AU2006277557A1 - Novel compounds as GPL-I agonists - Google Patents

Description

WO 2007/017892 PCT/IN2006/000154 NOVEL COMPOUNDS AS GLP-1 AGONISTS Field of Invention The present invention relates to novel compounds of general formula (I), their tautomeric forms, novel intermediates involved in their synthesis, their 5 pharmaceutically acceptable salts and pharmaceutical compositions containing them. A-X- S-Y-S 2

-X

2 -B (I) In particular, the present invention relates to novel Glucagon-Like Peptide-1 10 (GLP-1) peptide mimics (peptidomimetic), which act as GLP-1 receptor agonists and exhibit most of the biological activity of the native GLP-1. Furthermore, these GLP-1 peptidomimetics exhibit increased stability to proteolytic cleavage, especially against DPP-IV (Dipeptidyl peptidase-IV) enzyme and can be delivered by both invasive and various non-invasive routes of administrations such as oral, nasal, buccal, pulmonary 15 and transdermal route of administration, for the treatment or prevention of diabetes and related conditions. The present invention also relates to a process of preparing compounds of general formula (I), their tautomeric forms, their pharmaceutically acceptable salts, pharmaceutical compositions containing them, and novel intermediates involved in 20 their synthesis. Background to the invention The GLP-1 (7-36) amide is a product of the preproglucagoi gene, which is secreted from intestinal L-cells, in response to the ingestion of food. The physiological action of GLP-1 has gained considerable interest. GLP-1 exerts multiple action by 25 stimulating insulin secretion from pancreatic P-cells, in a glucose dependent manner (insulinotropic action). GLP-1 also lowers circulating plasma glucagon concentration, by inhibiting its secretion from ot-cells (Drucker D. J, Endocrinology, 142, 521-527, 2001). More recently, it has become clear that GLP-1 also exhibits properties like stimulation of p-cell growth, appetite suppression, delayed gastric emptying and 30 stimulation of insulin sensitivity (Nauck, Horm. Metab. Res., 47, 1253-1258, 1997). The venom of the Gila Monster Heloderma Suspectum contains a 39 amino acid peptide called Exendin4 (EX-4) that shares around 50 % sequence identity to GLP-1 itself, exhibits a very potent GLP-1R (Glucagon like peptide-1 receptor) agonist activity (Thorens B., Diabetes, 42, 1678 - 1682, 1993). Indeed, it was found that EX-4 35 is much more potent than native GLP-1 peptide, because of its relatively longer half- WO 2007/017892 PCT/IN2006/000154 life (25 min., iv route of administration), compared to GLP-1 (2-5 min., iv route of administration). Exendin-4 binds with greater affinity to the GLP-1R, due to presence of the nine extra C-terminal sequence (Doyle M.E., Regulatory Peptides, 114, 153-158, 2003). Thus, the above stated pharmacological properties of GLP-1R agonists make it a 5 highly desirable therapeutic agent for the treatment of diabetes. Native or synthetic GLP-1 peptide is rapidly metabolized by the proteolytic enzymes, such as dipeptidyl peptidase-IV (DPP-IV) into an inactive metabolite, thereby limiting the use of GLP-1 as a drug. Currently, various analogs of GLP-1 and EX-4, such as Liraglutide / NN2211 (Novo Nordisk; Phase-III; WO 1998 008871), BIM 10 51077 (Ipsen; Phase-II; WO 2000 034331), CJC-1131 (ConjuChem; Phase-II; WO 2000 069911), ZP-10 (Zealand & Aventis; Phase-II; WO 2001 004156) are in different stages of clinical development (Nauck M.A., Regulatory Peptides, 115, 13-19, 2004). However, all these peptides require delivery via parenteral route of administration, including BYETTA* (Exendin-4, AC 2933; WO 2001 051078), which is recently 15 launched in the market (Amylin & Lilly). Thus, there exists a critical need to develop a biologically active GLP- 1 mimic that possesses extended pharmacodynamic profiles. The GLP-1 R is a seven-transmembrane domain G-protein-coupled receptor (GPCR) and it is located on the cell membrane of pancreatic P-cells. The effector system of GLP- 1. R is the Adenylyl Cyclase (AC) enzyme. Interaction of GLP- 1 agonist 20 with GLP-1R causes activation of AC, which converts ATP to cAMP. Increase in the intracellular cAMP level raises the ratio of ADP/ATP, thereby initiating the cell depolarization (due to closure of KATP channel). Increase in the intracellular cAMP level also activates Protein Kinase (PK-A & PK-C), which raises the cystolic Ca concentration, by opening of L-type of Ca 2 ' channel. An increase in the intracellular 25 Ca?" leads to exocytosis of insulin, in pancreatic P-cells (Fehmann, H.C., Endocr. Rev., 16, 390 - 410, 1995). A general mechanism of peptide ligand interaction with class-B GPCRs has emerged recently, termed the 'two-domain' model (Hoare S.R.J., Drug Discovery Today, Vol. 10 (6), 417-427, 2005). In this two-domain model, the C-terminal portion 30 of the peptide binds to the N-domain of the receptor and the N-terminal ligand region binds to the J-domain (transmembrane) region of GPCR. This interaction activates the receptor and thereby stimulates intracellular signaling. The receptor binding and activation occurs in two separate domains of Exendin, but they are closely coupled in GLP-1 (Eng J., J.B.C., 272 (34), 21291-21296, 1997). -2- WO 2007/017892 PCT/IN2006/000154 Prior art Earlier, Bristol-Myers Squibb (BMS), Princeton, NJ (US), reported human GLP-1 mimics, with general formula Xaal-Xaa 11, wherein Xaal-Xaa9 represent the first 1-9 residues of GLP-1 peptide with some analogs wherein Xaa2 represents either 5 Ala or is optionally replaced with Aib, and Xaa6 represents Phe or is optionally replaced with a-Me-Phe(2-F)-OH and XaalO & Xaall represents combination of substituted or unsubstituted biphenyl alanine (Bip) derivatives (WO 03/ 033671A2; US 2004/ 0127423 Al; WO 2004/ 094461 A2; US 2006 / 0004222 Al and WO 2006/ 014287 Al). 10 The present invention provides novel GLP-1 peptide mimics of formula (I) (hereinafter referred to as peptidomimetics), which act as a GLP-lR agonist and exhibit most of the biological activity of the native GLP-1 peptide. Furthermore, these GLP-1 peptidomimetics exhibit increased stability to proteolytic cleavage, especially against DPP-IV enzyme and therefore, surprisingly found to have an increased half-life making 15 them suitable for the treatment / mitigation / prophylaxis of both type 1 & type 2 diabetes, metabolic disorders, obesity and related disorders. Summary of the-invention The present invention describes a group of novel peptidomimetics useful for the treatment of diabetes. These compounds are defined by the general formula (I) as given 20 below. The compounds of the present invention are useful in the treatment of the human or animal body, by regulation of insulin secretion. The compounds of this invention are therefore suitable for the treatment/mitigation/regulation or prophylaxis of both type 1 & type 2 diabetes and obesity. 25 Preferred embodiments The main object of the present invention is to provide novel compounds of general formula (I), their tautomeric forms, novel intermediates involved in their synthesis, their pharmaceutically acceptable salts, their pharmaceutically acceptable solvates and pharmaceutical compositions containing them or their mixtures, suitable 30 for the treatment treatment/mitigation/regulation of diabetes. In an embodiment is provided a process for the preparation of novel compounds of general formula (I), their tautomeric forms, their pharmaceutically acceptable salts, pharmaceutically acceptable solvates and pharmaceutical compositions containing them. -3- WO 2007/017892 PCT/IN2006/000154 In another embodiment, is provided pharmaceutical compositions containing compounds of general formula (I), their tautomeric forms, their pharmaceutically acceptable salts, solvates and their mixtures having pharmaceutically acceptable carriers, solvents, diluents, excipients and other media normally employed in their 5 manufacture. In a further another embodiment is provided the use of the novel compounds of the present invention as antidiabetic agents, by administering a therapeutically effective & non-toxic amount of the compound of formula (I), or their pharmaceutically acceptable compositions to the mammals those are need of such treatment. 10 Abbreviations used The following abbreviations are employed in the examples and elsewhere herein: Aib = c-Aminoisobutyric acid, ACN or MeCN Acetonitrile, 15 Bip = Biphenylalanine residue, Bip(4-fluro)= 4-fluoro-biphenylalanine residue, Bip(2-Me)= 2-methyl biphenyl residue, Bip(2-Et)= 2-ethyl biphenyl residue, Bip(2-CN)= 2-nitrile biphenyl residue, 20 Bip(2-Ipr)= 2-Isopropyl biphenyl residue, Bip(2'-Et-4'-OMe)= 2-ethyl-4-methoxy-biphenyl residue, Bip(2-F)= 2-fluro-biphenyl residue, Bn = Benzyl, Boc = tert-Butoxycarbonyl, 25 But= 0-tert-butyl group, cAMP= Adenosine 3',5'-cyclic monophosphate, DCM Dichloromethane, DMF =N,N-Dimethylformamide, DIPCDI= Di-isopropylcarbodiimide, 30 DIPEA= Diisopropylethylamine, 4-DBF=4-dibenzofuran-Phe-OH residue, 4-DBT=4-dibenzothiophene-Phe-OH residue, Dihydro-Phen=2-(9,10-Dihydro-phenanthrenyl]-Ala-OH residue, Et = Ethyl, -4- WO 2007/017892 PCT/IN2006/000154 Et 2 O = Diethyl ether, Fmoc = Fluorenylmethoxycarbonyl, 2-Flu=2-Fluorenyl-Ala-OH residue, g = Gram (s), 5 GTT = Glucose Tolerance Test, GLP-1R = Glucagon Like Peptide-1 Receptor, h = Hour (s), HOBt = Hydroxybenzotriazole, HOAT= 7-Aza-hydroxybenzotriazole, 10 HBTU= 2-(1H-benzotriazole-1-yl)-1,1,3,3-tetramethyl aminium hexafluorophosphate, HPLC = High Performance Liquid Chromatography, L = Liter, LC /MS = Liquid Chromatography / Mass Spectrometry, 4-(2'-Me-Ph)-3-Pyr-Ala= 4-(2'-methylphenyl)-3-pyridylalanine residue, 15 Me = Methyl, Min = minute (s), ml = milliliter, pl = microliter, mg = milligram (s), 20 mmol = millimole (s), finol = fantomolar MS= Mass Spectrometry, 1-Nap=4-(1-Naphthyl)-Phe residue, 2-Nap=4-(2-Naphthyl)-Phe residue, 25 Phen=2-(Phenanthrenyl)-Ala-OH residue, Pbf= Pentamethylbenzofuran-5-sulfonyl, PyBOP = Benzotriazole-1-yl-oxy-tris-pyrrolidino-phosphonium hexafluorophosphate, SPPS = Solid Phase Peptide Synthesis, Sc = sub-cutaneous, 30 TrPh=4-phenyl-biphenylalanine residue, TMS = Trimethylsilyl, TIPS = Triisopropylsilane, TFA = Trifluoroacetic acid, TBTU= 2-(1H-benzotriazole-1-yl)-1,1,3,3-tetramethylaminium tetrafluoroborate, -5- WO 2007/017892 PCT/IN2006/000154 Trt= Trityl group, (ax-Me)Phe(2-F)= x-methyl-2-fluoro-phenylalanine residue, -(N(Me))-= N-methylated amide bond, D-Alanine represented by 'a' and D-Bip represent 'D'-Biphenyl alanine residue, 5 ip = intra-peritoneal, Sequence of GLP-1 peptide

