ATRIAL PEPTIDE DERIVATIVES

Abstract: The present invention provides novel peptides which exhibit useful hypotensive, natriuretic, diuretic, renovasodilating, reno-protective, smooth muscle relaxant, and vasorelaxant activities. The novel atrial peptides of the instant invention are encompassed by formula (I) or a pharmaceutically acceptable salt, ester or amide thereof, wherein R<1> is selected from hydrogen, AcetylArg, Aha, Arg, Cit, His, Lys, Orn and Ser-Ser; R<2> is a sulfur-containing group; R<3> is a hydrophobic amino acid or dipeptide; R<4> is a dipeptide spacer or a tripeptide of the formula X-Y, where X is a dipeptide spacer and Y is a basic amino acid; R<5> is a hydrophobic amino acid; R<6> is a peptide of up to three amino acids; R<7> is selected from Cha, Phe, Cha-Arg, Phe-Arg, (D)Phe-Arg, Phe-(D)Arg, Phe< psi >Arg, Leu-Arg, Ala-Arg, Arg and Gly-Ala; and R<8> is a sulfur-containing group.

Description: ATRIAL PEPTIDE DERIVATIVES This application is a continuation-in-part of U.S. Appli¬ cation Serial No. 07/356,980, filed May 24, 1989 and now pending. Technical Field The present invention relates to derivatives of atrial natriuretic polypeptides (ANP) which exhibit useful hypotensive, natriuretic, diuretic, renovasodilating, renoprotective, vasorelaxant and smooth muscle relaxant activity. Background of the Invention Heretofore, hypertension has been classified as either hypertension having clear factor disease or hypertension having obscure factor disease. Hypertension having clear factor disease is also known as secondary hypertension and involves mainly hypertension caused by kidney disease, endocrine disease, toxemia of pregnancy, arterial embolism, atherosclerosis, central nervous system disease and the like. The conditions of secondary hypertension can be improved by treatment of the factor disease. However, eighty to ninety per cent of all hypertensive patients suffer from hypertension having obscure factor disease, commonly known as essential hypertension. The treatment of patients having essential hypertention has been affected by agents such as hypotensive diuretics or vasodilators which provide symptomatic relief. With these antihypertensive agents side effects, including lightheadedness, fatique, nausea, respiratory distress, headache, palpitations, depression and impotence are common. Recently, alpha-human atrial polypeptide (alpha-hANP) has been isolated from human atrium and identified as a polypeptide consisting of twenty eight amino acids having the following formula: Ser-Leu-Arg-Arg-Ser-Ser-Cys-Phe-Gly-Gly-Arg-Met-Asp-Arg- Ile-Gly-Ala-Gln-Ser-Gly-Leu-Gly-Cys-Asn-Ser-Phe-Arg-Tyr Alpha-hANP is a peptide hormone which reacts with specific receptors on the plasma membrane of cells in target tissues and effects a number of hemodynamic and metabolic events in humans. It has been suggested that the above alpha- hANP is one of the substances involved in the control of hypertension, congestive heart failure, cirrhosis, renal failure, cerebral edema and the maintenance of normal extracellular fluid volume. It has also been reported that the diuretic action of alpha-hANP is about 1000 times as strong as that of furosemide which is used as a hypotensive diuretic. Others have found that alpha-hANP increases urinary sodium concentration and urinary output. Known analogs of alpha-hANP have been reported to show biological potency that correlates well with their affinity for the alpha-hANP receptors (Jacobs, J.W. Vlasuk, G.P.; Rosenblatt, M. F.ndnπrinoloσy and Metabolism Clinics of North America. 16, 63-77 (1987) ) . However, alpha-hANP or derivatives thereof which are chemically and enzymatically stable and have therapeutically useful potency and duration of action have not been commercially available. For this reason, the search for alpha-hANP derivatives with these favorable properties has been actively pursued. In addition, it is considered desirable to prepare analogs of ANP in order to isolate the regions of ANP responsible for binding to the cellular plasma membrane receptor and also for eliciting subsequent biological activities mediated via receptor occupation. U.S. Patent No. 4,757,048 discloses alpha-hANP analogs which vary in size from 8 to 25 amino acid residues. The compounds of the present invention are distinctly different from these prior art compounds in several important aspects, specifically in their amino acid sequences and in their ability to elicit receptor-mediated synthesis of cGMP. Additionally, there are no known analogs of ANP which are characterized by incorporation within the disulfide ring of a truncated C-terminal amino acid sequence as described in the present invention. Summary of the Inven ion In accordance with the present invention, novel peptides are provided which exhibit useful hypotensive, natriuretic, diuretic, renovasodilating, reno-protective, smooth muscle relaxant and vasorelaxant activities. The compounds of the invention include biologically active peptides having the following amino acid sequence: (Formula I) or a pharmaceutically acceptable salt, ester or amide thereof, 1 In the above formula, R is selected from hydrogen, AcetylArg, Aha, Arg, Cit, His, Lys, Orn and Ser-Ser; R 2 is a sulfur-contai.ni.ng group; 3 R is a hydrophobic amino acid or dipeptide; 4 R is a dipeptide spacer, or a tripeptide containing a dipeptide spacer plus a basic amino acid residue; R is a hydrophobic amino acid; a R is a peptide of up to three amino acids; 7 R is selected from Cha, Phe, Cha-Arg, Phe-Arg, (D)Phe-Arg, Phe-(D)Arg, Phe-Arg, Leu-Arg, Ala-Arg, Arg and Gly-Ala; and Q R is a sulfur-containing group. The present invention also relates to the use of the atrial peptide derivatives of formula (I) in the treatment of ANP-related diseases. The invention further relates to compositions comprising a therapeutically effective amount of the polypeptide of formula (I) and a pharmaceutically acceptable carrier or diluent. Detailed Description of the Invention The present invention provides novel peptides which exhibit useful hypotensive, natriuretic, diuretic, renovasodilating, reno-protective, smooth muscle relaxant and vasorelaxant activities. The compounds of the invention comprise peptides having the following amino acid sequence: (Formula I) or a pharmaceutically acceptable salt, ester or amide thereof, wherein R is selected from hydrogen, AcetylArg, Aha, Arg, Cit, His, Lys, Orn and Ser-Ser, and is preferably hydrogen (when R 2 is Mpa) or a basic am o acid; 2 R is a sulfur-containing group; 3 R is a hydrophobic amino acid or dipeptide, examples of which include Phe, (D)Phe, Phe-Gly, Phg, (D)Phg, Cha, (D)Cha, Chg, Cha-(D)Ala, (D)Ala-Cha, Arg-Cha, Pic, Tic and 3,5-diiodoTyr (3,5-l 2 T yr), and is preferably a hydrophobic amino acid containing a cycloalkyl group; 4 R is a dipeptide spacer such as Gly-Gly or (D) la-Ala, or a tripeptide of the formula X-Y where X is a dipeptide spacer and Y is a basic amino acid, as for example Gly-Gly-Arg, Gly- Gly-(D)Arg, Gly-Gly-Lys, Gly-Arg-Arg, (D) la-Arg-Arg, (D)Ala- Ala-Arg and (D)Ala-(D)Ala-Arg; R 5 is a hydrophobic ammo acid; - R is a peptide of up to three amino acids, such as Asp-Arg- Ile, (D)Asp-Arg-Ile, Asp-Arg-(D)lie, βAsp-Arg-Ile, Asp-Arg- Ala, Asp-Arg-Nva, Asp-Ala-Ile, Glu-Arg-Ile, His-Arg-Ile or Ala-Arg-Ile; 7 R is selected from Cha, Phe, Cha-Arg, Phe-Arg, (D)Phe-Arg, Phe-(D)Arg, Phe^Arg, Leu-Arg, Ala-Arg, Arg and Gly-Ala; and R 8 is a sulfur-containing group. The methods of the present invention comprise the use of atrial peptide derivatives of formula (I) in the treatment of ANP-related diseases including, for example, congestive heart failure, renal failure and hypertension. The pharmaceutical compositions of the invention include compositions comprising a therapeutically effective amount of a polypeptide of formula (I) and a pharmaceutically acceptable carrier or diluent. Representative of the preferred compounds of this invention include the following polypeptides, as well as their pharmaceutically acceptable salts, esters and amides: Arg-Cys-Cha-(D)Ala-Gly-Gly-Arg-Leu-Asp-Arg-Ile-Phe-Arg-Cys-NH2; Ser-Ser-Cys-Cha-Gly-Gly-Arg-Ile-Asp-Arg-Ile-Phe-Arg-Cys; Ser-Ser-Cys-Cha-Gly-Gly-Arg-Ile-Asp-Arg-Ile-Cha-Arg-Cys; Arg-Cys-Phe-Gly-Gly-Arg-Ile-Asp-Arg-Ile-Phe-Arg-Cys-NH2; Arg-Cys-(D)Ala-Cha-Gly-Gly-Arg-Leu-Asp-Arg-Ile-Phe-Arg-Cys-NH2; Arg-Cys-Cha-Gly-Gly-Arg-Ile-Asp-Arg-Ile-Phe-Arg-Cys; Ser-Ser-Cys-Cha-Gly-Gly-(D)Arg-Ile-Asp-Arg-Ile-Phe-Arg-Cys; Cys-Cha-Gly-Gly-Arg-Ile-Asp-Arg-Ile-Phe-Arg-Cys; Cys-Arg-Cha-Gly-Gly-Arg-Ile-Asp-Arg-Ile-Phe-Arg-Cys; Arg-Cys-Cha-Gly-Gly-Arg-Ile-Asp-Arg-Ile-Phe-Arg-Cys-NH2; Arg-Cys-Cha-(D) la-Ala-Arg-Ile-Asp-Arg-Ile-Phe-Arg-Cys-NH2; Arg-Cys-Tic-Gly-Gly-Arg-Ile-Asp-Arg-Ile-Phe-Arg-Cys-NH2 ; Arg-Cys-Phe-Gly-Gly-Ile-Asp-Arg-Ile-Phe-Arg-Cys-NH2 ; His-Cys-Cha-Gly-Gly-Arg-Ile-Asp-Arg-Ile-Phe-Arg-Cys-NH2 ; Arg-Cys-Cha-Gly-Gly-Arg-Phe-Asp-Arg-Ile-Phe-Arg-Cys-NH2 ; Cys-Cha-Gly-Gly-Arg-Ile-Asp-Arg-Ile-Phe-Arg-Cys-NH2 ; Orn-Cys-Cha-Gly-Gly-Arg-Ile-Asp-Arg-Ile-Phe-Arg-Cys-NH2 ; AcetylArg-Cys-Cha-Gly-Gly-Arg-Ile-Asp-Arg-Ile-Phe-Arg-Cys-NH2 ; Cit-Cys-Cha-Gly-Gly-Arg-Ile-Asp-Arg-Ile-Phe-Arg-Cys-NH2 ; Arg-Cys-Cha-Gly-Gly-Arg-Ile-Asp-Arg-Ile-Phe-Cys-NH2 ; Arg-Cys-3 , 5-l2Tyr-Gly-Gly-Arg-Ile-Asp-Arg-Ile-Phe-Arg-Cys-NH2 ; Arg-Cys-Cha -Gly-Gly-Arg-Ile-Asp-Arg-Ile-Arg-Cys-NH2 ; Arg-Cys-Cha-Gly-Gly-Lys-Ile-Asp-Arg-Ile-Phe-Arg-Cys-NH2 ; Arg-Cys-Cha-Gly-Gly-Arg-Ile-Asp-Arg-Ile-Gly-Ala-Cys-NH2 ; Arg-Cys-Cha-Gly-Gly-Arg-Ile- (D) Asp-Arg-Ile-Phe-Arg-Cys-NH2 ; (D) Arg-Cys-Cha-Gly-Gly-Arg-Ile-Asp-Arg-Ile-Phe-Arg-Cys-NH2 ; Arg-Cys-Chg-Gly-Gly-Arg-Ile-Asp-Arg-Ile-Phe-Arg-Cys-NH2 ; Arg-Cys-Cha-Gly-Gly-Arg-Ile-Asp-Arg-Ala-Phe-Arg-Cys-NH2; Arg-Cys- (D) Cha-Gly-Gly-Arg-Ile-Asp-Arg-Ile-Phe-Arg-Cys-NH2; Arg-Cys-Cha-Gly-Gly-Arg-Ile-Ala-Arg-Ile-Ala-Arg-Cys; Mpa-Cha-Gly-Gly-Arg-Ile-Asp-Arg-Ile-Phe-Arg-Cys-NH2 ; Arg-Cys-Cha-Gly-Gly- (D) Arg-Ile-Asp-Arg-Ile-Phe-Arg-Cys; Arg-Cys-P ic-Gly-Gly-Arg-I le-Asp-Arg-I le-Phe-Ar g-Cys ; Ser-Ser-Cys-Phe-Gly-Gly-Arg-Ile-Asp-Arg-Ile-Phe-Arg-Cys; Cys-Cha-Gly-Gly-Arg-Ile- (D) Asp-Arg-Ile-Phe-Arg-Cys-NH2; Cys-Cha-Gly-Gly-Arg-Ile-Asp-Arg-Ala-Phe-Arg-Cys-NH2 ; Cys-Cha-Gly-Gly-Arg-Ile-Asp-Ala-Ile-Phe-Arg-Cys-NH2 ; Mpa-Cha-Gly-Gly-Arg-Ile-beta-Asp-Arg-Ile-Phe-Arg-Cys-NH2 ; Cys-Cha-Gly-Gly-Arg-Ile-Asp-Arg- (D) Ile-Phe-Arg-Cys-NH2 ; Cys-Cha-Gly-Gly-Arg-Nva-Asp-Arg-Nva-Phe-Arg-Cys-NH2 ; Cys- (D) Phe-Gly-Gly-Arg-Ile-Asp-Arg-Ile-Phe-Arg-Cys-NH2; Mpa-Cha-Gly-Gly-Arg-Ile-Asp-Arg-Ile-Phe- (D) Arg-Cys -NH2 ; Mpa-Cha-Gly-Gly-Arg-Ile-Asp-Arg-Ile-Phe-Arg- (D) Cys-NH2; Mpa-Cha- (D) Ala-Arg-Arg-Ile-Asp-Arg-Ile-Phe-Arg-Cys-NH2 ; Cys-Phe-Gly-Gly-Arg-Leu-Asp-Arg-Ile-Leu-Arg-Cys-NH2 ; Mpa-Cha-Gly-Gly-Arg-Ile-Glu-Arg-Ile-Phe-Arg-Cys-NH2 ; Mpa-Cha-Gly-Gly- (D) Arg-Ile-Asp-Arg-Ile-Phe-Arg-Cys-NH2 ; Mpa-Cha-Gly-Gly-Arg-Ile-Asp-Arg-Ile- (D) Phe-Arg-Cys-NH2 ; Aha-Cys-Cha- (D) Ala- (D) Ala-Arg-Ile-Asp-Arg-Ile-Phe-Arg-Cys-NH2 ; Mpa-Cha-Gly-Gly-Arg-Ile-His-Arg-Ile-Phe-Arg-Cys-NH2 ; Mpa-Phe-Gly-Gly-Arg-Ile-Asp-Arg-Ile-Phe-Arg-Cys-NH2 ; Mpa-Cha- (D) Ala-Ala-Arg-Ile-Asp-Arg-Ile-Phe-Arg- (D) Cys-NH2 ; and Mpa-Cha-(D)Ala-Ala-Arg-Ile-Asp-Arg-Ile- [PheSlArg]- (D)Cys-NH2. Preferred compounds of this invention include the following polypeptides, as well as their pharmaceutically acceptable salts, esters and amides: Ser-Ser-Cys-Cha-Gly-Gly-Arg-Ile-Asp-Arg-Ile-Phe-Arg-Cys; Ser-Ser-Cys-Cha-Gly-Gly-Arg-Ile-Asp-Arg-Ile-Cha-Arg-Cys; Cys-Cha-Gly-Gly-Arg-Ile-Asp-Arg-Ile-Phe-Arg-Cys; Cys-Arg-Cha-Gly-Gly-Arg-Ile-Asp-Arg-Ile-Phe-Arg-Cys; Arg-Cys-Cha-Gly-Gly-Arg-Ile-Asp-Arg-Ile-Phe-Arg-Cys-NH2; Arg-Cys-Cha- (D) Ala-Ala-Arg-Ile-Asp-Arg-Ile-Phe-Arg-Cys-NH2 ; His-Cys-Cha-Gly-Gly-Arg-Ile-Asp-Arg-Ile-Phe-Arg-Cys-NH2 ; Cys-Cha-Gly-Gly-Arg-Ile-Asp-Arg-Ile-Phe-Arg-Cys-NH2 ; Arg-Cys-Cha-Gly-Gly-Arg-Ile-Asp-Arg-Ile-Phe-Cys-NH2 ; Arg-Cys-Cha-Gly-Gly-Arg-Ile-Asp-Arg-Ile-Arg-Cys-NH2 r Arg-Cys-Cha-Gly-Gly-Lys-Ile-Asp-Arg-Ile-Phe-Arg-Cys-NH2 ; (D) Arg-Cys-Cha-Gly-Gly-Arg-Ile-Asp-Arg-Ile-Phe-Arg-Cys-NH2 ; Arg-Cys-Cha-Gly-Gly-Arg-Ile-Asp-Arg-Ala-Phe-Arg-Cys-NH2 ; Arg-Cys-Cha-Gly-Gly-Arg-Ile-Ala-Arg-Ile-Ala-Arg-Cys ; Mpa-Cha-Gly-Gly-Arg-Ile-Asp-Arg-Ile-Phe-Arg-Cys-NH2 ; Cys-Cha-Gly-Gly-Arg-Ile-Asp-Arg-Ala-Phe-Arg-Cys-NH2 ; Cys-Cha-Gly-Gly-Arg-Ile-Asp-Arg- (D) Ile-Phe-Arg-Cys-NH2; Cys- (D) Phe-Gly-Gly-Arg-Ile-Asp-Arg-Ile-Phe-Arg-Cys-NH2 ; Mpa-Cha-Gly-Gly-Arg-Ile-Asp-Arg-Ile-Phe-Arg- (D ) Cys-NH2 ; Mpa-Cha- (D) Ala-Arg-Arg-Ile-Asp-Arg-Ile-Phe-Arg-Cys-NH2 ; Aha-Cys-Cha- (D) la- (D) Ala-Arg-Ile-Asp-Arg-Ile-Phe-Arg-Cys-NH2 ; Mpa-Cha-Gly-Gly-Arg-Ile-Glu-Arg-Ile-Phe-Arg-Cys-NH2; and Mpa-Cha-(D)Ala-Ala-Arg-Ile-Asp-Arg-Ile-[Phe^Arg]- (D) Cys-NH2. The amino acid components of the above compounds are designated by conventional abbreviations as follows : mino Αcϊ Abbreviated Designation one e er c.ad- Alanine Ala A 6-Aminohexanoic acid Aha Aminoisobutyric acid Aib Arginine Arg R Aspartic acid Asp D Citrulline Cit Cyclohexylalanine Cha Cyclohexylglycine Chg Cysteine Cys C Glutamic acid Glu E Glycine Gly G Histidine His H α-Homocysteine hCys Isoleucine lie I Leucine Leu L Lysine Lys K Mercaptopropionic acid Mpa Methionine Met M Norvaline Nva Ornithine Orn Penicillamine Pen Phenylalanine Phe F Am no Acid Abbreviated Designation One T.e er C.nή~ Phenylalanyl-Arginine reduced amide (Na[1-(2-amino-3-phenyl- propyl) ]arginine) [Phe-±-Arg] Phenylglycine Phg Per-Hydroindane carboxylic acid Pic Serine Ser S Tetrahydroisoquinoline- 3-carboxylic acid Tic Tryptophan Trp W Tyrosine Tyr Y Valine Val V All of the above amino acids can be either in the l or 11 configuration as well as mixtures thereof including a racemic mixture of the two isomers. Unless expressly stated otherwise, all of the amino acids are optically active and have the It- configuration. The term "AcetylArg" as used herein refers to a group wherein an acetyl group is attached through the carbonyl carbon of the acetyl group to the alpha amino group of the amino acid arginine. The term "acidic amino acid" as used herein refers to amino acids which have a group, in addition to the alpha- carboxylic acid group, which exists in ionized form in neutral aqueous solution, as for example Asp, Glu and the like. The term "basic amino acid" as used herein refers to amino acids which have a group, in addition to the alpha-amino group, which exists in protonated form in neutral aqueous solution, as for example Lys, Orn, Arg and the like. The term "cycloalkyl" as used herein refers to a three to seven carbon cyclic radical. These radicals can be unsubstituted, or they can be substituted provided that any such substituents not interfere with the affinity of the peptide for atrial natriuretic polypeptide receptors. The term "hydrophobic amino acid" as used herein refers to amino acids which lack an affinity for water, such as Ala, lie, Leu, Val, Met, Nva, Phe, Phg, Cha, Chg, Tic, and the like. The term "sulfur-containing group" as used herein refers to a group having a sulfur substituent which is available to participate in bonding to form a disulfide bridge, as for example Cys, Mpa, Pen and hCys. By "pharmaceutically acceptable salts, esters, or amides" it is meant those salts, esters and amides which are, within the scope of sound medical judgment, suitable for use in contact with the tissues of humans and lower animals without undue toxicity, irritation, allergic response, and the like, commensurate with a reasonable benefit/risk ratio, and effective for their intended use. Examples of pharmaceutically acceptable, nontoxic addition salts are salts formed with inorganic acids such as hydrochloric acid, hydrobromic acid, phosphoric acid, sulfuric acid and perchloric acid or with organic acids such as acetic acid, oxalic acid, maleic acid, tartaric acid, citric acid, succinic acid or malonic acid. Other pharmaceutically acceptable salts include nitrate, bisulfate, formate, valerate, lactate, fumarate, oleate, palmitate, stearate, laurate, borate, benzoate, mesylate, ascorbate, p-toluene-sulfonate, glucoheptonate, lactobioate, lauryl sulfate and the like or metal salts such as sodium, potassium, calcium or magnesium salts or amino salts such as ammonium, triethylamine salts, and the like and they may be prepared according to conventional methods. Examples of pharmaceutically acceptable, non-toxic esters of the compounds of Formula (I) include Cl to C6 alkyl esters wherein the alkyl group is straight or branched chain. Acceptable esters also include C5 to C7 cycloalkyl esters. Cl to C4 alkyl esters are preferred. Esters of the compounds of Formula (I) may be prepared according to conventional methods. Examples of pharmaceutically acceptable, nontoxic amides of the compounds of Formula (I) include amides derived from ammonia, primary Cl to C6 alkyl amines and secondary Cl to C6 dialkyl amines wherein the alkyl groups are straight or branched chain. In the case of secondary, amines the amine may also be in the form of a five or six membered heterocycle containing one nitrogen atom. Amides derived from ammonia, Cl to C3 alkyl primary amines and Cl to C2 dialkyl secondary amines are preferred. Amides of the compounds of Formula (I) are prepared according to the conventional methods. The daily dose of the compounds of the present invention may be suitably defined, according to the condition of the patient, by those skilled in the art, but generally may be administered in an amount of 0.2 - 250 mg/kg body weight. Unit dosage compositions may contain such amounts of submultiples thereof to make up the daily dose. The amount of active ingredient that may may be combined with carrier material to produce a single dosage form will vary depending upon the host treated and the particular mode of administration. It will be understood, however, that the specific dose level for any particular patient will depend upon a variety of factors including the activity of the specific compound employed; the age, body weight, general health, sex and diet of the patient; the route of administration and the rate of excretion of the specific compound; drug combination used and the severity of the particular disease being treated. The compounds of the present invention may be administered orally, parenterally, by inhalation spray, rectally or topically in unit dosage formulations containing conventional nontoxic pharmaceutically acceptable carriers, adjuvants and vehicles as desired. The term parenteral as used herein includes subcutaneous injections, intravenous, intramuscular, intrasternal injection or infusion techniques. Injectable preparations, as for example sterile injectable aqueous or oleaginous suspensions, may be formulated according 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 nontoxic parenterally acceptable diluent or solvent, as for example 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 including synthetic mono- or diglycerides . In addition, fatty acids such as oleic acid find use in the preparation of injectables. Suppositories for rectal administration of the drug can be prepared by mixing the drug with a suitable nonirritating excipient such as cocoa butter and polyethylene glycol which are solid at ordinary temperature but liquid at the rectal temperature and will therefore melt in the rectum and release the drug. Solid dosage forms for oral administration may include capsules, tablets, pills, powders and granules. In such solid dosage forms the active compound may be admixed with at least one inert diluent such as sucrose, lactose or starch. Such dosage forms may also comprise, as is normal practice, additional substances other than inert diluents, as for example lubricating agents such as magnesium stearate. In the case of capsules, tablets and pills, the dosage forms may also comprise buf ering agents. Tablets and pills can additionally be prepared with enteric coatings. Liquid dosage forms for oral administration may include pharmaceutically acceptable emulsions, solutions, suspensions, syrups and elixirs containing inert diluents commonly used in the art such as water. Such compositions may also comprise adjuvants, such as wetting agents; emulsifying and suspending agents; and sweetening, flavoring and perfuming agents. The novel polypeptides and salts thereof of the invention can be utilized effectively as vasorelaxant agents, diuretics, natriuretic agents, renovasodilators or renoprotective agents. Accordingly the present invention further relates to vasorelaxant, diuretic, natriuretic, renovasodilating or renoprotective compositions comprising a novel polypeptide having the general formula (I) or salts thereof as an active component. The polypeptides of the invention may be prepared by the synthetic method of elongation of a peptide chain through condensation of one amino acid by one, or several amino acids, or by a combination of these methods in accordance with conventional peptide synthesis methods. The condensation of two amino acids, the condensation of an amino acid with a peptide or the condensation of one peptide with another peptide may be effected in accordance with conventional condensation methods such as the azide method, the mixed acid anhydride method, the DCC (dicyclohexylcarbodiimide) method, the active ester method (p- nitrophenyl ester method, N-hydroxysuccinic acid imide ester method, cyanomethyl ester method and the like) , the Woodward reagent K method, the DCC-HOBT (1-hydroxy-benzotriazole) method and the like. These condensation reactions may be done by either solution methods or solid phase synthetic methods. When the peptide chain is elongated by solid phase methods, the C-terminal amino acid is linked to an insoluble carrier. Any insoluble carrier may be used which can produce a detachable bond by reacting with a carboxyl group in a C- terminal amino acid, as for example halomethyl resins such as chloromethyl or bromomethyl resins; hydroxymethyl resin; aminomethyl resin; benzhydrylamine resin and t- alkyloxycarbonyl hydrazide resin. As in conventional polypeptide synthesis, branched chain amino and carboxyl groups at alpha and omega positions in amino acids may be protected and deprotected if necessary. The protecting groups for amino groups which can be used involve, for example, benzyloxycarbonyl (Z) , o-chloro- benzyloxycarbonyl ( (2-C1)Z) , p-nitrobenzyloxycarbonyl (Z(NO2) ) , p-methoxybenzyloxycarbonyl (Z(OMe)), t-butoxycarbonyl (Boc) , t-amyloxycarbonyl (Aoc) , isobornealoxycarbonyl, adamantyloxycarbonyl (Adoc) , 2- (4-biphenyl) -2-propyloxy carbonyl (Bpoc) , 9-fluorenyl-methoxycarbonyl (Fmoc) , methylsulfonylethoxy carbonyl (Msc) , trifluoroacetyl, phthalyl, formyl, 2-nitrophenylsulfenyl (Nps) , diphenylphosphinothioyl (Ppt) and dimethylphosphino-thioyl (Mpt) . The examples of protecting groups for carboxyl groups involve, for example, benzyl ester (OBzl) , cyclohexyl ester, 4-nitrobenzyl ester (OBZINO 2 ) / t-butyl ester (OtBu) , 4- pyridylmethyl ester (OPic) and the like. In the course of the synthesis of the following peptides, specific amino acids having functional groups other than amino and carboxyl groups in the branched chain such as arginine, cysteine, serine and the like may be protected, if necessary, with suitable protecting groups. It is preferable that, for — example, the guanidino group (N ) in arginine may be protect with nitro, p-toluenesulfonyl (Tos) , benzyloxycarbonyl (Z) , adamantyloxycarbonyl (Adoc) , p-methoxybenzenesulfonyl, 4- methoxy-2, 6-dimethyl-benzenesulfonyl (Mts) and the like, and the thiol group in cysteine may be protected with benzyl, p- methoxybenzyl, triphenylmethyl, acetamidomethyl, ethylcarbamyl, 4-methylbenzyl (4-MeBzl) , 2,4,6,- trimethylbenzyl (Tmb) and the like, and the hydroxy group in serine may be protected with benzyl (Bzl) , t-butyl, acetyl, tetrahydropyranyl (THP) and the like. The compounds of the invention are prepared by standard solid phase peptide synthesis conditions as described in "Solid Phase Peptide Synthesis" by John M Stewart and Janis D. Young, Second Edition (1984) and illustrated in Examples 1 and 2 in the experimental section. The compounds of the