a divalent moiety of the formula L3 or L ; L R 2 ^CH^O 1 11 -O-CH—C- L3 R l R 2 CH 0 I II -N-CH—C- L 4 I Rl wherein D9 is a divalent moiety of the formula L 4 or L5; R l R 2 ^CH-^O I II -N-CH—C- L 4 I *1 CO H 0 I Δ II -V 1 -CH-(CH 2 ) m -C- L 5 wherein E o - Fx is a divalent moiety of any of the formula Lg to L ] _ Q , or a monovalent moiety of the formula L^ : T- - Lg ■ NH- - L 7 *3 C CHH 2 ' R 4 0 I -NH-CH-CH -NH-CH-C- H CH 0 0 I II II ■NH-CH C-CF 2 -C- Lg CHo OH OH I I I -NH-CH CH — CH-CH 2 -Pχ l wherein Gχ 2 is absent or a divalent moiety of the formula L 3; wherein H 13 is a) -0-R5 or b) -N(Rχ)(R 5 ); wherein X is a) H 2 N-, b) H 2 NC(CH 3 ) 2 -, c) H0 2 C-, d) (H 2 N)(H0 2 C)CH- or e) 0 (H0) 2 P0-; wherein Ql is a) -CH 2 -, b) -CH(OH)-, c) -0-, or d) -S-; wherein M is a) -C(O)- or b) -CH 2 -; wherein τ is a) -0- or b) -N(Rχ)-; wherein Y is a) -OH or b) -NH 2 ; wherein P is a) -N 3 , b) -CN, c) C ] _-Cg alkyl, d) Cχ-Cg cycloalkyl, e) aryl, or f) Het; wherein m is 1 or 2; wherein n is 1 to 5, inclusive; wherein p is 0 to 5, inclusive; wherein aryl is phenyl or naphthyl, substituted by 0 to 3 of the following a) C ] _-C 5 alkyl, b) hydroxy, c) hydroxy (Cχ-C 5 alkyl), d) C -C5 alkoxy, e) amino, f) amino(Cχ-C5 alkyl), s ) halogen, h) -CHO, i) -C0 2 H, j) -C0 2 -(C -C 5 alkyl), k) -C0NH 2 , 1) -C0NH(C -C 5 alkyl), m) nitro, n) mercapto, o) mercapto (C -C5 alkyl), P) -S0 3 H, q) -S0 2 NH 2 , r) -CN; wherein Het is a 5- or 6-membered saturated or unsaturated ring containing from 1 to 3 heteroatoms (nitrogen, oxygen, sulfur) , and including any bicyclic group in which any of the above heterocyclic rings is fused to a benzene ring or another heterocycle, and if chemically feasible, the nitrogen and sulfur atoms may be in the oxidized forms; and substituted by 0 to 3 of the following: a) C -C5 alkyl, b) hydroxy, c) hydroxy (Cχ-C 5 alkyl), d) Cχ-C 5 alkoxy, e) amino, f) amino(Cχ-C 5 alkyl), g) halogen, h) -CHO, i) -C0 2 H, j) -C0 2 -(Cχ-C 5 alkyl), k) -C0NH 2 , 1) alkyl), m) nitro, n) mercapto, o) mercapto C -C5 alkyl), P) -S0 3 H, q) -S0 2 NH 2 , r) -CN; wherein R is a) hydrogen or b) C -C 5 alkyl; wherein R 2 is a) hydrogen, b) Cχ-Cg alkyl, c) -(CH 2 ) p -aryl, d) -(CH 2 )p-Het, e) -(CH 2 ) p -C0 2 H, f) -(CH 2 ) p -NH 2 , g) -(CH 2 ) p -CH(NH 2 )(C0 