NH

2

-HAEGTFTSDVSSYLEGQAAKEFIAWLVKGR-CONH

2 (30 amino acids). The 30 amino acids of said GLP-1 peptide are shown in Seq ID 1. HAEGTFTSDVSSYLEGQAAKEFIAWLVKGR ---Seq ID 1 10 Sequence of Exendin-4 =

NH

2

-HGEGTFTSDLSKQMEEEAVRLFIEWLKNGGPSSGAPPPS-CONH

2 (39 amino acids). The 39 amino acids of Extendin -4 are shown in Seq ID 2. HGEGTFTSDLSKQMEEEAVRLFIEWLKNGGPSSGAPPPS ---Seq ID 2 15 Detailed description In accordance with the present invention, synthetic GLP-1 analog peptides / peptidomimetics are provided, which have the structural formula (I),

A-X

1 - S 1

-Y-S

2

-X

2 -B (I) wherein, 20 A represents -NH-R 1 , wherein R 1 represents hydrogen, groups selected from linear or branched (C 1

-C

1 5 ) alkyl chain, such as methyl, ethyl, propyl, isopropyl, n-butyl, iso butyl, t-butyl, pentyl, isopentyl, hexyl, heptyl, octyl, decyl groups and the like, an amino acid or peptide containing one, two or three natural amino acid residues, R 3

-CO

group, such as (2-Hydroxy-phenyl)-acetyl group and the like, R 3 0-C(O)- group, such 25 as Fmoc group and the like, a sulfonyl group of formula R 3 -S0 2 -, each of these groups may be substituted, wherein R 3 is selected from linear or branched (C 1 -Cio) alkyl, such as methyl, ethyl, propyl, isopropyl, n-butyl, iso-butyl, t-butyl, pentyl, isopentyl, hexyl, heptyl, octyl, decyl groups and the like, (C 3

-C

6 ) cycloalkyl, such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl groups and the like, aryl groups selected from 30 phenyl, napthyl, indanyl, fluorenyl, biphenyl and the like, heteroaryl groups selected from pyridyl, thienyl, furyl, imidzolyl, benzofuranyl and the like, arylalkyl groups selected from benzyl, naphthylmethyl and the like, each of these groups may be substituted; -6- WO 2007/017892 PCT/IN2006/000154 B represents -COOR 2 , -CONHR 2 or CH 2

OR

2 , R2 represents H, groups selected from linear or branched (C-Cio) alkyl group, such as methyl, ethyl, propyl, isopropyl, n butyl, iso-butyl, t-butyl, pentyl, isopentyl, hexyl, heptyl, octyl, decyl groups and the like, aryl groups selected from phenyl, napthyl, indanyl, fluorenyl, biphenyl and the 5 like, aralkyl groups, each of these groups may be substituted, each of S 1 and S2 may independently be a bond or independently represents a group '

NH-(CH

2 )n-COO-', where, n=1-9; such as derivatives of amino acetic acid, amino propionic acid, amino butanoic acid, amino pentanoic acid, amino hexanoicacid, amino heptanoic acid, amino octanoic acid, amino-nonanoic acid, amino-decanoic acid and 10 the like; Y represents a bond or -CO-, -(CH 2 )m- (m = 1-3), '0', 'S', -CO-NH-, -CO-NR4-, or represents a short peptide containing one or two or three amino acids selected from natural or non-natural amino acids; where R 4 represents H, optionally substituted groups selected from linear or branched (C-C 10 ) alkyl group such as methyl, ethyl, 15 propyl, isopropyl, n-butyl, iso-butyl, t-butyl, pentyl, isopentyl, hexyl, heptyl, octyl, decyl groups and the like, aryl groups selected from phenyl, napthyl, indanyl, fluorenyl, biphenyl and the like; with the proviso that i) when S-Y-S 2 represents a bond,

X

1 is selected from the following amino acid sequences 20 HAEGTFTSD (Seq ID 3), HAEGTFTSDV (Seq ID 4), HAEGTFTSDVS (Seq ID 5), HAEGTFTSDVSS (Seq ID 6), HAEGTFTSDVSSY (Seq ID 7), HAEGTFTSDVSSYL (Seq ID 8), HAEGTFTSDVSSYLE (Seq ID 9), HAEGTFTSDVSSYLEG (Seq ID 10), HAEGTFTSDVSSYLEGQ (Seq ID 11), HAEGTFTSDVSSYLEGQA (Seq ID 12), HAEGTFTSDVSSYLEGQAA (Seq ID 13), 25 HAEGTFTSDVSSYLEGQAAK (Seq ID 14), HAEGTFTSDVSSYLEGQAAKE (Seq ID 15), HAEGTFTSDVSSYLEGQAAKEF (Seq ID - 16), HAEGTFTSDVSSYLEGQAAKEFI (Seq ID 17), with the further option that one or more of these amino acids may be replaced by unnatural amino acids, and X 2 is selected from the following amino acid sequences 30 GPSSGAPPPS (Seq ID 18)or KELEKLL (Seq ID 19)or GPPS or (Seq ID 20) VKGR (Seq ID 21); ii) and when S-Y-S 2 does not represent a bond -7- WO 2007/017892 PCT/IN2006/000154

X

1 is selected from the following amino acid sequences HA (Seq ID 22), HAE (Seq ID 23), HAEG (Seq ID 24), HAEGT (Seq ID 25), HAEGTF (Seq ID 26), HAEGTFT (Seq ID 27), HAEGTFTS (Seq ID 28), HAEGTFTSD (Seq ID 29) with the further option that one or more of these amino 5 acids may be replaced by unnatural amino acids;