invention may also be prepared by partial solid phase synthesis, fragment condensation methods and classical solution methods as exemplified by the methods described in "Peptide Synthesis", Second Edition, M. Bodansky, Y.S. Klausner and M.A. Ondetti (1976) . The foregoing may be better understood by reference to the following examples which are provided for illustration and not limitation of the practice of the invention. Example ,1 Arσinyl (W^-Tos) -Cysteinvl (4-MeBzl) -Cyπlohexylalanyl - (O) - ~ Alanyl-Glycyl-Glvcyl-Arσinvl (N^-Tos ) -Leucyl-Aspartyl (beta- cyclohexylϊ -Αi-σi nγ] (N^- os ) -Isoleucyl-Phenylalanyl -Argi nyl ( -Tos . -Cysteinyl-p-Methylbenzhydrylamine Protected Peptide Resin. Resin (p-methylbenzhydrylamine functionalized styrene- divinylbenzene copolymer, 0.5 g, commercially available from Bachem, Inc.) was placed in a solid phase peptide synthesis vessel and amino acids were attached to the peptide resin sequentially in the following order: Boc-Cys (4-MeBzl) , Boc- Arg(N -Tos) , Boc-Phe, Boc-Ile, Boc-Arg(N -Tos) , Boc-Asp(beta- Q cyclohexyl) , Boc-Leu, Boc-Arg(N -Tos), Boc-Gly, Boc-Gly, Boc- ~ (D)Ala, Boc-Cha, Boc-Cys (4-MeBzl) , Boc-Arg(N -Tos), according to the protocol outlined in Agenda A to yield the protected peptide resin: Arginyl-Cysteinyl (4-MeBzl) -Cyclohexylalanyl- (D)Alanyl-Glycyl-Glycyl-Arginyl (N -Tos) -Leucyl-Aspartyl (beta- cyclohexyl) -Arginyl (N G-Tos) -Isoleucyl-Phenylalanyl-Arginyl (NG- Tos) -Cysteinyl (4-MeBzl) -p-Methylbenzhydrylamine resin. Following the synthesis, the protected peptide was removed from the reaction vessel by washing the resin three times with 20 mL N,N-dimethyl formamide (DMF) into a 60 mL sintered glass funnel, followed by washing the resin three times with 30 mL methylene chloride (CH 2 CI 2 ) • The resin was dried JLD. vacuo for three hours, then weighed. Agenda A 1. Deblock: 50% Trifluoroacetic acid (TFA) in CH„C1 ? containing 2% Anisole, 0.5% Ethanedithiol (v/v/v) . 2. Neutralization: 10% Diisopropylethylamine: (DIEA) in CH 2 C1 2 (v/v) . 3. Single Coupling: 0.2 M Boc-amino acid derivative in DMF, 0.2 M diisopropylcarbodiimide in CH2CI2, reaction time 60 minutes. 4. Resin Clean Up: 10% DIEA in CH 2 CI2. 5. Single Coupling: 0.2 M Boc-amino acid derivative (same as Step 3) in DMF; 0.2 M diisopropylcarbodiimide in CH 2 CI 2 , reaction time 60 min. 6. Cap: 0.3 M Acetylimidazole in DMF. 7. Go to next amino acid residue. 8. Upon attachment of the final amino acid to the growing peptide chain, the protecting group (t-Boc) is removed as in Step 1. Example 2 Arginyl-Cys einyl-Cvclohexvlalanvl-(D)Alanvl-GIvcvl -G1yr-.yl- Arginyl-Lencyl-Aspartyl-Arginvl-Isoleucvl-Phenyla1πnyl- Arginyl-Cysteinyl Carboxamide Cyclic Disulfide. Protected resin (0.50 g) of Example 1 was treated with 1.3 mL anisole and 13 mL liquid hydrogen fluoride (HF) for 60 o minutes at 0 C. The HF and anisole were removed from the resin in vacuo and the resin was washed, under a nitrogen atmosphere, with 2 X 25 mL portions of diethyl ether or ethyl acetate. The crude peptide was extracted from the resin by treatment with 6 X 50 mL portions of deoxygenated 20% aqueous acetic acid. The acetic acid solution was diluted to 1.5 L with distilled water and the pH of the solution was adjusted to about 7.2 using concentrated ammonium hydroxide. The solution was oxidized with 17 L of 0.01N iodine solution (in ethanol) . The resultant yellow solution was stirred for 60 minutes at room temperature while the pH was maintained at about 7.2. The excess iodine was removed from the solution by first adjusting the pH to about 5.5 with 50 mL glacial acetic acid and then adding 3-6 mL of 0.01N sodium thiosulfate solution. The combined aqueous solution was applied to a column containing 300 g XAD-16 molecular adsorbent resin (commercially available from Rohm and Haas Company) . The sample was desalted by first washing the column with 3 L distilled water. The sample was eluted from the column with 1.5 L 50% aqueous ethanol. The combined ethanol fractions were concentrated to approximately 100 mL in vacuo, taken up in an additional 100 mL distilled water and lyophilized to a dry amorphous powder. The dry powder was purified by High Performance Liquid Chromatography (HPLC) using 0.1% aqueous trifluoroacetic acid (TFA) and acetonitrile as organic modifiers. The preparative HPLC was performed using a Dynamax (RAININ) Ciβ reverse-phase column (2.1 cm i.d. X 25 cm) at a flow rate of 12-15 mL/mi . The sample was purified by linear solvent-gradient elution from 10% acetonitrile/90% aq. solvent (0.1% TFA in H 2 O) to 35% acetonitrile/65% aqueous solvent. Analytical HPLC was performed using a VYDAC 218 TP 10 micron C 1 8 reverse-phase column (0.46 cm i.d. X 20 cm) . There was obtained 2.5 mg of the title compound as a white powder. Amino acid Analysis: Ala (1.1), Arg (4.0), Asp (1.1), Cha (0.9), Cys (1.4), Gly (2.2), lie (1.2) Leu (1.2), Phe (1.2) . FAB (M+H) + at M/Z: 1672. The 300 MHz H NMR spectrum was found to be consistent with the proposed structure. Example 3 Seryl-Seryl-πys einyl-Cyclohexvlalanvl-Glγπvl-Glγcyl-Arginyl- Isoleucyl-Aspartyl-Arg nvl-Isoleucyl-Phenylalanyl-Arσinyl- Oys einvl Cyclic Disnl ide Protected peptide resin (0.50 g) , prepared (as described in Example 1) from Boc-Cys (4-MeBzl)-0- Merrifield resin (commercially available from Bachem, Inc.) and the amino acids ζ~ added sequentially in the following order: Boc-Arg(N -Tos), — Boc-Phe, Boc-Ile, Boc-Arg(N -Tos), Boc-Asp(beta-cyclohexyl) , Boc-Ile, Boc-Arg(N -Tos), Boc-Gly, Boc-Gly, Boc-Cha, Boc- Cys (4-MeBzl) , Boc-Ser(Bzl) , Boc-Ser(Bzl) , was treated with HF (liquid) and purified as described in Example 2. The title compound was obtained as a white powder, 17 mg. Amino Acid Analysis: Arg (3.0), Asp (1.0), Cys (0.8), Gly (2.1), He (2.0), Phe (1.0), Ser (2.0) . FAB (M+H) + at M/Z: 1621. The 300 MHz H NMR spectrum was found to be consistent with the proposed structure. Example 4 Serγl-Sery1-r:y.q e πyl-Cγr,1nh xylalanvl-Glvcvl-Glycvl-Arginyl- Isoleucyl-Aspartyl-Aroinyl-Isoleucyl-Cyclohexylalanyl-Arginyl- r.y~t ~i -y- Cyclic Dia.ilfide Protected peptide resin (0.50 g) , prepared (as described in Example 1) from Boc-Cys (4-MeBzl) -O-Merrifield resin and the amino acids added sequentially in the following order: Boc- Arg(N -Tos), Boc-Cha, Boc-Ile, Boc-Arg(N -Tos), Boc-Asp(beta- cyclohexyl), Boc-Ile, Boc-Arg(N -Tos), Boc-Gly, Boc-Gly, Boc- Cha, Boc-Cys (4-MeBzl) , Boc-Ser(Bzl) , Boc-Ser(Bzl) , was treated with HF (liquid) and purified as described in Example 2. The title compound was obtained as a white powder, 18.1 mg. Amino Acid Analysis: Arg (3.0), Asp (1.0), Cha (2.0), Cys (1.5), Gly (2.0), He (2.0), Ser (1.5) . FAB (M+H) + at M/Z: 1628. The 300 MHz H spectrum was found to be consistent with the proposed structure. Exa ple 5 Arσinyl-Cyfiteiny -Phenylalanvl-Glvcvl-Glyryl-Arσinyl- Tsole-1-ιcyl-AHpartyl-Arσinyl-Isoleucvl-Phenγ alanyl-Αrσ nyl- Cysteinyl Carboxamide Cyclic Disnlfide Protected peptide resin (0.50 g) , prepared (as described in Example 1) from p-methylbenzhydrylamine resin and the amino acids added sequentially in the following order: Boc-Cys (4- c c MeBzl), Boc-Arg(N -Tos), Boc-Phe, Boc-Ile, Boc-Arg(N -Tos), — Boc-Asp(beta-cyclohexyl) , Boc-Ile, Boc-Arg(N -Tos), Boc-Gly, ~ Boc-Gly, Boc-Phe, Boc-Cys (4-MeBzl) , Boc-Arg(N -Tos), was treated with HF (liquid) and purified as described in Example 2. The title compound was obtained as a white powder, 15 mg. Amino Acid Analysis: Arg (3.9), Asp (0.9), Cys (1.8), He (2.1), Gly (1.9), Phe (2.0) . FAB (M+H) + at M/Z: 1597. The 300 MHz 1H NMR spectrum was found to be consistent with the proposed structure. Example 6 Arginyl-Cysteinyl-(D)Alanγl-Cvclohexvlalanvl-Glvcvl-Glvcyl- Arσinγl-Leucγl-Aspartγl-Arginvl-Isoleucvl-Phenvlalanvl- Arginyl-Cysteinyl Carboxamide Cyclic Disulfide Protected peptide resin (0.50 g) , prepared (as described in Example 1) from p-methylbenzhydrylamine resin and the amino acids added sequentially in the following order: Boc-Cys (4- C G MeBzl), Boc-Arg(N -Tos) , Boc-Phe, Boc-Ile, Boc-Arg(N -Tos), Boc-Asp(beta-cyclohexyl) , Boc-Leu, Boc-Arg(N -Tos), Boc-Gly, Boc-Gly, Boc-Cha, Boc-(D)Ala, Boc-Cys (4-MeBzl) , Boc-Arg(N G - Tos), was treated with HF (liquid) and purified as described in Example 2. The title compound was obtained as a white powder, 15 mg. Amino Acid Analysis: Ala (0.9), Arg (4.1), Asp (0.9), Cha (1.0), Cys (1.7), Gly (2.0), He (1.1), Leu (1.1), Phe (1.0) . FAB (M+H) + at M/Z: 1672. The 300 MHz H NMR spectrum was found to be consistent with the proposed structure. Example 7 Arginγl-Cysteinyl-Cyclohexylalanγl-Glycyl-Glycyl-Arginyl- Isoleucyl-Λspartyl-Arginyl-Isoleucyl-Phenylalanyl-Λrginyl- Cysteinyl Cyclic isulfide Protected peptide resin (0.50 g) , prepared (as described in Example 1) from Boc-Cys (4-MeBzl)-O-Merrifield resin and the amino acids added sequentially in the following order: Boc- G G Arg(N -Tos), Boc-Phe, Boc-Ile, Boc-Arg(N -Tos), Boc-Asp(beta- — cyclohexyl), Boc-Ile, Boc-Arg(N -Tos), Boc-Gly, Boc-Gly, Boc- Cha, Boc-Cys (4-MeBzl) , Boc-Arg(N -Tos), was treated with HF (liquid) and purified as described in Example 2. The title compound was obtained as a white powder, 13 mg. Amino Acid Analysis: Arg (4.1), Asp (1.0), Cha (1.0), Cys (1.9), Gly (1.9), He (2.0), Phe (1.0) . FAB (M+H) + at M/Z: 1604. 1 The 300 MHz H NMR spectrum was found to be consistent with the proposed structure. Sery1-Serγl-Cγsteinγl-Cvclohexvlalanvl-Glvcvl-G]vcyl- . - Arginyl-Tsoleucyl-Aspartyl-Arginvl-Iso.leπcvl-Phenyl ~1anyl- Arginyl-Cyst. inyl Cyclic Pisulfide Protected peptide resin (0.50 g) , prepared (as described in Example 1) from Boc-Cys (4-MeBzl)-O-Merrifield resin and the amino acids added sequentially in the following order: Boc- c~ c Arg(N -Tos), Boc-Phe, Boc-Ile, Boc-Arg(N -Tos), Boc-Asp(beta- Q cyclohexyl), Boc-Ile, Boc-(D)Arg(N -Tos), Boc-Gly, Boc-Gly, Boc-Cha, Boc-Cys (4-MeBzl) , Boc-Ser (Bzl) , Boc-Ser(Bzl) , was treated with HF (liquid) and purified as described in Example 2. The title compound was obtained as a white powder, 17.5 mg. Amino Acid Analysis: Arg (3.2), Asp (1.0), Cha (0.9), Cys (1.8), Gly (1.9), He (2.0), Phe (0.9), Ser (1.4) . FAB (M+H) + at M/Z: 1620. The 300 MHz H NMR spectrum was found to be consistent with the proposed structure. Example 9 Cysteinγl-Cyclohexylalanγl-Glvcvl-Glvcvl-Arginvl-Isoleτ3cγl- Aspartyl-Arginyl-Iso_lencyl-Phenylalanyl-Arginyl-Cysteinyl Cyclic Disul ide Protected peptide resin (0.50 g) , prepared (as described in Example 1) from Boc-Cys (4-MeBzl)-O-Merrifield resin and the amino acids added sequentially in the following order: Boc- C C Arg(N -Tos), Boc-Phe, Boc-Ile, Boc-Arg(N -Tos), Boc-Asp(beta- cyclohexyl), Boc-Ile, Boc-Arg(N -Tos), Boc-Gly, Boc-Gly, Boc- Cha, Boc-Cys (4-MeBzl) , was treated with HF (liquid) and purified as described in Example 2. The title compound was obtained as a white powder, 25.1 mg. Amino Acid Analysis: Arg (3.0), Asp (1.0), Cha (1.0), Cys (1.7), Gly (2.1), He (2.0), Phe (1.0) . FAB (M+H) + at M/Z: 1446. 