Title of Invention	HEPTA-OCTA- AND NONAPEPTIDES HAVING ANTIANGIOGENIC ACTIVITY
Abstract	Hepta-Octa-and Nonapeptides having antiangiogenic activity Compounds of formula (SEQ ID NO:1), which are useful for treating conditions that arise from or are exacerbated by angiogenesis, are described. Also disclosed are pharmaceutical compositions comprising these compounds, methods of treatment using these compounds, and methods of inhibiting angiogenesis

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THE PATENTS ACT, 1970 COMPLETE SPECIFICATION Section 10 Hepta-Octa- and Nonapeptides having antiangiogenic activity Abbott Laboratories, a corporation organized and existing under the laws of USA, of Dept. 377 BIdg Ap6A-1, 100 Abbott Park Road, Abbott Park, Illinois 60064-6008 USA. The following specification particularly describes the invention and the manner in which it is to be performed: ORIGINAL 255/MUMNP/2004 31/10/2004 Technical Field The present invention relates to hepta-, octa- and nanopeptides having antiangiogenic activity which can be used for inhibiting angiogenesis and consequently for the treatment of cancer and other conditions arising from or exacerbated by angiogenesis. Pharmaceutical compositions describing the peptides are also disclosed. Background of the Invention Angiogenesis is the fundamental process by which new blood vessels are formed and is essential to a variety of normal body activities (such as reproduction, development and wound repair). Although the process is not completely understood, it is believed to involve a complex interplay of molecules which both stimulate and inhibit the growth of endothelial cells, the primary cells of the capillary blood vessels. Under normal conditions these molecules appear to maintain the 20 microvasculature in a quiescent state (i.e., one of no capillary growth) for prolonged periods that may last for weeks, or in some cases, decades. However, when necessary, such as during wound repair, these same cells can undergo rapid proliferation and turnover within as little as five days. Although angiogenesis is a highly regulated process under normal conditions, many diseases (characterized as "angiogenic diseases") are driven by persistent unregulated angiogenesis. Otherwise stated, unregulated angiogenesis may either cause a particular disease directly or exacerbate an existing pathological condition. For example, the growth and metastasis of solid tumors have been shown to be angiogenesis-dependent. Based on these findings, there is a continuing need for compounds which demonstrate antiangiogenic activity due to their potential use in the treatment of various diseases such as cancer. Peptides having angiogenesis inhibiting 30 properties have been described in commonly-owned WO01/38397, WO01/38347, W099/61476, and U.S. Patent Application Ser. No. 09/915,956. However, it would be desirable to prepare antiangiogenic compounds having improved profiles of activity and smaller size. Summary of the Invention In its principle embodiment, the present invention provides a compound of formula (1) Xaa'-Xaa2-Xaa3-Xaa4-Xaa5-Xaa6-Xaa7-Xaas-Xaa9-Xaa 0 (1), (SEQ ID NO: 1) or a therapeutically acceptable salt thereof, wherein Xaar is selected from the group consisting of hydrogen and R-(CH2) ,rC(0)-, wherein n is an integer from 0 to 8 and R is selected from the group consisting of alkoxy, alkyl, amino, aryl, do carboxyl, cycloalkenyl, cycloalkyl, and heterocycle; 2 510 15 20 25 30 35 40 In another preferred embodiment, the present invention provides compound of formula (I), or a therapeutically acceptable salt thereof, wherein Xaa2 is selected from the group consisting of glutaminyl and D-glutaminyl, and Xaa1, Xaa3, Xaa4, Xaa5, Xaag, Xaa7, Xaa8, Xaa9, and Xaaioare as described for formula (I). 5 In another preferred embodiment, the present invention provides a compound of formula (I), or a therapeutically acceptable salt thereof, wherein Xaa2 is glycyl; Xaa3 is selected from the group consisting of arginyl, asparaginyl, D-asparaginyl, citrullyl, lysyl(N-epsilon-acetyi), and histidyl; and Xaa1, , Xaa4, Xaa5, Xaag, Xaa7, Xaa8, Xaa9,, and Xaa10 are as described for formula (1). In another preferred embodiment, the present invention provides a compound of formula (I), 10 or a therapeutically acceptable salt thereof, wherein Xaa2 is glycyl; Xaa3 is selected from the group consisting of valyl and N-methyivalyl, Xaag is selected from the group consisting of norvalyl and N-methylnorvalyl; and Xaa1, , Xaa4, Xaa5, Xaag, Xaa7, Xaa8, Xaa9,, and Xaa10 are as described for formula (I). In another preferred embodiment, the present invention provides a compound of formula (I), or a therapeutically acceptable salt thereof, wherein Xaa2 is glycyl; Xaa3 is selected from the group 15 consisting of valyl and N-methylvalyl, Xaag is selected from the group of glutaminyl, seryl, and threonyl; andXaa1, , Xaa4, Xaa5, Xaag, Xaa7, Xaa8, Xaa9,, and Xaa10 are as described for formula (I). In another preferred embodiment, the present invention provides a compound of formula (I), or a therapeutically acceptable salt thereof, wherein Xaa2 is glycyl; Xaa3 is selected from the group consisting of glutaminyl, D-glutaminyl, phenylalanyl, and N-methylphenylalanyl, Xaa7 is isoleucyl; 20 and Xaa1, , Xaa4, Xaa5, Xaag, Xaa7, Xaa8, Xaa9,, and Xaa10are as described for formula (I). In another preferred embodiment, the present invention provides a compound of formula (1), or a therapeutically acceptable salt thereof, wherein Xaa2 is glycyl; Xaa3 is selected from the group consisting of glutaminyl, D-glutaminyl, and phenylalanyl; Xaa7 is selected from the group consisting of D-isoleucyl, lysyI(N-epsi!on acetyl), and D-prolyl; andXaa1, , Xaa4, Xaa5, Xaa6, Xaa8, 25 Xaa9 and Xaa10 are as described for formula (I). In another embodiment, the present invention provides a pharmaceutical composition comprising a compound of formula (I), or a therapeutically acceptable salt thereof, in combination with a therapeutically acceptable carrier. In another embodiment, the present invention provides a method of inhibiting angiogenesis 30 in a mammal in recognized need of such treatment comprising administering to the mammal a therapeutically acceptable amount of a compound of formula (I) or a therapeutically acceptable salt thereof. In another embodiment, the present invention provides a method of treating cancer in a mammal in recognized need of such treatment comprising administering to the mammal a 35 therapeutically acceptable amount of a compound of formula (1) or a therapeutically acceptable salt thereof. Detailed Description of the Invention As used herein, the singular forms "a", "an", and "the" include plural reference unless the 40 context clearly dictates otherwise. As used in the present specification the following terms have the meanings indicated: The term "alkoxy," as used herein, represents an alky! group attached to the parent molecular moiety through an oxygen atom. The term "alkyl," as used herein, represents a monovalent group derived from a straight or 5 branched chain saturated hydrocarbon by the removal of a hydrogen atom. Preferred alkyl groups for the present invention invention are alkyl groups having from one to six carbon atoms (C1-C6 alkyl). Alkyl groups of one to three carbon atoms (C1-C3 alkyl) are more preferred for the present invention. The term "alkylcarbonyl," as used herein, represents an alkyl group attached to the parent 10 molecular moiety through a carbonyl group. The term "amino," as used herein, represents-NRaR , wherein Ra and R are independently selected from the group consisting of hydrogen, alkyl, and alkylcarbonyl. The term "aryl," as used herein, represents a phenyl group, or a bicyclic or tricyclic fused ring system wherein one or more of the fused rings is a phenyl group. Bicyclic fused ring systems 15 are exemplified by a phenyl group fused to a cycloalkenyl group, as defined herein, a cycloalkyi group, as defined herein, or another phenyl group. Tricyclic fused ring systems are exemplified by a bicyclic fused ring system fused to a cycloalkenyl group, as defined herein, a cycloalkyi group, as defined herein or another phenyl group. Representative examples of aryl include, but are not limited to, anthracenyl, azulenyl, fluorenyl, indanyl, indenyl, naphthyl, phenyl, and tetrahydronaphthyl. 20 The aryl groups of the present invention can be optionally substituted with one, two, three, four, or five substituents independently selected from the group consisting of alkoxy, alkyl, carboxyl, halo, and hydroxy I. The term "carbonyl," as used herein, represents-C(O)-. The term "carboxyl," as used herein, represents-CO2H. 25 The term "cycloalkenyl," as used herein, refers to a non-aromatic cyclic or bicyclic ring system having three to ten carbon atoms and one to three rings, wherein each five-membered ring has one double bond, each six-membered ring has one or two double bonds, each seven- and eight-membered ring has one to three double bonds, and each nine-to ten-membered ring has one to four double bonds. Examples of cycloalkenyl groups include cyclohexenyl, octahydronaphthalenyl, 30 norbornylenyl, and the like. The cycloalkenyl groups of the present invention can be optionally substituted with one, two, three, four, or five substituents independently selected from the group consisting of alkoxy, alkyl, carboxyl, halo, and hydroxyl. The term "cycloalkyi," as used herein, refers to a saturated monocyclic, bicyclic, or tricyclic hydrocarbon ring system having three to twelve carbon atoms. Examples of cycloalkyi groups 35 include cyciopropyl, cyclopentyl, bicyc!o[3.1.1 jheptyl, adamantyl, and the like. The cycloalkyi groups of the present invention can be optionally substituted with one, two, three, four, or five substituents independently selected from the group consisting of alkoxy, alkyl, carboxyl, halo, and hydroxyl. The term "halo," as used herein, represents F, CI, Br, or 1. The term "heterocycle," as used herein, refers to a five-, six-, or seven-membered ring containing one, two, or three heteroatoms independently selected from the group consisting of nitrogen, oxygen, and sulfur. The five-membered ring has zero to two double bonds and the six-and seven-membered rings have zero to three double bonds. The term "heterocycle" also includes 5 bicyclic groups in which the heterocycle ring is fused to an aryl group, as defined herein. The heterocycle groups of the present invention can be attached through a carbon atom or a nitrogen atom in the group. Examples of heterocycles include, but are not limited to, furyl, thienyl, pyrrolyl, pyrrolidinyl, oxazolyl, thiazolyl, imidazolyl, imidazolinyl, pyrazolyl, isoxazolyl, isothiazolyl, piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl, pyridinyl, indolyl, indolinyl, benzothienyl, 10 and the like. The heterocycle groups of the present invention can be optionally substituted with one, two, three, or four substituents independently selected from the group consisting ofalkoxy, alkyl, carboxyl, halo, and hydroxyl. The term "hydroxyl," as used herein, represents -OH. The term "therapeutically acceptable salt," as used herein, represents salts or zwitterionic 15 forms of the compounds of the present invention which are water or oil-soluble or dispersible, which are suitable for treatment of diseases without undue toxicity, irritation, and allergic response; which are commensurate with a reasonable benefit/risk ratio, and which are effective for their intended use. The salts can be prepared during the final isolation and purification of the compounds or separately by reacting an amino group with a suitable acid. Representative acid addition salts 20 include acetate, adipate, alginate, citrate, aspartate, benzoate, benzenesulfonate, bisulfate, butyrate, camphorate, camphorsulfonate, digluconate, glycerophosphate, hemisulfate, heptanoate, hexanoate, formate, fumarate, hydrochloride, hydrobromide, hydroiodide, 2-hydroxyethansulfonate, lactate, maleate, mesitylenesulfonate, methanesulfonate, naphthylenesulfonate, nicotinate, 2-naphthalenesulfonate, oxalate, pamoate, pectinate, persulfate, 3-phenylproprionate, picrate, pivalate, 25 propionate, succinate, tartrate, trichloroacetate,trifluoroacetate, phosphate, glutamate, bicarbonate, para-toluenesulfonate, and undecanoate. Also, amino groups in the compounds of the present invention can be quaternized with methyl, ethyl, propyl, and butyl chlorides, bromides, and iodides; dimethyl, diethyl, dibutyl, and diamyl sulfates; decyl, lauryl, myristyl, and steryl chlorides, bromides, and iodides; and benzyl and phenethyl bromides. Examples of acids which can be 30 employed to form therapeutically acceptable addition salts include inorganic acids such as hydrochloric, hydrobromic, sulfuric, and phosphoric, and organic acids such as oxalic, maleic, succinic, and citric. Unless indicated otherwise by a "D" prefix, e.g., D-Ala or NMe-D-lle, the stereochemistry of the a-carbon of the amino acids and aminoacyl residues in peptides described in this specification 35 and the appended claims is the natural or "L" configuration. The Cahn-lngold-Prelog "R" and "S" designations are used to specify the stereochemistry of chiral centers in certain acylsubstituents at the N-terminus of the peptides of this invention. The designation "R,S" is meant to indicate a racemic mixture of the two enantiomeric forms. This nomenclature follows that described in R.S. Cahn, aid.. Angew. Chcm. Int. Ed. Engl,5, 385-415 (1966). All peptide sequences are written according to the generally accepted convention whereby the a-N-terminal amino acid residue is on the left and the a-C-terminal is on the right. As used herein, the term "a-N -terminus" refers to the free a-amino group of an amino acid in a peptide, and the term "a-C-terminus" refers to the free a-carboxylic acid terminus of an amino acid in a peptide. 5 For the most part, the names on naturally occurring and non-naturally occurring aminoacyl residues used herein follow the naming conventions suggested by the IUPAC Commission on the Nomenclature of Organic Chemistry and the IUPAC-IUB Commission on Biochemical Nomenclature as set out in "Nomenclature of a-Amino Acids (Recommendations, 1974) " Biochemistry, 14(2), (1975). To the extent that the names and abbreviations of amino acids and 10 aminoacyl residues employed in this specification and appended claims differ from those suggestions, they will be made clear to the reader. Some abbreviations useful in describing the invention are defined below in the following Table 1. . Table 1 When not found in the table above, nomenclature and abbreviations may be further clarified by reference to the Calbiochem-Novabiochem Corp. 1999 Catalog and Peptide Synthesis Handbook or the Chem-Impex International, Inc. Tools for Peptide & Solid Phase Synthesis 1998-1999 5 Catalogue. Compositions The compounds of the invention, including not limited to those specified in the examples, possess anti-angiogenic activity. As angiogenesis inhibitors, such compounds are useful in the treatment of both primary and metastatic solid tumors, including carcinomas of breast, colon, rectum, lung, oropharynx, hypopharynx, esophagus, stomach, pancreas, liver, gallbladder and bile 5 ducts, small intestine, urinary tract (including kidney, bladder and urothelium), female genital tract (including cervix, uterus, and ovaries as well as choriocarcinoma and gestational trophoblastic disease), male genital tract (including prostate, seminal vesicles, testes and genu cell tumors), endocrine glands (including the thyroid, adrenal, and pituitary glands), and skin, as well as hemangiomas, melanomas, sarcomas (including those arising from bone and soft tissues as well as 10 Kaposi's sarcoma) and tumors of the brain, nerves, eyes, and meninges (including astrocytomas, gliomas, glioblastomas, retinoblastomas, neuromas, neuroblastomas, Schwannomas, and meningiomas). Such compounds may also be useful in treating solid tumors arising from hematopoietic malignancies such as leukemias (i.e., chloromas, plasmacytomas and the plaques and tumors of mycosis fungosides and cutaneous T-cell lymphoma/leukemia) as well as in the treatment 15 of lymphomas (both Hodgkin's and non-Hodgkin's lymphomas). In addition, these compounds may be useful in the prevention of metastases from the tumors described above either when used alone or in combination with radiotherapy and/or other chemotherapeutic agents. Further uses include the treatment