X

2 is selected from GPSSGAPPPS (Seq ID 18) or KELEKLL (Seq ID 19)or GPPS (Seq ID 20)or 10 VKGR (Seq ID 21)or a dipeptide, selected from combination of two amino acids, consisting of natural or unnatural amino acids, having a side chain containing an arylalkyl or heteroarylalkyl moieties selected from benzyl, napthylmethyl, pyridylmethyl, thienylmethyl, furylmethyl, imidazolylmethyl, isooxazolylmethyl, quinolylmethyl, 15 benzofuranylmethyl, benzothienylmethyl, indolinylmethyl, indolylmethyl, dibenzofuranylmethyl, dibenzothienylmethyl, benzodihydrofuranylmethyl, benzodihydrothienylmethyl, thienopyrimidylmethyl, benzimidazolylmethyl, phenanthrenylmethyl, dihydrophenanthrenylmethyl, fluorenylmethyl, dibenzofuranylmethyl, dibenzothiophenyl methyl groups and the like, where each of 20 these groups may be optionally substituted with (CI-C 6 )alkyl group such as methyl, ethyl, propyl, isopropyl, n-butyl, iso-butyl, t-butyl, pentyl, isopentyl, hexyl groups and the like, (CI-C 6 )alkoxy group such as methoxy, ethoxy, propoxy, butoxy, pentoxy, hexanoxy groups, cyano, halo group such as chloro, bromo, iodo, fluoro groups, hydroxy or optionally substituted aryl or heteroaryl groups selected from phenyl, 25 napthyl, pyridyl, thienyl, furyl, imidazolyl, isooxazolyl, quinolyl, benzofuranyl, benzothienyl, indolinyl, indolyl, dibenzofuranyl, dibenzothienyl, benzodihydrofuranyl, benzodihydrothienyl, thienopyrimidyl, benzimidazolyl, phenanthrenyl, dihydrophenanthrenyl, fluorenyl, dibenzofuranyl, dibenzothiophenyl and the like, with the further provision that such aryl or heteroaryl substituents may further be optionally 30 substituted with (CI-C 6 )alkyl, (CI-C 6 )alkoxy, cyano, halo, hydroxy or aryl or heteroaryl groups. In a preferred embodiment, the dipeptide sequence may comprise of one or more amino acids selected from Bip, Bip(2-Me), Bip(2-Et), Bip(2-Ipr), Bip(2-CN), Bip(2'-Et-4'-OMe), Bip(4'-fluoro), Bip(4'-Phenyl), 2-(9,10-Dihydro-phenanthrenyl] -8 - WO 2007/017892 PCT/IN2006/000154 Ala, 2-(Phenanthrenyl)-Ala, 4-(2-Naphthyl)-Phe, 4-(1-Naphthyl)-Phe, 2-Fluorenyl-Ala, 4-dibenzofuran-Phe, 4-dibenzothiophene-Phe, 4-(2'-methylphenyl)-3-pyridylalanine; The term 'natural amino acids' indicates all those twenty amino acids, which are present in nature. 5 The term 'unnatural amino acids' or 'non-natural amino acids' represents either replacement of L-amino acids with corresponding D-amino acids such as replacement of L-Ala with D-Ala or L-Pro with D-Pro and the like or suitable modifications of the L or D amino acids, amino alkyl acids, either by - a-alkylation such as substitution of Ala with a-methyl Ala (Aib), replacement of 10 Phe with a-methyl Phe, replacement of substituted Bip with with a-methyl Bip; - N-alkylation with groups selected from (Ci-C 6 )alkyl or (C3-C 6 )cycloalkyl groups; - modification of side chain such as replacement of His with histidine analogs such as 1 -imidazolyl-alanine (II) or des-amino-His, N

H

2 N OH 0 (II) 15 or replacement of phenyl ring of Phe with pyridyl, napthyl, biphenyl groups; - substitution on the side chain of amino acid such as substitution of aromatic amino acid side chain with halogen, (CI-C 3 )alkyl, aryl groups, more specifically the replacement of Phe with 2 & 4-halo Phe; Such 'unnatural amino acids' or 'non-natural amino acids' may be represented 20 generally by the following structure: R R6 NJ OH H Rs 0 (Ha) wherein R 5 is selected from H, F, (CI-C 5 ) alkyl, the stereochemical configuration at the carbon bearing R5 may be (R) or (S); R 6 is selected from H or (C 1

-C

3 ) alkyl; each of R 7 25 and R 8 is independently selected from H, (C 1

-C

3 ) alkyl, such as methyl and ethyl or halogen atom, preferably fluorine atom; R9 represents groups, selected from (C 1