1 The 300 MHz H NMR spectrum was found to be consistent with the proposed structure. Example 10. Cystβ_nyl-Arginyl-Cyclohexvlalanvl-G1ycy1-G]ycyl-Arginyl- Isoleucyl-Aspartyl-Arginyl-Isoleucyl-Phenylalanyl-Λrginyl- Cysteinyl Cyclic Disulfide Protected peptide resin (0.50 g) , prepared (as described in Example 1) from Boc-Cys(4-MeBzl)-O-Merrifield resin and the amino acids added sequentially in the following order: Boc- G G Arg(N -Tos), Boc-Phe, Boc-Ile, Boc-Arg(N -Tos), Boc-As (beta- — cyclohexyl), Boc-Ile, Boc-Arg(N -Tos), Boc-Gly, Boc-Gly, Boc- Cha, Boc-Arg(N -Tos), Boc-Cys (4-MeBzl) , was treated with HF (liquid) and purified as described in Example 2. The title compound was obtained as a white powder, 18 mg. Amino Acid Analysis: Arg (3.9), Asp (0.9), Cha (1.0), Cys (0.6), Gly (2.1), He (2.0), Phe (1.0) . FAB (M+H) + at M/Z: 1602. The 300 MHz H NMR spectrum was found to be consistent with the proposed structure. Example 11 Arαinyl-Cysteinyl-Cvclohexvlalanvl-Glvcvl-Glvcvl-Αrσinyl- Isoleucyl-Aspartyl-Arginyl-Isoleucyl-Phenylalanyl-Arginyl- Cys e nyl Carboxamide Cyclic Dis.ilfide Protected peptide resin (0.50 g) , prepared (as described in Example 1) from p-methylbenzhydrylamine resin and the amino acids added sequentially in the following order: Boc-Cys (4- c c MeBzl), Boc-Arg(N -Tos) , Boc-Phe, Boc-Ile, Boc-Arg(N -Tos), Q Boc-Asp(beta-cyclohexyl) , Boc-Ile, Boc-Arg(N -Tos), Boc-Gly, — Boc-Gly, Boc-Cha, Boc-Cys (4-MeBzl) , Boc-Arg(N -Tos), was treated with HF (liquid) and purified as described in Example 2. The title compound was obtained as a white powder, 12.4 mg. Amino Acid Analysis: Arg (3.9), Asp (1.0), Cha (1.0), Cys (1.2), Gly (2.1), He (2.0), Phe (1.0) . FAB (M+H) + at M/Z: 1602. The 300 MHz H NMR spectrum was found to be consistent with the proposed structure. Example 12 Arginy.1-Cysteinyl-Cyclohexylalanvl- (D)Alanvl-Alanvl-Arginyl- Tsolency]-Αsparty1-Arginvl-Isoleucvl-Phenγlalanvl-Arσ ny_l- Cysteinyl Carboxamide Cyclic Disnlfide Protected peptide resin (0.50 g) , prepared (as described in Example 1) from p-methylbenzhydrylamine resin and the amino acids added sequentially in the following order: Boc-Cys (4- c c MeBzl), Boc-Arg(N -Tos) , Boc-Phe, Boc-Ile, Boc-Arg(N -Tos), ~ Boc-Asp(beta-cyclohexyl) , Boc-Ile, Boc-Arg(N -Tos), Boc-Ala, — Boc-,(D)Ala, Boc-Cha, Boc-Cys (4-MeBzl) , Boc-Arg(N -Tos), was treated with HF (liquid) and purified as described in Example 2. The title compound was obtained as a white powder, 40 mg. Amino Acid Analysis: Ala (1.9), Arg (4.0), Asp (0.9), Cha (1.0), Cys (1.7), He (2.0), Phe (1.0). FAB (M+H) + at M/Z: 1629. 1 The 300 MHz H NMR spectrum was found to be consistent with the proposed structure. Example 13 Arginyl-Cysteinyl-Tetrahydroisoquinolin-3-oyl-Glycyl-Glycyl- Arginvl-If * ;oleι-ιcγl -Απpπrtyl-Arginvl-Isoleucγl-Phe-nv1 a lany1 - Arσinyl-Cystei nyl Carboxamide Cyclic Disulfide Protected peptide resin (0 . 50 g) , prepared (as described in Example 1) from p-methylbenzhydrylamine resin and the amino acids added sequentially in the following order : Boc-Cys (4- G C MeBzl) , Boc-Arg (N -Tos) , Boc-Phe, Boc-Ile, Boc-Arg (N -Tos) , — Boc-Asp(beta-cyclohexyl) , Boc-Ile, Boc-Arg(N -Tos), Boc-Gly, Boc-Gly, Boc-Tic, Boc-Cys (4-MeBzl) , Boc-Arg(N -Tos), was treated with HF (liquid) and purified as described in Example 2. The title compound was obtained as a white powder, 14.6 mg. Amino Acid Analysis: Arg (4.0), Asp (1.1), Cys (1.7), Gly (1.9), He (2.1), Phe (1.0) . FAB (M+H) + at M/Z: 1607. The 300 MHz H NMR spectrum was found to be consistent with the proposed structure. Exam le 14 Arginy -CystP.inyl-Phenvlalanvl-Glvcvl-Glvcvl-Tsolwiπyl- Α.qpar-t-y1-Αrσiny1-Tsoleucvl-Phenvlalanvl-Arginv1-Cy.qt.«qiny1 Carboxamide Cyclic Disulfide Protected peptide resin (0.50 g) , prepared (as described in Example 1) from p-methylbenzhydrylamine resin and the amino acids added sequentially in the following order: Boc-Cys (4- C G MeBzl), Boc-Arg(N -Tos) , Boc-Phe, Boc-Ile, Boc-Arg(N -Tos), Boc-Asp(beta-cyclohexyl) , Boc-Ile, Boc-Gly, Boc-Gly, Boc-Phe, Q Boc-Cys (4-MeBzl) , Boc-Arg(N -Tos), was treated with HF (liquid) and purified as described in Example 2. The title compound was obtained as a white powder, 31 mg. Amino Acid Analysis: Arg (3.0), Asp (1.0), Cys (1.8), Gly (1.9), He (2.1), Phe (2.0) . FAB (M+H) + at M/Z: 1439. 1 The 300 MHz H NMR spectrum was found to be consistent with the proposed structure. Example 15 His idyl-Cys einyl-Cyclohexvlalanvl-Glγcyl-Glvcγl-Arginyl- Isole.icy1-Asparty1-Arginyl-Isoleucyl-Phenylalanyl-Arginy1- Cysteiny.1 Carboxam de Cyclic Disulfide Protected peptide resin (0.50 g) , prepared (as described in Example 1) from p-methylbenzhydryamine resin and the amino acids added sequentially in the following order: Boc-Cys(4- G G MeBzl), Boc-Arg(N -Tos) , Boc-Phe, Boc-Ile, Boc-Arg(N -Tos), Boc-Asp(beta-cyclohexyl) , Boc-Ile, Boc-Arg(N -Tos), Boc-Gly, Boc-Gly, Boc-Cha, Boc-Cys (4-MeBzl) , Boc-His (N-Im-Tos) , was treated with HF (liquid) and purified as described in Example 2. The title compound was obtained as a white powder, 13 mg. Amino Acid Analysis: Arg (2.9), Asp (0.9), Cha (1.0), dys (1.5), Gly (1.9), His (0.8), He (2.0), Phe (1.0) . FAB (M+H) + at M/Z: 1583. The 300 MHz H NMR was found to be consistent with the proposed structure. Example 16 Arginyl-Cysteinyl-Cyclohexylalanyl-Glycyl-Glycyl-Arginyl- Phenylalanyl -Α. pa rtyl-ΑrCTinvl-lRoleucvl-Phenvla lanvl-Arσinyl - Cysteinyl Carboxamide Cyclic Disulfide Protected peptide resin (0 .50 g) , prepared (as described in Example 1) from p-methylbenzhydrylamine resin and the amino acids added sequentially in the following order : Boc-Cys (4- — — MeBzl) , Boc-Arg (N -Tos) , Boc-Phe, Boc-Ile, Boc-Arg (N -Tos) , Boc-Asp(beta-cyclohexyl) , Boc-Phe, Boc-Arg(N -Tos), Boc-Gly, Boc-Gly, Boc-Cha, Boc-Cys (4-MeBzl) , Boc-Arg(N -Tos), was treated with HF (liquid) and purified as described in Example 2. The title compound was obtained as a white powder, 25.1 mg. Amino Acid Analysis: Arg (4.0), Asp (0.9), Cha (1.0), Cys (1.8), Gly (1.9), He (1.1), Phe (2.1) . FAB (M+H) + at M/Z: 1635. The 300 MHz H NMR spectrum was found to be consistent with the proposed structure. F.xample 17 Cysteinyl-Cyclohexylalanγl-Glvcvl-Glycvl-Arginγ1-Tsnlβιιcyl- Aspartyl-Arginyl-T.soleucvl-Phenvlalanvl-Arginyl-Cy.gte nyl Carboxamide Cyclic Disulfide Protected peptide resin (0.31 g) , prepared (as described in Example 1) from p-methylbenzhydrylamine resin and the amino acids added sequentially in the following order: Boc-Cys(4- MeBzl), Boc-Arg(N -Tos) , Boc-Phe, Boc-Ile, Boc-Arg(N -Tos), ~ Boc-Asp(beta-cyclohexyl) , Boc-Ile, Boc-Arg(N -Tos), Boc-Gly, Boc-Gly, Boc-Cha, Boc-Cys (4-MeBzl) , was treated with HF (liquid) and purified as described in Example 2. The title compound was obtained as a white powder, 2.3 mg. Amino Acid Analysis: Arg (2.7), Asp (0.8), Cha (0.9), Cys (1.6), Gly (1.8), He (1.9), Phe (1.1). FAB (M+H) + at M/Z: 1445. 1 The 300 MHz H NMR spectrum was consistent with the proposed structure. Example 18 Ornithinyl-Cysteinyl-Cyclohexylalanyl-Glycyl-Glycyl-Arσinyl- Tsoleucyl-As-Dartyl-Arginyl-Isole-ucyl-PhenvlalanyT-Arginyl- Cys einyl Carboxami e Cyclic Disnlfide Protected peptide resin (0.37 g) , prepared (as described in Example 1) from p-methylbenzhydrylamine resin and the amino acids added sequentially in the following order: Boc-Cys(4- MeBzl), Boc-Arg(N -Tos), Boc-Phe, Boc-Ile, Boc-Arg(N -Tos), Boc-Asp(beta-cyclohexyl) , Boc-Ile, Boc-Arg(N -Tos), Boc-Gly, Boc-Gly, Boc-Cha, Boc-Cys, Boc-Orn(Cbz) , was treated with HF (liquid) and purified as described in Example 2. The title compound was obtained as a white powder, 20.0 mg. Amino Acid Analysis: Arg (3.0), Asp (0.9), Cha (1.0), Cys (1.7), Gly (2.0), He (2.1), Orn (1.0), Phe (1.0) . FAB (M+H) + at M/Z: 1559. The 300 MHz H NMR spectrum was found to be consistent with the proposed structure. Example 19 AcetylArginy1-Cyπteinyl-Cyclohexvlalanyl-Glyc.γl-G1γcyl- Arginyl-Isoleucyl-Aspartyl-Arginyl-Isoleucyl-Phenylalanyl- Arginyl-Cysteinyl Carboxamide Cyclic Disulfide Protected peptide resin (0.30 g) , prepared (as described in Example 1) from p-methylbenzhydrylamine resin and the amino acids added sequentially in the following order: Boc-Cys (4- G G MeBzl), Boc-Arg(N -Tos), Boc-Phe, Boc-Ile, Boc-Arg(N -Tos), — Boc-Asp(beta-cyclohexyl) , Boc-Ile, Boc-Arg(N -Tos), Boc-Gly, Boc-Gly, Boc-Cha, Boc-Cys, Boc-Arg(N -Tos), was treated with HF and purified as described in Example 2. The N-terminal Arginyl residue was acetylated prior to purification with 0.3 M acetylimidazble in DMF (according to Step 6, Agenda A of Example 1) . The title compound was obtained as a white powder, 2.3 mg. Amino Acid Analysis: Arg (4.1), Asp (1.0), Cha (1.0), Cys (1.6), Gly (1.9), He (2.0), Phe (1.1). FAB (M+H) + at M/Z: 1645. 1 The 300 MHz H NMR spectrum was found to be consistent with the proposed structure. Example 20 Ci .rπl 1 inyl -Cys ei nyl-Cyclohexvlalanvl-Glycvl-Glyπyl -Arσinyl- Tsolencyl-ABpartyl-Arginvl-Isoleucvl-Phenvlalanvl-ArCT nyl- Cys einyl Carboxamide Cyclic Disulfide Protected peptide resin (0.42 g) , prepared (as described in Example 1) from p-methylbenzhydrylamine resin and the amino acids added sequentially in the following order: Boc-Cys(4- MeBzl), Boc-Arg(N -Tos), Boc-Phe, Boc-Ile, Boc-Arg(N -Tos), Boc-Asp(beta-cyclohexyl) , Boc-Ile, Boc-Arg(N -Tos), Boc-Gly, Boc-Gly, Boc-Cha, Boc-Cys (4-MeBzl) , Boc-Cit, was treated with HF (liquid) and purified as described in Example 2. The title compound was obtained as a white powder, 24.9 mg. Amino Acid Analysis: Arg (3.0), Asp (1.0), Cys (1.2), Gly (1.6), He (1.6), Phe (1.2). FAB (M+H) + at M/Z: 1602. The 300 MHz H NMR spectrum was found to be consistent with the proposed structure. Example 21 Arginyl-Cy.qf.P. nγ1-Cyclohexγlalanvl-Glvcγl-Glycγl-Arginγl- Isoleucyl-Aspar yl-Arginyl-Isoleucyl-Phenylalanyl-Cvsteinyl Carboxamide Cyclic isulfide Protected peptide resin (0.50 g) , prepared (as described in Example 1) from p-methylbenzhydrylamine resin and the amino acids added sequentially in the following order: Boc-Cys(4- — MeBzl), Boc-Phe, Boc-Ile, Boc-Arg(N -Tos), Boc-Asp (beta- Q cyclohexyl), Boc-Ile, Boc-Arg(N -Tos), Boc-Gly, Boc-Gly, Boc- Q Cha, Boc-Cys(4-MeBzl) , Boc-Arg(N -Tos), was treated with HF (liquid) and purified as described in Example 2. The title compound was obtained as a white powder, 20.6 mg. Amino Acid Analysis: Arg (3.0), Asp (1.0), Cha (1.0), Cys (1.7), Gly (1.9), He (2.0), Phe (1.1) . FAB (M+H) + at M/Z: 1447. The 300 MH H NMR spectrum was found to be consistent with the proposed structure. Example 22 Arσinγ.1-Cys einyl-3.5-Diiodotvrosinvl-Glycvl-Glycyl-Arginyl- Isoleucyl-Aspartyl-Arginyl-Isoleucyl-Phenylalanyl-Arginyl- Cysteinyl Carboxamide Cyclic Disulfide Protected peptide (0.50 g) , prepared (as described in Example 1) from p-methylbenzhydrylamine resin and the amino acids added sequentially in the following order: Boc-Cys (4- G C MeBzl), Boc-Arg(N -Tos), Boc-Phe, Boc-Ile, Boc-Arg(N -Tos) , — Boc-Asp(beta-cyclohexyl) , Boc-Ile, Boc-Arg(N -Tos), Boc-Gly, Boc-Gly, Boc-Tyr(2-BrCbz) , Boc-Cys (4-MeBl) , Boc-Arg(N -Tos), was treated with HF (liquid) and purified as described in Example 2. Iodination of the tyrosine occurred during the oxidation (i.e. cyclization) of the peptide with 0.01 N iodine solution as described in Example 2. The title compound was obtained as a white powder, 25 mg. Amino Acid Analysis: Arg (4.0), Asp (1.1), Cys (1.4), Gly (1.9), He (2.0), Phe (1.0), Tyr (1.0) . FAB (M+H) + at M/Z: 1865. The 300 MHz H NMR spectrum was found to be consistent with the proposed structure. Example 23 Arσinyl-Cys e nyl-Cyclohexvlalanvl-Glvcyl-Glyπyl-Arg nyl- Isolencvl-AsOartvl-Arginvl-Isoleucvl-Arginvl-Cvste nyl Carboxamide Cyclic Disulfide Protected peptide resin (0.50 g) , prepared (as described in Example 1) from p-methylbenzhydrylamine resin and the amino acids added sequentially in the following order: Boc-Cys (4- C G MeBzl), Boc-Arg(N -Tos) , Boc-Ile, Boc-Arg(N -Tos), Boc- — Asp(beta-cyclohexyl) , Boc-Ile, Boc-Arg(N -Tos), Boc-Gly, Boc- Gly, Boc-Cha, Boc-Cys (4-MeBzl) , Boc-Arg(N -Tos), was treated with HF (liquid) as described in Example 2. The title compound was obtained as a white powder, 28 mg. Amino Acid Analysis: Arg (4.2), Asp (1.1), Cha (1.0), Cys (1.6), Gly (2.0), He (1.8) . FAB (M+H) + at M/Z: 1455. 