and prophylaxis of autoimmune diseases such as rheumatoid, immune and degenerative arthritis; various ocular diseases such as diabetic retinopathy, 20 retinopathy of prematurity, corneal graft rejection, retrolental fibroplasia, neovascular glaucoma, rubeosis, retinal neovascularization due to macular degeneration, hypoxia, angiogenesis in the eye associated with infection or surgical intervention, and other abnormal neovascularization conditions of the eye; skin diseases such as psoriasis; blood vessel diseases such as hemagiomas, and capillary proliferation within atherosclerotic plaques; Osier-Webber Syndrome; myocardial angiogenesis; 25 plaque neovascularization; telangiectasia; hemophiliac joints; angiofibroma; and wound granulation. Other uses include the treatment of diseases characterized by excessive or abnormal stimulation of endothelial cells, including not limited to intestinal adhesions, Crohn's disease, atherosclerosis, scleroderma, and hypertrophic scars (i.e., keloids). Another use is as a birth control agent, by inhibiting ovulation and establishment of the placenta. The compounds of the invention are also 30 useful in the treatment of diseases that have angiogenesis as a pathologic consequence such as cat scratch disease (Rochele minulesalia quintosd) and ulcers {Helicobacterpylori). The compounds of the invention are also useful to reduce bleeding by administration prior to surgery, especially for the treatment of resectable tumors. The compounds of the invention may be used in combination with other compositions and 35 procedures for the treatment of diseases. For example, a tumor may be treated conventionally with surgery, radiation or chemotherapy combined with a peptide of the present invention and then a peptide of the present invention may be subsequently administered to the patient to extend the dormancy of micrometastases and to stabilize and inhibit the growth of any residual primary tumor. Additionally, the compounds of the invention may be combined with pharmaceutically acceptable excipients, and optionally sustained-release matrices, such as biodegradable polymers, to form therapeutic compositions. A sustained-release matrix, as used herein, is a matrix made of materials, usually polymers, which are degradable by enzymatic or acid-base hydrolysis or by dissolution. Once inserted into the 5 body, the matrix is acted upon by enzymes and body fluids. A sustained-release matrix desirably is chosen from biocompatible materials such as liposomes, polylactides (polylactic acid), polyglycolide (polymer of glycolic acid), polylactide co-glycolide (copolymersof lactic acid and glycolic acid) polyanhydrides, poly(ortho)esters, polypeptides, hyaluronic acid, collagen, chondroitin sulfate, carboxylic acids, fatty acids, phospholipids, polysaccharides, nucleic acids, 10 polyamino acids, amino acids such as phenylalanine, tyrosine, isoleucine, polynucleotides, polyvinyl propylene, polyvinylpyrrolidone and silicone. A preferred biodegradable matrix is a matrix of one of either polylactide, polyglycolide, or polylactide co-glycolide (co-polymers of lactic acid and glycolic acid). When used in the above or other treatments, a therapeutically effective amount of one of the 15 compounds of the present invention may be employed in pure form or, where such forms exist, in pharmaceutically acceptable salt form. By a "therapeutically effective amount" of the compound of the invention is meant a sufficient amount of the compound to treat an angiogenic disease, (for example, to limit tumor growth or to slow or block tumor metastasis) at a reasonable benefit/risk ratio applicable to any medical treatment. It will be understood, however, that the total daily usage 20 of the compounds and compositions of the present invention will be decided by the attending physician within the scope of sound medical judgment. The specific therapeutically effective dose level for any particular patient will depend upon a variety of factors including the disorder being treated and the severity of the disorder; activity of the specific compound employed; the specific composition employed, the age, body weight, general health, sex and diet of the patient; the time of 25 administration, route of administration, and rate of excretion of the specific compound employed; the duration of the treatment; drugs used in combination or coincidential with the specific compound employed; and like factors well known in the medical arts. For example, it is well within the skill of the art to start doses of the compound at levels lower than those required to achieve the desired therapeutic effect and to gradually increase the dosage until the desired effect is achieved. 30 Alternatively, a compound of the present invention may be administered as pharmaceutical compositions containing the compound of interest in combination with one or more pharmaceutically acceptable excipients. A pharmaceutically acceptable carrier or excipient refers to a non-toxic solid, semi-solid or liquid filler, diluent, encapsulating material or formulation auxiliary of any type. The compositions may be administered parenterally, intracisternally, htravaginally, 35 intraperitoneally, topically (as by powders, ointments, drops or transdermal patch), rectally, or bucally. The term "parenteral" as used herein refers to modes of administration which include intravenous, intramuscular, intraperitoneal, intrasternal, subcutaneous and intraarticular injection and infusion. Pharmaceutical compositions for parenteral injection comprise pharmaceutically-acceptable 40 sterile aqueous or nonaqueous solutions, dispersions, suspensions or emulsions, as well as sterile powders for reconstitution into sterile injectable solutions or dispersions just prior to use. Examples of suitable aqueous and nonaqueous carriers, diluents, solvents or vehicles include water, ethanol, polyols (such as glycerol, propylene glycol, polyethylene glycol, and the like), carboxymethylcellulose and suitable mixtures thereof, vegetable oils (such as olive oil), and 5 injectable organic esters such as ethyl oleate. Proper fluidity may be maintained, for example, by the use of coating materials such as lecithin, by the maintenance of the required particle size in the case of dispersions, and by the use of surfactants. These compositions may also contain adjuvants such as preservative, wetting agents, emulsifying agents, and dispersing agents. Prevention of the action of microorganisms may be 10 ensured by the inclusion of various antibacterial and antifungal agents, for example, paraben, chlorobutanol, phenol sorbic acid, and the like. It may also be desirable to include isotonic agents such as sugars, sodium chloride, and the like. Prolonged absorption of the injectable pharmaceutical form may be brought about by the inclusion of agents which delay absorption, such as aluminum monostearate and gelatin. 15 Injectable depot forms are made by forming microencapsule matrices of the drug in biodegradable polymers such as polylactide-polyglycolide, poly(orthoesters), poly(anhydrides), and (poly)glycols, such as PEG. Depending upon the ratio of drug to polymer and the nature of the particular polymer employed, the rate of drug release can be controlled. Depot injectable formulations are also prepared by entrapping the drug in liposomes or microemulsions which are 20 compatible with body tissues. The injectable formulations may be sterilized, for example, by filtration through a bacterial-retaining filter, or by incorporating sterilizing agents in the form of sterile solid compositions which can be dissolved or dispersed in sterile water or other sterile injectable medium just prior to use. Topical administration includes administration to the skin or mucosa, including surfaces of 25 the lung and eye. Compositions for topical administration, including those for inhalation, may be prepared as a dry powder which may be pressurized or non-pressurized. In non-pressurized powder compositions, the active ingredient in finely divided form may be used in admixture with a larger-sized pharmaceutically-acceptable inert carrier comprising particles having a size, for example, of up to 100 micrometers in diameter. Suitable inert carriers include sugars such as lactose. Desirably, 30 at least 95% by weight of the particles of the active ingredient have an effective particle size in the range of 0.01 to 10 micrometers. Alternatively, the composition may be pressurized and contain a compressed gas, such as nitrogen or a liquified gas propellant. The liquified propellant medium and indeed the total composition is preferably such that the active ingredient does not dissolve therein to any substantial 35 extent. The pressurized composition may also contain a surface active agent, such as a liquid or solid non-ionic surface active agent or may be a solid anionic surface active agent. It is preferred to use the solid anionic surface active agent in the form of a sodium salt. A further form of topical administration is to the eye. A compound of the invention is delivered in a pharmaceutically acceptable ophthalmic vehicle, such that the compound is 40 maintained in contact with the ocular surface for a sufficient time period to allow the compound to penetrate the corneal and internal regions of the eye, as for example the anterior chamber, posterior chamber, vitreous body, aqueous humor, vitreous humor, cornea, iris/ciliary, lens, choroid/retina and sclera. The pharmaceutically-acceptable ophthalmic vehicle may, for example, be an ointment, vegetable oil or an encapsulating material. Alternatively, the compounds of the invention may be 5 injected directly into the vitreous and aqueous humour. Compositions for rectal or vaginal administration are preferably suppositories which may be prepared by mixing the compound? of this invention with suitable non-irritating excipients or carriers such as cocoa butter, polyethylene glycol or a suppository wax which are solid at room temperature liquid at body temperature and therefore melt in the rectum or vaginal cavity and 10 release the active compound. Compounds of the present invention may also be administered in the form of liposomes. As is known in the art, liposomes are generally derived from phospholipids or other lipid substances. Liposomes are formed by mono- or multi-lamellar hydrated liquid crystals that are dispersed in an aqueous medium. Any non-toxic, physiologically-acceptable and metabolizable lipid capable of 15 forming liposomes can be used. The present compositions in liposome form can contain, in addition to a compound of the present invention, stabilizers, preservatives, excipients, and the like. The preferred lipids are the phospholipids and the phosphatidyl cholines (lecithins), both natural and synthetic. Methods to form liposomes are known in the art. See, for example, Prescott, Ed., Methods in Cell Biology, Volume XIV, Academic Press, New York, N.Y. (1976), p. 33et seq. 20 While the compounds of the invention can be administered as the sole active pharmaceutical agent, they may also be used in combination with one or more agents which are conventionally administered to patients for treating angiogenic diseases. For example, the compounds of the invention are effective over the short term to make tumors more sensitive to traditional cytotoxic therapies such as chemicals and radiation. The compounds of the invention also enhance the 25 effectiveness of existing cytotoxic adjuvant anti-cancer therapies. The compounds of the invention may also be combined with other antiangiogenic agents to enhance their effectiveness, or combined with other antiangiogenic agents and administered together with other cytotoxic agents. In particular, when used in the treatment of solid tumors, compounds of the invention may be administered with IL-12, retinoids, interferons, angiostatin, endostatin, thalidomide, 30 thrombospondin-1, thrombospondin-2, captopryl, angioinhibins, TNP-470, pentosan polysulfate, platelet factor 4, LM-609, SU-5416, CM-I01, Tecogalan, plasminogen-K-5, vasostatin, vitaxin, vasculostatin, squalamine, marimastat or other MMP inhibitors, anti-neoplastic agents such as alpha inteferon, COMP (cyclophosphamide, vincristine, methotrexate and prednisone), etoposide, mBACOD (methortrexate, bleomycin, doxorubicin, cyclophosphamide, vincristine and 35 dexamethasone), PRO-MACE/MOPP (prednisone, methotrexate (w/leucovin rescue), doxorubicin, cyclophosphamide, cisplatin, taxol, etoposide/mechlorethamine, vincristine, prednisone and procarbazine), vincristine, vinblastine, and the like as well as with radiation. Total daily dose of the compositions of the invention to be administered to a human or other mammal host in single or divided doses may be in amounts, for example, from 0.0001 to 300 mg/kg 40 body weight daily and more usually 1 to 300 mg/kg body weight. It will be understood that agents which can be combined with the compound of the present invention for the inhibition, treatment or prophylaxis of angiogenic diseases are not limited to those listed above, include in principle any agents useful for the treatment or prophylaxis of angiogenic diseases. 5 Determination of Biological Activity In Vitro Assay for Angiogenic Activity The human microvascular endothelial (HMVEC) migration assay was run according to the procedure of S. S. Tolsma, O. V. Volpert, D. J. Good, W. F. Frazier, P. J. Polverini and N. Bouck, J. 10 Cell Biol. 1993,122, 497-511. The HMVEC migration assay was carried out using Human Microvascular Endothelial Cells-Dermal (single donor) and Human Microvascular Endothelial Cells, (neonatal). The HMVEC cells were starved overnight in DME containing 0.01% bovine serum albuminutes (BSA). Cells were then harvested with trypsin and resuspended in DME with 0.01% BSA at a concentration of 15 1.5 X 106 cells per mL. Cells were added to the bottom of a 48 well modified Boyden chamber (Nucleopore Corporation, Cabin John, MD). The chamber was assembled and inverted, and cells were allowed to attach for 2 hours at 37 °C to polycarbonate chemotaxis membranes (5|im pore size) that had been soaked in 0.01% gelatin overnight and dried. The chamber was then reinverted, and test substances (total volume of 50 uL), including activators, 15 ng/mL bFGF/VEGF, were 20 added to the wells of the upper chamber. The apparatus was incubated for 4 hours at 37 °C. Membranes were recovered, fixed and stained (Diff Quick, Fisher Scientific) and the number of cells that had migrated to the upper chamber per 3 high power fields counted. Background migration to DME + 0.1 BSA was subtracted and the data reported as the number of cells migrated per 10 high power fields (400X) or, when results from multiple experiments were combined, as the 25 percent inhibition of migration compared to a positive control. Representative compounds inhibited human endothelial cell migration in the above assay by at least 50% when tested at a concentration of 1 nM. Preferred compounds inhibited human endothelial cell migration by approximately 65% to 90% when tested at a concentration of 1 nM and most preferred compounds inhibited human endothelial cell migration by approximately 50% to 30 95% at a concentration of 0.1 nM. As shown by these results, the compounds of the present invention demonstate enhanced potency. Synthesis of the Peptides This invention is intended to encompass compounds having formula (I) when prepared by 35 synthetic processes or by metabolic processes. Preparation of the compounds of the invention by metabolic processes include those occurring in the human or animal body (in vivo) or processes occurring in vitro. The polypeptides of the present invention may be synthesized by many techniques that are known to those skilled in the art. For solid phase peptide synthesis, a summary of the many 40 techniques may be found in J.M. Stewart and J.D. Young, Solid Phase Peptide Synthesis, W.H. Freeman Co. (San Francisco), 1963 and J. Meienhofer, Hormonal Proteins and Peptides, vol. 2, p. 46, Academic Press (New York), 1973. For classical solution synthesis see G. Schroder and K. Lupke, The Peptides, vol. 1, Academic Press ("New York), 1965. Reagents, resins, amino acids, and amino acid derivatives are commercially available and 5 can be purchased from Chem-Impex International, Inc. (Wood Dale, IL, U.S.A.) or Calbiochem-Novabiochem Corp. (San Diego, CA, U.S.A.) unless otherwise noted herein. In general, these methods comprise the sequential addition of one or more amino acids or suitably protected amino acids to a growing peptide chain. Normally, either the amino or carboxyl group of the first amino acid is protected by a suitable protecting group. The protected or 10 derivatized amino acid can then be either attached to an inert solid support or utilized in solution by adding the next amino acid in the sequence having the complimentary (amino or carboxyl) group suitably protected, under conditions suitable for forming the amide linkage. The protecting group is then removed from this newly added amino acid residue and the next amino acid (suitably protected) is then added, and so forth. After all the desired amino acids have been linked in the 15 proper sequence, any remaining protecting groups (and any solid support) are removed sequentially or concurrently, to afford the final polypeptide. By simple modification of this general procedure, it is possible to add more than one amino acid at a time to a growing chain, for example, by coupling (under conditions which do not racemize chiral centers) a protected tripeptide with a properly protected dipeptide to form, after deprotection, a pentapeptide. 