2 H), h) C 3"C7 cycloalkyl, or i) 1- or 2-adamantyl; wherein R 3 is a) hydrogen, b) C 1 -C 5 alkyl, c) aryl, d) C 3 -C 7 cycloalkyl, e) Het, f) Cχ-C 3 alkoxy, or g) C ] _-C3 alkylthio; wherein R 4 is a) hydrogen, b) C -C 8 alkyl, c) C 3 -C7 cycloalkyl, or d) -CH(R 1 )(R 6 ); wherein R 5 is a) hydrogen, b) C 1 -C 10 alkyl, c) (CH 2 ) p -alkyl, d) (CH 2 )p-Het, e) -(CH 2 ) p -cycloalkyl, , f) -(CH 2 ) p -CH(NH 2 )(C0 2 H), g) -CR 1 ((CH 2 ) p NH 2 )C(0)-Het; or h) -(CH 2 ) n -R 7 ; wherein R 6 is a) hydrogen, b) hydroxy, c) Cχ-C5 alkyl, d) C -C cycloalkyl, e) aryl, f) Het, g) C ] _-C 3 alkoxy, or h) Cχ-C 3 alkylthio; wherein R 7 is a) hydroxy, b) amino, c) -C0 H, d) -S0 3 H, e) -S0 2 NH 2 , f) guadinyl, or g) polyhydroxy-substituted-alkyl moiety; or a carboxy- , amino-, or other reactive group protected form thereof; or a pharmaceutically acceptable acid or base addition salts thereof; wherein for each occurrence, for all of the defined variables, is independently variable; with the provisos that 1) when Eχg-Fχχ is l , both Gχ 2 and Hχ are absent, and 2) when X j _ is H 2 N- , H 2 NC(CH 3 ) 2 - or H0 2 C-, E 10 -F is not L . 4. A peptide of claim 3 wherein Ag is a monovalent moiety of formula L wherein Xx is (H 2 N)(H0 2 C)CH- and n is 2; wherein B is absent, Pro or a derivative thereof; wherein Cg is Phe, (0CH 3 )Tyr or a derivative thereof; wherein D9 is N-MeHis, His, jS-Asp or a derivative thereof; wherein Eχø-Fχχ is LVA, CVA, CVG or a derivative thereof; wherein Gχ 2 is absent, He or a derivative thereof; wherein H 3 is AMP, AMP-NO, MBA or NH(CH 2 ) 4 CH(NH 2 ) (COOH) . 5. A peptide of claim 4 selected from the group consisting of: 7-Glu-Pro-Phe-N-MeHis-LVA-Ile-AMP or L-Histidinamide, L-7- glutamyl-L-prolyl-L-phenylalanyl-N- [2-hydroxy-5-methyl-1-(2-methyl- propyl) -4- [ [ [2-methyl-l- [ [ (2-pyridinylmethyl)amino]carbonyl]butyl- ]amino]carbonyl]hexyl] -Nα-methyl- , [IS- [1R*,2R*,4R*(1R*,2R*) ] ] - , tris(trifluoroacetate) (salt); 7-Glu-Pro-Phe-N-MeHis-LVA-He-AMP-NO or L-Histidinamide, L-7-glutamyl-L-prolyl-L-phenylalanyl-N- [2-hydroxy-5-methyl-1-(2-meth- ylpropyl) -4- [ [ (2-methyl-l- [ [ (2-pyridinylmethyl)amino]carbonyl]but- yl]amino]carbonyl]hexyl] -Nα-methyl-, N-oxide, [IS[1R*,2R*,4R*(1R*, - 2R*)] ] -, tris(trifluoroacetate) (salt) ; 