-C

5 ) alkyl, aryl or heteroryl moieties selected from phenyl, napthyl, pyridyl, thienyl, furyl, -9- WO 2007/017892 PCT/IN2006/000154 imidazolyl, isooxazolyl, quinolyl, benzofuranyl, benzothienyl, indolinyl, indolyl, dibenzofuranyl, dibenzothienyl, benzodihydrofuranyl, benzodihydrothienyl, thienopyrimidyl, benzimidazolyl, phenanthrenyl, dihydrophenanthrenyl, fluorenyl, dibenzofuranyl, dibenzothiophenyl groups, where each of these groups may be 5 optionally substituted with (CI-C 6 )alkyl, (Ci-C 6 )alkoxy, cyano, halo, hydroxy or optionally substituted aryl or heteroaryl groups, with the further provision that such aryl or heteroaryl substituents may further be optionally substituted with (CI-C 6 )alkyl, (C 1 C 6 )alkoxy, cyano, halo, hydroxy or aryl or heteroaryl groups. -10- WO 2007/017892 PCT/IN2006/000154 List of Fmoc protected Rip analogs used for the synthesis of GLP-1 peptidomimetics O CN CN Fmoc-N OH OFmoc-N OH H Fmoc-N OH H H H 0 Fmoc-4-(2'-methylphenyl)-3-pyridylalanine-OH Fmoc-Bip(2'-Et- 4'-OMe)-OH Fmoc-Bip(2-CN)-OH Fmoc-N OH H O Fmoc-N OH Fmoc-N OH 0 H O H 0e Fmoc-Bip(2-Me)-OH Fmoc-Bip-OH Fmoc-Bip(2-1pr)-OH Fmoc-N OH HF Fmoc-N OH Fmocs O H N COOH Fmoc-Bip(2-Et)-OH Fmoc-4-(1-Naphthy)-Phe-OH Fmoc-2-(9,O-Dihydro-phenanthrenyl ~- '.. F Ala-OH Fmoc-N OH Fmoc-N OH Fmoc H H N COOH 0 H Fmoc-Bip(4-Ph)-OH Fmoc-Bip(4-F)-OH Fmoc-2-(Phenanthreny1)-Ala-OH -(oc 'N-/\ FmcN COOH H Fmoc-N-' OH Fmoc=-N OH H H-1 Fmoc-2-Fluorenyl-Ala-OH H 0 Fmoc-4-dibenzoffhran-Phe-OH Fmoc-4-dibenzothiophene-Phe-OH 5 The suitable substituents include, but are not limited to the following radicals, 10 alone or in combination with other radicals - hydroxyl, oxo, halo, thio, nitro, amino, cyano, alkyl, haloalkyl, alkoxy, haloalkoxy, cycloalkyl, aryl, aryloxy, aralkyl, aralkoxy, - 11 - WO 2007/017892 PCT/IN2006/000154 heteroaryl, heteroaralkyl, heteroaryloxy, heteroaralkoxy, acyl, acyloxy, carboxylic acid and its derivatives such as esters and amides; The various groups, radicals and substituents used anywhere in the specification are described in the following paragraphs. 5 The term "alkyl" used herein, either alone or in combination with other radicals, denotes a linear or branched radical containing one to ten carbons, such as methyl, ethyl, n-propyl, iso-propyl, n-butyl,- sec-butyl, tert-butyl, amyl, t-amyl, n-pentyl, n hexyl, iso-hexyl, heptyl, octyl, decyl and the like. The term "cycloalkyl" used herein, either alone or in combination with other 10 radicals, denotes a radical containing three to seven carbons, such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl and the like. The term "aryl" or "aromatic" used herein, either alone or in combination with other radicals, denotes an aromatic system containing one, two or three rings wherein such rings may be attached together in a pendant manner or may be fused, such as 15 phenyl, naphthyl, tetrahydronaphthyl, indane, biphenyl, and the like. The term 'arylalkyl" denotes an alkyl group, as defined above, attached to an aryl, such as benzyl, phenylethyl, naphthylmethyl, and the like. The term "aryloxy" denotes an aryl radical, as defined above, attached to an alkoxy group, such as phenoxy, naphthyloxy and the like, which may be substituted. 20 The term "aralkoxy" denotes an arylalkyl moiety, as defined above, such as benzyloxy, phenethyloxy, naphthylmethyloxy, phenylpropyloxy, and the like, which may be substituted. The term "heteroaryl" or "heteroaromatic" used herein, either alone or in combination with other radicals, denotes an aromatic system containing one, two or 25 three rings wherein such rings may be attached together in a pendant manner or may be fused containing one or more hetero atoms selected from 0, N or S, such as pyridyl, thienyl, furyl, pyrrolyl, oxazolyl, thiazolyl, isothiazolyl, imidazolyl, isoxazolyl, oxadiazolyl, thiadiazolyl, triazolyl, tetrazolyl, benzopyranyl, benzopyranonyl, benzofuranyl, benzothienyl, indolinyl, indolyl, azaindolyl, azaindolinyl, 30 benzodihydrofuranyl, benzodihydrothienyl, pyrazolopyrimidinyl, pyrazolopyrimidonyl, azaquinazolinyl, azaquinazolinoyl, pyridofuranyl, pyridothienyl, thienopyrimidyl, thienopyrimidonyl, quinolinyl, pyrimidinyl, pyrazolyl, quinazolinyl, quinazolonyl, pyrimidonyl, pyridazinyl, triazinyl, benzoxazinyl, benzoxazinonyl, benzothiazinyl, benzothiazinonyl, benzoxazolyl, benzothiazolyl, benzimidazolyl, benzotriazolyl, -12- WO 2007/017892 PCT/IN2006/000154 phthalazynil, naphthylidinyl, purinyl, carbazolyl, phenothiazinyl, phenoxazinyl, and the like. The term "heteroaralkyl" used herein, either alone or in combination with other radicals, denotes a hete'roaryl group, as defined above, attached to a straight or 5 branched saturated carbon chain containing 1 to 6 carbons, such as (2-furyl)methyl, (3 furyl)methyl, (2-thienyl)methyl, (3-thienyl)methyl, (2-pyridyl)methyl, 1-methyl-1-(2 pyrimidyl)ethyl and the like. The terms "heteroaryloxy", "heteroaralkoxy", "heterocycloxy denotes heteroaryl, heteroarylalkyl, groups respectively, as defined above, attached to an oxygen atom. 10 The term "acyl" used herein, either alone or in combination with other radicals, denotes a radical containing one to eight carbons such as formyl, acetyl, propanoyl, butanoyl, iso-butanoyl, pentanoyl, hexanoyl, heptanoyl, benzoyl and the like, which may be substituted. The term "carboxylic acid" used herein, alone or in combination with other 15 radicals, denotes a -COOH group, and includes derivatives of carboxylic acid such as esters and amides. The term "ester" used herein, alone or in combination with other radicals, denotes -COO- group, and includes carboxylic acid derivatives, where the ester moieties are alkoxycarbonyl, such as methoxycarbonyl, ethoxycarbonyl, and the like, which may be substituted. 20 Unless otherwise indicated, the term 'amino acid' as employed herein alone or as part of another group includes, without limitation, an amino group and a carboxyl group linked to the same carbon, referred to as 'c' carbon. The absolute 'S' configuration at ihe 'a' carbon is commonly referred to as the ' or natural configuration. The 'R' configuration at the 'c' carbon is commonly 25 referred to as the 'D' amino acid. In the case where both the 'a-substituents' is equal, such as hydrogen or methyl, the amino acids are Gly or Aib and are not chiral. The term 'receptor modulator' refers to a compound that acts at the GLP-1 receptor to alter its ability to regulate downstream signaling events. Example of receptor modulators includes agonist, partial agonist, inverse agonist, allosteric 30 potentiators. Preferably, the isolated peptidomimetics are a 3-30 mer and such peptide bind to and activates the GLP- 1 receptor. In accordance with the present invention, the synthetic isolated peptidomimetics described herein possess the ability to mimic the biological activity of GLP-1 peptide, - 13 - WO 2007/017892 PCT/IN2006/000154 with preference for agonist activity at GLP-1R. These synthetic peptidomimetics GLP 1 mimetic exhibit desirable in-vivo properties, thus making them ideal therapeutic candidates for oral or parenteral administration. The present invention provides for compounds of formula (I) pharmaceutical 5 compositions employing such compounds either alone or in combination and for methods of using such compounds. In particular, the present invention provides a pharmaceutical composition comprising a therapeutically effective amount of a compound of formula (I), alone or in combination(s), with a pharmaceutically acceptable carrier. 10 Further provided is a method for treating or delaying the progression or onset of diabetes, especially type II diabetes, including complications of diabetes, including retinopathy, neuropathy, nephropathy and delayed wound healing and related diseases such as insulin resistance (impaired glucose homeostasis), hyperglycemia, hyperinsulinemia, elevated blood levels of fatty acids or glycerol, obesity, 15 hyperlipidemia including hypertriglyceridemia, syndrome X, atherosclerosis and hypertension, wherein a therapeutically effective amount of a compound of formula (I) or their combination(s) are administered to a mammal, example, human, a patient in need of treatment. Several synthetic routes can be employed to prepare the compounds of the present 20 invention well known to one skilled in the art of peptide synthesis. The compounds of formula (I), where all symbols are as defined earlier can be synthesized using the methods described below, together with conventional techniques known to those skilled in the art of peptide synthesis, or variations thereon as appreciated by those skilled in the art. Referred methods include, but not limited to those described below. 25 The peptidomimetics thereof described herein may be produced by chemical synthesis using suitable variations of various solid-phase techniques generally known such as those described in G. Barany & R. B. Merrifield, "The peptides: Analysis, synthesis, Biology"; Volume 2- "Special methods in peptide synthesis, Part A", pp. 3 284, E. Gross & J. Meienhofer, Eds., Academic Press, New York, 1980; and in J. M. 30 Stewart and J. D. Young, "Solid-phase peptide synthesis" 2nd Ed., Pierce chemical Co., Rockford, II, 1984. The preferred strategy for preparing the peptidomimetics of this invention is based on the use of Fmoc-based SPPS approach, wherein Fmoc (9-Fluorenyl-methyl methyloxycarbonyl) group is used for temporary protection of the a-amino group, in -14- WO 2007/017892 PCT/IN2006/000154 combination with the acid labile protecting groups, such as t-butyloxy carbonyl (Boc), tert-butyl (But), Trityl (Trt) group for temporary protection of the amino acid side chains (see for example E. Atherton & R.C. Sheppard, "The Fluorenylmethoxycarbonyl amino protecting group", in "The peptides: Analysis, synthesis, Biology"; Volume 9 5 "Special methods in peptide synthesis, Part C", pp. 1-38, S. Undenfriend & J. Meienhofer, Eds., Academic Press, San Diego, 1987). Examples of orthogonally protected amino acids used in Fmoc-solid phase peptide synthesis for the synthesis of peptidomimetics T 0 -Fmoc= N Fmoc-NH OH Fmoc--NH OH Fmoc-NH OH O 0 0 Fmoc-His(Trt)-OH Fmoc-Glu(Bu t )-OH Fmoc-Thr(Bu t )-OH tBut Boc Fmoc-NH OH Fmoc-NH OH oO Fmoc--NH OH 0 Fmoc-Ser(Bu t )-OH Fmoc-Asp(Bu t )-OH Fmoc-Lys(Boc)-OH H O Pbf--N NHBoc N 0 Trt o, / Fmoc-NH OH Fmoc-NH OH O moc-NIH Oi O 10 Fmoc-Gn(Trt)-OH Fmoc-Arg(Pbf)-OH Fmoc-Trp(Boc)-OH The peptidomimetics can be synthesized in a stepwise manner on an insoluble polymer support (resin), starting form the C-terminus of the peptide. In an embodiment, the synthesis is initiated by appending the C-terminal amino acid of the peptide to the 15 resin through formation of an amide, ester or ether linkage. This allows the eventual - 15 - WO 2007/017892 PCT/IN2006/000154 release of the resulting peptide as a C-terminal amide, carboxylic acid or alcohol, respectively. In the Fmoc-based SPPS, the C-terminal amino acid and all other amino acids used in the synthesis are required to have their a-amino groups and side chain 5 functionalities (if present) differentially protected (orthogonal protection), such that the a-amino protecting group may be selectively removed during the synthesis, using suitable base such as 20% piperidine solution, without any premature cleavage of peptide from resin or deprotection of side chain protecting groups, usually protected with the acid labile protecting groups. 10 The coupling of an amino acid is performed by activation of its carboxyl group as an active ester and reaction thereof with unblocked a-amino group of the N-terminal amino acid appended to the resin. After every coupling and deprotection, peptidyl-resin was washed with the excess of solvents, such as DMF, DCM and diethyl ether. The sequence of a-amino group deprotection and coupling is repeated until the desired 15 peptide sequence is assembled. The peptide is then cleaved from the resin with concomitant deprotection of the side chain functionalities, using an appropriate cleavage mixture, usually in the presence of appropriate scavengers to limit side reactions. The resulting peptide is finally purified by reverse phase HPLC. The synthesis of the peptidyl-resins required as precursors to the final peptides 20 utilizes commercially available cross-linked polystyrene polymer resins (Novabiochem, San Diego, CA). Preferred for use in this invention are Fmoc-PAL-PEG-PS resin, 4-(2', 4'-dimethoxyphenyl-Fmoc-aminomethyl)-phenoxyacetyl-p-methy benzhydrylamine resin (Fmoc-Rink amide MBHA resin), 2-chloro-Trityl-chloride resin or p benzyloxybenzyl alcohol resin (HMP resin) to which the C-terminal amino acid may or 25 may not be already attached. If the C-terminal amino acid is not attached, its attachment may be achieved by HOBt active ester of the Fmoc-protected amino acid formed by its reaction with DIPCDI. In case of 2-Chloro-trityl resin, coupling of first Fmoc-protected amino acid was achieved, using DIPEA. For the assembly of next amino acid, N terminal protection of peptidyl resin was selectively deprotected using a solution of 10 30 20 % piperidine solution. After every coupling and deprotection, excess of amino acids and coupling reagents was removed by washed with a DMF, DCM and ether. Coupling of the subsequent amino acids can be accomplished using HOBt or HOAT active esters produced from DIPCDI/ HOBt or DIPCDI/HOAT, respectively. In case of some difficult coupling, especially coupling of those amino acids, which are hydrophobic or - 16 - WO 2007/017892 PCT/IN2006/000154 amino acids with bulky side chain protections, complete coupling can be achieved using a combination of highly efficient coupling agents such as HBTU, PyBOP or TBTU, with additives such as DIPEA. 5 General Scheme for Fmoc-Based SPPS: M e O H o "0 4O-PEG-PS MeO Fmoc-PAL-PEG-PS Resin 20% Piperidine Deprotection MeO