1 The 300 MHz H NMR spectrum was found to be consistent with the proposed structure. Example 24 Arginyl-Cysteinyl-Cyclohexylalanyl-Glycyl-Glycyl- rcyc.lo(Lysinyl-Isoleucvl-Asr.artyl) 1-Arginy.1-Tsolencyl- Phenylalanyl-ftrginyl- Cys inyl Carboxamide Cyclic Disulfide Protected peptide resin (0.43 g) , prepared (as described in Example 1) from p-methylbenzhydrylamine resin and the amino acids added sequentially in the following order: Boc-Cys (4- c c MeBzl), Boc-Arg(N -Tos) , Boc-Phe, Boc-Ile, Boc-Arg(N -Tos), Boc-Lys-He-Asp, Boc-Gly, Boc-Gly, Boc-Cha, Boc-Cys (4-MeBzl) , Boc-Arg(N -Tos), was treated with HF (liquid) and purified as described in Example 2. The side chain amino group of lysine in the tripeptide Lys-Ile-Asp was cyclized with the side chain carboxylic acid group of aspartic acid by standard DPPA coupling techniques. The tripeptide was incorporated during the solid phase synthesis as the Boc-protected cyclized tripeptide acid dissolved in N-methyl pyrrolidone. The title compound was obtained as a white powder, 2.8 mg. Amino Acid Analysis: Arg (3.2), Asp (0.8), Cha (1.0), Cys (0.9), Gly (2.0), He (2.0), Lys (0.9), Phe (1.1) . FAB (M+H) + at M/Z: 1556. ι The 300 MHz H NMR spectrum was found to be consistent with the proposed structure. Example 25 Arginvl-Cysteinyl-Cyclohexylalanyl-Glycyl-Glycyl-Arginyl- Isoleucyl-Aspartyl-Arginyl-Isoleucyl-Glycyl-Alanyl-Cysteinyl Carboxamide Cyclic Pisulfide Protected peptide resin (0.50 g) , prepared (as described in Example 1) from p-methylbenzhydrylamine resin and the amino acids added sequentially in the following order: Boc-Cys (4- — MeBzl), Boc-Ala, Boc-Gly, Boc-Ile, Boc-Arg(N -Tos), Boc- — Asp(beta-cyclohexyl) , Boc-Ile, Boc-Arg(N -Tos), Boc-Gly, Boc- Gly, Boc-Cha, Boc-Cys (4-MeBzl) , Boc-Arg(N -Tos), was treated with HF (liquid) and purified as described in Example 2. The title compound was obtained as a white powder, 15 mg. Amino Acid Analysis: Ala (1.0), Arg (3.0), Asp (1.0), Cha (1.0), Cys (1.8), Gly (3.0), He (2.2) . FAB (M+H) + at M/Z: 1426. 1 The 300 MHz H NMR spectrum was found to be consistent with the proposed structure. Example 26 Arginγl-Cysteinyl-Cvclohexvlalanv3-Glycvl-G3ycy1-Arginyl- Isoleucyl-(D)Aspartyl-Arginyl-Iso.leucyl-Phenylalanyl-Arginyl- Cysteinyl Carboxamide Cyclic Distilf de Protected peptide resin (0.50 g) , prepared (as described in Example 1) from p-methylbenzhydrylamine resin and the amino acids added in the following order: Boc-Cys (4-MeBzl) , Boc- Arg(N -Tos), Boc-Phe, Boc-He> Boc-Arg(N -Tos), Boc-(D)- ~ Asp (beta-Bzl) , Boc-Ile, Boc-Arg(N -Tos), Boc-Gly, Boc-Gly, Boc-Cha, Boc-Cys (4-MeBzl) , Boc-Arg(N -Tos), was treated with HF (liquid) and purified as described in Example 2. The title compound was obtained as a white powder, 15.3 mg. Amino Acid Analysis: Arg (3.7), Asp (1.1), Cha (0.9), Cys (1.4), Gly (2.2), He (2.2), Phe (0.9) . FAB (M+H) + at M/Z: 1602. 1 The 300 MHz H NMR spectrum was found to be consistent with the proposed .structure. Example 27 (P)Arginyl-Cysteinyl-Cyclohexylalanyl-Glycyl-Glycyl-Arginyl- Isole cyl-Aspar yl-Arσinvl-Isoleucvl-PhenvlalanyJ-Arginyl- Cyste nyl Carboxamide Cyclic Disulfide Protected peptide resin (0.50 g) , prepared (as described in Example 1) from p-methylbenzhydrylamine resin and the amino acids added sequentially in the following order: Boc-Cys (4- G C MeBzl), Boc-Arg(N -Tos), Boc-Phe, Boc-Ile, Boc-Arg(N -Tos) , Boc-Asp(beta-cyclohexyl) , Boc-Ile, Boc-Arg(N -Tos), Boc-Gly, — Boc-Gly, Boc-Cha, Boc-Cys (4-MeBzl) , Boc-(D)Arg(N -Tos), was treated with HF (liquid) and purified as described in Example 2. The title compound was obtained as a white powder, 18.7 mg. Amino Acid Analysis: Arg (4.0), Asp (0.9), Cha (1.0), Cys (1.3), Gly (2.1), He (2.2), Phe (0.9) FAB (M+H) + at M/Z: 1601. The 300 MHz H NMR spectrum was found to be consistent with the proposed structure. Example 28 Arσinyl-Cys einyl -Cyclohexvlσlvcine-Glycvl-GIvcvl-Arginyl- Isoleucyl-Aspartyl-Arginyl-Isoleucyl-Phenylalanyl-Arginyl- Cysteinyl Carboxamide Cyclic Disulfide Protected peptide resin (0.50 g) , prepared (as described in Example 1) from p-methylbenzhydrylamine resin and the amino acids added sequentially in the following order: Boc-Cys (4- c c MeBzl), Boc-Arg(N -Tos) , Boc-Phe, Boc-Ile, Boc-Arg(N -Tos), Boc-Asp(beta-cyclohexyl) , Boc-Ile, Boc-Arg(N -Tos), Boc-Gly, Boc-Gly, Boc-Chg, Boc-Cys (4-MeBzl) , Boc-Arg(N -Tos), was treated with HF (liquid) and purified as described in Example 2. The title compound was obtained as a white powder, 30 mg. Amino Acid Analysis: Arg (4.2), Asp (0.8), Cys (1.9), Gly (1.8), He (2.1), Phe (1.0) . FAB (M+H) + at M/z: 1588. ι The 300 MHz H NMR spectrum was found to be consistent with the proposed structure. Example 29 Arσinyl -Cys einyl-Cyclohexγlalanvl-Glvcyl-Glγcγ3-Arσinyl - Iso1.snnyl-asparf.v1-Arσinvl-Alanvl-Phenvlalanvl-Arginyl- Cysteinyl Carboxamide Cyclic Disnlfi P Protected peptide resin (0.50 g) , prepared from p- methylbenzhydrylamine resin and the amino acids added sequentially in the following order: Boc-Cys (4-MeBzl) , Boc- C G Arg(N -Tos), Boc-Phe, Boc-Ala, Boc-Arg(N -Tos), Boc-Asp (beta- — cyclohexyl), Boc-Ile, Boc-Arg(N -Tos), Boc-Gly, Boc-Gly, Boc- Cha, Boc-Cys (4-MeBzl) , Boc-Arg(N -Tos), was treated with HF (liquid) and purified as described in Example 2. The title compound was obtained as a white powder, 30 mg. Amino Acid Analysis: Ala (1.0), Arg (4.2), Asp (0.9), Cha (1.0), Cys (1.3), Gly (1.8), He (1.2), Phe (1.0) . FAB (M+H) + at M/Z: 1560. The 300 MHz H NMR spectrum was found to be consistent with the proposed structure. Example 3Q Arginyl-Cysteinyl- (D. Cyclohexylalanyl-Glycy -Glycyl-Arginyl- Isoleucyl-Aspartyl-Arginyl-Isoleucyl-Phenylalanyl-Arginyl- Cysteinyl Carboxamide Cyclic Disulfide Protected peptide resin (0.50 g) , prepared (as described in Example 1) from p-methylbenzhydrylamine resin and the amino acids added sequentially in the following order: Boc-Cys (4- — ~ MeBzl), Boc-Arg(N -Tos), Boc-Phe, Boc-Ile, Boc-Arg(N -Tos), — Boc-Asp(beta-cyclohexyl) , Boc-Ile, Boc-Arg(N -Tos), Boc-Gly, Q Boc-Gly, Boc-(D) Cha, Boc-Cys (4-MeBzl) , Boc-Arg(N -Tos), was treated with HF (liquid) and purified as described in Example 2. The title compound was obtained as a white powder, 8 mg. Amino Acid Analysis: Arg (3.7), Asp (1.1), Cha (1.1), Cys (0.7), Gly (2.1), He (2.0), Phe (1.0) FAB (M+H) + at M/Z: 1602. 1 The 300 H NMR spectrum was found to be consistent with the proposed structure. Example 31 Argjnvl-Cvs einvl-Cvclohexvlalanvl-Glvcvl-Glvr.vl-ArCTinyl- Iπoleucyl-Alanyl-Arginvl-Isoleucvl-Alanvl-Arginyl-Cysteinyl Cyclic Disulfide Protected peptide resin (0.50 g) , prepared (as described in Example 1) from Boc-Cys (4-MeBzl)-O-Merrifield resin and the amino acids added sequentially in the following order: Boc- — ~ Arg(N -Tos), Boc-Ala, Boc-Ile, Boc-Arg(N -Tos), Boc-Ala, Boc- — He, Boc-Arg(N -Tos), Boc-Gly, Boc-Gly, Boc-Cha, Boc-Cys (4- Q MeBzl), Boc-Arg(N -Tos), was treated with HF (liquid) and purified as described in Example 2. The title compound was obtained as a white powder, 22.4 mg. Amino Acid Analysis: Ala (1.7), Arg (4.3), Cha (1.0), Cys (1.7), Gly (1.9), He (2.0) . FAB (M+H) + at M/Z: 1482. 1 The 300 MHz H NMR was found to be consistent with the proposed structure. Example 32 Me cap oprornnnv1-Cvclohexvl lanvl-G vcvJ-Glvcvl-Arc,inyl- Isoleucvl-Aspartyl-Arσinvl-Isoleucvl-Phenvlalanyl-Arginyl- Cysteinyl Carboxamide Cyclic Disul i e Protected peptide resin (0.30 g) , prepared (as described in Example 1) from p-methylbenzhydrylamine resin and the amino acids added sequentially in the following order: Boc-Cys (4- c c MeBzl), Boc-Arg(N -Tos) , Boc-Phe, Boc-Ile, Boc-Arg(N -Tos), Q Boc-Asp(beta-cyclohexyl) , Boc-Ile, Boc-Arg(N -Tos), Boc-Gly, Boc-Gly, Boc-Cha, Mpa (4-MeBzl) , was treated with HF (liquid) and purified as described in Example 2. The title compound was obtained as a white powder, 27.0 mg. Amino Acid Analysis: Arg (2.9), Asp (1.0), Cha (1.0), Cys (1.2), Gly (2.1), He (2.0), Phe (1.0) . FAB (M+H) + at M/Z: 1430. The 300 MHz H NMR spectrum was found to be consistent with the proposed structure. Example 33 rginyl-Cysteinyl-Cyclohexylalanyl-Glycyl-Glycyl-(P) rginyl- Isoleucyl-Aspartyl-Arginyl-Isoleucyl-Phenylalanyl-Argjnyl- Cysteinyl Cyclic Disulfide Protected peptide resin (0.50 g) , prepared (as described in Example 1) from Boc-Cys (4-MeBzl) -O-Merrifield resin and the amino acids added sequentially in the following order: Boc- c ~ Arg(N -Tos), Boc-Phe, Boc-Ile, Boc-Arg(N -Tos), Boc-Asp(beta- — cyclohexyl), Boc-Ile, Boc-(D)Arg(N -Tos), Boc-Gly, Boc-Gly, ~ Boc-Cha, Boc-Cys (4-MeBzl) , Boc-Arg(N -Tos), was treated with HF (liquid) and purified as described in Example 2. The title compound was obtained as a white powder, 40 mg. Amino Acid Analysis: Arg (4.0), Asp (1.0), Cys (1.8), Gly (2.0), He (2.1), Phe (1.0) . FAB (M+H) + at M/Z: 1602. The 300 MHz H NMR spectrum was found to be consistent with the proposed structure. Example 34 Arginyl-Cys inyl-Per-Hydroindanecarbonyl-Glγcyl-G3ycy1- Arginvl-Isoleucyl-Aspartvl-Arginvl-Isoleucvl-Phenvlalanyl- Arσiny]-Cysteinv3 Cyclic Disulfide Protected peptide resin (0.97 g) , prepared (as described in Example 1) from Boc-Cys (4-MeBzl) -O-Merrifield resin and the amino acids added sequentially in the following order: Boc- — — Arg(N -Tos), Boc-Phe, Boc-Ile, Boc-Arg(N -Tos), Boc-Asp(beta- cyclohexyl), Boc-Ile, Boc-Arg(N -Tos), Boc-Gly, Boc-Gly, Boc- — Pic, Boc-Cys (4-MeBzl) , Boc-Arg(N -Tos), was treated with HF (liquid) and purified as described in Example 2. The title compound was obtained as a white powder, 81 mg. Amino Acid Analysis: Arg (3.6), Asp (1.0), Cys (1.5), Gly (1.9), He (2.3), Phe (1.2) . FAB (M+H) + at M/Z: 1614. The 300 MHz H NMR spectrum was found to be consistent with the proposed structure. Example 35 Servl-Serγl-Cγsteinvl-Phenvlalanvl-Glvcvl-Glvcyl-Arσiny-1- Isoleucyl-Aspartyl-Arginvl-Isoleucvl-Phenylalany]-Arginy_l- Cysteinyl Cyclic Disulfide Protected peptide resin (0.79 g) , prepared (as described in Example 1) from Boc-Cys (4-MeBzl) -O-Merrifield resin and the amino acids added sequentially in the following order: Boc- c c Arg(N -Tos), Boc-Phe, Boc-Ile, Boc-Arg(N -Tos), Boc-Asp(beta- — cyclohexyl), Boc-Ile, Boc-Arg(N -Tos), Boc-Gly, Boc-Gly, Boc- Phe, Boc-Cys (4-MeBzl) , Boc-Ser (Bzl) , Boc-Ser(Bzl) , was treated with HF (liquid) and purified as described in Example 2. The title compound was obtained as a white powder, 70 mg. Amino Acid Analysis: Arg (2.7), Asp (1.0), Cys (1.8), Gly (2.0), He (2.0), Phe (1.9), Ser (1.8) . FAB (M+H) + at M/Z: 1615. The 300 MHz H NMR spectrum was found to be consistent with the proposed structure. Example 36 Cvsteinyl-Cyclohexylalanvl-Glvcvl-Glvcvl-Arginvl-Isoleucvl- ■D) spar yl-Arginyl-Isol ucyl-Phenylalanvl-Arσinyl-Cysteinyl Carboxamide Cyclic Disulfide Protected peptide resin (0.50 g) , prepared (as described in Example 1) from p-methylbenzhydrylamine resin and the amino acids added sequentially in the following order: Boc-Cys (4- — G MeBzl), Boc-Arg(N -Tos) , Boc-Phe, Boc-Ile, Boc-Arg(N -Tos), Q Boc-(D)Asp(beta-Bzl) , Boc-Ile, Boc-Arg(N -Tos), Boc-Gly, Boc- Gly, Boc-Cha, Boc-Cys (4-MeBzl) , was treated with HF (liquid) and purified as described in Example 2. The title compound was obtained as a white powder, 37.6 mg. Amino Acid Analysis: Arg (3.1), Asp (1.0), Cha (0.9), Cys (1.7), Gly (1.8), He (2.1), Phe (0.9) . FAB (M+H) + at M/Z: 1445. 1 The 300 MHz H NMR spectrum was found to be consistent with the proposed structure. Example 37 Cysteinyl-Cyclohexylalanyl-Glycyl-Glycyl-ftrginyl-Isoleucyl- Aspartyl-Arginyl-Alanyl-Phenylalanyl-Argjnyl-Cysteinyl Carboxamide Cyclic Disulfide Protected peptide resin (0.50 g) , prepared (as described in Example 1) from p-methylbenzhydrylamine resin and the amino acids added sequentially in the following order: Boc-Cys (4- G MeBzl), Boc-Arg(N -Tos), Boc-Phe, Boc-Ala, Boc-Arg(N -Tos) , Boc-Asp(beta-cyclohexyl) , Boc-Ile, Boc-Arg(N -Tos), Boc-Gly, Boc-Gly, Boc-Cha, Boc-Cys (4-MeBzl) , was treated with HF (liquid) and purified as described in Example 2. The title compound was obtained as a white powder, 30.7 mg. Amino Acid Analysis: Ala (1.0), Arg (3.1), Asp (1.0), Cha (0.9), Cys (1.5), Gly (1.8), He (1.1), Phe (1.0) . FAB (M+H) + at M/Z: 1403. The 300 MHz H NMR spectrum was found to be consistent with the proposed structure. Example 38 y PJnyl -Cyclohoxy1 a1anv3 -G1vcvl-Glvcyl -Arginyl -Tsoleuryl- Aspartyl-Alanyl-Tso_1eucv -Phenvlalanyl-Arσinyl-Cys gi nyl Carboxamide Cyclic Disulfide Protected peptide resin (0.50 g) , prepared (as described in Example 1) from p-methylbenzhydrylamine resin and the amino acids added sequentially in the following order: Boc-Cys(4- — MeBzl), Boc-Arg(N -Tos), Boc-Phe, Boc-Ile, Boc-Ala, Boc- Asp(beta-cyclohexyl) , Boc-Ile, Boc-Arg(N -Tos), Boc-Gly, Boc- Gly, Boc-Cha, Boc-Cys (4-MeBzl) , was treated with HF (liquid) and purified as described in Example 2. The title compound was obtained as a white powder, 16.0 mg. ■ Amino Acid Analysis: Ala (1.0), Arg (2.0), Asp (1.1), Cys (1.4), Gly (1.9), He (2.0), Phe (1.0). FAB (M+H) + at M/Z: 1360. ι The 300 MHz H NMR spectrum was found to be consistent with the proposed structure. Example 39 Mercaptopropionyl-Cyclohexylalanyl-Glycyl-Glycyl-Λrginyl- Isoleucyl-beta-Aspartvl-Arginvl-Isoleucyl-Phenylalanyl- Arginyl-Cysteinyl Carboxamide Cyclic Disulfide Protected peptide resin (0.50 g) , prepared (as described in Example 1) from p-methylbenzhydrylamine resin and the amino acids added sequentially in the following order: Boc-Cys(4- MeBzl), Boc-Arg(N G-Tos), Boc-Phe, Boc-Ile, Boc-Arg(NG-Tos), Boc-Asp(alpha-Bzl) , Boc-Ile, Boc-Arg(N -Tos), Boc-Gly, Boc- Gly, Boc-Cha, Mpa(4-MeBzl) , was treated with HF (liquid) and purified as described in Example 2. The title compound was obtained as a white powder, 50.0 mg. Amino Acid Analysis: Arg (3.1), Asp (1.0), Cha (0.8), Cys (0.5), Gly (1.9), He (1.9), Phe (1.0) . FAB (M+H) + at M/Z: 1430. 