7-Glu-Pro-Phe-N-MeHis-CVG or L-Histidinamide, L-7-glutamyl-L- prolyl-L- phenylalanyl-N-[1-(cyclohexylmethyl)-2,3-dihydroxy-5-meth- ylhexyl] -Nα-methyl-, [IS-(1R*,2S*,3R*) bis(trifluoroacetate) (salt); 7-Glu-Pro-(0CH 3 )Tyr-His-CVG or L-Histidinamide, L-7-glutamyl-L- prolyl-O-methyl-L-tyrosyl-N- [1-(cyclohexylmethyl)-2,3-dihydroxy- 5-meth lhexyl]-, [1R*,2S*,3R*)] -, bis (trifluoroacetate) (salt); 7-Glu-Pro-Phe-N-MeHis-LVA-He-NH(CH 2 ) 4 CH(C00H)(NH 2 ) or L-Lysine, N6- [N-(5- [ [N- [N- (l-D-7-glutamyl-L-prolyl)-L-phenylalanyl] -N-methyl-L- histidyl]amino] -4-hydroxy-7-methyl-2-(1-methylethyl)-1-oxooctyl] -L- isoleucyl]-, [2S-(2R*,4R*,5R*)] - , tris(trifluoroacetate) (salt); 7-Glu-Pro-Phe-N-MeHis-CVA-Ile-NH(CH 2 ) 4 CH(C00H)(NH 2 ) or L-Lysine, No- [N- [6-cyclohexyl-5- [ [N[(1-L- -glutamyl-L-prolyl) -L-phenylalanyl] - N-methyl-L-histidyl amino]-4-hydroxy-2-(1-methylethyl)-1-oxohexyl] -L- isoleucyl], [2S-(2R*.4R*,5R*)] - , tris(trifluoroacetate) (salt); 7-Glu-Pro-Phe-N-MeHis-CVA-NH(CH 2 ) CH(C00H)(NH 2 ) or L-His¬ tidinamide, L-7-glutamyl-L-prolyl-L-phenylalanyl-N- [4- [ [(5-amino- 5-carboxypentyl)amino]carbonyl] -1- (cyclohexylmethyl) -2-hydroxy- 5-methylhexyl] -Nα-methyl- , [IS- [1R*,2R*,4R*(R*) ] ]-, tris(trifluoro¬ acetate) (salt) ; 7-Glu-Pro-Phe-N-MeHis-CVA-MBA or L-Histidinamide, L-7-glutam- yl-L-prolyl- -phenylalanyl-N-cyclohexylmethyl) -2-hydroxy-5-methyl- - [ [(2-methylbutyl)amino]carbonyl]hexyl] -Nα-methyl- , [IS- [1R*.2R*,4R*- (R*)]]-, bis(trifluoroacetate) (salt); 7-Glu-Pro-Phe-N-MeHis-CVA-Ile-AMP or L-Histidinamide, L-7- glutamyl-L-prolyl-L-phenylalanyl-N- [1-(cyclohexylmethyl)-2-hydroxy- 5-methyl-4- [ [ [2-methyl-l- [ [ (2-pyridinylmethyl)amino]carbonyl]butyl] - amino]carbonyl]hexyl] -Nα-methyl-, [1S-[1R*, ,2R*,4R*(1R*,2R*)] ] - , tris(trifluoroacetate) (salt); 7-Glu-Pro-Phe-N-MeHis-CVA-Ile-AMP-NO or L-Histidinamide, L-7- glutamyl-L-propyl-L-phenylalanyl-N- [1-(cyclohexylmethyl)-2-hydroxy-5- methyl-4- [ [ [2-methyl-l- [ [ (2-pyridinylmethyl)amino]carbonyl]butyl] - amino]carbonyl]hexyl]-Nα-methyl-, N-oxide, [IS-[1R*,2R*,4R*(1R*, - 2R*)] ]- , tris(trifluoroacetate) (salt) ; 7-Glu-Pro-Phe-N-MeHis-LVA-MBA or L-Histidinamide, L-7-glutam- yl-L-prolyl-L-phenylalanyl-N- [2-ydroxy-5-methyl-4- [[2-methylbutyl)- amino]carbonyl]-1-(2-methylpropyl)hexyl-Nα-methyl- , [IS- [1R*,2R*,4R*- (R*)]]-, bis(trifluoroacetate) (salt); 