H

2 N - O 4 O-PEG-PS MeO Fmoc-PAL-PEG-PS Resin FmocN OH Acylation H HOBt & DIPCDI 0 MeO FmocN HN N 4 O-PEG-PS 0 MeO Deprotection Acylation Final cleavage with TFA mixture Peptide + Resin -17- WO 2007/017892 PCT/IN2006/000154 The synthesis of the peptide analogs described herein can be carried out by using batchwise or continuos flow peptide synthesis apparatus. The non-natural non commercial amino acids present at different position were incorporated into the peptide chain, using one or more methods known in the art. In one approach, a Fmoc-protected 5 non-natural amino acid was prepared in solution, using appropriate literature procedures. For example, the Fmoc-protected Bip analogs, described above, were prepared using modified Suzuki cross coupling method, as known in literature (for e.g. Tetrahedron Letter 58, 9633-9695, 2002). The Fmoc-protected ca-methylated amino acids were prepared using asymmetric Strecker synthesis, as described for e.g. in Org. 10 Letters 3(8), 1121-1124, 2001. The Fmoc-protected N-methylated amino acids were prepared using a literature method as described in for e.g. JOC, 2005, 70, 6918-6920. The resulting derivative was then used in the step-wise synthesis of the peptide. Alternatively, the required non-natural amino acid was built on the resin directly using synthetic organic chemistry procedures and a linear peptide chain were build. 15 The peptide-resin precursors for their respective peptidominietics may be cleaved and deprotected using suitable variations of any of the standard cleavage procedures described in the literature (see, for example, D. S. King et al. Int. J. peptide Protein res. 36, 1990, 255 - 266). A preferred method for use in this invention is the use of TFA cleavage mixture, in the presence of water and TIPS as scavengers. Typically, 20 the peptidyl-resin was incubated in TFA / Water /TIPS (94:3:3; V: V: V; 10 ml / 100 mg of peptidyl resin) 'for 1.5-2 hrs at room temperature. The cleaved resin is then filtered off, the TFA solution is concentrated or dried under reduced pressure. The resulting crude peptide is either precipitated or washed with Et 2 O or is re-dissolved directly into DMF or 50 % aqueous acetic acid for purification by preparative HPLC. 25 Peptidomimetics with the desired purity can be obtained by purification using preparative HPLC. The solution of crude peptide is injected into a semi-Prep column (Luna 10t; C 18 ; 100 A), dimension 250 X 50 mm and eluted with a linear gradient of ACN in water, both buffered with 0.1 % TFA, using a flow rate of 15 -50 ml /min with effluent monitoring by PDA detector at 220 nm. The' structures of the purified 30 peptidomimetics can be confirmed by Electrospray Mass Spectroscopy (ES-MS) analysis. All the peptide prepared were isolated as trifluoro-acetate salt, with TFA as a counter ion, after the Prep-HPLC purification. However, some peptides were subjected for desalting, by passing through a suitable ion exchange resin bed, preferably through anion-exchange resin - 18- WO 2007/017892 PCT/IN2006/000154 Dowex SBR P(Cl) or an equivalent basic anion-exchange resin. In some cases, TFA counter ions were replaced with acetate ions, by passing through suitable ion-exchange resin, eluted with dilute acetic acid solution. For the preparation of the hydrochloride salt of peptides, in the last stage of the manufacturing, selected peptides, with the acetate salt was treated with 4 M 5 HCL. The resulting solution was filtered through a membrane filter (0.2 pm) and subsequently lyophilized to yield the white to off-white HCI salt. Following similar techniques and/or such suitable modifications, which are well within the scope of persons skilled in the art, other suitable pharmaceutically acceptable salts of the peptidomimetics of the present invention were prepared. 10 In a preferred embodiment, the present invention provides a method of making a peptidomimetics that mimics the activity of an endogenous polypeptide GLP-1R agonist. In another preferred embodiment, the polypeptide receptor agonist is GLP-1. The novel compounds of the present invention can be formulated into suitable pharmaceutically acceptable compositions by combining with suitable excipients as are 15 well known. The pharmaceutical composition is provided by employing conventional techniques. Preferably the composition is in unit dosage form containing an effective amount of the active component, that is, the compounds of formula (I) either alone or combination, according to this invention. 20 The quantity of active component, that is, the compounds of formula (I) according to this invention, in the pharmaceutical composition and unit dosage form thereof may be varied or adjusted widely depending upon the particular application method, the potency of the particular compound and the desired concentration. By way of guidance, the daily oral dosage of the active ingredient, when used for the indicated 25 effects, will range between about 0.001 to 1000 mg/kg of body weight, preferably between about 0.01 to 100 mg/kg of body weight per day and most preferably between about 0.6 to 20 mg/kg/day. General method of preparation of peptidomimetics, using SPPS approach: Assembly ofpeptidomimetics on resin: 30 Sufficient quantity (50-100 mg) of Fmoc-PAL-PEG-PS resin or Fmoc-Rink amide MBHA resin, loading: 0.5-0.6 mmol / g was swelled in DMF (1-10 ml /100 mg of resin) for 2-10 minutes. The Fmoc-group on resin was then removed by incubation of resin with 10-30 % piperidine in DMF (10-30 ml / 100 mg of resin), for 10-30 minutes. Deprotected resin was filtered and washed excess of DMF, DCM and ether 35 (50 ml X 4). Washed resin was incubated in freshly distilled DMF (1 ml / 100 mg of -19- WO 2007/017892 PCT/IN2006/000154 resin), under nitrogen atmosphere for 5 minutes. A 0.5 M solution of first Fmoc protected amino acid (1-3 eq.), pre-activated with HOBt (1-3 eq.) and DIPCDI (1-2 eq.) in DMF was added to the resin, and the resin was then shaken for 1-3 hrs, under nitrogen atmosphere. Coupling completion was monitored using a qualitative ninhydrin 5 test. After the coupling of first amino acid, the resin was washed with DMF, DCM and Diethyl ether (50 ml X 4). For the coupling of next amino acid, firstly, the Fmoc protection on first amino acid, coupled with resin was deprotected, using a 10-20% piperidine solution, followed by the coupling the Fmoc-protected second amino acid, using a suitable coupling agents, and as described above. The repeated cycles of 10 deprotection, washing, coupling and washing were performed until the desired peptide chain was assembled on resin, as per general scheme above. Finally, the Fmoc-protected peptidyl-resin prepared above was deprotected by 20% piperidine treatment as described above and the peptidyl-resins were washed with DMF, DCM and Diethyl ether (50 ml X 4). Resin containing desired peptide was dried 15 under nitrogen pressure for 10-15 minutes and subjected for cleavage/ deprotection. Cleavage and deprotection: The desired peptidomimetics were cleaved and deprotected from their respective peptidyl-resins by treatment with TFA cleavage mixture as follows. A solution of TFA / Water / Triisopropylsilane (95: 2.5: 2.5) (10 ml / 100 mg of peptidyl 20 resin) was added to peptidyl-resins and the mixture was kept at room temperature with occasional starring. The resin was filtered, washed with a cleavage mixture and the combined filtrate was evaporated to dryness. Residue obtained was dissolved in 10 ml of water and the aqueous layer was extracted 3 times with ether (20 ml each) and finally the aqueous layer was freeze-dried. Crude peptide obtained after freeze-drying 25 was purified by preparative HPLC as follows: Preparative HPLC purification of the crude peptidomimetics: Preparative HPLC was carried out on a Shimadzu LC-8A liquid chromatograph. A solution of crude peptide dissolved in DMF or water was injected into a semi-Prep column (Luna 10pt; C 18 ; 100 A 0 ), dimension 250 X 50 mm and eluted with a linear 30 gradient of ACN in water, both buffered with 0.1 % TFA, using a flow rate of 15 -50 ml / min, with effluent monitoring by PDA detector at 220 nm. A typical gradient of 20 % to 70 % of water-ACN mixture, buffered with 0.1 % TFA was used, over a period of 50 minutes, with 1% gradient change per minute. The desired product eluted were -20 - WO 2007/017892 PCT/IN2006/000154 collected in a single 10-20 ml fraction and pure peptidomimetics were obtained as amorphous white powders by lyophilisation of respective HPLC fractions. IIPLC analysis of the purified peptidomimetics After purification by preparative HPLC as described above, each peptide was 5 analyzed by analytical RP-HPLC on a Shimadzu LC-10AD analytical HPLC system. For analytic HPLC analysis of peptidomimetics, Luna 5p; C 18 ; 100 A', dimension 250 X 4.6 mm column was used, with a linear gradient of 0.1% TFA and ACN buffer and the acquisition of chromatogram was carried out at 220 nm, using a PDA detector. Characterization by Mass Spectrometry 10 Each peptide was characterized by electrospray ionisation mass spectrometry (ESI-MS), either in flow injection or LC/MS mode. Triple quadrupole mass spectrometers (API-3000 (MDS-SCIES, Canada) was used in all analyses in positive and negative ion electrospray mode. Full scan data was acquired over the mass range of quadrupole, operated at unit resolution. In all cases, the experimentally measured 15 molecular weight was within 0.5 Daltons of the calculated monoisotopic molecular weight. Quantification of the mass chromatogram was done using Analyst 1.4.1 software. Utilizing the synthetic methods described herein along with other commonly known techniques and suitable variations thereof, the following GLP-1 20 peptidomimetics were prepared. This list is indicative of the various groups of peptidomimetics, which can be prepared according to the present invention, and are expected to at least include obvious variations of these compounds. However, such disclosure should not be construed as limiting the scope of the invention in any way. Table 1: S. Sequence No. 1I HGEGTFTSD-(CH 2