20 A particularly preferred method of preparing compounds of the present invention involves solid phase peptide synthesis. In this particularly preferred method the ot-amino function is protected by an acid or base sensitive group. Such protecting groups should have the properties of being stable to the conditions of peptide linkage formation, while being readily removable without destruction of the growing peptide chain or racemization of any of the chiral centers contained 25 therein. Suitable protecting groups are 9-fluorenylmethyloxycarbonyl (Fmoc), t-butoxycarbonyl (Boc), benzyioxycarbonyi (Cbz), biphenyiisopropyi-oxycarbonyi, t-amyioxycarbonyl, isobornyloxycarbonyl, (a,a)-dimethyl-3,5-dimethoxybenzyloxycarbonyl, O-nitrophenylsulfenyl, 2-cyano-t-butyloxycarbonyl, and the like. The 9-fluorenylmethyloxycarbonyl (Fmoc) protecting group is preferred. 30 Particularly preferred side chain protecting groups are: for arginine: 2,2,5,7,8- pentamethylchroman-6-sulfonyl (Pmc), and 2,2,4,6,7-pentamethyldihydrobenzofuran-S-sulfonyl (Pbf); for asparagine: trityl (Trt); for aspartic acid: t-buyl (t-Bu); for glutamine: trityl (Trt); for N-methylglutamic acid: t-butyl (t-Bu); for histidine: trityl (Trt); for lysine: t-butoxycarbonyl (Boc); for seryl: t-butyl (t-Bu); for threonine and allothreonine: t-butyl (t-Bu); for tryptophan: t- 35 butoxycarbonyl (Boc); and for tyrosine: t-butyl (t-Bu). In the solid phase peptide synthesis method, the C-terminal amino acid is attached to a suitable solid support or resin. Suitable solid supports useful for the above synthesis are those materials which are inert lo the reagents and reaction conditions of the stepwise condensation-deprotection reactions, as well as being insoluble in the media used. The preferred solid support for 40 synthesis of C-terminal carboxyl peptides is Sieber amide resin or Sieber ethylamide resin. The preferred solid support for C-terminal amide peptides is Sieber ethylamide resin available from Novabiochem Corporation. The C-terminal amino acid is coupled to the resin by means of a coupling mediated by N,N'-dicyclohexylcarbodiimide (DCC), N,N'-diisopropylcarbodiimide (D1C), [0-(7-azabenzotriazoI-l-5 y I)-1,1,3,3-tetramethyluronium hexafluorophosphate] (HATU), or 0-benzotriazol-l-yl-N,N,N',N'-tetramethyluroniumhexafluorophosphate (HBTU), with or without 4-dimethylaminopyridine (DMAP), 1-hydroxybenzotriazole (HOBT), N-methylmorpholine (NMM), benzotriazol-1-yloxy-tris(dimethylamino)phosphonium-hexafJuorophosphate (BOP) or bis(2-oxo-3-oxazolidinyl)phosphine chloride (BOPC1), for about 1 to about 24 hours at a temperature of between 10 10 °C and 50 °C in a solvent such as dichloromethane or DMF. When the solid support is Sieber amide or Sieber ethylamide resin, the Fmoc group is cleaved with a secondary amine, preferably piperidine, prior to coupling with the C-terminal amino acid as described above. The preferred reagents used in the coupling to the deprotected 4-(2',4'-dimethoxyphenyI-Fmoc-aminomethyl)phenoxyacetamidoethyl resin are O-benzotriazoi-i-yl- 15 N,N,N\N'-tetramethyluroniumhexafluorophosphate(HBTU, 1 equiv.) with 1-hydroxybenzotriazole (HOBT, 1 equiv.), or [0-(7-azabenzotriazol-l-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate] (HATU, 1 equiv.) with N-methylmorpholine (1 equiv.) in DMF. The coupling of successive protected amino acids can be carried out in an automatic polypeptide synthesizer as is well known in the art. In a preferred embodiment, thea-amino 20 function in the amino acids of the growing peptide chain are protected with Fmoc. The removal of the Fmoc protecting group from the N-terminal side of the growing peptide is accomplished by treatment with a secondary amine, preferably piperidine. Each protected amino acid is then introduced in about 3-fold molar excess and the coupling is preferably carried out in DMF. The coupling agent is normally 0-benzotriazol-l-yl-N,N,N',N'-tetramethyluroniumhexafluorophosphate 25 (HBTU, I equiv.) or [ At the end of the solid phase synthesis, the polypeptide is removed from the resin and deprotected, either in succession or in a single operation. Removal of the polypeptide and deprotection can be accomplished in a single operation by treating the resin-bound polypeptide with 30 a cleavage reagent, for example trifluoroacetic acid containing thianisole, water, or ethanedithiol. In cases where the C-terminus of the polypeptide is an alky lam ide, the resin is cleaved by aminolysis with an alkylamine. Alternatively, the peptide may be removed by transesterification, e.g. with methanol, followed by aminolysis or by direct transamidation. The protected peptide may be purified at this point or taken to the next step directly. The removal of the side chain protecting 35 groups is accomplished using the cleavage cocktail described above. The fully deprotected peptide is purified by a sequence of chromatographic steps employing any or all of the following types: ion exchange on a weakly basic resin in the acetate form; hydrophobic adsorption chromatography on underivitized polystyrene-divinylbenzene (for example, AMBERLITE XAD); silica gel adsorption chromatography; ion exchange chromatography on 40 carboxymethylcellulose; partition chromatography, e.g., on SEPHADEX* C-25, LH-20 or 10 15 countercurrent distribution; high performance liquid chromatography (HPLC), especially reverse-phase HPLC on octyl- oroctadecylsilyl-silica bonded phase column packing. The foregoing may be better understood in light of the examples which are meant to describe compounds and process which can be carried out in accordance with the invention and are not intended as a limitation on the scope of the invention in any way. Abbreviations which have been used the following examples are: DMF for N,N-dimethylformamide; HBTU forO-benzotriazol-l-yl-N,N,N',N*-tetramethyluroniumhexafluorophosphate; NMM for N-methylmorpholine; and TFA for trifluoroacetic acid. Example 1 N-Ac-Gly-Val-D-Ile-Thr-Nva-fle-Arg-ProNHCH2CH2 In the reaction vessel of a Rainin peptide synthesizer was placed Fmoc-Pro-Sieber ethylamide resin (0.25 g, 0.4 mmol/g loading). The resin was solvated with DMF and amino acids were coupled sequentially according to the following synthetic cycle: (1) 3 x 1.5 minute washes with DMF; (2) 2 x15 minute deprotection using 20% piperidine; (3) 6 x3 minute washes with DMF; (4) addition of amino acid; (5) activation of amino acid with 0.4 M HBTU/NMM and coupling; (6) 3 x1.5 minute washes with DMF. The protected amino acids were coupled to the resin in the following order: Protected Amino Acid Coupling time Fmoc-Arg(Pmc) 30 minutes Fmoc-Ile 30 minutes Fmoc-Nva 30 minutes Fmoc-Thr(t-Bu) 30 minutes Fmoc-D-lle 30 minutes Fmoc-Val 30 minutes Fmoc-Gly 30 minutes acetic acid 30 minutes - Upon completion of the synthesis the peptide was cleaved from the resin using a mixture of (95:2.5:2.5) TFA/anisole/water for 3 hours. The peptide solution was concentrated under vacuum 25 and then precipitated with diethyl ether and filtered. The crude peptide was purified by HPLC using a C-18 column and a solvent system varying over 50 minutes in a gradient of 5% to 100% acetonitrile/water containing 0.01% TFA. The pure fractions were lyophilized to provideN-Ac-Gly-Val-D-lle-Thr-Nva-lle-Arg-ProNHCH2CH3 as the trifluoroacetate salt: Rt= 3.16 minutes (gradient varying over 10 minutes from 20% to 80% acetonitrile/water containing 0.01% TFA); MS (ESI) m/e 923 (M+H)+; Amino Acid Anal.: 0.96 Gly; 1.01 Val; 1.98 lie; 0.46 Thr; 0.94 Nva; 1.03 Arg; 0.98 Pro. Example 2 5 N-Ac-Gly-Val-D-alle-Thr-Nva-lle-Arg-ProNHCHjCHj The desired product was prepared by substituting Fmoc-D-alle for Fmoc-D-lle in Example 1. After cleavage of the peptide from the resin and workup the crude product was purified by HPLC using a C-18 column and a solvent system varying over 50 minutes in a gradient of 5% to 100% acetonitrile/water containing 0.01% TFA. The pure fractions were lyophilized to provideN-Ac-10 Gly-Val-D-aHe-Thr-Nva-IIe-Arg-ProNHCH2CH3 as the trifluoroacetate salt: Rt = 2.97 minutes (gradient varying over 10 minutes from 20% to 80% acetonitrile/water containing 0.01% TFA); MS (ESI) m/e 923.7 (M+H)+; Amino Acid Anal.: 0.94 Gly; 0.98 Val; 2.06 lie; 0.51 Thr; 1.04 Nva; 1.00 Arg; 0.97 Pro. 15 Example 3 N-Ac-Gly-Val-D-Ile-alloThr-Nva-lle-Arg-ProNHCHjCHT The desired product was prepared by substituting Fmoc-alloThr(t-Bu) for Fmoc-Thr(t-Bu) in Example 1. After cleavage of the peptide from the resin and workup the crude product was purified by HPLC using a C-18 column and a solvent system varying over 50 minutes in a gradient of 5% to 20 100%> acetonitrile/water containing 0.01 % TFA. The pure fractions were lyophilized to provide N-Ac-Gly-VaI-D-Ile-alloThr-Nva-Ile-Arg-ProNHCH2CH3 as the trifluoroacetate salt: Rt = 2.95 minutes (gradient varying over 10 minutes from 20% to 80% acetonitrile/water containing 0.01% TFA); MS (ESI) m/e 923.7 (M+H)+; Amino Acid Anal.: 1.01 Gly; 0.92 Val; 2.03 He; 0.58 Thr; 0.99 Nva; 1.05 Arg; 0.97 Pro. 25 Example 4 N-Ac-Gly-Val-D-Ile-Thr-Gln-He-Arg-ProNHCrbCFh The desired product was prepared by substituting Fmoc-Gln(Trt) for Fmoc-Nva in Example 1. After cleavage of the peptide from the resin and workup the crude product was purified by HPLC 30 using a C-18 column and a solvent system varying over 50 minutes in a gradient of 5% to 100% acetonitrile/water containing 0.0}% TFA. The pure fractions were lyophilized to provideN-Ac-Gly-Val-D-lle-Thr-Gln-Ile-Arg-ProNHCH2CH3 as the trifluoroacetate salt: Rt = 2.48 minutes (gradient varying over 10 minutes from 20% to 80% acetonitrile/water containing 0.01% TFA); MS (ESI) m/e 952.7 (M+H)+; Amino Acid Anal.: 1.03 Gly; 1.00 Val; 2.10 Me; 0.53 Thr; 0.90 Giu; 0.95 35 Arg; 1.03 Pro. Example 5 N-e-Me-nicotinvl-Glv-Val-D-lle-Thr-Nva-lle-Ar^-ProNHCH^CHj The desired product was prepared by substituting 6-methylnicotinic acid for acetic acid in 40 Example 1. After cleavage of the peptide from the resin and workup the crude product was purified by HPLC using a C-l 8 column and a solvent system varying over 50 minutes in a gradient of 5% to 100% acetonitrile/water containing 0.01% TFA. The pure fractions were lyophilized to provide N-6-Me-nicotinyl-Gly-Val-D-I]e-Thr-Nva-lle-Arg-ProNHCH2CH3 as the trifluoroacetate salt: Rt = 2.62 minutes (gradient varying over 10 minutes from 20% to 80% acetonitrile/water containing 5 0.01% TFA); MS (ESI) m/e 1000.6 (M+H)+; Amino Acid Anal.: 1.01 Gly; 0.94 Val; 2.13 lie; 0.55 Thr; 1.00 Nva; 1.01 Arg; 1.04 Pro. Example 6 N-Ac-Gly-Phe-D-lle-Thr-Nva-lle-Arg-Pro-D-AlaNH? 10 The desired product was prepared by substituting Fmoc-D-Ala-Sieber amide resin for Fmoc- Pro-Sieber ethylamide, Fmoc-Phe for Fmoc-Val, and adding a coupling with Fmoc-Pro before the coupling with Fmoc-Arg(Pmc) in Example 1. After cleavage of the peptide from the resin and workup the crude product was purified by HPLC using a C-l8 column and a solvent system varying over 50 minutes in a gradient of 5% to 100% acetonitrile/water containing 0.01% TFA. The pure 15 fractions were lyophilized to provide N-Ac-Gly-Phe-D-Ile-Thr-Nva-Ile-Arg-Pro-D-AlaNH2 as the trifluoroacetate salt: Rt = 3.15 minutes (gradient varying over 10 minutes from 20% to 80% acetonitrile/water containing 0.01% TFA); MS (ESI) m/e 1014.6 (M+H)+; Amino Acid Anal.: 1.01 Gly; 0.97 Phe; 2.03 He; 0.43 Thr; 1.03 Nva; 1.11 Arg; 0.99 Pro; 0.93 Ala. 20 Example 7 N-Ac-Gly-Val-D-alle-Ser-Ser-Ile-Arg-ProNHCH2CH3 The desired product was prepared by substituting Fmoc-D-alle for Fmoc-D-Ile and Fmoc-Ser(t-Bu) for both Fmoc-Thr(t-Bu) and Fmoc-Nva in Example 1. After cleavage of the peptide from the resin and workup the crude product was purified by HPLC using a C-l 8 column and a solvent 25 system varying over 50 minutes in a gradient of 5% to 100% acetonitrile/water containing 0.01 % TFA. The pure fractions were lyophilized to provideN-Ac-GIy-Val-D-alle-Ser-Ser-Ile-Arg-ProNHCH2CH3 as the trifluoroacetate salt: Rt = 2.32 minutes (gradient varying over 10 minutes from 20% to 80% acetonitrile/water containing 0.01% TFA); MS (ESI) m/e 897.5 (M+H)+; Amino Acid Anal.: 0.96 Gly; 0.91 Val; 2.11 He; 0.59 Ser; 1.06 Arg; 1,04 Pro. 30 Example 8 N-Ac-Gly-Val-D-aIle-Thr-Ser-lle-Arg-ProNHCHzCH3 The desired product was prepared by substituting Fmoc-D-alle for Fmoc-D-Ile and Fmoo Ser(t-Bu) for Fmoc-Nva in Example 1. After cleavage of the peptide from the resin and workup the 35 crude product was purified by HPLC using a C-l 8 column and a solvent system varying over 50 minutes in a gradient of 5% to 100% acetonitrile/water containing 0.01% TFA. The pure fractions were lyophilized to provide N-Ac-Gly-Val-D-alle-Thr-Ser-Ile-Arg-ProNHCH2CH3 as the trifluoroacetate salt: R, = 2.35 minutes (gradient varying over 10 minutes from 20% to 80% acetonitrile/water containing 0.01% TFA); MS (ESI) m/e 911.5 (M+H)+; Amino Acid Anal.: 0.98 40 Gly; 1.03 Val; 2.09 lie; 0.48 Thr; 0.27 Ser; 1.05 Arg; 1.01 Pro. Example 9 N-Ac-Gly-Val-D-aIle-Ser-Thr-Ile-Arg-ProNHCH2CH-| The desired product was prepared by substituting Fmoc-D-alle for Fmoc-D-lle, Fmoc-Ser(t-5 Bu) for Fmoc-Thr(t-Bu) and Fmoc-Thr(t-Bu) for Fmoc-Nva in Example 1. After cleavage of the peptide from the resin and workup the crude product was purified by HPLC using a C-18 column and a solvent system varying over 50 minutes in a gradient of 5% to 100% acetonitrile/water containing 0.01% TFA. The pure fractions were lyophilized to provideN-Ac-Gly-Val-D-alle-Ser-Thr-Ile-Arg-ProNHCH2CH3 as the trifluoroacetate salt: Rt = 2.36 minutes (gradient varying over 10 10 minutes from 20% to 80% acetonitrile/water containing 0.01% TFA); MS (ESI) m/e 911.5 (M+H)+; Amino Acid Anal.: 0.96 Gly; 0.93 Val; 2.04 He; 0.31 Ser; 0.50 Thr; 1.04 Arg; 0.99 Pro. Example 10 N-Ac-Gly-Vai-D-alie-Ser-Gln-Ile-Arg-ProNHCH^CHj 15 The desired product was prepared by substituting Fmoc-D-alle for Fmoc-D-lle, Fmoc-Ser(t- Bu) for Fmoc-Thr(t-Bu) and Fmoc-GIn(Trt) for Fmoc-Nva in Example 1. After cleavage of the peptide from the resin and workup the crude product was purified by HPLC using a C-18 column and a solvent system varying over 50 minutes in a gradient of 5% to 100% acetonitrile/water containing 0.01 % TFA. The pure fractions were lyophilized to provideN-Ac-Gly-Val-D-alle-Ser- 20 Gln-Ile-Arg-ProNHCH2CH3 as the trifluoroacetate salt: R, = 2.39 minutes (gradient varying over 10 minutes from 20% to 80% acetonitrile/water containing 0.01% TFA); MS (ESI) m/e 938.5 (M+H)+; Amino Acid Anal.: 1.00 Gly; 0.95 Val; 2.10 He; 0.33 Ser; 1.04 Glu; 1.02 Arg; 1.04 Pro. Example 11 25 N-Ac-Gly-Gln-D-Ile-Thr-Nva-lle-Arg-Pro-P-AlaNH? The desired product was prepared by substituting Fmoc-D-Ala-Sieber amide resin for Fmoc-Pro-Sieber ethylamide, Fmoc-Gln(Trt) for Fmoc-Val, and adding a coupling with Fmoc-Pro before the coupling with Fmoc-Arg(Pmc) in Example 1. After cleavage of the peptide from the resin and workup the crude product was purified by HPLC using a C-l 8 column and a solvent system varying 30 over 50 minutes in a gradient of 5% to 100% acetonitrile/water containing 0.01% TFA. The pure fractions were lyophilized to provide N-Ac-Gly-Gln-D-lle-Thr-Nva-Ile-Arg-Pro-D-AlaNH2 as the trifluoroacetate salt: R, = 1.42 minutes (gradient varying over 10 minutes from 20% to 80% acetonitrile/water containing 0.01% TFA); MS (ESI) m/e 995.5 (M+H)+; Amino Acid Anal.: 1.01 Gly; 1.03 Glu; 2.03 He; 0.51 Thr; 1.01 