7-Glu-Phe-^-Asp-LVA-MBA or L-Asparagine, N2-(N-L-7-glutamyl-L- phenylalanyl) -N- [2-hydroxy-5-methyl-4- [ [(2-methylbutyl)amino]carb¬ onyl] -l-(2-methylpropyl)hexyl] , [IS- [1R*,2R*,4R*(R*)] ]- , mono( ri¬ fluoroacetate) (salt)]; 7-Glu-Phe-N-MeHis-LVA-He-AMP or L-Histidinamide, L-7-glutam- yl-L-phenylalanyl-N-[2-hydroxy-5-methyl-l-(2-methylproρyl)-4- [[ [2- methyl-] - [ [2-pyridinylmethyl)amino]carbonyl]butyl]amino]carbonyl]hex- yl] -Nα-methyl- , [IS- [1R*,2R*,4R*(1R*,2R*) ] ] - , tris(trifluoroacetate) - - (salt); 7-Glu-Phe-N-MeHis-LVA-MBA or L-Histidinamide, L-7-glutamyl-L- phenylalanyl-N- [ 2-hydroxy-5-methyl-4- [ [ (2 -me thy lbutyl) amino] carbon¬ yl] -1- (2-methylpropyl)hexyl] -Nα-methyl- , [IS- [1R*,2R*,4R*(R*) - . 5 bis (trifluoroacetate) (salt); 7-Glu-Phe-N-MeHis -CVA-MBA or L-Histidinamide, L-7-glutamyI-L- phenylalanyl-N- [1- (cyclohexylmethyl) -2 -hydroxy -5 -methyl -4- [ [ ( 2-meth - y lbutyl) mino] carbonyl] hexyl] -Nα-methyl- , [IS- [1R*,2R*,4R*(R*) ] ] - , bis (trifluoroacetate) (salt); 10 7-Glu-Phe-N-MeHis-LVA-He-AMP-NO or L-Histidinamide, L-7-glut- amyl -L-phenylalanyl-N- [2-hydroxy-5-methyl-l- (2-methylpropyl) -4- [ [ [2- me thyl - 1 - [ [ 2 - py r idiny lme thyl ) amino ] carbonyl ] - 2 -methylbutyl ] amino ] - carbonyl] hexyl] -Nα-methyl- , N-oxide, [IS- [1R*.2R*,4R*(1R*,2R*) ] ] - , tris(trifluoroacetate) (salt); or 15 7-Glu-Phe-N-MeHis-CVA-He-AMP-NO or L-Histidinamide, L-7-glutam- yl -L-phenylalanyl-N- [1- (cyclohexylmethyl) -2 -hydroxy- 5 -methyl -4- [ [ [2- methyl- 1- [ [ ( 2 -pyridinylmethyl) amino ] carbonyl ] butyl ] amino] - carbonyl] hexyl] -Nα-methyl- , N-oxide, [IS- [1R*.2R*,4R*(1R*,2R*) ] ] - , tris (trifluoroacetate) (salt). 20 6. A peptide of claim 3 wherein Ag is a monovalent moiety of formula L wherein Xx is H 2 NC(CH 3 ) 2 - and n is 1; wherein B7 is absent; 25 wherein Cg is Phe or a derivative thereof; wherein D9 is N-MeHis, β-As-p or a derivative thereof; wherein Eχg-Fχχ is LVA, CVA or a derivative thereof; wherein Gχ is absent, He or a derivative thereof; wherein Hχ 3 is AMP, AMP-NO, MBA, NH(CH 2 ) 4 CH(NH 2 ) (COOH) , Ampip or 30 NH-CH((CH 2 ) 4 NH 2 )C(0) -Ampip. 