)

3 -GPSSGAPPPS 2 HGEGTFTSD-(CH 2

)

4 -GPSSGAPPPS 3 HGEGTFTSD-(CH 2

)

5 -GPSSGAPPPS 4 HGEGTFTSD-(CH 2

)

6 -GPSSGAPPPS 5 HGEGTFTSD-(CH 2

)

7 -GPSSGAPPPS 6 HGEGTFTSD-(CH 2

)

10 -GPSSGAPPPS 7 HGEGTFTSD-(CH 2

)

1 1 -GPSSGAPPPS -21- WO 2007/017892 PCT/1N2006/000154 8 HGEGTFTSDLSKQM-(CH 2

)

3 -GPSS 9 HGEGTFTSDLSKQM-(CH 2

)

4 -GPSS 10 HGEGTFTSDLSKQM-(CH 2

)

5 -GPSS 11 HGEGTFTSDLSKQM-(CH 2

)

6 -GPSS 12 HGEGTFTSDLSKQM-(CH 2

)

7 -GPSS 13 HGEGTFTSDLSKQM-(CH 2 )lo-GPSS 14 HGEGTFTSDLSKQM-(CH 2

)

1 1 -GPSS 15 HGEGTFTSDLSKQME-G-GPSSGAPPPS 16 HGEGTFTSDLSKQME-(CH 2

)

2 -GPS SGAPPPS 17 HGEGTFTSDLSKQME-(CH 2

)

3 -GPSSGAPPPS 18 HGEGTFTSDLSKQME-(CH 2

)

4 -GPSSGAPPPS 19 IIGEGTFTSDLSKQME-(CH 2

)

5 -GPSSGAPPPS 20 HGEGTFTSDLSKQME-(CH 2

)

6 -GPSSGAPPPS 21 HGEGTFTSDLSKQME-(CH 2

)

7 -GPSSGAPPPS 22 HGEGTFTSDLSKQME-(CH 2

)

10 -GPSSGAPPPS 23 HGEGTFTSDLSKQME-(C1 2

)

1 1 -GPSSGAPPPS Table 2: S. Sequence No. I HAEGTFTSD-(CH 2

)

2 -VKGR 2 HAEGTFTSD-(C.H 2

)

3 -VKGR 3 HAEGTFTSD-(CH 2

)

4 -VKGR 4 HAEGTFTSD-(CH 2

)

5 -VKGR 5 HAEGTFTSD-(C1 2

)

6 -VKGR 6 HAEGTFTSD-(CI 2

)

10 -VKGR 7 HAibEGTFTSD-(CH 2

)

2 -VKGR 8 HAibEGTFTSD-(CH 2

)

3 -VKGR 9 L{AibEGTFTSD-(CH 2

)

4 -VKGR 10 HAibEGTFTSD(CH 2

)

5 -VKGR 11 1{AibEGTFTSD-(C11 2

)

6 -VKGR -22 - WO 2007/017892 PCT/1N2006/000154 12 HAibEGTFTSD-(CH 2 )io-VKGR Table 3: S. Sequence No. 1 HGEGTFTSDLSKQMKELEKLL 2 HAEGTFTSDKELEKLL 3 HGEGTFTSDKELEKLL 4 i-JAibEGTFTSDGKjELEKLL, 5 HGGTFTSDGKELEKLL 6 HGEGTFTSDVSKELEKLL 7 HAEGTFTSDVSKELEKLL 8 HAEGTFTSDVSEKELEKLL 9 HAEGTFTSDVSGKELEKL 10 IIAEGTFTSDVS SYLEKELEKLL I1I HAEGTFTSDVSSYLEGKELEKLL 12 IIGEGTFTSDVS SYLEGKELEKLL 13 HaEGTFTSDVSSYLEGKELEKLL 14 HAibEGTFTSDVSSYLEGKELEKLL 15 HAEGTFTSDVS SYLEGKELEKLLVKG 16 HAEGTFTSDVSSYLEPKELEKL -17 HIAEGTFTSDVS SYLEGQAAKELEKLL 18 HAEGTFTSDVSSYLEGQAAKEFIKELEKIL 19 IJAibEGTFTSDVSSYLEGQAAKEFIKELEKLL 20 FIAibEGT-(cc-Me)Phe(2-F) TSDVSSYLEGQAAKEFIKELEK~LL 21 Des-amino-HAibEGT-(c&-Me)Phe(2-F) TSDVSSYLEGQAAKEFJKELEKLL 22 HAEGTFTSD-(CH 2

)

3 -KELEKLL 23 HAEGTFTSD-(CH 2

)

4 -KELEKLL 24 HAEGTFTSD-(CH 2 )5-KELEKLL 25 HAEGTFTSD-(GJJ 2 ),-KELEKLL 26H-(CH2)3-DVSSYLEGQAAKEFIKELEKLL - 23 - WO 2007/017892 PCT/IN2006/000154 27 HAib-(CH 2

)

3 -DVSSYLEGQAAKEFIKELEKLL 28 HAibEGTFTSDVSSYLEGQ-(CH 2

)

2 -KELEKLL 29 HAibEGTFTSDVSSYLEGQ-(CH 2

)

3 -KELEKLL 30 HAibEGTFTSDVSSYLE-(CH 2

)

2 -FIKELEKLL Table 4: S. Sequence No. 1 HGEGTFTSD-(CH 2

)

3 -Bip-Bip 2 HAibEGTFTSD-(CH 2

)

3 -Bip-Bip 3 HAibEGT-(o-Me)-Phe(2-F)-TSD-(CH 2

)

3 -Bip-Bip 4 HAEGTFTSD-G-Bip(2-Me)-Bip(2-Me) 5 HAibEGTFTSD-G-Bip(2-Me)-Bip(2-Me) 6 HAibEGT-(a-Me)-Phe(2-F)-TSD-G-Bip(2-Me)-Bip(2-Me) 7 HAEGTFTS-G-Bip(2-Me)-Bip(2-Me) 8 HAibEGTFTS-G-Bip(2-Me)-Bip(2-Me) 9 HAibEGT-(ac-Me)-Phe(2-F)-TS-G-Bip(2-Me)-Bip(2-Me) 10 HIAEGTFTS-(CH 2

)

2 -Bip(2-Me)-Bip(2-Me) 11 HAibEGTFTS-(CH 2

)

2 -Bip(2-Me)-Bip(2-Me) 12 HAibEGT-(a-Me)-Phe(2-F)-TS-(CH 2

)

2 -Bip(2-Me)-Bip(2-Me) 13 HAEGTFT-(CH 2

)

2 -Bip(2-Me)-Bip(2-Me) 14 HAibEGTFT-(CH 2

)

2 -Bip(2-Me)-Bip(2-Me) 15 HAibEGT-(a-Me)-Phe(2-F)-T-(CH 2

)

2 -Bip(2-Me)-Bip(2-Me) 16 HAEGTF-(CH 2

)

2 -Bip(2-Me)-Bip(2-Me) 17 HAibEGTF-(CH 2

)

2 -Bip(2-Me)-Bip(2-Me) 18 IAibEGT-(a-Me)-Phe(2-F)-(CH 2

)

2 -Bip(2-Me)-Bip(2-Me) 19 HAEGT-(CH 2

)

2 -Bip(2-Me)-Bip(2-Me) 20 HAibEGT-(CH 2

)

2 -Bip(2-Me)-Bip(2-Me) 21 HAEG-(CH 2

)

2 -Bip(2-Me)-Bip(2-Me) 22 HAibEG-(CH 2

)

2 -Bip(2-Me)-Bip(2-Me) 23 HAEGTFTSD-(CH 2

)

2 -Bip(2-Me)-Bip(2-Me) 24 HAibEGTFTSD-(CH 2

)

2 -Bip(2-Me)-Bip(2-Me) -24- WO 2007/017892 PCT/1N2006/000154 25HAibEGT-(a-Me)-Phe(2-F)-TSD(CH 2

)