1 The 300 MHz H NMR spectrum was found to be consistent with the proposed structure. Example 40 Cvsteinyl-Cyr-.lohexylalanvl-Glvcvl-Glvcvl-Arginvl-Isoleucyl- Asparty.1-Arginyl- (D ) Tsnleucyl-Phenvlalanyl-Arginyl-Cys einyl Carboxamide Cycl c Disulfide Protected peptide resin (0.45 g) , prepared (as described in Example 1) from p-methylbenzhydrylamine resin and the amino acids added sequentially in the following order: Boc-Cys (4- c c MeBzl), Boc-Arg(N -Tos), Boc-Phe, Boc-(D)He, Boc-Arg(N -Tos), ri Boc-Asp(beta-cyclohexyl) , Boc-Ile, Boc-Arg(N -Tos), Boc-Gly, Boc-Gly, Boc-Cha, Boc-Cys (4-MeBzl) , was treated with HF (liquid) and purified as described in Example 2. The title compound was obtained as a white powder, 28.0 mg. Amino Acid Analysis: Arg (3.2), Asp (1.0), Cha (1.0), Cys (1.8), Gly (2.1), He (1.8), Phe (1.1) . FAB (M+H) + at M/Z: 1445. 1 The 300 MHz H NMR spectrum was found to be consistent with the proposed structure. Example 41 Cysteiny -Cvolohexvlalanvl-Glvcvl-Glvcvl-Arσinvl-Norva.1yi- Aspartyl-Arginvl-Norvalvl-Phenvlalanvl-Arginyl-Cysteinyl Carboxamide Cyclic Disulfide Protected peptide resin (0.50 g) , prepared (as described in Example 1) from p-methylbenzhydrylamine resin and the amino acids added sequentially in the following order: Boc-Cys (4- MeBzl) , Boc-Arg(N G -Tos) , Boc-Phe, Boc-Nva, Boc-Arg(N G -Tos) , Boc-Asp(β-Bzl) , Boc-Nva, Boc-Arg(N G -Tos) , Boc-Gly, Boc-Gly, Boc-Cha, Boc-Cys (4-MeBzl) , was treated with HF (liquid) and purified as described in Example 2. The title compound was obtained as a white powder, 23 mg. Amino Acid Analysis: Arg (3.1), Asp (0.9), Cys (1.7), Gly (2.0), Nva (2.0), Phe (1.0) plus Cha. FAB (M+H) + at M/Z: 1417. The 500 MHz -^H NMR spectrum was found to be consistent with the proposed structure. Example 42 Cysteinyl- (O) henylglycyl-Glycyl-Glycyl-Arginyl-Tsoleucyl- Aspartyl-Arginyl-Isoleucvl-Phenylalanyl-Arginyl-Cysteinyl Carboxamide Cyclic Disulfide Protected peptide resin (0.50 g) , prepared (as described in Example 1) from p-methylbenzhydrylamine resin and the amino acids added sequentially in the following order: Boc-Cys (4- MeBzl), Boc-Arg(N G -Tos) , Boc-Phe, Boc-Ile, Boc-Arg(N G -Tos) , Boc-Asp(β-Bzl) , Boc-Ile, Boc-Arg(N G -Tos) , Boc-Gly, Boc-Gly, Boc-(D)Phg, Boc-Cys (4-MeBzl) , was treated with HF (liquid) and purified as described in Example 2. The title compound was obtained as a white powder, 25 g. Amino Acid Analysis: Arg (3.0), Asp (1.0), Cys (1.8), Gly (2.0), He (2.0), Phe (1.0) . FAB (M+H) + at M/Z: 1425. The 500 MHz -H NMR spectrum was found to be consistent for the proposed structure. Example 43 3-Mercaptopropionyl-Cyclohexylalanyl-Glycyl-Glycyl-Arσiny.l- Isoleucyl-Λspartyl-Λrginyl-Isoleυcyl-Phenylalanyl- (D) _ 5 irginyl- Cvst inyl Carboxamide Cyclic Disulfide Protected peptide resin (0.50 g) , prepared (as described in Example 1) from p-methylbenzhydrylamine resin and the amino acids added sequentially in the following order: Boc-Cys (4- MeBzl) , Boc-(D)Arg(N G -Tos) , Boc-Phe, Boc-Ile, Boc-Arg(N G -Tos) , Boc-Asp (β-tert-butyl) , Boc-Ile, Boc-Arg(N G -Tos) , Boc-Gly, Boc- Gly, Boc-Cha, Mpa (4-MeBzl) , was treated with HF (liquid) and purified as described in Example 2. The title compound was obtained as a white powder, 19.1 mg. Amino Acid Analysis: Arg (2.9), Asp (1.0), Cys (0.5), Gly (2.0), He (2.1), Phe (1.0) plus Cha, Mpa. FAB (M+H) + at M/Z: 1431. The 500 MHz -E NMR spectrum was found to be consistent for the proposed structure. Example 44 3-Mercaptopropinnyl -Cyclohexvlalanvl-Glvcvl-G ycyl-Arginyl- Isoleucyl-Aspartyl-Arginyl-Isoleucyl-Phenylalanyl-Arginyl- ■D)Cysteinyl Carboxamide Cyclic Disulfide Protected peptide resin (0.50 g) , prepared (as described in Example 1) from p-methylbenzhydrylamine resin and the amino acids added sequentially in the following order: Boc-(D)Cys (4- MeBzl), Boc-Arg(N G -Tos) , Boc-Phe, Boc-Ile, Boc-Arg(N G -Tos) , Boc-Asp(β-benzyl) , Boc-Ile, Boc-Arg(N G -Tos) , Boc-Gly, Boc-Gly, Boc-Cha, Mpa (4-MeBzl) , was treated with HF (liquid) and purified as described in Example 2. The title compound was obtained as a white powder, 12.0 mg. Amino Acid Analysis: Arg (3.0), Asp (1.0), Cys (0.5), Gly (1.7), He (2.0), Phe (1.0) plus Cha, Mpa. FAB (M+H) + at M/Z: 1430. The 500 MHz --H NMR spectrum was found to be consistent for the proposed structure. Example 45 3-Me captoprop onyl-Cyclohexylalanyl-(D) lanvl-Arσinyl- Arσinγl-Tsolf * .ucy1-Aspartyl-Arginvl-Isoleucvl-Phenvlalanγl- Arginyl-Cysteinyl Carboxamide Cyclic Disulfide Protected peptide resin (0.50 g) , prepared (as described in Example 1) from p-methylbenzhydrylamine resin and the amino acids added sequentially in the following order: Boc-Cys (4- MeBzl), Boc-Arg(N G -Tos) , Boc-Phe, Boc-Ile, Boc-Arg(N G -Tos) , Boc-Asp(β-tert-butyl) , Boc-Ile, Boc-Arg(N G -Tos) , Boc-Arg(N G - Tos), Boc-(D)Ala, Boc-Cha, Mpa (4-MeBzl) , was treated with HF (liquid) and purified as described in Example 2. The title compound was obtained as a white powder, 51 mg. Amino Acid Analysis: Ala (0.9), Arg (4.2), Asp (0.9), Cys (0.4), He (2.0), Phe (1.0) plus Cha, Mpa. FAB (M+H) + at M/Z: 1545. The 500 MHz ^H NMR spectrum was found to be consistent for the proposed structure. Exampl 46 Cysteinyl-Phenylalanyl-Glycyl-Glycyl-Arginyl-Arg nyl-Leucyl- Aspartyl-Arginyl-Isoleucyl-Leucyl-Arσinyl-Cysteinyl Carboxamide Cyclic Disulfide Protected peptide resin (0.50 g) , prepared (as described in Example 1) from p-methylbenzhydrylamine resin and the amino acids added sequentially in the following order: Boc-Cys (4- MeBzl) , Boc-Arg(N G -Tos) , Boc-Leu, Boc-Ile, Boc-Arg(N G -Tos) , Boc-Asp(β-Bzl) , Boc-Leu, Boc-Arg(N G -Tos) , Boc-Arg(N G -Tos) , Boc-Gly, Boc-Gly, Boc-Phe, Boc-Cys (4-MeBzl) , was treated with HF (liquid) and purified as described in Example 2. The title compound was obtained as a white powder, 54 mg. Amino Acid Analysis: Arg (4.2), Asp (0.9), Cys (1.8), Gly (0.9), He (1.0), Leu (2.1), Phe (1.0) . FAB at M/Z: 1505. The 500 MHz --R NMR spectrum was found to be consistent for the proposed structure. Exa ple 47 3-Mercap npronionvl-Cvclohexvlalanvl-Glvcvl-GIvcvl-Arαinyl- Tso.1eucyl-G1uta vl-Arginvl-Isoleucvl-Phenvla1anvl-Arαinyl- Oysteinyl Carboxamide Cyclic Disulfide Protected peptide resin (0.50 g) , prepared (as described in Example 1) from p-methylbenzhydrylamine resin and the amino acids added sequentially in the following order: Boc-Cys (4- MeBzl) , Boc-Arg(N G -Tos) , Boc-Phe, Boc-Ile, Boc-Arg(N G -Tos) , Boc-Glu(Bzl) , Boc-Ile, Boc-Arg(N G -Tos) , Boc-Gly, Boc-Gly, Boc- Cha, Mpa (4-MeBzl) , was treated with HF (liquid) and purified as described in Example 2. The title compound was obtained as a white powder, 140 mg. Amino Acid Analysis: Arg (3.1), Cys (0.4), Glu (1.0), Gly (2.1), He (2.0), Phe (1.0) plus Cha, Mpa. FAB (M+H) + at M/Z: 1445. The 500 MHz ^H NMR spectrum was found to be consistent for the proposed structure Example 48 3-M rcaptopro ionyl-Cvclohexvlalanyl-Glvcvl-Glvcvl- (O)Arσinyl- Isoleucyl-Aspar vl-Arginyl-Isoleucyl-Phenvlalanyl-Arginyl- Cyst inyl Carboxamide Cyclic Disulfide Protected peptide resin (0.50 g) , prepared (as described in Example 1) from p-methylbenzhydrylamine resin and the amino acids added sequentially in the following order: Boc-Cys (4- MeBzl) , Boc-Arg(N G -Tos) , Boc-Phe, Boc-Ile, Boc-Arg(N G -Tos) , Boc-Asp(β-Bzl) , Boc-Ile, Boc-(D)Arg(N G -Tos) , Boc-Gly, Boc-Gly, Boc-Cha, Mpa (4-MeBzl) , was treated with HF (liquid) and purified as described in Example 2. The title compound was obtained as a white powder, 47 mg. Amino Acid Analysis: Arg (3.0), Asp (1.0), Cys (0.5), Gly (1.6), He (1.6), Phe (1.0) plus Cha, Mpa. FAB (M+H) + at M/Z: 1430. The 500 MHz --R NMR spectrum was found to be consistent for the proposed structure. Example 49 3-Mercaptopropionyl-Cyclohexylalanyl-Glycyl-Glycyl-Arginyl- Isoleucyl-Aspartyl-Arginyl-Isoleucyl-(D)Phenylalanyl-Ar inyl- Cysteinyl Carboxamide Cyclic Disulfide Protected peptide resin (0.50 g) , prepared (as described in Example 1) from p-methylbenzhydrylamine resin and the amino acids added sequentially in the following order: Boc-Cys (4- MeBzl) , Boc-Arg(N G -Tos) , Boc-(D)Phe, Boc-Ile, Boc-Arg(N G -Tos) , Boc-Asp(β-tert-butyl) , Boc-Ile, Boc-Arg(N G -Tos) , Boc-Gly, Boc- Gly, Boc-Cha, Mpa(4-MeBzl) , was treated with HF (liquid) and purified as described in Example 2. The title compound was obtained as a white powder, 12.0 mg. Amino Acid Analysis: Arg (3.1), Asp (1.0), Cys (0.6), Gly (2.0), He (2.0), Phe (1.1) plus Cha, Mpa. FAB (M+H) + at M/Z: 1431. The 500 MHz --R NMR spectrum was found to be consistent for the proposed structure. Example 50 S-Aminohexanovl-Cvsteinvl-Cvclohexvl 1 nyl- .D. Al anyl- (Di Alanyl-Arginyl-Isoleucvl-Aspartvl-Arginyl-Isoleucyl- Phenylalanyl-Arginyl-Cvsteinvl Carboxamide Cycl c Disulfide Protected peptide resin (0.50 g) , prepared (as described in Example 1) from p-methylbenzhydrylamine resin and the amino acids added sequentially in the following order: Boc-Cys (4- MeBzl), Boc-Arg(N G -Tos) , Boc-Phe, Boc-Ile, Boc-Arg(N G -Tos) , Boc-Asp(β-Bzl) , Boc-Ile, Boc-Arg(N G -Tos) , Boc-(D)Ala, Boc- (D)Ala, Boc-Cha, Boc-Cys (4-MeBzl) , Boc-Aha, was treated with HF (liquid) and purified as described in Example 2. The title compound was obtained as a white powder, 39 mg. Amino Acid Analysis: Ala (1.9), Arg (3.2), Asp (1.0), Cys (1.6), He (2.0), Phe (1.0) plus Cha. FAB (M+H) + at M/Z: 1587. The 500 MHz ^H NMR spectrum was found to be consistent for the proposed structure Example 51 3-Mercaptopropinnyl-Cyclohexvlalanvl-GIycv3-G1 ycvl-Arginyl- Isoleucyl-Hist.idinyl-Arginvl-Isoleucvl-Phenylalanyl-Arσinyl- Cysteinyl Carboxamide Cyclic Disulfide Protected peptide resin (0.50 g) , prepared (as described in Example 1) from p-methylbenzhydrylamine resin and the amino acids added sequentially in the following order: Boc-Cys (4- MeBzl), Boc-Arg(N G -Tos) , Boc-Phe, Boc-Ile, Boc-Arg(N G -Tos) , Boc-His(Nim-Tos) , Boc-Ile, Boc-Arg (N G -Tos) , Boc-Gly, Boc-Gly, Boc-Cha, Mpa(4-MeBzl) , was treated with HF (liquid) and purified as described in Example 2. The title compound was obtained as a white powder, 10.0 mg. Amino Acid Analysis: Arg (3.2), Cys (0.5), Gly (2.5), His (0.9), He (1.9), Phe (1.0) plus Cha, Mpa. FAB (M+H) + at M/Z: 1453. The 500 MHz --R NMR spectrum was found to be consistent for the proposed structure. Example 52 3-Mercaptopropionyl-Phenylalanyl-Glycyl-Glycyl-Arginyl- Isoleucyl-Aspartyl-Arginyl-Isoleucyl-Phenvlalanyl-Arginyl- Cysteinyl Carboxamide Cyclic Disulfide Protected peptide resin (0.50 g) , prepared (as described in Example 1) from p-methylbenzhydrylamine resin and the amino acids added sequentially in the following order: Boc-Cys (4- MeBzl) , Boc-Arg(N G -Tos) , Boc-Phe, Boc-Ile, Boc-Arg(N G -Tos) , Boc-Asp(β-Bzl) , Boc-Ile, Boc-Arg(N G -Tos) , Boc-Gly, Boc-Gly, Boc-Phe, Mpa(4-MeBzl) , was treated with HF (liquid) and purified as described in Example 2. The title compound was obtained as a white powder, 25 