7. A peptide of claim 6 selected from the group consisting of: β -Val -Phe -N-MeHis -LVA- He -AMP -NO or L-Histidinamide, N-(3- amino-3 -methyl- 1 - oxobutyl) -L-phenylalanyl-N- [ 2 -hydroxy- 5-me thyl- 1 - (2 - 35 methylpropyl)-4- [ [ [2-methyl-l- [[ (2 -pyridinylme hyl) amino] carbonyl ] - butyl] amino] carbonyl] hexyl] -Nα-methyl-, N-oxide, [IS- [ 1R* , 2R* , 4R* - (1R*,2R*)] ]-, tris (trifluoroacetate) (salt); / 8-Val-Phe-N-MeHis-CVA-MBA or L-Histidinamide, N-(3-amino-3- methyl-1-oxobutyl) -L-phenylalanyl-N- [1- (cyclohexylmethyl) -2-hydr- oxy-5-methyl-4- [ [ (2 -me thy lbutyl) amino] carbonyl] hexyl] -Nα-methyl- , [lS-[lR*,2R*,4R*(R*)]]- f bis (trifluoroacetate) (salt); /3-Val-Phe-N-MeHis-CVA-Ile-AMP or L-Histidinamide, N- (3-amino-3- methyl -1-oxobutyl) -L-phenylalanyl-N- [1- (cyclohexylmethyl) - 2 -hydroxy - 5 -methyl -4- [ [ [ 2-methyl-l- [ [ (2 - pyridinylmethyl ) amino] carbonyl] but¬ yl] amino ] carbonyl] hexyl] -Nα-methyl- , [1S-[1R*.2R*,4R*(1R*,2R*)]]-, tris (trifluoroacetate) (salt); 0-Val-Phe-N-MeHis-CVA-Ile-AMP-NO or L-Histidinamide, N-(3- amino -3 -me thy 1 - 1 - oxobutyl ) -L-phenylalanyl-N- [1- (cyclohexylmethyl) -2- hydroxy-5-methyl-4- [ [ [2-methyl-l- [ [ (2-pyridinylmethyl)amino]carbon- yl] butyl] amino] carbonyl] hexyl] -Nα-methyl- , N-oxide, [IS- [1R*,2R*, - 4R*(1R*,2R*)]] - , tris (trifluoroacetate) (salt); -Val-Phe-/?-Asp-LVA-MBA or L-asparagine, N 2 - [N- (3-amino-3- methyl-1 -oxobutyl) -L-phenylalanyl] -N- [ 2-hydroxy-5-methyl-4- [ [ (2- methylbutyl) amino] carbonyl] -l-(2-methylpropyl)hexyl] - , [IS- [1R*,2R*, 4R*(R*) ] ] - , mono (trifluoroacetate) (salt) ; -Val-Phe- 3-Asp-LVA-Ile-AMP or L-asparagine, N 2 - [N-(3-amino-3- methyl-1 -oxobutyl) -L-phenylalanyl] -N- [2-hydroxy-5-methyl-l-(2-meth- yipropyl) -4- [ [ [2-methyl-l- [ ( 2 -pyridinylmethyl) amino ] carbonyl ] but¬ yl ]amino]carbonyl] hexyl] - , [1S-[1R*,2R*. 4R*(1R*,2R*)]]-, bis(tri- fluoroacetate) (salt) ; β -Val -Phe -N-MeHis -LVA-MBA or L-histidinamide, N- (3-amino-3- methyl-1-oxobutyl) -L-phenylalanyl-N- [2-hydroxy-5-methyl-4- [ [ (2- methylbutyl) amino] carbonyl] -1- (2-methylpropyl)hexyl] -Nα-methyl- , [1S- [1R*,2R*,4R*(R*)]]-, bis (trifluoroacetate) (salt); S-Val-Phe-N-MeHis-LVA-Ile-AMP or L-histidinamide, N- (3-amino-3- methyl-1-oxobutyl) -L-phenylalanyl-N- [2 -hydroxy- 5 -methyl-1- (2- ethylpropyl) -4- [ [ [2-methyl-l- [ [ (2-pyridinylmethyl)amino]carbonyl]bu- tyl] amino] carbonyl] hexyl] -Nα-methyl- , [IS- [1R*,2R*,4R*(1R*,2R*) ] ] - , tris (trifluoroacetate) (salt); S-Val-Phe-NC(CH 3 )His-LVA-He-NH(CH 2 ) 4 CH(COOH)(NH 2 ) or L-Lysine, N6- [N- [5- [ [N- [N- (3-amino-3-methyl-l-oxobutyl) -L-phenylalanyl] -N- me thyl -L-his tidy 1] amino] -4 -hydroxy -7 -methyl- 2- (1-methylethyl) -1- oxooctyl] -L-isoleucyl]-, [2S-(2R*,4R*,5R*) ] , tris (trifluoroacetate) (salt) ; -Val-Phe-NC(CH 3 )His-CVA-Ile-NH(CH 2 ) 4 CH(COOH)(NH 2 ) or L-Lysine, N6- [N- [5- [ [N- [N- (3-amino-3-methyl-l-oxobutyl) -L-phenylalanyl] -N-meth- yl-L-histidyl]amino] -6-cyclohexyl-4-hydroxy-2-(1-methylethyl)-1-oxo- hexyl]-L-isoleucyl]- , [2S-(2R*,4R*,5R*)]- , tris(trifluoroacetate) (salt) ; -Val-Phe-NC(CH 3 )His-CVA-NH(CH 2 ) 4 CH(COOH)(NH 2 ) or L-Histidin- amide, N- (3-amino-3-methyl-1-oxobutyl) -L-phenylalanyl-N- [4- [ [ (5- amino-5-carboxypentyl)amino carbonyl -1-(cyclohexylmethyl)-2-hydrox- y-5-methylhexyl -Nα-methyl- , [IS-[1R*,2R*,4R*(R*)] ] - , tris(trifluoro¬ acetate) (salt); ^-Val-Phe-NC(CH 3 )His-LVA-He-AMPip or L-Histidinamide, N-(3- amino-3-methyl-1-oxobutyl)-L-phenylalanyl-N- [2-hydroxy-5-methyl-1-(2- m thylpropyl)-4- [ [ [2-methyl-l- [ [(4-piperidylmethyl)amino]carbonyl]bu- tyl]amino]carbonyl]hexyl]-Nα-methyl- , [IS- [1R*,2R*,4R*(1R*,2R*)] ] - , tris(trifluoroacetate) (salt); or -Val-Phe-NC(CH 3 )His-LVA-NH-CH((CH 2 ) NH 2 )C(0)-AMPip or L-His- tidinamide, N-(3-amino-3-methyl-1-oxobutyl)-L-phenylalanyl-N- [2- hydroxy-5-methyl-l-(4-aminobutyl) -4- [ [ [2-methyl-l-[ [(4-piperidyl- methyl)amino]carbonyl]butyl]amino]carbonyl]hexyl]-Nα-methyl- , [1S- [1R*,2R*,4R*(1R*,2R*)]]-, tetrabis( rifluoroacetate) (salt). 8. A peptide of claim 3 wherein Ag is a monovalent moiety of formula L wherein X is (H0) 2 P(0)0- and n is 1 or 3; wherein B is absent, Pro or a derivative thereof; wherein Cg is Phe or a derivative thereof; wherein D9 is yS-Asp, N-MeHis or a derivative thereof; wherein Eχø-Fχ-^ is LVA, CVG or a derivative thereof; wherein Gχ 2 is absent, He or a derivative thereof; wherein Hχ 3 is absent, AMP, AMP-NO or MBA. 9. A peptide of claim 8 selected from the group consisting of: (HO) 2 P(0)OCH 2 C(0)-Phe- J 5-Asp-LVA-He-AMP or L-Asparagine, N-[2- hydroxy-5-methyl-l-(2-methylpropyl)-4-[ [ [2-methyl-l-[ [(2-pyridinyl- methyl)amino]carbonyl]butyl]amino]carbonyl]hexyl] -N2- [N-[(phosphono- oxy)acetyl] -L-phenylalanyl]-, monohydrochloride, [IS-[1R*,2R*,4R*- (1R*,2R*)]]-; (HO) 2 P(0)OCH 2 C(0) -Phe-N-MeHis-LVA-He-AMP or L-Histidinamide , N- [ (phosphonooxy) acetyl] -L-phenylalanyl-N- [2-hydroxy-5-methyl-l- (2- methylpropyl) -4- [ [ [2-methyl-l- [ [ (2-pyridinylmethyl)amino] carbonyl]bu- tyl]amino]carbonyl]hexyl] -Nα-methyl- , dihydrochloride, [IS- [1R*,2R*, - 4R*(1R*,2R*)]] ; (H0) 2 P(0)0CH 2 C(0)-Pro-Phe-N-MeHis-LVA-He-AMP or L-Histidin- amide, N- [N-[1-[(phosphonooxy)acetyl]-L-prolyl] -L-phenylalanyl] -N- [2- hydroxy-5-methyl-1- (2-methylpropyl)-4- [ [ [2-methyl-l-[ [(2-pyridinyl¬ methyl)amino]carbonyl]butyl]amino]carbonyl]hexyl] -Nα-methyl- , di¬ hydrochloride, [IS- [1R*,2R*,4R*(2R*.2R*) ] ] - ; (H0) 2 P(0)0CH 2 C(0)-Pro-Phe-N-MeHis-LVA-He-AMP-N0 or L-His¬ tidinamide, 1- [(phosphonooxy)acetyl] -L-prolyl-L-phenylalanyl-N- [2- hydroxy-5-methyl-1- (2-methylpropyl)-4- [ [ [2-methyl-l- [ [(2-pyridinyl¬ methyl)amino]carbonyl]butyl]amino]carbonyl]hexyl] -Nα-methyl- , N- oxide, dihydrochloride, [IS- [1R*,2R*,4R*(1R*,2R*)] ] - ; (H0) 2 P(0)0(CH 2 ) 3 C(0)-Pro-Phe-N-MeHis-LVA-He-AMP or L-His¬ tidinamide, N- [ [1- [l-oxo-4-(phosphonooxy)butyl] -3-pyrrolidinyl]car- bonyl] -L-phenylalanyl-N- [2-hydroxy-5-methyl-1-(2-methylpropyl)-4- [ [ [2-methyl-1- [ [(2-2-pyridinylmethyl)amino]carbonyl]butyl]amino]car- bonyl]hexyl]-Nα-methyl-, dihydrochloride, [IS- [1R*(S*) ,2R*,4R*- (1R*)]]-; (H0) 2 P(0)0(CH 2 ) 3 C(0)-Pro-Phe-N-MeHis-LVA-He-AMP-N0 or L-Hist- idina ide, N-[ [1-[l-oxo-4-(phosphonooxy)butyl] -3-pyrrolidinyl] - carbonyl] -L-phenylalanyl-N- [2-hydroxy-5-methyl-l-(2-methylpropyl)-4- [ [ [2-methyl-l- [ [ (2-2-pyridinylmethyl)amino]carbonyl]butyl]amino] - carbonyl]hexyl] -Nα-methyl- , N-oxide, monohydrochloride, [1S-[1R*- (S*),2R*,4R*(1R*,2R*)]]-; or (H0) 2 P(0)0CH 2 C(0)-Pro-Phe-N-MeHis-CVG or L-Histidinamide, 1- [ (phosphonooxy)acetyl] -L-prolyl-L-phenylalanyl-N- [1-(cyclohexyl¬ methyl)-2,3-dihydroxy-5-methylhexyl] -Nα-methyl- , monohydrochloride, [1S-(1R*,2S*,3R*)]-.

Inventors: THAISRIVONGS SUVIT, THAISRIVONGS, SUVIT
Applicants: UPJOHN CO, THE UPJOHN COMPANY
Application year: 1990
Main classification: A61K37
IPC codes: A61K38, A61P9, A61P31, C07K5, C07K14