Nva; 1.05 Arg; 0.97 Pro; 1.04 Ala. 35 Example 12 N-Ac-Gly-Gln-D-llerThr-Nva-D-)le-Ar»-ProNHCHzCHj The desired product was prepared by substituting Fmoc-Gln(Trt) for Fmoc-Val and Fmoc-D-Ile for Fmoc-Ile in Example'1. After cleavage of the peptide from the resin and workup the crude 40 product was purified by HPLC using a C-18 column and a solvent system varying over 50 minutes in a gradient of 5% to 100% acetonitrile/water containing 0.01% TFA. The pure fractions were lyophilized to provide N-Ac-Gly-Gln-D-Ue-Thr-Nva-D-]le-Arg-ProNHCH2CH3 as the trifluoroacetate salt: Rt = 1.98 minutes (gradient varying over 10 minutes from 20% to 80% acetonitrile/water containing 0.01% TFA); MS (ESI) m/e 952.5 (M+H)+; Amino Acid Anal.: 1.03 5 Gly; 0.99 Glu; 2.09 He; 0.53 Thr; 0.98 Nva; 1.03 Arg; 0.98 Pro. Example 13 N-Ac-Gly-Val-D-He-Thr-Nva-P-Ile-Arg-ProNHCH2CH3 The desired product was prepared by substituting Fmoc-D-IIe for Fmoc-lle in Example I. 10 After cleavage of the peptide from the resin and workup the crude product was purified by HPLC using a C-l 8 column and a solvent system varying over 50 minutes in a gradient of 5% to 100% acetonitrile/water containing 0.01% TFA. The pure fractions were lyophilized to provideN-Ac-Gly-Val-D-lle-Thr-Nva-D-lle-Arg-ProNHCH2CH3 as the trifluoroacetate salt: Rt = 3.04 minutes (gradient varying over 10 minutes from 20% to 80% acetonitrile/water containing 0.01% TFA); MS 15 (ESI) m/e 923.5 (M+H)+; Amino Acid Anai.: 0.99 Gly; 1.02 Val; 2.i2 lie; 0.5i Thr; 0.98 Nva; 1.04 Arg; 1.07 Pro. Example 14 N-Ac-Gly-Val-lle-Thr-Nva-D-Ile-Arg-ProNHCHzCH:t 20 The desired product was prepared by substituting Fmoc-lle for Fmoc-D-IIe and Fmoc-D-IIe for Fmoc-lle in Example 1. After cleavage of the peptide from the resin and workup the crude product was purified by HPLC using a C-l 8 column and a solvent system varying over 50 minutes in a gradient of 5% to 100% acetonitrile/water containing 0.01 % TFA. The pure fractions were lyophilized to provide N-Ac-Gly-Val-!le-Thr-Nva-D-Ile-Arg-ProNHCH2CH3 as the trifluoroacetate 25 salt: Rt = 2.71 minutes (gradient varying over 10 minutes from 20% to 80% acetonitrile/water containing 0.01 % TFA); MS (ESI) m/e 923.5 (M+H)+; Amino Acid Anal.: 0.97 Gly; ! .03 Val; 2.10 lie; 0.55 Thr; 0.93 Nva; 1.02 Arg; 0.95 Pro. Example 15 30 N-Ac-Gly-Val-D-Ile-Thr-Nva-Pro-Arg-ProNHCH2CH2 The desired product was prepared by substituting Fmoc-Pro for Fmoc-lle in Example I. After cleavage of the peptide from the resin and workup the crude product was purified by HPLC using a C-l 8 column and a solvent system varying over 50 minutes in a gradient of 5% to 100% acetonitrile/water containing 0.01% TFA. The pure fractions were lyophilized to provideN-Ac-35 Gly-Val-D-lle-Thr-Nva-Pro-Arg-ProNHCH2CH3 as the irifluoroacetate salt: Rt = 2.45 minutes (gradient varying over 10 minutes from 20% to 80% acetonitrile/water containing 0.01% TFA); MS (ESI) m/e 907.5 (M+H)+; Amino Acid Anal.: 1.05 Gly; 1.00 Val; 1.10 He; 0.49 Thr; 1.01 Nva; 1.04 Arg; 2.12 Pro. 40 Example 16 N-Ac-Gly-Val-D-lle-Thr-Nva-Lys(Ac)-Arg-ProNHCH2CH2 The desired product was prepared by substituting Fmoc-Lys(Ac) for Fmoc-Ue in Example ). After cleavage of the peptide from the resin and workup the crude product was purified by HPLC using a C-l 8 column and a solvent system varying over 50 minutes in a gradient of 5% to 100% 5 acetonitrile/water containing 0.01% TFA. The pure fractions were lyophilized to provideN-Ac-GlyvVa!-D-[le-Thr-Nva-Lys(Ac)-Arg-ProNHCH2CH3 as the trifluoroacetate salt: Rt= 2.39 minutes (gradient varying over 10 minutes from 20% to 80% acetonitrile/water containing 0.01% TFA); MS (ESI) m/e 980.5 (M+H)+; Amino Acid Anal.: 0.97 Gly; 1.02 Val; 1.08 He; 0.49 Thr; 1.04 Nva; 0.89 Lys; 1.01 Arg; 1.03 Pro. 10 Example 17 N-Ac-Gly-Gln-D-Ile-Thr-Nva-lle-Arg-ProNHCH^CH^ The desired product was prepared by substituting Fmoc-GlnfTrt) for Fmoc-Val in Example 1. After cleavage of the peptide from the resin and workup the crude product was purified by HPLC 15 using a C-18 column and a solvent system varying over 50 minutes in a gradient of 5% to 100%o acetonitrile/watercontaining 0.01 % TFA. The pure fractions were lyophilized to pTvvideN-Ac-Gly~Gln-D-Ile-Thr-Nva-Ile-Arg-ProNHCH2CH3 as the trifluoroacetate salt: Rt= 2.02 minutes (gradient varying over 10 minutes from 20% to 80% acetonitrile/water containing 0.01% TFA); MS (ESI) m/e 952.5 (M+H)+; Amino Acid Anal.: 0.94 Gly; 1.04 Glu; 2.07 He; 0.43 Thr; 1.01 Nva; 1.10 20 Arg; 0.97 Pro. Example 18 N-Ac-Gly-Gln-D-aIle-Thr-Nva-lle-Arg-Pro-D-AlaNH2 The desired product was prepared by substituting Fmoc-D-Ala-Sieber amide resin for Fmoc- 25 Pro-Sieber ethylamide, Fmoc-Gln(Trt) for Fmoc-Val, Fmoc-D-alle for Fmoc-D-Ile, and adding a coupling with Fmoc-Pro before the coupling with Fmoc-Arg(Pmc) in Example 1. After cleavage of the peptide from the resin and workup the crude product was purified by HPLC using a C-l 8 column and a solvent system varying over 50 minutes in a gradient of 5% to 100% acetonitrile/water containing 0.01 % TFA. The pure fractions were lyophilized to provideN-Ac- 30 G)y-G}n-D-aHe-Thr-Nva-Ue-Arg-Pro-D-A}aNH2 as the trifluoroacetate salt: Rt = 1.20 minutes (gradient varying over 10 minutes from 20% to 80% acetonitrile/water containing 0.01% TFA); MS (ESI) m/e 995.5 (M+H)+. Example 19 35 N-Ac-Gly-Val-D-lle-Thr-Mva-Ile-Ar^-Pro-D-AlaNH? The desired product was prepared by substituting Fmoc-D-Ala-Sieber amide resin for Fmoc-Pro-Sieber ethylamide and adding a coupling with Fmoc-Pro before the coupling with Fmoc-Arg(Pmc) in Example 1 After cleavage of the peptide from the resin and workup the crude product was purified by HPLC using a C-18 column and a solvent system varying over 50 minutes in a 40 gradient of 5% to 100% acetonitrile/water containing 0.0i% TFA. The pure fractions were lyophilized to provide N-Ac-Gly-Val-D-ile-Thr-Nva-Ile-Arg-Pro-D-AlaNH2 as the trifluoroacetate salt: R( = 2.34 minutes (gradient varying over 10 minutes from 20% to 80% acetonitrile/water containing 0.01% TFA); MS (ESI) m/e 966.7 (M+H)+. 5 Example 20 N-Ac-G)y-G)n-D-}te-Thr-Nva-D-PrD-Arg-Pro-D-Alamz The desired product was prepared by substituting Fmoc-D-Ala-Sieber amide resin for Fmoc-Pro-Sieber ethylamide, Fmoc-Gln(Trt) for Fmoc-Val, Fmoc-D-Pro for Fmoc-I|e, and adding a coupling with Fmoc-Pro before the coupling with Fmoc-Arg(Pmc) in Example 1. After cleavage of 10 the peptide from the resin and workup the crude product was purified by HPLC using a C-l 8 column and a solvent system varying over 50 minutes in a gradient of 5%.to 100% acetonitrile/water containing 0.01% TFA. The pure fractions were lyophilized to provideN-Ac-Gly-Gln-D-Ile-Thr-Nva-D-Pro-Arg-Pro-D-AlaNH2 as the trifluoroacetate salt: R, = 1.05 minutes (gradient varying over 10 minutes from 20% to 80% acetonitrile/water containing 0.01 % TFA); MS 15 (ESI) m/e 979.6 (M+H)+. Example 21 N-Ac-Gly-Val-P-lle-Thr-Gln-Ile-Arg-Pro-D-AlaNH2 The desired product was prepared by substituting Fmoc-D-Ala-Sieber amide resin for Fmoc-20 Pro-Sieber ethylamide, Fmoc-Gln(Trt) for Fmoc-Nva, and adding a coupling with Fmoc-Pro before the coupling with Fmoc-Arg(Pmc) in Example I. After cleavage of the peptide from the resin and workup the crude product was purified by HPLC using a C-18 column and a solvent system varying over 50 minutes in a gradient of 5% to 100% acetonitrile/water containing 0.01% TFA. The pure fractions were lyophilized to provide N-Ac-Gly-Val-D-lle-Thr-Gln-lle-Arg-Pro-D-AlaNH2 as the 25 trifluoroacetate salt: R, = 1.65 minutes (gradient varying over 10 minutes from 20% to 80% acetonitrile/water containing 0.01% TFA); MS (ESI) m/e 995.7 (M+H)+. Example 22 N-Ac-Gly-Gln-D-Ile-alloThr-Nva-Ile-Arg-Pro-D-AlaNH; 30 The desired product was prepared by substituting Fmoc-D-AIa-Sieber amide resin for Fmoc- Pro-Sieber ethylamide, Fmoc-Gln(Trt) for Fmoc-Vai, Fmoc-alloThr(t-Bu) for Fmoc-Thr(t-Bu), and adding a coupling with Fmoc-Pro before the coupling with Fmoc-Arg(Pmc) in Example I. After cleavage of the peptide from the resin and workup the crude product was purified by HPLC using a C-18 column and a solvent system varying over 50 minutes in a gradient of 5% to 100% 35 acetonitrile/vvater containing 0.01 % TFA. The pure fractions were lyophilized to provide N-Ac-Gly-Gln-D-||e-alloThr-Nva-Ile-Arg-Pro-D-AlaNH2 as the trifluoroacetate salt: R( = 1.24 minutes (gradient varying over 10 minutes from 20% to 80% acetonitrile/water containing 0.01% TFA); MS (ESI) m/e 995.7 (M+H)+. 40 Example 23 N-Ac-Glv-Gln-D-He-Thr-Nva-Lvs(Ac)-Arg-Pro-D-AlaNH? The desired product was prepared by substituting Fmoc-D-Ala-Sieber amide resin for Fmoc-Pro-Sieber ethyiamide, Fmoc-Gln(Trt) for Fmoc-Val, Fmoc-Lys(Ac) for Fmoc-Ile, and adding a coupling with Fmoc-Pro before the coupling with Fmoc-Arg(Pmc) in Example 1. After cleavage of 5 the peptide from the resin and workup the crude product was purified by HPLC using a C-l 8 column and a solvent system varying over 50 minutes in a gradient of 5% to 100% acetonitrile/water containing 0.01% TFA. The pure fractions were lyophilized to provideN-Ac-Gly-GIn-D-lle-Thr-Nva-Lys(Ac)-Arg-Pro-D-AlaNH2 as the trifluoroacetate salt: Rt = 0.94 minutes (gradient varying over 10 minutes from 20% to 80% acetonitrile/water containing 0.01% TFA); MS 10 (ESI) m/e 1052.7 (M+H)+. Example 24 N-Ac-Gly-Gln-D-lle-Thr-Ser-Ile-Arg-Pro-D-AlaNH? The desired product was prepared by substituting Fmoc-D-Ala-Sieber amide resin for Fmoc-i5 Pro-Sieber ethyiamide, Fmoc-Gln(Trt) for Fmoc-Val, Fmoc-Ser(t-Bu) for Fmoc-Nva, and adding a coupling with Fmoc-Pro before the coupling with Fmoc-Arg(Pmc) in Example 1. After cleavage of the peptide from the resin and workup the crude product was purified by HPLC using a C-l 8 column and a solvent system varying over 50 minutes in a gradient of 5% to 100% acetonitrile/water containing 0.01% TFA. The pure fractions were lyophilized to provideN-Ac-20 Gly-Gln-D-Ile-Thr-Ser-Ile-Arg-Pro-D-AlaNH2 as the trifluoroacetate salt: Rt = 0.92 minutes (gradient varying over 10 minutes from 20% to 80% acetonitrile/water containing 0.01 % TFA); MS (ESI) m/e 983.6 (M+H)+. Example 25 25 N-Ac-Glv-Gln-D-lle-Thr-Nva-D-lle-Arg-Pro-D-AlaNH; The desired product was prepared by substituting Fmoc-D-Ala-Sieber amide resin for Fmoc-Pro-Sieber ethyiamide, Fmoc-Gln(Trt) for Fmoc-Val, Fmoc-D-Ile for Fmoc-Ile, and adding a coupling with Fmoc-Pro before the coupling with Fmoc-Arg(Pmc) in Example 1. After cleavage of the peptide from the resin and workup the crude product was purified by HPLC using a C-l 8 30 column and a solvent system varying over 50 minutes in a gradient of 5% to 100% acetonitrile/water containing 0.01% TFA. The pure fractions were lyophilized to provideN-Ac-Gly-Gln-D-Ile-Thr-Nva-D-Ile-Arg-Pro-D-AlaNH2 as the trifluoroacetate salt: Rt= 1.41 minutes (gradient varying over 10 minutes from 20% to 80% acetonitrile/water containing 0.01% TFA); MS (ESI) m/e 995.7 (M+H)+ 35 Example 26 N-Ac-Gly-D-Gln-D-lle-Thr-Nva-lle-Arg-Pro-D-AlaNH2 The desired product was prepared by substituting Fmoc-D-Ala-Sieber amide resin for Fmoc-Pro-Sieber ethyiamide, Fmoc-D-Gln(Trt) for Fmoc-Val, and adding a coupling with Fmoc-Pro 40 before the coupling with Fmoc-Arg(Pmc) in Example I. After cleavage of the peptide from the resin and workup the crude product was purified by HPLC using a C-18 column and a solvent system varying over 50 minutes in a gradient of 5% to 100% acetonitrile/water containing 0.01% TFA. The pure fractions were Iyophilized to provideN-Ac-Gly-D-GIn-D-Ile-Thr-Nva-lle-Arg-Pro-D-AlaNHi as the trifluoroacetate salt: Rt = 1.14 minutes (gradient varying over 10 minutes from 5 20% to 80% acetonitrile/water containing 0.01 % TFA); MS (ESI) m/e 995.5 (M+H)+. Example 27 N-Ac-Gln-Val-D-lle-Thr-Nva-lle-Arg-Pro-D-AlaNH2 The desired product was prepared by substituting Fmoc-D-AIa-Sieber amide resin for Fmoc-10 Pro-Sieber ethylamide, Fmoc-Gln(Trt) for Fmoc-GIy, and adding a coupling with Fmoc-Pro before the coupling with Fmoc-Arg(Pmc) in Example 1. After cleavage of the peptide from the resin and workup the crude product was purified by HPLC using C-I8 column and with a solvent mixture varying over 50 minutes in a gradient from 5% to 100% acetonitrile-water containing 0.01% TFA. The pure fractions were Iyophilized to give N-Ac-Gln-Val-D-Ue-Thr-Nva-Ile-Arg-Pro-D-AlaNH2 as 15 the trifluoroacetate salt: Rt = 2.71 minutes (gradient varying over 10 minutes from 20% to 80% acetonitrile/water containing 0.01% TFA); MS (ESI) m/e 1037.6 (M+H)+; Amino Acid Anal.: 0.89 Glu; 1.01 Val;2.05 lie; 0.54 Thr; 0.98 Nva; 0.99 Arg; 1.01 Pro; 1.01 Ala. Example 28 20 N-Ac-Gln-Val-D-lle-Thr-Nva-Ile-Arg-ProNHCHzCH3 The procedure described in Example 1 was used but substituting Fmoc-Gln(Trt) for Fmoc-GIy. After cleavage of the peptide from the resin and workup the crude product was purified by HPLC using C-18 column and with a solvent mixture varying over 50 minutes in a gradient from 5% to 100% acetonitrile-water containing 0.01% TFA. The pure fractions were Iyophilized to give 25 N-Ac-Gln-Vai-D-Ile-Thr-Nva-Ile-Arg-ProNHCH2CH3 as the trifluoroacetate salt: R, = 2.86 minutes (gradient varying over 10 minutes from 20% to 80% acetonitrile/water containing 0.01% TFA); MS (ESI) m/e 994.6 (M+H)+; Amino Acid Anal.: 0.96 Glu; 1.02 Val; 1.98 lie; 0.59 Thr; 1.01 Nva; 1.06 Arg; 0.99 Pro. 30 Example 29 N-Ac-H-CH^Phe-Gln-D-lle-Thr-Nva-lle-Arg-Pro-D-AlaNH; The desired product was prepared by substituting Fmoc-D-Ala-Sieber amide resin for Fmoc-Pro-Sieber ethylamide, Fmoc-(4-CH3)Phe for Fmoc-GIy, Fmoc-GIn(Trt) for Fmoc-Val, and adding a coupling with Fmoc-Pro before the coupling with Fmoc-Arg(Pmc) in Example 1. After cleavage 35 of the peptide from the resin and workup the crude product was purified by HPLC using C-18 column and with a solvent mixture varying over 50 minutes in a gradient from 5% to 100% acetonitrile-water containing 0.01% TFA. The pure fractions were Iyophilized to give N-Ac-(4-CH3)Phe-Gln-D-Ile-Thr-Nva-Ile-Arg-Pro-D-AlaNH2as the trifluoroacetate salt: R, = 3.19 minutes (gradient varying over 10 minutes from 20% to 80% acetonitrile/water containing 0.01% TFA); MS (ESI) m/e 1099.7 (M+H)+; Amino Acid Anal.: 1.00 Glu; 2.03 lie; 0.51 Thr; 1.03 Nva; 1.02 Arg; 1.10 Pro; 1.02 Ala. Example 30 5 N-Ac-(4-CN)Phe-Gln-D-Ile-Thr-Nva-He-Arg-Pro-D-AlaNH2 The desired product was prepared by substituting Fmoc-D-Ala-Sieber amide resin for Fmoc-Pro-Sieber ethylamide, Fmoc-(4-CN)Phe for Fmoc-Gly, Fmoc-Gln(Trt) for Fmoc-Val, and adding a coupling with Fmoc-Pro before the coupling with Fmoc-Arg(Pmc) in Example 1. After cleavage of the peptide from the resin and workup the crude product was purified by HPLC using C-l 8 column 10 and with a solvent mixture varying over 50 minutes in a gradient from 5% to 100% acetonitrtle- water containing 0.01% TFA. The pure fractions were lyophilized to give N-Ac-(4-CN)Phe-Gln-D-Ile-Thr-Nva-Ile-Arg-Pro-D-AlaNH2as the trifluoroacetate salt: Rt= 2.88 minutes (gradient varying over 10 minutes from 20% to 80% acetonitrile/water containing 0.01% TFA); MS (ESI) m/e 1110.6 (M+H)+; Amino Acid Anal.: 0.97 Glu;-2.11 lie; 0.49 Thr; 1.01 Nva; 0.95 Arg; 1.04 Pro; 1.01 Ala. 15 Example 31 N-Ac-Gly-Asn-D-He-Thr-Nva-Ile-Arg-Pro-D-AlaNH2 The desired product was prepared by substituting Fmoc-D-Ala-Sieber amide resin for Fmoc-Pro-Sieber ethylamide, Fmoc-Asn(Trt) for Fmoc-Val, and adding a coupling with Fmoc-Pro before 20 the coupling with Fmoc-Arg(Pmc) in Example 1. After cleavage of the peptide from the resin and workup the crude product was purified by HPLC using C-l 8 column and with a solvent mixture varying over 50 minutes in a gradient from 5% to 100% acetonitrile-water containing 0.01% TFA. The pure fractions were lyophilized to give N-Ac-Gly-Asn-D-He-Thr-Nva-Ile-Arg-Pro-D-AlaNFbas the trifluoroacetate salt: Rt = 1.75 minutes (gradient varying over 10 minutes from 20% to 80% 25 acetonitrile/water containing 0.01% TFA); MS (ESI) m/e 981.6 (M+H)+; Amino Acid Anal.: 0.99 Gly; 0.96 Asp; 2.05 lie; 0.55 Thr; 1.02 Nva; 1.01 Arg; 1.00 Pro; 1.02 Ala. Example 32 N-Ac-Gly-Cit-D-lle-Thr-Nva-lle-Arg-Pro-D-AlaNH2 30 The desired product was prepared by substituting Fmoc-D-Ala-Sieber amide resin for Fmoc- Pro-Sieber ethylamide, Fmoc-Cit for Fmoc-Val, and adding a coupling with Fmoc-Pro before the coupling with Fmoc-Arg(Pmc) in Example I. After cleavage of the peptide from the resin and workup the crude product was purified by HPLC using C-l 8 column and with a solvent mixture varying over 50 minutes in a gradient from 5% to 100% acetonitrile-water containing 0.01% TFA. 35 The pure fractions were lyophilized to give N-Ac-Gly-Cit-D-lle-Thr-Nva-Ile-Arg-Pro-D-AlaNH2as the trifluoroacetate salt: Rt = 4.08 minutes (gradient varying over 10 minutes from 20% to 80% acetonitrile/water containing 0.01% TFA); MS (ESI) m/e 1024.6 (M+H)+; Amino Acid Anal.: 1.03 Gly; 0.94 Cit; 2.07 He; 0.53 Thr; 1.00 Nva;0.99 Arg; 0.97 Pro; 1.01 Ala. 40 Example 33 N-Ac-Gly-Lys(Ac)-P-Ile-Thr-Nva-Ile-Arg-Pro-D-AlaNH7 The desired product was prepared by substituting Fmoc-D-Ala-Sieber amide resin for Fmoc-Pro-Sieber ethylamide, Fmoc-Lys(Ac) for Fmoc-Val, and adding a coupling with Fmoc-Pro before the coupling with Fmoc-Arg(Pmc) in Example 1. After cleavage of the peptide from the resin and 5 workup the crude product was purified by HPLC using C-l 8 column and with a solvent mixture varying over 50 minutes in a gradient from 5% to 100% acetonitrile-water containing 0.01% TFA. The pure fractions were lyophilized to give N-Ac-Gly-Lys(Ac)-D-Ile-Thr-Nva-lle-Arg-Pro-D-AlaNF^as the trifluoroacetate salt: Rt = 4.16 minutes (gradient varying over 10 minutes from 20% to 80% acetonitrile/water containing 0.01% TFA); MS (ESI) m/e 1037.7 (M+H)+. 