mg. Amino Acid Analysis: Arg (3.0), Asp (0.9) Cys (0.5), Gly (2.0), He (2.0), Phe (2.0) plus Mpa. FAB (M+H) + at M/Z: 1424. The 500 MHz --R NMR spectrum was found to be consistent for the proposed structure. Example 53 3-Mercaptopropionγ.l-Cγclohexylalanvl-(D. Alanyl-Alanyl-Arginy.1- Isoleucyl-Aspartyl-Arginyl-Isoleucyl-Pheny] lanyl-Arginyl- (T))Cysteinvl Carboxamide Cyclic Disulfide Protected peptide resin (0.50 g) , prepared (as described in Example 1) from p-methylbenzhydrylamine resin and the amino acids added sequentially in the following order: Boc-(D)Cys (4- MeBzl), Boc-Arg(N G -Tos) , Boc-Phe, Boc-Ile, Boc-Arg(N G -Tos) , Boc-Asp (b-tert-butyl) , Boc-Ile, Boc-Arg(N G -Tos) , Boc-Ala, Boc- (D)Ala, Boc-Cha, Mpa (4-MeBzl) , was treated with HF (liquid) and purified as described in Example 2. The title compound was obtained as a white powder, 33.1 mg. Amino Acid Analysis: Ala (1.6), Arg (3.2), Asp (1.0), Cys (0.5), He (2.0), Phe (1.0) plus Cha, Mpa. FAB (M+H) + at M/Z: 1459. The 500 MHz --R NMR spectrum was found to be consistent for the proposed structure. Example 54 3-Mercaptopropionyl-Cγclohexylalanvl-(D)Alanyl-Alanvl-Arginvl- Isoleuπyl-Aspartyl-Arσinyl-Isoleucyl-N 6 —r3-(l-Phenyl-2- a inopropionyl) 1Aroinvl- (D) Cysteinvl Carboxamide Cyclic Disu ide Protected peptide resin (0.50 g) , prepared (as described in Example 1) from p-methylbenzhydrylamine resin and the amino acids added sequentially in the following order: Boc- (D)Cys (4- MeBzl) , Boc-Phe-Arg(N G -Tos) reduced amide, Boc-Ile, Boc- Arg(N G -Tos), Boc-Asp (β-tert-butyl) , Boc-Ile, Boc-Arg(N G -Tos) , Boc-Ala, Boc-(D)Ala, Boc-Cha, Mpa(4-MeBzl) , was treated with HF (liquid) and purified as described in Example 2. The title compound was obtained as a white powder, 7.4 mg. Amino Acid Analysis: Ala (2.0), Arg(2.2), Asp (0.8), Cys (0.5), He (1.6) plus Cha, Mpa. FAB (M+H) + at M/Z: 1445. The 500 MHz --R NMR spectrum was found to be consistent for the proposed structure. Example 55 The representative compounds of the invention described in the above examples are summarized in Table 1, below: Table 1 ANP Agonist Sequences Example No. Sequence 2 R-C-Cha-(D)A-G-G-R-L-D-R-I-F-R-C-Amide 3 S-S-C-Cha-G-G-R-I-D-R-I-F-R-C 4 S-S-C-Cha-G-G-R-I-D-R-I-Cha-R-C 5 R-C-F-G-G-R-I-D-R-I-F-R-C-Amide .6 R-C-(D)A-Cha-G-G-R-L-D-R-I-F-R-C-Amide 7 R-C-Cha-G-G-R-I-D-R-I-F-R-C 8 S-S-C-Cha-G-G-(D)R-I-D-R-I-F-R-C 9 C-Cha-G-G-R-I-D-R-I-F-R-C 10 C-R-Cha-G-G-R-I-D-R-I-F-R-C 11 R-C-Cha-G-G-R-1-D-R-1-F-R-C-Amide 12 R-C-Cha-(D)A-A-R-I-D-R-I-F-R-C-Amide 13 R-C-Tic-G-G-R-I-D-R-I-F-R-C-Amide R-C-F-G-G-I-D-R-I-F-R-C-Amide H-C-Cha-G-G-R-I-D-R-I-F-R-C-Amide R-C-Cha-G-G-R-F-D-R-I-F-R-C-Amide C-Cha-G-G-R-I-D-R-I-F-R-C-Amide Orn-C-Cha-G-G-R-I-D-R-I-F-R-C-Amide AcetylR-C-Cha-G-G-R-I-D-R-I-F-R-C-Amide Cit-C-Cha-G-G-R-I-D-R-I-F-R-C-Amide R-C-Cha-G-G-R-I-D-R-I-F-C-Amide R-C-3,5-l2Y-G-G-R-I-D-R-I-F-R-C-Amide R-C-Cha-G-G-R-I-D-R-I-R-C-Amide R-C-Cha-G-G-cyclo (K-I-D) -R-I-F-R-C-Amide R-C-Cha-G-G-R-I-D-R-I-G-A-C-Amide R-C-Cha-G-G-R-I- (D)D-R-I-F-R-C-Amide (D) R-C-Cha-G-G-R-I-D-R-I-F-R-C-Amide R-C-Chg-G-G-R-I-D-R-I-F-R-C-Amide R-C-Cha-G-G-R-I-D-R-A-F-R-C-Amide R-C- (D) Cha-G-G-R-I-D-R-I-F-R-C-Amide R-C-Cha-G-G-R-I-A-R-I-A-R-C Mpa-Cha-G-G-R-I-D-R-I-F-R-C-Amide R-C-Cha-G-G- (D)R-I-D-R-I-F-R-C R-C-Pic-G-G-R-I-D-R-I-F-R-C S-S-C-F-G-G-R-I-D-R-I-F-R-C C-Cha-G-G-R-I- (D)D-R-I-F-R-C-Amide C-Cha-G-G-R-I-D-R-A-F-R-C-Amide C-Cha-G-G-R-I-D-A-I-F-R-C-Amide Mpa-Cha-G-G-R-I-betaD-R-I-F-R-C-Amide C-Cha-G-G-R-I-D-R-(D) I-F-R-C-Amide C-Cha-G-G-R-Nva-D-R-Nva-F-R-C-Amide C- (D)F-G-G-R-I-D-R-I-F-R-C-Amide Mpa-Cha-G-G-R-I-D-R-I-F- (D)R-C-Amide Mpa-Cha-G-G-R-I-D-R-I-F-R- (D) C-Amide Mpa-Cha- (D)A-R-R-I-D-R-I-F-R-C-Amide C-F-G-G-R-R-L-D-R-I-L-R-C-Amide 47 Mpa-Cha-G-G-R-I-E-R-I-F-R-C-Amide 48 Mpa-Cha-G-G-(D)R-1-D-R-I-F-R-C-Amide 49 Mρa-Cha-G-G-R-I-D-R-I-(D)F-R-C-Amide 50 Aha-C-Cha-(D)A-(D)A-R-I-D-R-I-F-R-C-Amide 51 Mpa-Cha-G-G-R-I-H-R-I-F-R-C-Amide 52 Mρa-F-G-G-R-I-D-R-I-F-R-C-Amide 53 Mpa-Cha-(D)A-A-R-I-D-R-I-F-R-(D) C-Amide 54 Mpa-Cha-(D)A-A-R-I-D-R-I-[F^R]-(D)C-Amide Other peptides of the invention which can be synthesized according to the methods of Examples 1 and 2 include the following: Cys-Phe-Gly-Gly-Arg-Ile-Asp-Arg-He-Phe-Arg-Cys; Cys-Phe-Gly-Gly-(D)Arg-Ile-Asp-Arg-He-Phe-Arg-Cys; Cys-Phe-Gly-Gly-Arg-Phe-Asp-Arg-He-Phe-Arg-Cys; Cys-Phe-Gly-Gly-Ile-Asp-Arg-He-Phe-Arg-Cys; Ser-Ser-Cys-Phe-Gly-Gly-(D)Arg-Ile-Asp-Arg-He-Phe-Arg-Cys; Ser-Ser-Cys-Phe-Gly-Gly-Arg-Leu-Asp-Arg-He-Phe-Arg-Cys; Ser-Ser-Cys-Phe-Gly-Gly-Arg-Phe-Asp-Arg-He-Phe-Arg-Cys; Ser-Ser-Cys-Phe-Gly-Gly-Ile-Asp-Arg-He-Phe-Arg-Cys; Arg-Cys-Phe-Gly-Gly-(D)Arg-Ile-Asp-Arg-He-Phe-Arg-Cys; Arg-Cys-Phe-Gly-Gly-Arg-Leu-Asp-Arg-He-Phe-Arg-Cys; Arg-Cys-Phe-Gly-Gly-Arg-Phe-Asp-Arg-He-Phe-Arg-Cys; Arg-Cys-Phe-Gly-Gly-He-Leu-Arg-Ile-Phe-Arg-Cys; His-Cys-Phe-Gly-Gly-Arg-Ile-Asp-Arg-He-Phe-Arg-Cys; His-Cys-Phe-Gly-Gly-(D)Arg-Ile-Asp-Arg-He-Phe-Arg-Cys; His-Cys-Phe-Gly-Gly-Arg-Leu-Asp-Arg-He-Phe-Arg-Cys; His-Cys-Phe-Cys-Gly-Gly-Arg-Phe-Asp-Arg-He-Phe-Arg-Cys; His-Cys-Phe-Gly-Gly-Ile-Asp-Arg-He-Phe-Arg-Cys; hCys-Phe-(D)Ala-Ala-Arg-Ile-Asp-Arg-He-Phe-Arg-Cys; hCys-Phe- (D ) Ala-Ala- (D) Arg-I le-Asp-Arg-He-Phe-Arg-Cys ; hCys-Phe- (D ) Ala-Ala-Arg-Leu-Asp-Arg-He-Phe-Arg-Cys ; hCys-Phe- (D) Ala-Ala-Arg-Phe-Asp-Arg-He-Phe-Arg-Cys ; hCys-Phe- (D ) Ala-Ala-Ile-Asp-Arg-He-Phe-Arg-Cys ; Ser-Ser-Cys-Phe- (D) Ala-Ala-Arg-Ile-Asp-Arg-He-Phe-Arg-Cys ; Ser-Ser-Cys-Phe- (D) Ala-Ala-Arg-Leu-Asp-Arg-He-Phe-Arg-Cys ; Ser-Ser-Cys-Phe- (D) Ala-Ala-Arg-Phe-Asp-Arg-He-Phe-Arg-Cys ; Ser-Ser-Cys-Phe- (D) Ala-Ala-Ile-Asp-Arg-He-Phe-Arg-Cys ; Ser-Arg-Cys-Phe- (D) Ala-Ala-Arg-Ile-Asp-Arg-He-Phe-Arg-Cys ; Arg-Cys-Phe- (D) Ala-Ala- (D) Arg-Ile-Asp-Arg-He-Phe-Arg-Cys ; Arg-Cys-Phe- (D) Ala-Ala-Arg-Leu-Asp-Arg-Ile-Phe-Arg-Cys ; Arg-Cys-Phe- (D) Ala-Ala-Arg-Phe-Asp-Arg-Ile-Phe-Arg-Cys ; Arg-Cys-Phe- (D) Ala-Ala-Ile-Asp-Arg-He-Phe-Arg-Cys ; Cys-Phe-Gly-Gly- (D) Arg-Ile-Asp-Arg-He-Phe-Arg-Cys ; Ser-Ser-Cys-Phe-Gly-Gly-Arg-Leu-Asp-Arg-He-Phe-Arg-Cys ; Ser-Ser-Cys-Phe-Gly-Gly-Arg-Phe-Asp-Arg-He-Phe-Arg-Cys ; Arg-Cys-Phe-Gly-Gly- (D) Arg-Ile-Asp-Arg-He-Phe-Arg-Cys ; Arg-Cys-Phe-Gly-Gly-Arg-Leu-Asp-Arg-He-Phe-Arg-Cys ; His-Cys-Phe-Gly-Gly-Arg-Phe-Asp-Arg-He-Phe-Arg-Cys ; His-Cys-Phe-Gly-Gly-Arg-Ile-Asp-Arg-He-Phe-Arg-Cys ; His-Cys-Phe-Gly-Gly- (D) Arg-Ile-Asp-Arg-He-Phe-Arg-Cys ; His-Cys-Phe-Gly-Gly-Arg-Leu-Asp-Arg-He-Phe-Arg-Cys ; His-Cys-Phe-Cys-Gly-Gly-Arg-Phe-Asp-Arg-He-Phe-Arg-Cys ; His-Cys-Phe-Gly-Gly-Ile-Asp-Arg-He-Phe-Arg-Cys ; hCys-Phe- (D ) Ala-Ala-Arg-Ile-Asp-Arg-He-Phe-Arg-Cys ; hCys-Phe- (D) Ala-Ala- (D) Arg-Ile-Asp-Arg-He-Phe-Arg-Cys; hCys-Phe- (D ) Ala-Ala-Arg-Leu-Asp-Arg-He-Phe-Arg-Cys ; hCys-Phe- (D ) Ala-Ala-Arg-Phe-Asp-Arg-He-Phe-Arg-Cys ; hCys-Phe- (D ) Ala-Ala-Ile-Asp-Arg-He-Phe-Arg-Cys ; Ser-Ser-Cys-Phe- (D) Ala-Ala-Arg-Ile-Asp-Arg-He-Phe-Arg-Cys ; Ser-Ser-Cys-Phe- (D) Ala-Ala-Arg-Leu-Asp-Arg-He-Phe-Arg-Cys ; Ser-Ser-Cys-Phe- (D) Ala-Ala-Arg-Phe-Asp-Arg-He-Phe-Arg-Cys ; Ser-Ser-Cys-Phe- (D) Ala-Ala-Ile-Asp-Arg-He-Phe-Arg-Cys ; Arg-Cys-Phe-(D)Ala-Ala-Arg-Ile-Asp-Arg-He-Phe-Arg-Cys; Arg-Cys-Phe-(D)Ala-Ala-(D)Arg-Ile-Asp-Arg-He-Phe-Arg-Cys; Arg-Cys-Phe-(D)Ala-Ala-Arg-Leu-Asp-Arg-He-Phe-Arg-Cys; Arg-Cys-Phe-(D)Ala-Ala-Arg-Phe-Asp-Arg-He-Phe-Arg-Cys; His-Cys-Phe-(D)Ala-Ala-Ile-Asp-Arg-He-Phe-Arg-Cys; His-Cys-Phe-(D)Ala-Ala-Arg-Ile-Asp-Arg-He-Phe-Arg-Cys; His-Cys-Phe-(D)Ala-Ala- (D)Arg-Ile-Asp-Arg-He-Phe-Arg-Cys; His-Cys-Phe-(D)Ala-Ala-Arg-Leu-Asp-Arg-He-Phe-Arg-Cys; and His-Cys-Phe-(D)Ala-Ala-Arg-Phe-Asp-Arg-He-Phe-Arg-Cys. Example 56 Preparation of Plasma Membranes Adrenal cell membranes were prepared for use in binding assays as follows: Weighed frozen mature rabbit adrenals (Pel-Freez) were pulverized in a liquid-nitrogen-cooled mortar. The plasma membrane powder was transferred to assay buffer (50mM HEPES (4- (2-hydroxyethyl)-1-piperazine- ethanesulfonic acid) , 100 mM NaCl, 5 mM EGTA (ethylene glycol bis ( .beta.-aminoethyl ether)-N,N,N' ,N'-tetraacetic acid), 1 mM PMSF (phenyl methylsulfonyl fluoride), 0.01% Brij-35 detergent, 0.01% Bovine Serum Albumin, 0.1% Bacitracin, 5 mM MnCl2 # - 1 micromolar leupeptin, 1 micromolar phosphoramidon, pH 7.4) and homogenized in a Polytron three times at 10 seconds each time. The homogenate was centrifuged at 20,000 g for 15 min at 4 C. The supernatant was decanted. The pellet was resuspended in assay buffer and homogenized with the Polytron (2 X 10 sec) and again centrifuged at 20,000 g at 4°C. The supernatant decantation and pellet resuspension were repeated two additional times. The final homogenate was diluted to a concentration of 0.16 mg/mL (wet tissue weight) in assay buffer and stored at -80 C until used. Example 57 ANP Receptor Binding Assay The In vitro receptor binding of the compounds of the present invention was studied as follows: 0.53 mg rabbit adrenal plasma membranes were incubated with 26.1 pM 125I-rat ANP and various concentrations of competing analogs for 90 min at 4 C in a total volume of 0.2 mL of assay buffer. Bound 125 I-rat ANP was separated from free ligand by rapid filtration through 0.1% polyethylenimine-treated 240-1 glass- fiber filter strips (Cambridge Technology) , followed by rapid washing with ice cold saline. The. filters were counted for radioactivity in a LKB 1277 Gammamaster counter with 76% counting efficiency. Triplicate determinations of bound 125I- rat ANP were used for data analysis. Binding data was analyzed by computer assisted non-linear regression analysis using the LIGAND program (Munson, P.J. and M. Rodbard, Analytical Biochemis ry r 107, 220-239 (1980)) for determination of density of binding sites on the membrane and for determination of the competing analog's affinity for the binding sites. In the case of selective analogs only the low affinity binding values (PKL) are reported. Table 2, below, which contains the ANP receptor binding data, demonstrates the affinity of the atrial peptide derivatives of the present invention for ANP binding receptor sites. Table ANP receptor binding data Ex. No. pj£. 2 6.34 20 5.70 38 5.44 3 6.94 21 6.97 39 6.11 4 6.93 22 5.88 40 6.84 5 6.06 23 6.71 41 5.94 6 6.22 24 7.24 42 6.90 7 6.34 25 5.91 43 6.42 8 5.66 26 6.22 44 6.02 9 6.14 27 6.75 45 6.68 10 6.60 28 6.23 46 6.01 11 6.63 29 6:63 47 6.37 12 6.69 30 6.45 48 6.45 13 5.61 31 6.61 49 5.19 14 5.05 32 6.74 50 6.75 15 6.73 33 6.14 51 6.36 16 6.17 34 6.32 52 6.05 17 6.56 35 6.10 54 7.20 18 6.20 36 5.45 19 6.43 37 6.73 ** = Negative logarithm of ligand binding constant Example 58 In Vivo Testing The in vivo effect of the compounds of the present invention on blood pressure and sodium output were studied as follows: Male Sprague-Dawley rats (4-12 rats weighing 200-250 mg each) were anesthetized with inactin administered intraperotoneally at a dose of 100 mg/kg. The test compounds were infused intravenously in 0.1% bovine serum albumin (BSA) in saline solution at a rate of 1 mL per hour for 15 minutes at each dose level. For routine screening the doses administered were 0.1, 0.3, 1.0, 3.0, 10.0 and 30.0 μg/kg/min. Blood pressure, urine volume output, sodium and potassium secretion were measured over a 15 minute period at each dose. Test compounds were regarded as active if they produced either a three-fold increase in sodium excretion or a 5% decrease in blood pressure at the doses tested. The results for change in blood pressure and sodium output are shown in Table 3 and demonstrate the ability of the compounds of the present invention to modify vascular and 'renal function. TabIt* 3 Effect on Blood Pressure and Sodium Output Example Dose (μσ/kσ) A B.P. (%) Ml Δ Sodium* Ml 0.100 -0.20 8 0.22 5 0.300 0.11 8 0.24 5 1.000 3.11 8 0.44 5 3.000 -3.14 8 0.52 5 10.000 -7.25 8 0.82 5 30.000 -8.45 8 1.07 5 Table (cont i nued . Example Dose (μg/kg} A B.P. (%. ( ) A Sodium* (N) 5 0.100 0.35 8 0.11 6 0.300 0.86 8 0.18 6 1.000 -0.76 8 0.29 6 3.000 -3.30 8 0.43 6 10.000 -4.84 8 0.49 6 30.000 -6.79 8 0.59 6 6 0.100 -0.95 4 -0.07 4 0.300 -1.25 4 -0.02 4 1.000 -3.65 4 -0.13 4 3.000 -5.30 4 0.04 4 10.000 -7.93 4 0.04 4 30.000 -9.30 4 0.02 4 7 0.100 -0.47 6 0.10 6 0.300 -1.20 6 0.14 6 1.000 -2.90 6 0.36 6 3.000 -7.32 6 0.57 6 10.000 -8.88 6 0.75 6 30.000 -7.08 6 1.12 6 8 0.100 2.50 8 0.21 6 0.300 0.86 8 0.22 6 1.000 -0.89 8 0.42 6 3.000 -2.05 8 0.60 6 10.000 -4.55 8 0.64 6 30.000 -7.79 8 0.84 6 Table 3 (continued) Example Pose (μg/kg) Δ B.P. (%. (N) A Sodium* (N) 9 0.100 -2.60 6 0.05 5 0.300 -3.47 6 0.05 5 1.000 -4.68 6 0.17 5 3.000 -6.90 6 0.34 5 10.000 -12.00 6 0.62 5 30.000 -16.88 6 0.82 5 10 0.100 -1.98 12 -0.05 8 0.300 -3.51 12 0.00 8 1.000 -4.60 12 0.06 8 3.000 -5.25 12 0.22 8 10.000 -7.42 12 0.38 8 30.000 -7.92 12 0.77 8 11 0.100 -1.49 12 -0.01 9 0.300 -2.27 12 0.06 9 1.000 -4.64 12 0.07 9 3.000 -7.64 12 0.28 9 10.000 -10.93 12 0.46 9 30.000 -12.42 12 0.85 8 12 0.100 -3.08 5 0.25 4 0.300 -4.22 5 0.55 4 1.000 -8.70 5 0.66 4 3.000 -12.46 5 0.91 4 10.000 -17.54 5 1.14 4 30.000 -24.98 5 1.09 4 Table 3 (continued . Example Dose (μg/kg. A B.P. (%. ( ). A Sodium* (N) 14 0.100 -0.60 4 -0.03 4 0.300 -8.10 4 -0.10 4 1.000 -7.07 4 -0.13 4 3.000 -9.13 4 0.01 4 10.000 -9.20 4 0.14 4 30.000 -9.65 4 0.18 4 15 0.100 -0.25 6 -0.23 5 0.300 -3.72 6 -0.20 5 1.000 -8.60 6 0.15 5 3.000 -14.17 6 0.78 5 10.000 -17.95 6 0.97 5 30.000 -18.90 6 1.38 5 17 0.100 -0.42 11 0.19 4 0.300 -1.22 11 0.25 4 1.000 -2.49 11 0.56 4 3.000 -4.70 11 0.66 4 10.000 -8.63 11 0.67 4 30.000 -15.83 11 0.93 4 18 0.100 1.21 7 0.17 5 0.300 -0.63 7 0.17 5 1.000 -2.76 7 0.18 5 3.000 -4.57 7 0.25 5 10.000 -6.46 7 0.40 5 30.000 -11.19 7 0.90 5 Table 3 (cen i nner. ) Dose (μg/kg) A B.P. (%) (N) A Sodium* (N) 0.100 -1.35 6 -0.28 5 0.300 -4.87 6 0.01 5 1.000 -8.03 6 -0.01 5 3.000 -10.20 6 0.29 5 10.000 -15.67 6 0.62 5 30.000 -22.23 6 0.74 5 0.100 -1.20 13 0.09 9 0.300 -0.79 13 0.41 9 1.000 -0.63 13 0.52 9 3.000 -1.55 13 0.60 9 10.000 -3.58 13 0.58 9 30.000 -6.83 13 0.58 9 0.100 -2.48 10 -0.03 9 0.300 -4.85 10 -0.07 9 1.000 -9.20 10 0.03 9 3.000 -11.32 10 0.06 9 10.000 -15.77 10 0.24 9 30.000 -18.54 10 0.49 9 0.100 -0.28 6 0.07 5 0.300 -1.93 6 0.32 5 1.000 -3.55 6 0.37 5 3.000 -3.43 6 0.38 5 10.000 -4.03 6 0.46 5 30.000 -7.18 6 0.49 5 Table 3 (continued) Example Dose (μg/kg A B.P. (N) A Sodium* Ml 32 0.100 1.52 8 -0.03 6 0.300 0.79 8 -0.11 6 1.000 -0.90 8 -0.12 6 3.000 -6.06 8 0.37 6 10.000 -15.14 8 0.78 6 30.000 -18.61 8 0.89 6 36 0.100 0.22 8 0.07 4 0.300 -0.82 8 0.01 4 1.000 -1.51 8 0.02 4 3.000 -3.01 8 0.15 4 10.000 -4.25 8 0.19 4 30.000 -6.50 8 0.27 4 37 0.100 1.66 8 0.06 6 0.300 2.66 8 0.14 6 1.000 1.70 8 0.12 6 3.000 0.65 8 0.08 6 10.000 -0.04 7 0.33 6 30.000 -1.04 8 0.22 6 38 0.100 -2.01 8 -0.03 6 0.300 -2.13 8 -0.10 6 1.000 -2.17 8 -0.04 6 3.000 -4.82 8 0.21 6 10.000 -6.01 8 0.35 6 30.000 -5.28 8 0.48 6 Table 3 ( cont nued^ Example Dose (μg/kg) A B , P , ( % ) Ml A Sodivm* Ml 40 0.100 -1.11 8 -0.01 4 0.300 -2.03 8 0.11 4 1.000 -1.67 8 -0.28 4 3.000 -2.09 8 -0.18 4 10.000 -2.24 8 -0.14 4 30.000 -2.89 8 0.01 4 42 0.100 0.30 11 -0.04 4 0.300 0.78 11 0.28 4 1.000 0.86 11 0.40 4 3.000 0.51 11 0.26 4 10.000 -3.47 11 0.58 4 30.000 -8.62 11 0.81 4 43 0.100 1.70 8 -0.12 5 0.300 1.67 8 -0.15 5 1.000 1.34 8 -0.19 5 3.000 1.79 8 0.18 5 10.000 -2.85 8 0.04 5 30.000 -3.50 8 0.30 5 44 0.100 -0.35 8 -0.01 4 0.300 -2.50 8 -0.36 4 1.000 -6.24 8 -0.51 4 3.000 -8.54 8 0.83 4 10.000 -9.45 8 0.72 4 30.000 -14.10 8 0.68 4 Table 3 (continued. Example Dose (μg/kg) A B.P. (%. (N) Δ Sodium* ( ) 45 0.100 -0.89 8 0.07 6 0.300 -1.80 8 0.00 6 1.000 -3.26 8 0.17 6 3.000 -4.70 8 0.20 6 10.000 -4.31 8 0.13 6 30.000 -12.11 8 0.18 6 46 0.100 2.38 8 -0.04 5 0.300 -0.86 8 -0.10 5 1.000 -2.85 8 -0.06 5 3.000 -4.39 8 -0.02 5 10.000 -6.89 8 0.17 5 30.000 -8.61 8 0.36 5 47 0.100 -0.35 8 0.03 6 0.300 -1.60 8 -0.11 6 1.000 -3.90 8 0.05 6 3.000 -6.66 8 0.38 6 10.000 -15.09 8 0.58 6 30.000 -21.08 8 0.75 6 50 0.100 -1.99 8 0.14 5 0.300 -2.64 8 0.07 5 1.000 -5.38 8 -0.03 5 3.000 -9.01 8 0.31 5 10.000 -13.91 8 0.44 5 30.000 -31.71 7 0.14 5 = sodium excretion = log(t/c) where t = treated, c = control Exa ple 59 Treatment of Post-Tschemic Acute Renal Failure The ability of the compound of Example 11 to improve renal function after ischemically-induced renal failure was studied as follows: Male Sprague-Dawley rats were anesthetized with Inactin and surgically prepared for typical renal clearance measurements. Surgical preparation was followed by a 1 hour equilibration period. Bilateral ischemia was induced by complete occlusion of both renal arteries. After 30 minutes of ischemia, the test compound was infused intravenously at a dose of 10 μg/kg/min for two hours. Separate groups of animals were also treated with vehicle alone or ANF(l-28) (human ANF) . The results of testing are shown in Tables 4-6, below. Both the compound of Example 11 and ANF(1-28) produced significant short- and long-term improvement in post-ischemic renal function as measured in increased glomerular filtration rate, reduced plasma creatinine concentration, and reduced gross anatomical damage. These results demonstrate the renoprotective effect of the compounds of the invention and their usefulness in restoring kidney function in acute renal failure. Table 4 Effect on Glomerular Filtration Rate Glomerular Filtration Rate Group (ml /min/l OOg body wt) B Vehicle 0. 19 ± 0.04 8 Compound 11 0.39 ± 0.07 7 ANF (1-28) 0. 40 ± 0.04 6 Tahl 5 Effect on Plasma Creatinine Concentration (mσ%) Days Post- -Ischemia _£__ __2_ _^_ _i_ Vehicle (N=8) Mean 0.47 5.05 5.49 3.72 2.22 S.E. 0.11 0.41 1.19 0.99 0.62 Compound 11 (N=7) Mean 0.52 2.34 1.24 0.99 0.84 S.E. 0.07 0.58 0.71 0.60 0.40 ANF(1-28) (N=5) Mean 0.33 3.29 2.72 1.51 1.32 S.E. 0.08 0.61 0.77 0.71 0.51 Table 6 Gross Anatomical Evaluation -Group Evaluation Score* (Day 4) Vehicle 1.8 ± 0.1 Compound 11 1.0 ± 0.1 ANF(1-28) 1.7 ± 0.4 * Ratings are from 0 to 4 indicating least to greatest damage. The present invention has been described in terms of specific embodiments set forth in detail. It should be understood, however, that these embodiments are presented by way of illustration only, and that the invention is not necessarily limited thereto. For example, although synthetic methods are presented for the preparation of the peptides of the present invention, it is to be understood that these peptides can be prepared by enzymatic and recombinant DNA methodology. Other modifications and variations suggested by this disclosure and apparent to those skilled in the art are intended to be within the spirit and scope of the claims that follow.

Claims: WHAT IS CLAIMED TS. 1. A compound of the formula: or a pharmaceutically acceptable salt, ester or amide thereof, wherein R is selected from hydrogen, AcetylArg, Aha, Arg, Cit, His, Lys, Orn and Ser-Ser; 2 R is a sulfur-containing group; R 3 is a hydrophobic amino acid or dipeptide; 4 R is a dipeptide spacer or a tripeptide of the formula X-Y, where X is a dipeptide spacer and Y is a basic amino acid; 5 R is a hydrophobic ammo acid; R is a peptide of up to three amino acids; 7 R is selected from Cha, Phe, Cha-Arg, Phe-Arg, (D)Phe-Arg, Phe-(D)Arg, Phe^Arg, Leu-Arg, Ala-Arg, Arg and Gly-Ala; and o R is a sulfur-containing group. 2. The compound of Claim 1 wherein R is a basic amino acid; R 3 is a hydrophobi.c amm. o aci.d contai.ni.ng a cycloalkyl; c and R is a peptide of up to three amino acids containing an acidic amino acid. 1 3. The compound of Claim 1 wherein R is hydrogen; R 2 is 3 . mercaptopropionic acid; R is a hydrophobic ammo acid - containing a cycloalkyl; and R is a peptide of up to three amino acids containing an acidic amino acid. 4. A compound selected from the group consisting of: Arg-Cys-Cha-(D)Ala-Gly-Gly-Arg-Leu-Asp-Arg-He-Phe-Arg-Cys-NH2; Ser-Ser-Cys-Cha-Gly-Gly-Arg-Ile-Asp-Arg-He-Phe-Arg-Cys; Ser-Ser-Cys-Cha-Gly-Gly-Arg-Ile-Asp-Arg-He-Cha-Arg-Cys; Arg-Cys-Phe-Gly-Gly-Arg-Ile-Asp-Arg-He-Phe-Arg-Cys-NH2; Arg-Cys-(D)Ala-Cha-Gly-Gly-Arg-Leu-Asp-Arg-He-Phe-Arg-Cys-NH2; Arg-Cys-Cha-Gly-Gly-Arg-Ile-Asp-Arg-He-Phe-Arg-Cys; Ser-Ser-Cys-Cha-Gly-Gly-(D)Arg-Ile-Asp-Arg-He-Phe-Arg-Cys; Cys-Cha-Gly-Gly-Arg-Ile-Asp-Arg-He-Phe-Arg-Cys; Cys-Arg-Cha-Gly-Gly-Arg-Ile-Asp-Arg-He-Phe-Arg-Cys; Arg-Cys-Cha-Gly-Gly-Arg-He-Asp-Arg-Ile-Phe-Arg-Cys-NH2; Arg-Cys-Cha- (D) Ala-Ala-Arg-Ile-Asp-Arg-He-Phe-Arg-Cys-NH2; Arg-Cys-Tic-Gly-Gly-Arg-Ile-Asp-Arg-He-Phe-Arg-Cys-NH2; Arg-Cys-Phe-Gly-Gly-Ile-Asp-Arg-He-Phe-Arg-Cys-NH2 ; His-Cys-Cha-Gly-Gly-Arg-Ile-Asp-Arg-He-Phe-Arg-Cys-NH2; Arg-Cys-Cha-Gly-Gly-Arg-Phe-Asp-Arg-He-Phe-Arg-Cys-NH2; Cys-Cha-Gly-Gly-Arg-Ile-Asp-Arg-He-Phe-Arg-Cys-NH2 ; Orn-Cys-Cha-Gly-Gly-Arg-Ile-Asp-Arg-He-Phe-Arg-Cys-NH2 ; AcetylArg-Cys-Cha-Gly-Gly-Arg-Ile-Asp-Arg-He-Phe-Arg-Cys-NH2; Cit-Cys-Cha-Gly-Gly-Arg-Ile-Asp-Arg-He-Phe-Arg-Cys-NH2; Arg-Cys-Cha-Gly-Gly-Arg-Ile-Asp-Arg-He-Phe-Cys-NH2 ; Arg-Cys-3 , 5-l2Tyr-Gly-Gly-Arg-Ile-Asp-Arg-He-Phe-Arg-Cys-NH2 ; Arg-Cys-Cha-Gly-Gly-Arg-Ile-Asp-Arg-He-Arg-Cys-NH2 ; Arg-Cys-Cha-Gly-Gly-Lys-Ile-Asp-Arg-He-Phe-Arg-Cys-NH2; Arg-Cys-Cha-Gly-Gly-Arg-Ile-Asp-Arg-He-Gly-Ala-Cys-NH2; Arg-Cys-Cha-Gly-Gly-Arg-Ile- (D) Asp-Arg-He-Phe-Arg-Cys-NH2; ( D ) Arg-Cys-Cha-Gly-Gly-Arg-Ile-Asp-Arg-He-Phe-Arg-Cys-NH2 ; Arg-Cys-Chg-Gly-Gly-Arg-Ile-Asp-Arg-He-Phe-Arg-Cys-NH2 ; Arg-Cys-Cha-Gly-Gly-Arg-He-Asp-Arg-Ala-Phe-Arg-Cys-NH2 ; Arg-Cys- (D) Cha-Gly-Gly-Arg-Ile-Asp-Arg-He-Phe-Arg-Cys-NH2; Arg-Cys-Cha-Gly-Gly-Arg-He-Ala-Arg-Ile-Ala-Arg-Cys ; Mpa-Cha-Gly-Gly-Arg-Ile-Asp-Arg-He-Phe-Arg-Cys-NH2 ; Arg-Cys-Cha-Gly-Gly- (D) Arg-Ile-Asp-Arg-He-Phe-Arg-Cys ; Arg-Cys-Pic-Gly-Gly-Arg-Ile-Asp-Arg-He-Phe-Arg-Cys ; Ser-Ser-Cys-Phe-Gly-Gly-Arg-Ile-Asp-Arg-He-Phe-Arg-Cys ; Cy s-Cha-Gly-Gly-Arg-He- (D ) Asp-Arg-He-Phe-Arg-Cys-NH2 ; Cys-Cha-Gly-Gly-Arg-He-Asp-Arg-Ala-Phe-Arg-Cys-NH2 ; Cys-Cha-Gly-Gly-Arg-Ile-Asp-Ala-He-Phe-Arg-Cys-NH2 ; Mpa-Cha-Gly-Gly-Arg-Ile-beta-Asp-Arg-He-Phe-Arg-Cys-NH2 ; Cys-Cha-Gly-Gly-Arg-He-Asp-Arg- (D) Ile-Phe-Arg-Cys-NH2 ; Cys-Cha-Gly-Gly-Arg-Nva-Asp-Arg-Nva-Phe-Arg-Cys-NH2 ; Cys- (D) Phe-Gly-Gly-Arg-Ile-Asp-Arg-He-Phe-Arg-Cys-NH2 ; Mpa-Cha-Gly-Gly-Arg-Ile-Asp-Arg-He-Phe- (D) Arg-Cys-NH2 ; Mpa-Cha-Gly-Gly-Arg-Ile-Asp-Arg-He-Phe-Arg- (D) Cys-NH2 ; Mpa-Cha-(D)Ala-Arg-Arg-Ile-Asp-Arg-He-Phe-Arg-Cys-NH2; Cys-Phe-Gly-Gly-Arg-Leu-Asp-Arg-He-Leu-Arg-Cys-NH2; Mpa-Cha-Gly-Gly-Arg-Ile-Glu-Arg-He-Phe-Arg-Cys-NH2; Mpa-Cha-Gly-Gly-(D)Arg-Ile-Asp-Arg-He-Phe-Arg-Cys-NH2; Mpa-Cha-Gly-Gly-Arg-Ile-Asp-Arg-He-(D)Phe-Arg-Cys-NH2; Aha-Cys-Cha-(D)Ala-(D)Ala-Arg-Ile-Asp-Arg-He-Phe-Arg-Cys-NH2; Mpa-Cha-Gly-Gly-Arg-Ile-His-Arg-Ile-Phe-Arg-Cys-NH2; Mpa-Phe-Gly-Gly-Arg-Ile-Asp-Arg-He-Phe-Arg-Cys-NH2; Mpa-Cha-(D)Ala-Ala-Arg-Ile-Asp-Arg-He-Phe-Arg-(D)Cys-NH2; and Mpa-Cha-(D)Ala-Ala-Arg-Ile-Asp-Arg-Ile-[Phe^Arg]-(D)Cys-NH2; or a pharmaceutically acceptable salt, ester, or amide thereof. 5. A pharmaceutical composition comprising a therapeutically effective amount of the compound of Claim 1 and a pharmaceutically acceptable carrier or a diluent. 6. A method of producing natriuresis comprising administering, to a patient in need, a therapeutically effective amount of the compound of Claim 1. 7. A method of producing diuresis comprising administering, to a patient in need, a therapeutically effective amount of the compound of Claim 1. 8. A method of producing renovasodilation comprising administering, to a patient in need, a therapeutically effective amount of the compound of Claim 1. 9. A method of providing renoprotection comprising administering, to a patient in need, a therapeutically effective amount of the compound of Claim 1. 10. A method of treating ANP-related disorders comprising administering, to a patient in need, a therapeutically effective amount of the compound of Claim 1. 11. A method according to Claim 10 in which the ANP- related disorder is selected from hypertension, renal failure, cerebral edema, congestive heart failure and cirrhosis.

Inventors: DAVIDSEN STEVEN K, LUCAS SCOTT D, ROCKWAY TODD W, THOMAS A MITCHELL, VON GELDERN THOMAS W, DAVIDSEN, STEVEN, K., LUCAS, SCOTT, D., ROCKWAY, TODD, W., THOMAS, A., MITCHELL, VON GELDERN, THOMAS, W.
Applicants: ABBOTT LAB, ABBOTT LABORATORIES
Application year: 1990
Main classification: A61K37
IPC codes: A61K38, A61P7, A61P9, C07K7, C07K14