2 Bip(2-Me)-Bip(2-Me) 2f6 1JAEGTFTSD-G-Bip-Bip(2-Me) 27 HAibEGTFTSD-G-Bip-Bip(2-Me) 28 HAibEGT-(-Me).Phe(2-F)-SDGBip-.Bip(2-Me) 29 HAEGTFTSD-G-Bip(2-Me)-Bip 30 HAibEGTFTSD-G-Bip(2-Me)-Bip 31HAibEGT-(cc-Me)Phe(2F)TSD-GBip(2-Me)-Bip 32 HAEGTFTSD-G-Bip-Bip 33 HAibEGTFTSD-G-Bip-Bip 34 HAibEGT-(a-Me)-Phe(2-F)-TSD-G-.Bip..Bip 35 HAEGTFTSD-G-Bip-Bip(2-Et) 36 HAibEGTFTSD-G-Bip-Bip(2-Et) 37HAibE-GT-(Qx-Me)-Phe(2-F)-.TSDGBipBip(2-Et) 3- 8 ihAGTFTSD-G-Bip(2-Et)-Bip(2-Et) 39 HAibEGTFTSD-G-Bip(2-Et)-Bip(2-Et) 40 HAibEGT-(cx-Me)-Phe(2-F)-TSD-G-.Bip(2.Et)-.Bip(2-Et) 41- HAEGTFTSD-G-Bip(2-Et)-Bip r42- 1AibEGTFTSD-G-Bip(2-Et)-Bip 43 HAibEGT-(cc-Me)-Phe(2-F)-TSD-G-Bip(2-.Et)-Bip 44 HAEGTFTSD-G-Bip(2-Et)-Bip(2-Me) 45 HAibEGTFTSD-G-Bip(2-Et)-Bip(2-Me) 46HAibEGT-(a-Me)-Phe(2-F)-TSD-G.Bip(2-Et)-Bip(2-Me) 47 HAEGTFTSD-G.Bip(2-Me)-Bip(2-Et) 48 I-WbEU1IFTSD-G-Bip(2-Me)-Bip(24Et) 49 HAibEGT-.(a-Me)-Phe(2-F)-TSD..GBip(2-Me)-ip(2.Et) 530- HGEGTFTSD-G-Bip(2-Me)-Bip(2-.Me) 51HGEGT-(ca-Me)Phe(2.F)SDG-Bip(2-Me)-Bip(2-Me) 52 HGEGTFTSD-G-Bip(2-Et)-Bip(2-Et) 534 HGEGTFTSD-(CH 2

)

3 -Bip(2-Me)-Bip(2-Me) 55 HGEGT-(c-Me)-Phe(2-F)-SD-(CH 2

)

3 -. Bip(2-Me)-Bip(2.Me) 56 HGEGTFTSD-(CH 2

)

4 -Bip(2-Me)-Bip(2-.Me) -25- WO 2007/017892 PCT/IN2006/000154 57 HGEGT-(a-Me)-Phe(2-F)-TSD-(CH 2

)

4 -Bip(2-Me)-Bip(2-Me) 58 HGEGTFTSD-(CH 2

)

5 -Bip(2-Me)-Bip(2-Me) 59 HGEGT-(a-Me)-Phe(2-F)-TSD-(CH 2 )-Bip(2-Me)-Bip(2-Me) 60 HGEGTFTSD-(CH 2

)

6 -Bip(2-Me)-Bip(2-Me) 61 HGEGT-(a-Me)-Phe(2-F)-TSD-(CH 2

)

6 -Bip(2-Me)-Bip(2-Me) 62 HGEGTFTSD-(CH 2 )1o-Bip(2-Me)-Bip(2-Me) 63 HGEGT-(ia-Me)-Phe(2-F)-TSD-(CH 2 )1-Bip(2-Me)-Bip(2-Me) 64 HGEGTFTSD-(CH 2

)

3 -Bip(2-Et)-Bip(2-Et) 65 HGEGT-(a-Me)-Phe(2-F)-TSD-(CH 2

)

3 -Bip(2-Et)-Bip(2-Et) 66 HGEGTFTSD-(CH 2

)

4 -Bip(2-Et)-Bip(2-Et) 67 HGEGT-(a-Me)-Phe(2-F)-TSD-(CH 2

)

4 -Bip(2-Et)-Bip(2-Et) 68 14GEGTFTSD-(CH 2 )s-Bip(2-Et)-Bip(2-Et) 69 HGEGT-(a-Me)-Phe(2-F)-TSD-(CH 2 )s-Bip(2-Et)-Bip(2-Et) 70 HGEGTFTSD-(CH 2

)

6 -Bip(2-Et)-Bip(2-Et) 71 HGEGT-(a-Me)-Phe(2-F)-TSD-(CH 2

)

6 -Bip(2-Et)-Bip(2-Et) 72 HGEGTFTSD-(CH 2 )1o-Bip(2-Et)-Bip(2-Et) 73 HGEGT-(a-Me)-Phe(2-F)-TSD-(CH 2

)

10 -Bip(2-Et)-Bip(2-Et) 74 HGEGTFTSD-(CH 2

)

11 -Bip(2-Et)-Bip(2-Et) 75 HGEGT-(a-Me)-Phe(2-F)-TSD-(CH 2

)

1 -Bip(2-Et)-Bip(2-Et) 76 HGEGTFTS-(CH 2

)

3 -Bip(2-Me)-Bip(2-Me) 77 HGEGT-(a-Me)-Phe(2-F)-TS-(CH 2

)

3 -Bip(2-Me)-Bip(2-Me) 78 HGEGTFTS-(CH 2

)

4 -Bip(2-Me)-Bip(2-Me) 79 HGEGT-(a-Me)-Phe(2-F)-TS-(CH 2

)

4 -Bip(2-Me)-Bip(2-Me) 80 HGEGTFTS-(CH 2 )s-Bip(2-Me)-Bip(2-Me) 81 HGEGT-(a-Me)-Phe(2-F)-TS-(CH 2 )-Bip(2-Me)-Bip(2-Me) 82 HGEGTFTS-(CH 2

)

6 -Bip(2-Me)-Bip(2-Me) 83 HGEGT-(a-Me)-Phe(2-F)-TS-(CH 2

)

6 -Bip(2-Me)-Bip(2-Me) 84 HGEGTFTS-(CH 2 )1o-Bip(2-Me)-Bip(2-Me) 85 HGEGT-(a-Me)-Phe(2-F)-TS-(CH 2 )1o-Bip(2-Me)-Bip(2-Me) 86 HGEGTFTS-(CH 2

)

11 -Bip(2-Me)-Bip(2-Me) 87 HGEGT-(a-Me)-Phe(2-F)-TS-(CH 2

)

11 -Bip(2-Me)-Bip(2-Me) 88 HGEGTFTS-(CH 2

)

3 -Bip(2-Et)-Bip(2-Et) -26- WO 2007/017892 PCT/IN2006/000154 89 HGEGT-(ca-Me)-Phe(2-F)-TS-(CH 2

)

3 -Bip(2-Et)-Bip(2-Et) 90 HGEGT-(ca-Me)-Phe(2-F)-TS-(CH 2

)

4 -Bip(2-Et)-Bip(2-Et) 91 HGEGTFTS-(CH 2

)

4 -Bip(2-Et)-Bip(2-Et) 92 HGEGT-(ca-Me)-Phe(2-F)-TS-(CH 2

)

4 -Bip(2-Et)-Bip(2-Et) 93 HGEGTFTS-(CH 2 )s-Bip(2-Et)-Bip(2-Et) 94 HGEGT-(a-Me)-Phe(2-F)-TS-(CH 2

)

5 -Bip(2-Et)-Bip(2-Et) 95 HGEGTFTS-(CH 2

)

6 -Bip(2-Et)-Bip(2-Et) 96 HGEGT-(a-Me)-,Phe(2-F)-TS-(CH 2

)

6 -Bip(2-Et)-Bip(2-Et) 97 HGEGTFTS-(CH 2 )1o-Bip(2-Et)-Bip(2-Et) 98 HGEGT-(a-Me)-Phe(2-F)-TS-(CH 2

)

1 0 -Bip(-2-Et)-Bip(2-Et) 99 HGEGTFTS-(CH 2

)

11 -Bip(2-Et)-Bip(2-Et) 100 HGEGT-(ca-Me)-Phe(2-F)-TS-(CH 2

)

11 -Bip(2-Et)-Bip(2-Et) 101 HGEGTFTS-(CH 2

)

2 -Bip(2-Me)-Bip(2-Me) 102 HGEGT-(a-Me)-Phe(2-F)-TS-(CH 2

)

2 -Bip(2-Me)-Bip(2-Me) 103 HGEGTFTS-(CH 2

)

2 -Bip(2-Et)-Bip(2-Et) 104 HGEGT-(a-Me)-Phe(2-F)-TS-(CH 2

)

2 -Bip(2-Et)-Bip(2-Et) 105 HAEGTFTS-(CH 2

)

2 -Bip(2-Et)-Bip(2-Et) 106 HAibEGTFTS-(CH 2

)

2 -Bip(2-Et)-Bip(2-Et) 107 HAibEGT-(a-Me)-Phe(2-F)-TS-(CH 2

)

2 -Bip(2-Et)-Bip(2-Et) 108 HGEGTFTSD-(CH 2

)

2 -Bip(2-Et)-Bip(2-Et) 109 HGEGT-(a-Me)-Phe(2-F)-TSD-(CH 2

)

2 -Bip(2-Et)-Bip(2-Et) 110 HAEGTFTSD-(CH 2

)

2 -Bip(2-Et)-Bip(2-Et) 111 HAibEGTFTSD-(CH2)2-Bip(2-Et)-Bip(2-Et) 112 HAibEGT-(Q-Me)-Phe(2-F)-TSD-(CH 2

)

2 -Bip(2-Et)-Bip(2-Et) 113 HAEGTF-(CH 2

)

2 -Bip(2-Me)-Bip(2-Et) 114 tIAibEGTF-(CH 2

)