10 Example 34 N-Ac-Gly-His-D-He-Thr-Nva-Ile-Arg-ProNHCHgCHj The procedure described in Example 1 was used but substituting Fmoc-His(Trt) for Fmoc-Val. After cleavage of the peptide from the resin and workup the crude product was purified by 15 HPLC using C-l 8 column and with a solvent mixture varying over 50 minutes in a gradient from 5% to 100% acetonitrile-water containing 0.01 % TFA. The pure fractions were lyophilized to give N-Ac-GIy-His-D-lle-Thr-Nva-Ile-Arg-ProNHCH2CH3asthe trifluoroacetate salt: Rt= 3.88 minutes (gradient varying over 10 minutes from 20% to 80% acetonitrile/water containing 0.01% TFA); MS (ESI) m/e 961.6 (M+H)+. 20 Example 35 N-Ac-Gly-His-D-lle-Thr-Nva-lle-Arg-Pro-P-AlaNHg The desired product was prepared by substituting Fmoc-D-Ala-Sieber amide resin for Fmoc-Pro-Sieber ethylamide, Fmoc-His(Trt) for Fmoc-Val, and adding a coupling with Fmoc-Pro before 25 the coupling with Fmoc-Arg(Pmc) in Exampie 1. After cleavage of the peptide from the resin and workup the crude product was purified by HPLC using C-l8 column and with a solvent mixture varying over 50 minutes in a gradient from 5% to 100% acetonitrile-water containing 0.01% TFA. The pure fractions were lyophilized to give N-Ac-Gly-His-D-lle-Thr-"Nva-lle-Arg-Pro-D-AlaNH2as the trifluoroacetate salt: Rt = 3.70 minutes (gradient varying over 10 minutes from 20% to 80% 30 acetonitrile/water containing 0.01% TFA); MS (ESI) m/e 1004.6 (M+H)+. Example 36 N-Ac-Glv-Asn-D-ne-Thr-Nva-Ile-Arg-ProNHCH2CHj The procedure described in Example I was used but substituting Fmoc-Asn(Trt) for Fmoc-35 Val. After cleavage of the peptide from the resin and workup the crude product was purified by HPLC using C-l8 column and with a solvent mixture varying over 50 minutes in a gradient from 5% to 100% acetonitrile-water containing 0.01% TFA. The pure fractions were lyophilized to give N-Ac-Gly-Asn-D-lle-Thr-Nva-Ile-Arg-ProNHCH2CH3 as the trifluoroacetate salt: Rt = 3.88 minutes (gradient varying over 10 minutes from 20% to 80% acetonitrile/water containing 0.01% TFA); MS 40 (ESI) m/e 938.7 (M+H)+. Example 37 >J-Ac-Gly-D-Asn-D-Ile-Thr-Nva-Lys(Ac)-ArR-ProNHCH2CH3 The procedure described in Example 1 was used but substituting Fmoc-D-Asn(Trt) for 5 Fmoc-Val and Fmoc-Lys(Ac) for Fmoc-Ile. After cleavage of the peptide from the resin and workup the crude product was purified by HPLC using C-18 column and with a solvent mixture varying over 50 minutes in a gradient from 5% to 100% acetonitrile-water containing 0.01% TFA. The pure fractions were lyophilized to give N-Ac-Gly-D-Asn-D-Ile-Thr-Nva-Lys(Ac)-Arg-ProNHC^Cfy as the trifluoroacetate salt: Rt = 3.65 minutes (gradient varying over 10 minutes 10 from 20% to 80% acetonitrile/water containing 0.01% TFA); MS (ESI) m/e 995.6 (M+H)+. Example 38 N-Ac-G)y-Gln-D-He-Tyr-Nva-He-Arg-ProNHCHzCH2 The procedure described in Example 1 was used but substituting Fmoc-Gln(Trt) for Fmoc-15 Val and Fmoc-Tyr(t-Bu) for Fmoc-Thr(t-Bu). After cleavage of the peptide from the resin and workup the crude product was purified by HPLC using C-18 column and with a solvent mixture varying over 50 minutes in a gradient from 5% to 100% acetonitrile-water containing 0.01% TFA. The pure fractions were lyophilized to give N-Ac-GIy-GIn-D-IIe-Tyr-Nva-Ile-Arg-ProNHCH2CH3 as the trifluoroacetate salt: Rt = 4.43 minutes (gradient varying over 10 minutes from 20% to 80% 20 acetonitrile/water containing 0.01% TFA); MS (ESI) m/e 1014.5 (M+H)+. Example 39 N-Ac-Gly-Gln-D-Ile-Thr-Nva-Pro-Arg-Pro-D-AlaNPb The desired product was prepared by substituting Fmoc-D-AIa-Sieber amide resin for Fmoc-25 Pro-Sieber ethylamide, Fmoc-Gln(Trt) for Fmoc-Val, Fmoc-Pro for Fmoc-Ile, and adding a coupling with Fmoc-Pro before the coupling with Fmoc-Arg(Pmc) in Example J. After cleavage of the peptide from the resin and workup the crude product was purified by HPLC using C-l 8 column and with a solvent mixture varying over 50 minutes in a gradient from 5% to 100% acetonitrile-water containing 0.01% TFA. The pure fractions were lyophilized to give N-Ac-Gly-Gln-D-Ile-30 Thr-Nva-Pro-Arg-Pro-D-AlaNHi as the trifluoroacetate salt: Rt = 3.74 minutes (gradient varying over 10 minutes from 20% to 80% acetonitrile/water containing 0.01% TFA); MS (ESI) m/e 979.5 (M+H)+. Example 40 35 N-Ac-Gly-Gln-D-He-Met-Nva-Ile-Arfi-Pro-D-AlaNH2 The desired product was prepared by substituting Fmoc-D-AIa-Sieber amide resin for Fmoc-Pro-Sieber ethylamide, Fmoc-Gln(Trt) for Fmoc-Val, Fmoc-Met for Fmoc-Thr(t-Bu), and adding a coupling with Fmoc-Pro before the coupling with Fmoc-Arg(Pmc) in Example I. After cleavage of the peptide from the resin and workup the crude product was purified by HPLC using C-18 column 40 and with a solvent mixture varying over 50 minutes in a gradient from 5% to 100% acetonitrile- water containing 0.01% TFA. The pure fractions were lyophilized to give N-Ac-Gly-Gln-D-Ile-Met-Nva-Ile-Arg-Pro-D-AlaNI-h as the trifluoroacetate salt: R, =4.48 minutes (gradient varying over 10 minutes from 20% to 80% acetonitrile/water containing 0.01% TFA); MS (ESI) m/e 1025.5 (M+H)+. 5 Example 41 N-Ac-Gly-Gln-P-lle-Thr-Gln-Ile-Arg-Pro-P-AlaNH? The desired product was prepared by substituting Fmoc-D-Ala-Sieber amide resin for Fmoc-Pro-Sieber ethylamide, Fmoc-Gln(Trt) for Fmoc-Val and Fmoc-Nva, and adding a coupling with 10 Fmoc-Pro before the coupling with Fmoc-Arg(Pmc) in Example 1. After cleavage of the peptide from the resin and workup the crude product was purified by HPLC using C-l 8 column and with a solvent mixture varying over 50 minutes in a gradient from 5% to 100% acetonitrile-water containing 0.01% TFA. The pure fractions were lyophilized to give N-Ac-Gly-Gln-D-Ile-Thr-Gln-lle-Arg- Pro-D-AlaNH2 as the trifluoroacetate salt: Rt = 3.75 minutes (gradient varying over 10 15 minutes from 20% to 80% acetonitrile/water containing 0.01 % TFA); MS (ESI) m/e 1024.6 (M+H)+. Example 42 N-Ac-Gly-Arg-D-He-Thr-Nva-ile-Gln-Pro-D-AlaNH2 20 The desired product was prepared by substituting Fmoc-D-Ala-Sieber amide resin for Fmoc- Pro-Sieber ethylamide, Fmoc-Arg(Pmc) for Fmoc-Val, Fmoc-Gln(Trt) for Fmoc-Arg(Pmc), and adding a coupling with Fmoc-Pro before the coupling with Fmoc-Arg(Pmc) in Example 1. After cleavage of the peptide from the resin and workup the crude product was purified by HPLC using C-18 column and with a solvent mixture varying over 50 minutes in a gradient from 5% to 100% 25 acetonitrile-water containing 0.01% TFA. The pure fractions were lyophilized to give N-Ac-GIy-Arg-D-Tle-Thr-Nva-Ile-GIn-Pro-D-AlaNH2 as the trifluoroacetate salt: Rt = 3.96 minutes (gradient varying over 10 minutes from 20% to 80% acetonitrile/water containing 0.01% TFA); MS (ESI) m/e 995.6 (M+H)+. 30 Example 43 N-Ac-Gly-Gln-D-Ile-Tyr-Nva-lle-Arg-Pro-D-AlaNH2 The desired product was prepared by substituting Fmoc-D-Ala-Sieber amide resin for Fmoc-Pro-Sieber ethylamide, Fmoc-GIn(Trt) for Fmoc-Val, Fmoc-Tyr(t-Bu) for Fmoc-Thr(t-Bu), and adding a coupling with Fmoc-Pro before the coupling with Fmoc-Arg(Pmc) in Example 1. After 35 cleavage of the peptide from the resin and workup the crude product was purified by HPLC using C-18 column and with a solvent mixture varying over 50 minutes in a gradient from5% to 100% acetonitrile-water containing 0.01% TFA. The pure fractions were lyophilized to give N-Ac-Gly-Gln-D-lle-Tyr-Nva-lle-Arg-Pro-D-AlaNH2 as the trifluoroacetate salt: Rt = 4.41 minutes (gradient varying over 10 minutes from 20% to 80% acetonitrile/water containing 0.01% TFA); MS (ESI) m/e '10 1057.5 (M+H)+. Example 44 N-Ac-Gly-Gln-D-Leu-Thr-Nva-lle-Arg-Pro-D-AlaNH2 The desired product was prepared by substituting Fmoc-D-Ala-Sieber amide resin for Fmoc-5 Pro-Sieber ethylamide, Fmoc-Gln(Trt) for Fmoc-Val, Fmoc-D-Leu for Fmoc-D-Ile, and adding a coupling with Fmoc-Pro before the coupling with Fmoc-Arg(Pmc) in Example 1. After cleavage of the peptide from the resin and workup the crude product was purified by HPLC using C-18 column and with a solvent mixture varying over 50 minutes in a gradient from 5% to 100% acetonitrile-water containing 0.01% TFA. The pure fractions were lyophilized to give N-Ac-Gly-Gln-D-Leu-10 Thr-Nva-Ile-Arg-Pro-D-AlaNH2 as the trifluoroacetate salt: Rt = 4.00 minutes (gradient varying over TO minutes from 20% to 80% acetonitrile/water containing 0.01% TFA); MS (ESI) m/e 995.6 (M+H)+. Example 45 15 N-Ac-Gly-Gln-D-Leu-Ser-Nva-Ue-Arg-Pro-D-AlaNH2 The desired product was prepared by substituting Fmoc-D-Ala-Sieber amide resin for Fmoc-Pro-Sieber ethylamide, Fmoc-Gln(Trt) for Fmoc-Val, Fmoc-D-Leu for Fmoc-D-lle, Fmoc-Ser(t-Bu) for Fmoc-Thr(t-Bu), and adding a coupling with Fmoc-Pro before the coupling with Fmoc-Arg(Pmc) in Example 1. After cleavage of the peptide from the resin and workup the crude product 20 was purified by HPLC using C-18 column and with a solvent mixture varying over 50 minutes in a gradient from 5% to 100% acetonitrile-water containing 0.01% TFA. The pure fractions were lyophilized to give N-Ac-GIy-Gln-D-Leu-Ser-Nva-Ile-Arg-Pro-D-AlaNH2 as the trifluoroacetate salt: Rt = 4.05 minutes (gradient varying over 10 minutes from 20% to 80% acetonitrile/water containing 0.01% TFA); MS (ESI) m/e 981.5 (M+H)+. 25 Example 46 N-Ac-Gly-Gln-D-aIle-Thr-Ser-Fle-Arg-Pro-D-AlaNH2 The desired product was prepared by substituting Fmoc-D-Ala-Sieber amide resin for Fmoc-Pro-Sieber ethylamide, Fmoc-Gln(Trt) for Fmoc-Val, Fmoc-D-alle for Fmoc-D-Ile, Fmoc-Ser(t-Bu) 30 for Fmoc-Nva, and adding a coupling with Fmoc-Pro before the coupling with Fmoc-Arg(Pmc) in Example 1. After cleavage of the peptide from the resin and workup the crude product was purified by HPLC using C-18 column and with a solvent mixture varying over 50 minutes in a gradient from 5% to 100% acetonitrile-water containing 0.01% TFA. The pure fractions werelyophilized to give N-Ac-Gly-Gln-D-alle-Thr-Ser-Ue-Arg-Pro-D-AlaNH2 as the trifluoroacetate salt: Rt = 3.55 minutes 35 (gradient varying over 10 minutes from 20% to 80% acetonitriie/watercontaining 0.01% TFA); MS (ESI) m/e 983.5 (M+H)+. Example 47 N-Ac-Glv-Gln-D-alle-Thr-Nva-Lys(Ac)-Arg-Pro-D-AlaNH2 The desired product was prepared by substituting Fmoc-D-Ala-Sieber amide resin for Frfioc-Pro-Sieber ethylamide, Fmoc-Gln(Trt) for Fmoc-Val, Fmoc-D-alle for Fmoc-D-He, Fmoc-Lys(Ac) for Fmoc-fle, and adding a coupling with Fmoc-Pro before the coupling with fmoc-Arg(Pmc) in Example 1. After cleavage of the peptide from the resin and workup the crude product was purified 5 by HPLC using C-18 column and with a solvent mixture varying over 50 minutes in a gradient from 5% to 100% acetonitrile-water containing 0.01% TFA. The pure fractions were lyophilized to give N-Ac-Gly-(51n-D-aIle-Thr-Nva-Lys(Ac)-Arg-Pro-D-AlaNH2 as the trifluoroacetate salt: Rt = 3.70 minutes (gradient varying over 10 minutes from 20% to 80% acetonitrile/water containing 0.01% TFA); MS (ESI) m/e 1009.6 (M+H)+. 10 Example 48 N-Ac-Gly-Gln-D-Ile-Asp-Nva-He-Arg-Pro-D-AlaNH2 The desired product was prepared by substituting Fmoc-D-AJa-Sieber amide resin for Fmoc-Pro-Sieber ethylamide, Fmoc-Gln(Trt) for Fmoc-Vai, Fmoc-Asp(Ot-Bu) for Fmoc-Thr(t-Bu), and 15 adding a coupling with Fmoc-Pro before the coupling with Fmoc-Arg(Pmc) in Example 1. After cleavage of the peptide from the resin and workup the crude product was purified by HPLC using C-18 column and with a solvent mixture varying over 50 minutes in a gradient from 5% to 100% acetonitrile-water containing 0.01% TFA. The pure fractions were lyophilized to give N-Ac-Gly-Gln-D-Ile-Asp-Nva-Ile-Arg-Pro-D-AlaNH2 as the trifluoroacetate salt: Rt = 4.00 minutes (gradient 20 varying over 10 minutes from 20% to 80% acetonitrile/water containing 0.01 % TFA); MS (ESI) m/e 1009.5 (M+H)+. Example 49 N-Ac-Gly-Gln-D-lle-Thr-Trp-Ile-Arg-Pro-D-AlaNH2 25 The desired product was prepared by substituting Fmoc-D-Ala-Sieber amide resin for Fmoc- Pro-Sieber ethylamide, Fmoc-Gln(Trt) for Fmoc-Val, Fmoc-Trp(Boc) for Fmtfc-Nva, and adding a coupling with Fmoc-Pro before the coupling with Fmoc-Arg(Pmc) in Example 1. After cleavage of the peptide from the resin and workup the crude product was purified by HPLC using C-18 column and with a solvent mixture varying over 50 minutes in a gradient from 5% to 100% acetonitrile- 30 water containing 0.01% TFA. The pure fractions were lyophilized to give N-Ac-Gly-Gln-D-Ile- Thr-Trp-IIe'Arg-Pro-D-AlaNH2 as the trifluoroacetate salt: Rt = 4.46 minutes (gradient varying over 10 minutes from 20% to 80% acetonitrile/water containing 0.01% TFA); MS {ESI) m/e 1082.5 (M+H)+. 35 Example 50 N-Ac-Gln-Gln-D-lle-Thr-Nva-Lys(Ac)-Arg-Pro-D-AlaNH2 The desired product was prepared by substituting Fmoc-D-Ala-Sieber amide resin for Fmoc-Pro-Sieber ethylamide, Fmoc-Gln(Trt) for Fmoc-Gly and Fmoc-Val, Fmoc-Lys(Ac) for Fmoc-lle, and addino 3 coupling with Fmoc-Pro before the coupling with Fmoc-Arg(Pmc) in Example 1. 40 After cleavage of the peptide from the resin and workup the crude product was purified by HPLC using C-18 column and with a solvent mixture varying over 50 minutes in a gradient from 5% to 100% acetonitrile-water containing 0.01% TFA. The pure fractions were lyophilized to give N-Ac-Gln-Gln-D-Ile-Thr-Nva-Lys(Ac)-Arg-Pro-D-AlaNH2 as the trifluoroacetate salt: R, = 3.965 minutes (gradient varying over 10 minutes from 20% to 80% acetonitrile/water containing 0.01% TFA); MS 5 (ESI) m/e 1067.8 (M+H)+. Example 51 N-Ac-Ala-Gln-D-Ile-Thr-Nva-He-Arg-ProNHCHzCHj The procedure described in Example 1 was used but substituting Fmoc-Gln(Trt) for Fmoc-10 Val and Fmoc-Ala for Fmoc-GIy. After cleavage of the peptide from the resin and workup the crude product was purified by HPLC using C-l 8 column and with a solvent mixture varying over 50 minutes in a gradient from 5% to 100% acetonitrile-water containing 0.01% TFA. The pure fractions were lyophilized to give M-Ac-Ala-Gln-D-Ile-Thr-Nva-lle-Arg-ProNHCH2CH3 as the trifluoroacetate salt: Rt = 4.215 minutes (gradient varying over 10 minutes from 20% to 80% 15 acetonitrile/water containing 0.01 % TFA); MS (ESI) m/e 966.6 (M+H)+. Example 52 N-Ac-Asn-Val-D-Ile-Thr-Nva-lle-Arg-Pro-D-AlaNH2 The desired product was prepared by substituting Fmoc-D-Ala-Sieber amide resin for Fmoc-20 Pro-Sieber ethylamide, Fmoc-Asn(Trt) for Fmoc-GIy, and adding a coupling with Fmoc-Pro before the coupling with Fmoc-Arg(Pmc) in Example 1. After cleavage of the peptide from the resin and workup the crude product was purified by HPLC using C-l8 column and with a solvent mixture varying over 50 minutes in a gradient from 5% to 100% acetonitrile-water containing 0.01% TFA. The pure fractions were lyophilized to give N-Ac-Asn-VaI-D-lle-Thr-Nva-lle-Arg-Pro-D-AlaNH2 25 as the trifluoroacetate salt: Rt = 4.4155 minutes (gradient varying over 10 minutes from 20% to 80% ^to\\ta\tefmtev c mfe 1023.6 (M+Wf. Example 53 N-Ac-Ala-Gln-D-He-Thr-Nva-lle-Arg-Pro-D-AlaNH2 30 The desired product was prepared by substituting Fmoc-D-Ala-Sieber amide resin for Fmoc- Pro-Sieber ethylamide, Fmoc-Ala for Fmoc-GIy, Fmoc-Gln(Trf) for Fmoc-Val, and adding a coupling with Fmoc-Pro before the coupling with Fmoc-Arg(Pmc) in Example 1. After cleavage of the peptide from the resin and workup the crude product was purified by HPLC using C-l 8 column and with a solvent mixture varying over 50 minutes in a gradient from 5% to 100% acetonitrile- 35 water containing 0.01 % TFA. The pure fractions were lyophiiized'to give N-Ac-Ala-Gln-D-lle-Thr-Nva-Ile-Arg-Pro-D-AlaNH2 as the trifluoroacetate salt: R( = 3.995 minutes (gradient varying over 10 minutes from 20% to 80% acetonitrile/water containing 0.01% TFA); MS (ESI) m/e 1009.6 (M+H)+. 40 Example 54 N-Ac-Asr)-Val-D-lle-Thr-Nva-lle-Arg-ProNHCH2CH7 The procedure described in Example I was used but substituting Fmoc-Asn(Trt) for Fmoc-Gly. After cleavage of the peptide from the resin and workup the crude product was purified by HPLC using C-l 8 column and with a solvent mixture varying over 50 minutes in a gradient from 5 5% to 100% acetonitrile-water containing 0.01% TFA. The pure fractions were lyophiiized to give N-Ac-Asn-Val-D-lle-Thr-Nva-lle-Arg-ProNHCH2CH3 as the trifluoroacetate salt: R, = 4.62 minutes (gradient varying over 10 minutes from 20% to 80% acetonitrile/water containing 0.01% TFA); MS (ESI) m/e 980.7 (M+H)+. 10 v- "Example 55 N-A^Gly-Val-D-Ile-Ser-Gln-lle-Arg-ProNHCH2CH3 The procedure described in Example 1 can be used but substituting Fmoc-Ser(t-Bu) for Fmoc-Thr(t-Bu) and Fmoc-Gln(Trt) for Fmoc-Nva. After cleavage of the peptide from the resin and workup the crude product can be purified by HPLC using C-l 8 column and with a solvent mixture 15 varying over 50 minutes in a gradient from 5% to 100% acetonitrile-water containing 0.01 % TFA. The pure fractions can be lyophiiized to give N-Ac-Gly-Val-D-Ile-Ser-Gln-Ile-Arg-ProNHCH2CH3 as the trifluoroacetate salt. Example 56 20 N-Ac-Gly-Val-D-Leu-Ser-Gln-Ile-Arg-ProNHCHzCHj The procedure described in Example 1 can be used but substituting Fmoo-D-Leu for Fmoc-D-Ile, Fmoc-Ser(t-Bu) for FmocThr(t-Bu) and Fmoc-Gln(Trt) for Fmoc-Nva. After cleavage of the peptide from the resin and workup the crude product can be purified by HPLC using C-l 8 column and with a solvent mixture varying over 50 minutes in a gradient from 5% to 100%o acetonitrile-25 water containing 0.01% TFA. The pure fractions can be lyophiiized to give N-Ac-Gly-Val-D-Leu-Ser-Gln-Ile-Arg-ProNHCH2CH3 as the trifluoroacetate salt. Example 57 N-Ac^GlV-Phe-D-I le-Ser-G 1 n -I le-Arg-ProN HC H?CH 3 30 The procedure described in Example 1 can be used but substituting Fmoc-Phe for Fmoc-Val, Fmoc-Ser(t-Bu) for Fmoc-Thr(t-Bu) and Fmoc-Gln(Trt) for Fmoc-Nva. After cleavage of the peptide from the resin and workup the crude product can be purified by HPLC using C-l 8 column and with a solvent mixture varying over 50 minutes in a gradient from 5% to 100% acetonitrile-water containing 0.01%o TFA. The pure fractions can be lyophiiized to give N-Ac-Gly-Phe-D-Ile-35 Ser-G!n-lle-Arg-ProNHCH2CH3 as the trifluoroacetate salt. Example 58 N-Ac-Gly-Val-D-alle-Ser-Gln-Lys(Ac)-Arfi-ProNHCHzCHj The procedure described in Example I can be used but substituting Fmoc-D-alle for Fmoc-40 D-Ile, Fmoc-Ser(t-Bu) for Fmoc-Thr(t-Bu) and Fmoc-Gln(Trt) for Fmoc-Nva and Fmoc-Lys(Ac) for Fmoc-Ile. After cleavage of the peptide from the resin and workup the arude product can be purified by HPLC using C-l8 column and with a solvent mixture varying over 50 minutes in a gradient from 5% to 100% acetonitrile-water containing 0.01% TFA. The pure fractions can be lyophilized to give N-Ac-Gly-Val-D-alle-Ser-Gln-Lys(Ac)-Arg-ProNHCH2CH3 as the 5 trifluoroacetate salt. Example 59 N-Ac-Gly-Val-D-alle-Ser-Gln-lle-Arg-ProNHCHfCHj)? The procedure described in Example 1 can be used but substituting Fmoc-D-alle for Fmoc-10 D-Ile, Fmoc-Ser(t-Bu) for Fmoc-Thr(t-Bu) and Fmoc-Gln(Trt) for Fmoc-Nva and Fmoc-Pro-(4-(4-N-isopropylamino)methyl-3-methoxyphenoxy]butyryl AM resin instead of Fmoc-Pro Sieber ethylamide resin. After cleavage of the peptide from the resin and workup the crude product can be purified by HPLC using C-l8 column and with a solvent mixture varying over 50 minutes in a gradient from 5% to 100% acetonitrile-water containing 0.01% TFA. The pure fractions can be 15 lyophilized to give N-Ac-Gly-Val-D-aIle-Ser-Gln-Ile-Arg-ProNHCH(CH3)2 as the trifluoroacetate salt. Example 60 N-Ac-Gly-Val-D-alle-Tyr-Gln-Ile-Arg-ProNHCHjCHj 20 The procedure described in Example 1 can be used but substituting Fmoc-D-alle for Fmoc- D-Ile, Fmoc-Tyr(t-Bu) for Fmoc-Thr(t-Bu) and Fmoc-Gin(Trt) for Fmoc-Nva. After cleavage of the peptide from the resin and workup the crude product can be purified by HPLC using C-l 8 column and with a solvent mixture varying over 50 minutes in a gradient from 5% to 100% acetonitrile-water containing 0.01% TFA. The pure fractions can be lyophilized to give N-Ac-Gly-Val-D-alle-25 Tyr-GIn-IIe-Arg-ProNHCH2CH3 as the trifluoroacetate salt. Example 61 N-Ac-G)y-Gln-D-alle-Ser-Nva-lle-Arg-ProNHCH2CHj The procedure described in Example 1 can be used but substituting Fmoc-Gln(Trt) for 30 Fmoc-Val, Fmoc-D-alle for Fmoc-D-lle and Fmoc-Ser(t-Bu) for Fmoc-Thr(t-Bu). After cleavage of the peptide from the resin and workup the crude product can be purified by HPLC using C-l 8 column and with a solvent mixture varying over 50 minutes in a gradient from 5% to 100% acetonitrile-water containing 0.01% TFA. The pure fractions can be lyophilized to give N-Ac-GIy-Gln-D-alle-Ser-Nva-lle-Arg-ProNHCH2CH3 as the trifluoroacetate salt. 35 Example 62 N-Ac-Gly-Gin-D-alle-Ser-Gln-He-Arg-ProNHCH2CH^ The procedure described in Example I can be used but substituting Fmoc-Gln(Trt) for Fmoc-Val and Fmoc-Nva, Fmoc-D-alle for Fmoc-D-lle and Fmoc-Ser(t-Bu) for Fmoc-Thr(t-Bu). 40 After cleavage of the peptide from the resin and workup the crude product can be purified by HPLC using C-18 column and with a solvent mixture varying over 50 minutes in a gradient from 5% to 100% acetonitrile-water containing 0.01% TFA. The pure fractions can be lyophilized to give N-Ac-Gly-Gln-D-alle-Ser-Gln-lle-Arg-ProNHCH2CH3 as the trifluoroacetate salt. 5 Example 63 N-Ac-Gly-Val-D-alle-Ser-Gln-He-Arfl-Pro-D-AlaNH? The desired product can be prepared by substituting Fmoc-D-Ala-Sieber amide resin for Fmoc-Pro-Sieber ethylamide, D-alle for Fmoc-D-lle, Fmoc-Ser(t-Bu) for Fmoc-Thr(t-Bu), Fmoc-GlnfTrt) for Fmoc-Nva, and adding a coupling with Fmoc-Pro before the coupling with Fmoc-10 Arg(Pmc) in Example 1. After cleavage of the peptide from the resin and workup the crude product was purified by HPLC using C-18 column and with a solvent mixture varying over 50 minutes in a gradient from 5% to 100% acetonitrile-water containing 0.01% TFA. The pure fractions were lyophilized to give N-Ac-Gly-Val-D-alle-Ser-Gln-Ile-Arg-Pro-D-AlaNF^ as the trifluoroacetate salt. 15 Example 64 N-Ac-Gly-Val-D-aUe-Thr-Gln-lle-Arg-ProNHCH2CH2 The procedure described in Example 1 can be used but substituting Fmoo-D-alie for Fmoc-D-Ile and Fmoc-Gln(Trt) for Fmoc-Nva. After cleavage of the peptide from the resin and workup 20 the crude product can be purified by HPLC using C-18 column and with a solvent mixture varying over 50 minutes in a gradient from 5% to 100% acetonitrile-water containing 0.01% TFA. The pure fractions can be lyophilized to give N-Ac-Gly-Val-D-alle-Thr-Gln-Ile-Arg-ProNHCHiCHs as the trifluoroacetate salt. 25 Example 65 N-Ac-Gly-His-D-aIle-Ser-GIn-lle-Arg-ProNHCH2CHj The procedure described in Example 1 can be used but substituting Fmoc-His(Trt) for Fmoc-Val, Fmoc-D-alle for Fmoc-D-Ile, Fmoc-Ser(t-Bu) for Fmoc-Thr(t-Bu) and Fmoc-Gln(Trt) for Fmoc-Nva. After cleavage of the peptide from the resin and workup the crude product can be 30 purified by HPLC using C-18 column and with a solvent mixture varying over 50 minutes in a gradient from 5% to 100% acetonitrile-water containing 0.01% TFA. The pure fractions can be lyophilized to give N-Ac-GIy-His-D-aIle-Ser-Gln-lle-Arg-ProNHCH2CH3 as the trifluoroacetate salt. 35 Example 66 N-(6-Me-nicotinyl)-Gly-Val-D-alle-Ser-Gln-lle-Ara-ProNHCHzCHj The procedure described in Example 1 can be used but substituting 6-methyl-nicotinic acid lor acetic acid, Fmoc-D-alle for Fmoc-D-lle, Fmoc-Ser(t-Bu) for Fmoc-Thr(t-Bu) and Fmoc-* 'ln(Trt) for Fmoc-Nva. After cleavage of the peptide from the resin and workup the crude product can he purified by HPLC using C-18 column and with a solvent mixture varying over 50 minutes in a gradient from 5% to 100% acetonitrile-water containing 0.01% TFA. The pure fractions can be lyophilized to give N-(6-Me-nicotinyl)-GIy-Val-D-alIe-Ser-Gln-lle-Arg-ProNHCH2CH3 as the trifluoroacetate salt. 5 Example 67 N-Ac-Gly-NMeVal-D-lle-Thr-Nva-lle-Arg-ProNHCH^Hj The procedure described in Example 1 can be used but substituting Fmoc-NMeVal for Fmoc-Val and using HATU instead of HBTU in the coupling of the N-methylamino acid. After cleavage of the peptide from the resin and workup the crude product can be purified by HPLC using 10 C-18 column and with a solvent mixture varying over 50 minutes in a gradient from 5% to 100% acetonitrile-water containing 0.01% TFA. The pure fractions can be lyophilized to give N-Ac-Giy-NMeVal-D-Ile-Thr-Nva-Ile-Arg-ProNHCH2CH3 as the trifluoroacetate salt. Example 68 15 N-Ac-Gly-NMePhe-D-Ile-Thr-Nva-Ile-Arg-ProNHCHzCH3 The procedure described in Example 1 can be used but substituting Fmoc-NMePhe for Fmoc-Val and using HATU instead of HBTU in the coupling of the N-methylamino acid. After cleavage of the peptide from the resin and workup the crude product can be purified by HPLC using C-18 column and with a solvent mixture varying over 50 minutes in a gradient from 5% to 100% 20 acetonitrile-water containing 0.01% TFA. The pure fractions can be lyophilized to give N-Ac-Giy-NMePhe-D-lle-Thr-Nva-IIe-Arg-ProNHCH2CH3 as the trifluoroacetate salt. Example 69 N-Ac-Gly-Val-D-Ile-Thr-NMeNva-lle-Arg-ProNHCHzCHj 25 The procedure described in Example 1 can be used but substituting FmooNMeNva for Fmoc-Nva and using HATU instead of HBTU in the coupling of the N-methylamino acid. After cleavage of the peptide from the resin and workup the crude product can be purified by HPLC using C-18 column and with a solvent mixture varying over 50 minutes in a gradient from 5% to 100% acetonitrile-water containing 0.01% TFA. The pure fractions can be lyophilized to give N-Ac-Gly-30 Val-D-Ile-Thr-NMeNva-lle-Arg-ProNHCH2CH3 as the trifluoroacetate salt. Example 70 N-Ac-Gly-Val-D-He-NMeGlu-Nva-Ile-Arg-ProNHCHzCHj The procedure described in Example 1 can be used but substituting Fmoc-NMeGlu(t-Bu) for 35 Fmoc-Thr(t-Bu) and using HATU instead of HBTU in the coupling of the N-methylamino acid. After cleavage of the peptide frorrt the resin and workup the crude product can be purified by HPLC using C-18 column and with a solvent mixture varying over 50 minutes in a gradient from 5% to 100% acetonitrile-water containing 0.01% TFA. The pure fractions can be lyophilized to give N-Ac-Gly-Val-D-Ile-NMeGlu-Nva-lle-Arg-ProNHCH2CH3 as the trifluoroacetate salt. Example 71 N-Ac-Gly-Val-D-alle-Ser-Gln-Ile-ArgMHCH2CHi The procedure described in Example l was used but substituting Fmoc-Arg(Pbf)-[4-(4-N-ethyl)methyl-3-methoxyphenoxy]butryl AM resin for Fmoc-Pro Sieberethylamide resin, Fmoc-5 Gln(Trt) for Fmoc-Nva, Finoc-Ser(t-Bu) for Fmoc-Thr(t-Bu), Fmoc-D-alle for Fmoc-D-Ue, and omitting the coupling with Fmoc-Arg(Pmc) in example l. After cleavage of the peptide from the resin and workup the crude product was purified by HPLC usingC-18 column and with a solvent mixture varying over 50 minutes in a gradient from 5% to 100% acetonitrile-water containing 0.01% TFA. The pure fractions were Iyophilized to give N-Ac-GJy-VaJ-D-alle-Ser-Gln-Ile-10 ArgNHCH2CH3 as the trifluoroacetate salt. Rt= 0.83 minutes (gradient varying over 10 minutes from 20% to 80% aGelonitrileAvater containing 0.01% TFA); MS (ESI) m/e 841.6 (M+H)+. Example 72 N-Ac-Gly-Val-D-Ile-Thr-Nva-Ile-ArgNHCH2CHj 15 The procedure described in Example 1 can be used but substituting FmooArg(Pbf)-[4-(4-N- ethyl)methyl-3-rnethoxyphenoxy]butryl AM resin for Fmoc-Pro Sieber ethylamide resin and omitting the coupling with Fmoc-Arg(Pmc) in example 1. After cleavage of the peptide from the resin and workup the crude product can be purified by HPLC using C-18 column and with a solvent mixture varying over 50 minutes in a gradient from 5% to 100% acetonitrile-water containing 20 0.01% TFA. The pure fractions can be Iyophilized to give N-Ac-Gly-Val-D-IIe-Thr-Nva-Ile-ArgNHCH2CH3 as the trifluoroacetate salt. Example 73 N-(6-Me-nicotinyl)-Gly-Val-D-lle-Thr-Nva-lle-ArgNHCH2CHj 25 The procedure described in Example 1 can be used but substituting Fmoc-Arg(Pbf)-[4-(4-N- ethyI)methyl-3-methoxyphenoxy]butryl AM resin for Fmoc-Pro Sieber ethylamide resin, 6-methylnicotinic acid for acetic acid and omitting the coupling with Fmoc-Arg(Pmc) in example I. After cleavage of the peptide from the resin and workup the crude product can be purified by HPLC using C-18 column and with a solvent mixture varying over 50 minutes in a gradient from 5% to 30 100% acetonitrile-water containing 0.01 % TFA. The pure fractions can be Iyophilized to give N Example 74 N-Ac-Glv-Val-D-lle-alloThr-Nva-Ile-ArgNHCHzCHj 35 The procedure described in Example 1 can be used but substituting Fmoc-Arg(Pbf)-[4-(4-N- ethyl)methyl-3-methoxyphenoxy]butryl AM resin for Fmoc-Pro Sieber ethylamide resin, Fmoc-alloThr(t-Bu) for Fmoc-Thr(t-Bu) and omitting the coupling with Fmoc-Arg(Pmc) in example 1. After cleavage of the peptide from the resin and workup the crude product can be purified by HPLC using C-18 column and with a solvent mixture varying over 50 minutes in a gradient from 5% to 100% acetonitrile-water containing 0.01 % TFA. The pure fractions can be lyophilized to give N-Ac-Giy-Val-D-IIe-aIloThr-Nva-Ile-ArgNHCH2CH3 as the trifluoroacetate salt. Example 75 5 N-Ac-Gly-Gln-D-lle-Thr-Nva-lle-ArgNHCHzCHj The procedure described in Example 1 can be used but substituting Fmoc-Arg(Pbf)-[4-(4-N-emyf)memyf-3-rnethoxyphenoxyJ6utryf AM resin for Fmoc-Pro Sieber ethy/amide resin, Frnoc-Gln(Trt) for Fmoc-Val and omitting the coupling with Fmoc-Arg(Pmc) in example 1. After cleavage of the peptide from the resin and workup the crude product can be purified by HPLC using 10 C-18 column and with a solvent mixture varying over 50 minutes in a gradient from 5% to 100% acetonitrile-water containing 0.01% TFA. The pure fractions can be lyophilized to give N-Ac-Gly-Gln-D-lle-Thr-Nva-Ile-ArgNHCH2CH3 as the trifluoroacetate salt. Example 76 15 N-Ac-Gly-Val-D-alle-Thr-Nva-Ile-ArgNHCH2CHj The procedure described in Example 1 can be used but substituting Fmoo-Arg(Pbf)-[4-(4-N-ethyl)methyl-3-rnethoxyphenoxy]butryl AM resin for Fmoc-Pro Sieber ethylamttie resin, Fmoc-D-alle for Fmoc-D-Iie and omitting the coupling with Fmoc-Arg(Pmc) in example 1. After cleavage of the peptide from the resin and workup the crude product can be purified by HPLC using C-18 20 column and with a solvent mixture varying over 50 minutes in a gradient from 5% to 100% acetonitrile-water containing 0.01% TFA. The pure fractions can be lyophilized to give N-Ac-Gly-Val-D-aJIe-Thr-Nva-Ile-ArgNHCH2CH3 as the trifluoroacetate salt. Example 77 25 N-Ac-Gly-Val-D-alle-Ser-Ser-Ile-ArgNHCHzCH2 The procedure described in Example 1 can be used but substituting Fmoc-Arg(Pbf)-[4-(4-N-ethyf}methyf-3-rriethoxyphenoxyjbutryf AM resin for Fmoc-Pro Sieber ethyfamide resfn, Fmoc-D-alle for Fmoc-D-lle, Fmoc-Ser(t-Bu) for Fmoc-Thr(t-Bu) and Fmoc-Nva and omitting the coupling with Fmoc-Arg(Prnc) in example 1. After cleavage of the peptide from the resin and workup the 30 crude product can be purified by HPLC using C-18 column and with a solvent mixture varying over 50 minutes in a gradient from 5% to 100%acetonitrile-water containing 0.01% TFA. The pure fractions can be lyophilized to give N-Ac-Gly-Val-D-alle-Ser-Ser-Ile-ArgNHCH2CH3 as the trifluoroacetate salt. 35 Example 78 N-Ac-Gly-Val-D-lle-Thr-Gln-lle-ArgNHCHzCH3 The procedure described in Example 1 can be used but substituting Fmoc-Arg(Pbf)-[4-(4-N-ethyl)methyl-3-methoxyphenoxy]butryl AM resin for Fmoc-Pro Sieber ethylamide resin, Frnoc-Gln(Trt) for Fmoc-Nva and omitting the coupling with Fmoc-Arg(Pmc) in example I. After 40 cleavage of the peptide from the resin and workup the crude product can be purified by HPLC using C-l 8 column and with a solvent mixture varying over 50 minutes in a gradient from 5% to 100% acetonitrile-water containing 0.01% TFA. The pure fractions can be lyophilized to give N-Ac-Gly-Val-D-Ile-Thr-Gln-lle-ArgNHCH2CH3 as the trifluoroacetate salt. 5 Example 79 N-Ac-Gly-Val-D-lle-Thr-Ser-Ile-ArgNHCH2CHj The procedure described in Example 1 can be used but substituting Fmoc-Arg(Pbf)-[4-(4-N-ethy!)methyl-3-methoxyphenoxy]butryl AM resin for Fmoc-Pro Sieber ethylarnide resin, Fmoc-Ser(t-Bu) for Fmoc-Nva and omitting the coupling with Fmoc-Arg(Pmc) in example 1. After 10 cleavage of the peptide from the resin and workup the crude product can be purified by HPLC using C-l8 column and with a solvent mixture varying over 50 minutes in a gradient from 5% to 100% acetonitrile-water containing 0.01% TFA. The pure fractions can be lyophilized to give N-Ac-Gly-Val-D-Ile-Thr-Ser-Ile-ArgNHCH2CH3 as the trifluoroacetate salt. 15 Example 80 N-Ac-Gly-Val-D-Ile-Thr-Nva-P-lle-ArgNHCH^CHj The procedure described in Example I can be used but substituting Fmoc-Arg(Pbf)-[4-(4-N-ethyl)methv£3-methoxyphenoxy]butryl AM resin for Fmoc-Pro Sieber ethylarnide resin, Fmoc-D-Ile for Fmoc-Ile and omitting the coupling with Fmoc-Arg(Pmc) in Example 1. After cleavage of 20 the peptide from the resin and workup the crude product can be purified by HPLC using C-l 8 column and with a solvent mixture varying over 50 minutes in a gradient from 5% to 100% acetonitrile-water containing 0.01% TFA. The pure fractions can be lyophilized to give N-Ac-Gly-Val-D-Ile-Thr-Nva-D-IIe-ArgNHCH2CH3 as the trifluoroacetate salt. 25 Example 81 N-Ac-Gln-Val-D-ne-Thr-Nva-Ile-ArgNHCFbCHi The procedure described in Example 1 can be used but substituting FmooArg(Pbf)-[4-(4-N-ethyl)methyl-3-methoxyphenoxy]butryl AM resin for Fmoc-Pro Sieber ethylarnide resin, Fmoc-Gln(Trt) for Fmoc-Gly and omitting the coupling with Fmoc-Arg(Pmc). After cleavage of the 30 peptide from the resin and workup the crude product can be purified by HPLC using C-l 8 column and with a solvent mixture varying over 50 minutes in a gradient from 5% to 100% acetonitrile-water containing 0.01% TFA. The pure fractions can be lyophilized to give N-Ac-Gln-Val-D-lle-Thr-Nva-lle-ArgNHCH2CH3 as the trifluoroacetate salt. 3 10 15 20 25 30 35 40 Example 87 N-Ac-Gln-Val-P-alle-Ser-Ser-He-Arg-ProNHC^CHt The procedure described in Example I can be used but substituting Fmoc-Gln(Trt) for . Fmoc-Gly, Fmoc-D-alle for Fmoc-D-lle, Fmoc-Ser(t-Bu) for Fmoc-Thr(t-Bu) and Fmoc-Nva. After 5 cleavage of the peptide from the resin and workup the crude product can be purified by HPLC using C-18 column and with a solvent mixture varying over 50 minutes in a gradient from 5% to 100% acetonitrile-water containing 0.01% TFA. The pure fractions can be lyophilized to give N-Ac-Gln-Val-D-alle-Ser-Ser-Ile-Arg-ProNHCH2CH3 as the trifluoroacetate salt. 10 Example 88 N-Ac-D-Gln-Val-D-alle-Ser-Ser-Ile-Arg-ProNHCHgCHj The procedure described in Example 1 can be used but substituting Fmoc-D-GIn(Trt) for Fmoc-Gly, Fmoc-D-alle for Fmoc-D-lle, Fmoc-Ser(t-Bu) for Fmoc-Thr(t-Bu) and Fmoc-Nva. After cleavage of the peptide from the resin and workup the crude product can be purified by HPLC using 15 C-18 column and with a solvent mixture varying over 50 minutes in a gradient from 5% to 100% acetonitrile-water containing 0.01 % TFA. The pure fractions can be lyophilized to give N-Ac-D-GIn-Val-D-aIle-Ser-Ser-lle-Arg-ProNHCH2CH3 as the trifluoroacetate salt. Example 89 20 N-Ac-Gln-Val-D-aUe-Ser-Gln-He-Ar°NHCH2CH2 The procedure described in Example 1 can be used but substituting Fmoc-Arg(Pbf)-[4-(4-N-ethyl)methyl-3-methoxyphenoxy]butryl AM resin for Fmoc-Pro Sieber ethylamide resin, Fmoc-Gln(Trt) for Fmoc-Gly, Fmoc-D-alle for Fmoc-D-lle, Fmoc-Ser(t-Bu) for Fmoc-Thr(t-Bu), Fmoc-Gln(Trt) for Fmoc-Nva and omitting the coupling with Fmoc-Arg(Pmc). After cleavage of the 25 peptide from the resin and workup the crude product can be purified by HPLC using C-18 column and with a solvent mixture varying over 50 minutes in a gradient from 5% to 100% acetonitrile-water containing 0.01% TFA. The pure fractions can be lyophilized to give N-Ac-Gln-Val-D-alle-Ser-Gln-Ile-ArgNHCH2CH3 as the trifluoroacetate salt. 30 Example 90 N-Ac-D-Gln-Val-D-alle-Ser-Gln-Ile-ArgNHCH2CHj The procedure described in Example 1 can be used but substituting Fmoc-Arg(Pbf)-[4-(4-N-ethyI)methyl-3-methoxyphenoxy]butryl AM resin for Fmoc-Pro Sieber ethylamide resin, Fmoc-D-Gln(Trt) for Fmoc-Gly, Fmoc-D-alle for Fmoc-D-lle, Fmoc-Ser(t-Bu) for Fmoc-Thr(t-Bu), Fmoc- 35 Gtn(Trt) for Fmoc-Nva and omitting the coupling with Fmoc-Arg(Pmc). After cleavage of the peptide from the resin and workup the crude product can be purified by HPLC using C-18 column and with a solvent mixture varying over 50 minutes in a gradient from 5% to 100% acetonitrile-water containing 0.01% TFA. The pure fractions can be lyophilized to give N-Ac-DGln-Val-D-alle-Ser-Gln-Iie-ArgNHCH2CH3 as the trifluoroacetate salt. 40 Example 91 N-Ac-Gln-Val-P-lle-Thr-Nva-Pro-ArgNHCH2CFh The procedure described in Example 1 can be used but substituting Fmoc-Arg(Pbf)-[4-(4-N-ethyl)methyl-3-methoxyphenoxy]butryI AM resin for Fmoc-Pro Sieber ethylamide resin, Fmoc-5 Gln(Trt) for Fmoc-Gly, Fmoc-Pro for Fmoc-lle and omitting the coupling with Fmoc-Arg(Pmc). After cleavage of the peptide from the resin and workup the crude product can be purified by HPLC using C-18 column and with a solvent mixture varying over 50 minutes in a gradient from 5% to 100% acetonitrile-water containing 0.01% TFA. The pure fractions can be lyophilized to give N-Ac-Gln-Val-D-Ile-Thr-Nva-Pro-ArgNHCH2CH3 as the trifluoroacetate salt. 10 Example 92 N-Ac-Ala-Gln-D-Ile-Thr-TSlva-lle-ArgNHCH2CH3 The procedure described in Example 1 can be used but substituting Fmoc-Arg(Pbf)-[4-(4-N-ethyI)methyl-3-methoxyphenoxy]butryl AM resin for Fmoc-Pro Sieber ethylamide resin, Fmoc-Ala 15 for Fmoc-Gly, Fmoc-Gln(Trt) for Fmoc-Val and omitting the coupling with Fmoc-Arg(Pmc). After cleavage of the peptide from the resin and workup the crude product can be purified by HPLC using C-18 column and with a solvent mixture varying over 50 minutes in a gradient from 5% to 100% acetonitrile-water containing 0.01% TFA. The pure fractions can be lyophilized to give N-Ac-Ala-Gln-D-Ile-Thr-Nva-Ile-ArgNHCH2CH3 as the trifluoroacetate salt. 20 Example 93 N-Ac-D-Ala-Val-D-lle-Thr-Gln-lle-Arg-ProNHCHzCHa The procedure described in Example 1 can be used but substituting Fmoc-D-Ala for Fmoc-Gly and Fmoc-Gln(Trt) for Fmoc-Nva. After cleavage of the peptide from the resin and workup the 25 - crude product can be purified by HPLC using C-18 column and with a solvent mixture varying over 50 minutes in a gradient from 5% to 100% acetonitrile-water containing 0.01% TFA. The pure fractions can be lyophilized to give N-Ac-D-Ala-Val-D-Tle-Thr-GIn-Ile-Arg-ProNHCH2CH3as the trifluoroacetate salt. Example 94 N-Ac-Ala-Gln-D-lle-Thr-Ser-lle-Arg-ProNHCHzCHj The procedure described in Example 1 can be used but substituting Fmoc-Ala for Fmoc-Gly and Fmoc-Gln(Trt) for Fmoc-Val, Fmoc-Ser(t-Bu) for Fmoc-Nva. After cleavage of the peptide from the resin and workup the crude product can be purified by HPLC using C-18 column and with a solvent mixture varying over 50 minutes in a gradient from 5% to 100% acetonitrile-water containing 0.01% TFA. The pure fractions can be lyophilized to give N-Ac-Ala-Gln-D-fle-Thr-Ser-Ile-Arg-ProNHCH2CH3 as the trifluoroacetate salt. Example 95 N-Ac-Ala-Val-D-alle-Ser-Gln-lle-Arg-ProNHCHyCHy The procedure described in Example 1 can be used but substituting Fmoc-Ala for Fmoc-Gly, Fmoc-D-alle for Fmoc-D-Ile, Fmoc-Ser(t-Bu) for Fmoc-Thr(t-Bu) and Fmoc-Gln(Trt) for Fmoc-Nva. After cleavage of the peptide from the resin and workup the crude product can be purified by HPLC using C-18 column and with a solvent mixture varying over 50 minutes in a gradient from 5 5% to 100% acetonitrile-water containing 0.01 % TFA. The pure fractions can be lyophilized to give N-Ac-Ala-Val-D-aIle-Ser-Gln-Ile-Arg-ProNHCH2CH3 as the trifluoroacetate salt. Example 96 N-Ac-Ala-Val-D-aHe-Ser-Gln-Ile-ArgNHCH^CHj !0 The procedure described in Example 1 can be used but substituting Fmoc-Arg(Pbf)-[4-(4-N- ethyI)methyl-3-methoxyphenoxy]butryl AM resin for Fmoc-Pro Sieber ethylamide resin, Fmoc-Ala for Fmoc-Gly, Fmoc-D-alle for Fmoc-DIle, Fmoc-Ser(!-Bu) for Fmoc-Thr-(t-Bu), Fmoc-Gln(Trt) for Fmoc-Nva and omitting the coupling with Fmoc-Arg(Pmc). After cleavage of the peptide from the resin and workup the crude product can be purified by HPLC using C-18 column and with a 15 solvent mixture varying over 50 minutes in a gradient from 5% to 100% acetonitrile-water containing 0.01% TFA. The pure fractions can be lyophilized to give N-Ac-Ala-Val-D-alle-Ser-Gln-Ile-ArgNHCH2CH3 as th£trifluoroacetate salt. Example 97 20 N-Ac-(4CH3)Phe-Gln-D-lle-Thr-Nva-]le-ArgNHCH?CH3 The procedure described in Example 1 can be used but substituting Fmoc-Arg(Pbf)-[4-(4-N-ethyl)methyl-3-methoxyphenoxy]butryl AM resin for Fmoc-Pro Sieber ethylamide resin, Fmoc-(4CH3)Phe for Fmoc-Gly, Fmoc-Gln(Trt) for Fmoc-Val and omitting the coupling with Fmoc-Arg(Pmc). After cleavage of the peptide from the resin and workup the crude product can be 25 purified by HPLC using C-18 column and with a solvent mixture varying over 50 minutes in a gradient from 5% to 100% acetonitrile-water containing 0.01% TFA. The pure fractions can be lyophilized to give N-Ac-(4CH3)Phe-Gln-D-Ile-Thr-Nva-Ile-ArgNHCH2CH3 as the trifluoroacetate salt, 30 Example 98 N-Ac-(4CH3)Phe-Gln-D-Ile-Thr-Gln-lle-Arg-ProNHCHzCH3 The procedure described in Example 1 can be used but substituting Fmoc-(4CH3)Phe for Fmoc-Gly and Fmoc-Gln(Trt) for Fmoc-Val and Fmoc-Nva. After cleavage of the peptide from the resin and workup the crude product can be purified by HPLC using C-18 column and with a solvent 35 mixture varying over 50 minutes in a gradient from 5% to 100% acetonitrile-water containing 0.01% TFA. The pure fractions can be lyophilized to give N-Ac-(4CH3)Phe-Gln-D-Ile-Thr-Gln-Ile-Arg-ProNHCH2CH3 as the trifluoroacetate salt. Example 99 40 N-Ac-Gln-Val-D-»e-Thr-Nva-Lys(Ac)-Arg-ProNHCH2CH-t The procedure described in Example 1 can be used but substituting Fmoc-Gln(Trt) for Fmoc-GIy and Fmoc-Lys(Ac) for Fmoc-lle. After cleavage of the peptide from the resin and workup the crude product can be purified by HPLC using C-l 8 column and with a solvent mixture varying over 50 minutes in a gradient from 5% to 100% acetonitrile-water containing 0.01% TFA. 5 The pure fractions can be lyophilized to give N-Ac-GIn-Val-D-lIe-Thr-Nva-Lys(Ac)-Arg-ProNHCH2CH3 as the trifluoroacetate salt. Example 100 N-Ac-(6-Me-nicotinyl)-Gly-Val-D-lle-Thr-Nva-lle-ArgNHCH2CHj 10 The procedure described in Example 1 can be used but substituting Fmoc-Arg(Pbf)-[4-(4-N- ethyl)methyl-3-methoxyphenoxy]butryl AM resin for Fmoc-Pro Sieber ethylamide resin, 6-methyl-nicotinic acid for acetic acid and omitting the coupling with Fmoc-Arg(Pmc). After cleavage of the peptide from the resin and workup the crude product can be purified by HPLC using C-l 8 column and with a solvent mixture varying over 50 minutes in a gradient from 5% to 100% acetonitrile-15 water containing 0.01% TFA. The pure fractions can be lyophilized to give N-Ac-(6-Me-nicotinyI)-Gly-Val-D-Ile-Thr-Nva-lle-ArgNHCH2CH3 as the trifluoroacetate salt. It will be evident to one skilled in the art that the present invention is not limited to the foregoing illustrative examples, and that it can be embodied in other specific forms without 20 departing from the essential attributes thereof. It is therefore desired that the examples be considered in all respects as illustrative and not restrictive, reference being made to the appended claims, rather than to the foregoing examples, and all changes which come within the meaning and range of equivalency of the claims are therefore intended to be embraced therein. We claim: 1. An antiangiogenic peptide of formula (1) Xaa1-Xaa2-Xaa3-Xaa4-Xaa5-Xaa6-Xaa7- Xaa8-Xaa9- Xaa10 (1) (SEQID NO; I) or a therapeutically acceptable salt thereof, wherein Xaai is selected from the group consisting of hydrogen and R-(CH2)n-C(0)-, wherein n is an integer from O to 8 and R is selected from the group consisting of alkoxy, alkyl, amino, aryl, carboxyl, cycloalkenyl, cycloalkyl, and heterocycle; Xaa2 is selected from the group consisting of alanyl, D-alanyl, (IS,3R)-1 aminocyclopentane-3- carbonyl, (I S,4R)-I-aminocyclopent-2-ene-4-carbonyl, (I R,4S)-I o aminocyclopent-2-ene-4-carbonyl, asparaginyl, 3- cyanophenylalanyl, 4- cyanophenylalanyl, 3,4 dimethoxyphenylalanyl, 4- fluorophenylalanyl, 3-(2-furyl)alanyl, glutaminyl, D-glutaminyl, glycyl, Iysyl(N-epsilon acetyl), 4-methylphenylalanyl, ndrvalyl, and sarcosyl; Xaa3 is selected from the group consisting of alanyl, (I R,4S)-1 - aminocyclopent-2-ene-4 carbonyl, arginyl, asparaginyl, D-asparaginyl, t- butylglycyl, citrullyl, cyclohexylglycyl, glutaminyl, D-glutaminyl, glutamyl, glycyl, histidyl, isoleucyl, leucyl, Iysyl(Nepsilon-acetyl), methionyl, norvalyl, phenylalanyl, N-methylphenylalanyl, prolyl, seryl, 3-(2-thienylalanyl), threonyl, valyl, and N-methylvalyl; Xaa4 is selected from the group consisting of D-alanyl, D-alloisoleucyl, D-allylglycyl, D- 4 chlorophenylalanyl, D-citrul Iyl, D-3 -cyanophenylalanyl, D-homophenylalany 1, D-homoseryl, isoleucyl, D-isoleucyl, D-leucyl, N- methyl-D-leucyl, D-norleucyl, D-norvalyl, D-penicillaminyl, D phenylalanyl, D-prolyl, D-seryl, D-thienylalanyl, and D-threonyl; Xaa5 is selected from the group consisting of allothreonyl, aspartyl, glutaminyl, D glutaminyl, N-methylglutaminyl, N-methylglutamyl, glycyl, histidyl, homoseryl, isoleucyl, Iysyl(N epsilon-acetyl), methionyl, seryl, N- methylseryl, threonyl, D-threonyl, tryptyl, tyrosyl, and tyrosyl(0- methyl); Xaa6 is selected from the group consisting of alanyl, N- methylalanyl, allothreonyl,; glutaminyl, glycyl, homoseryl, leucyl, Iysyl(N-epsilon-acetyl), norleucyl, norvalyl, D-norvalyl, N methyinorvalyl, octylglycyl, ornithyl(N-delta-acetyl), 3-(3-pyridyl) alanyl, sarcosyl, seryl, N methylseryl, threonyl, tryptyl, valyl, and N- methylvalyl; Xaa7 is selected from the group consisting of alanyl, alloisoleucyl, aspartyl, citrullyl, isoleucyl, D-isoleucyl, leucyl, D- leucyl, Iysyl(N-epsilon-acetyl), D-lysyl(N-epsilon-acetyl), N methylisoleucyl, norvalyl, phenylalanyl, prolyl, and D-prolyl; Xaag is selected from the group consisting of arginyl, D-arginyl, citrullyl, glutaminyl, histidyl, homoarginyl, Iysyl, Iysyl(N-epsilon-isopropyl), ornithyl, and 3{3-pyridyl)alanyl; Xaa8 is absent or selected from the group consisting of N-methyl-D-alanyl, 2-aminobutyryl,; D-glutaminyl, homoprolyl, hydroxyprolyl, leucyl, prolyl, D-prolyl, and D-valyl; and Xaaio is selected from the group consisting of D-alanylamide, azaglycylamide, glycylamide, D-lysyl(N-epsilon-acetyl)amide, a group represented by the formula -NH-(CH2)n-CHRIR2; and a group represented by the formula-NHR3, wherein n is an integer from 0 to 8; R1 is selected from the group consisting of hydrogen, alkyl, cycloalkenyl, and cycloalkyl; R2 is selected from the group consisting of hydrogen, alkoxy, alkyl, aryl, cycloalkenyl, cycloalky 1, heterocycle and hydroxyl, with the proviso that when n is 0, R2 is other than alkoxy or hydroxyl; and R3 is selected from the group consisting of hydrogen, cycloalkenyl, cycloalkyl, and hydroxyl. The peptide as claimed in claim 1, wherein Xaa2 is selected from the group consisting of alanyl, D-alanyl, asparaginyl, 4-cyanophenylalanyl, 4-methylphenylalanyl, and norvalyl or from the group consisting of glutaminyl and D-glutaminyl. 3. The peptide as claimed in claim 1, wherein Xaa2 is glycyl. 4. The peptide as claimed in claim 3, wherein Xaa3 is selected from the group consisting of valyl and N-methylvalyl. 5. The peptide as claimed in claim 4, wherein Xaa6 is selected from the group consisting of norvalyl and N-methylnorvalyl or from the group consisting of -glutaminyl, seryl, and threonyl. 6. The peptide as claimed in claim 3, wherein Xaa3 is selected from the group consisting of arginyl, asparaginyl, D-asparaginyl, citrullyl, lysyl (N-epsilon- acetyl), and histidyl. 7. The peptide as claimed in claim 3, wherein Xaa3 is selected from the group consisting of glutaminyl, D-giutaminyl, phenylalanyl, and N-methylphenylalanyl. 8. The peptide as claimed in claim 7, wherein Xaa7 is isoleucyl or is selected from the group consisting of D- isoleucyl, lysyl (N-epsilon acetyl), and D-prolyl. 9. The peptide as claimed in any one or more preceding claims selected from the group consisting of: 10. A peptide as claimed in any of the claims 1 to 9, which is N-Ac-Gly-Val-D- aile-Ser-Gln-Ile-Arg-ProNHGH2CH3. 11. A pharmaceutical composition comprising therapeutically effective amount of a peptide as claimed in claim 1 or a therapeutically acceptable salt thereof, in combination with a therapeutically acceptable carrier such as herein described. Dated this 29th day of April, 2004 ArchaSaShanker Of Anand and Anand, Advocates Attorney for the applicants

Documents:

255-mumnp-2004-abstract(28-08-2007).doc

255-mumnp-2004-abstract(28-08-2007).pdf

255-mumnp-2004-assignment(29-04-2004).pdf

255-mumnp-2004-cancelled page(28-08-2007).pdf

255-mumnp-2004-claim(granted)-(28-08-2007).pdf

255-mumnp-2004-claims(granted)-(28-08-2007).doc

255-mumnp-2004-correspondence 1(19-09-2007).pdf

255-mumnp-2004-correspondence 2(28-12-2005).pdf

255-mumnp-2004-correspondence(ipo)-(20-09-2006).pdf

255-mumnp-2004-form 1(28-08-2007).pdf

255-mumnp-2004-form 1(29-04-2004).pdf

255-mumnp-2004-form 13(28-08-2007).pdf

255-mumnp-2004-form 18(29-12-2005).pdf

255-mumnp-2004-form 2(granted)-(28-08-2007).doc

255-mumnp-2004-form 2(granted)-(28-08-2007).pdf

255-mumnp-2004-form 26(12-11-2002).pdf

255-mumnp-2004-form 3(24-04-2004).pdf

255-mumnp-2004-form 3(28-08-2007).pdf

255-mumnp-2004-form 5(24-04-2004).pdf

255-mumnp-2004-other document(19-09-2007).pdf

255-mumnp-2004-other document(28-08-2007).pdf

255-mumnp-2004-power of attorney(11-10-2005).pdf