2 -Bip(2-Me)-Bip(2-Et) 115 HAibEGT-(c-Me)-Phe(2-F)-(CH 2

)

2 -Bip(2-Me)-Bip(2-Et) 116 HAEGTFTSD-G-TrPh-TrPh 117 HAibEGTFTSD-G-TrPh-TrPh 118 HAibEGT-(a-Me)-Phe(2-F)-TSD-G-TrPh-TrPh 119 HAibEGT-(a-Me)-Phe(2-F)-(CH 2

)

2 -TrPh-TrPh 120 H{AibEG-(CH 2

)

2 -TrPh-TrPh -27- WO 2007/017892 PCT/1N2006/000154 121 HAibE-(CH 2

)

2 -TrPh-TrPh 122 HAib-(C14 2

)

3 -TrPh-TrPh 123 HAEGTFTSD-G-Nap-Nap 124 HAibEGTFTSD-G-Nap-Nap 125 HAibEGT-(X-Me)-Phe(2-F)-TSD-G-Nap-.Nap 126 HA-EGTFTSD-G-Bip(2-F)-Bip(2-F) 127 HAibEGTFTSD-G-Bip(2-F)-Bip(2-F) 128 HAibEGT-(c-Me)-Phe(2-F)-TSD-G-Bip(2-F)-Bip(2.I) 129 JIAEGTFTSD-G-Bip(2' -Et-4 '-OMe)-4-(2'-Me-Ph)-3-Pyr-Ala 130 HAiIEGTFTSD-G-Bip(2 '-Et-4' -OMe)-4-(2' -Me-Ph) -3 -Pyr-Ala 131 HAibEGT-(a-Me)-Phe(2-F)-TSD-G-Bip(2 '-Et-4' -OMe)-4-(2'-Me Ph)-3-Pyr-Ala 132 HAEGTFTSD-(CH 2

)

2 -Bip(2'-Et-4' -OMe)-4-(2'-Me-Ph)-3-Pyr-Ala 133 H-iibEGTFTSD-(CH 2

)

2 -Bip(2 '-Et-4'-OMe)-4-(2 '-Me-Ph)-3-Pyr Ala 134 HAibEGT-(cx-Me)-Phe(2-F)-TSD-(CH 2

)

2 -Bip(2'.-Et-4'OMe)-4.{2'. Me-Ph)-3-Pyr-Ala 135 IIAEGTFTS-(CH 2

)

2 -Bip(2'-Et-4 '-OMe)-4-(2 '-Me-Ph)-3-Pyr-Ala 136 fLAibEGTFTS-(C11 2

)

2 -Bip(2'-IEt-4' -OMe)-4-(2 '-Me-Ph)-3-Pyr-Ala 137 1IAibEGT-(cx-Me)-Phe(2-F)-TS-(CH 2

)

2 -Bip(2 '-Et-4'-OMe)-4-(2 ' Me-Ph)-3-Pyr-Ala 138 FIAEGTFT-(CH 2

)

2 -Bip(2 '-Et-4'-OMe)-4-(2'-Me-Ph)-3-Pyr-Ala 139 HAibEGTFT-(CFI 2

)

2 -Bip(2'-Et-4' -OMe)-4-(2'-Me-Ph)-3-Pyr-Ala 140 HAibEGT-(ax-Me)-Phe(2-F)-T-(CIH 2

)

2 -Bip(2' -Et-4'-OMe)-4-(2 ' Me-Ph)-3-Pyr-Ala 141 HAEGTF-(C11 2

)

2 -Bip(2 '-Et-4 '-OMe)-4-(2'-Me-Ph)-3-Pyr-Ala 142 HAibEGTF-(CH 2

)

2 -Bip(2 '-Et-4 '-OMe)-4-(2 '-Me-Ph)-3-Pyr-Ala 143 HlAibEGT-(c-~Me)-Phe(2-F)-(CH 2

)

2 -. Bip(2'..Et4'.OMe).4(2'Ne Ph)-3-Pyr-Ala 144 HAEGT-(C11 2

)

2 -Bip(2 '-Et-4'-OMe)-4-(2'-Me-Ph)-3-Pyr-Ala 145 HAibEGT-(CH 2

)

2 -Bip(2' -Et-4'-OMe)-4-(2'-Me-Ph)-3-Pyr-Ala 146 JIAEG-(CH2) 2 -Bip(2'-Et-4'-OMe)-4-(2'-Me-Ph)-3-Pyr.Ala -28- WO 2007/017892 PCT/1N2006/000154 147 TIAibEG-(C1 2

)

2 -Bip(2'-Et-4'-OMe)-4-(2'-Me-Ph)-3-Pyr-Ala 148 IIAEG-(GH 2

)

3 -Bip(2'-Et-4'-OMe)-4-(2'-Me-Ph)-3-Pyr-Ala 149 HAibEG-(C11 2

)

3 -Bip(2'-Et-4'-OMe)-4-(2'-Me-Ph)-3-Pyr-Ala Table 5: S. Sequence No. 1 HAEGT-(CH 2

)

2 -Bip(2-Me)-Bip(2-Me) 2 IIGEGT-(C11 2

)

3 -Bip(2-Me)-Bip(2-Me) 3 JIGEGT-(CH 2

)

4 -Bip(2-Me)-Bip(2-Me) 4 jHGEGT-(CH 2

)

5 -Bip(2-Me)-Bip(2-Me) 5 HGEGT-(CH 2

)

6 -Bip(2-Me)-Bip(2-Me) 6 HAEGT-(CH 2

)

2 -Bip(2-Me)-DBip(-2-Me) 7 IIAEGT-(G11 2

)

2 -DBip(2-Me)-Bip(2-Me) 8 IHaEGT-(CH 2

)

2 -Bip(2-Me)-Bip(2-Me) 9 HGEG-(CH 2

)

3 -Bip(2-Me)-Bip(2-Me) 10 HAEG-(CH 2

)

3 -Bip(2-Me)-Bip(2-Me) 11 I GEG-(CH 2

)

4 -Bip(2-Me)-Bip(2-Me) 12 HGEG-(CH 2

)

5 -Bip(2-Me)-Bip(2-Me) 13 HGEG-(CH 2

)

6 -Bip(2-Me)-Bip(2-Me) 14 1{AFG-(CH 2

)

3 -Bip(2-Et)-Bip(2-Me) 15 HAEG-(CH 2

)

3 -Bip(2-Me)-DBip(2-Me) 16 HAEG-(CH 2

)

4 -Bip(2-Me)-DBip(2-Me) 17 HAEG-(CH 2

)

5 -Bip(2-Mce)-DBip(2-Me) 18 HGEG-(CH 2

)

5 -DBip(2-Me)-Bip(2-Me) 19, HAE-(CH 2

)

3 -Bip(2-Me)-Bip(2-Me) 20 HAiE-(CLI 2

)

3 -Bip(2-Me)-DBip(2-Me) 21 HAE-(CH 2

)

2 -D-,Bip(2-Me)-Bip(2-Me) 22 IAE-(CH 2

)

3 -D-Bip(2-Me)-Bip(2-Me) 23 HIAE-(CH 2

)

4 -D-Bip(2-Me)-Bip(2-Me) 24 IIAE-(CH 2

)

4 -Bip(2-Me)-DBip(2-Me) 25 HAE-(CH 2

)

5 -D-Bip(2-Me)-Bip(2-Me) 26 HIAE-(CH 2

)

3 -Bip(2-Et)-Bip(2-Me) -29,- WO 2007/017892 PCT/1N2006/000154 27 HAE-(CH 2

)

2 -Bip(2-Me)-Bip(2-Me) Table 6: S. Sequence No. I H-(C11 2

)

3 -Bip(2-Me)-Bip(2-Me) 2 J1-(CH 2

)

4 -Bip(2-Me)-Bip(2-Me) 3 H-(CH 2

)

5 -Bip(2-Me)-Bip(2-Me) 4 H-(CH 2

)

3 -Bip(2-Et)-Bip(2-Me) 5 1I-(CH 2

)

4 -Bip(2-Et)-Bip(2-Me) 6 H-(C11 2

)

5 -Bip(2-Et)-Bip(2-Me,) 7 H-(CH 2

)

6 -Bip(2-Et)-Bip(2-Me) 8 H-(GH 2 )jo-Bip(2-Et)-Bip(2-Me-) 9 H-(CH 2 )5-Bip(2-Me)-DBip(2-Me) 10 H-(CH 2

)

5 -DBip(2-Me)-Bip(2-Me) 11 H-(CH 2 )s-DBip(2-Me)-DBip(2-Me) 12 HG-(C'H 2

)

3 -Bip(2-Me)-Bip(2-Me) 13 HG-(CH 2

)

4 -Bip(2-Me)-Bip(2-Me) 14 H-G-(CH 2

)

3 -Bip(2-Et)-Bip(2-Me) 15 HG-(CJI 2

)

4 -Bip(2-Et)-Bip(2-Me) 16 HG-(CH 2

)

3 -Bip(2-Et)-DBip(2-Me) 17 HG-(C1I 2

)

3 -Bip(2-Me)-DBip(2-Me) 18 FA-(CH 2

)

3 -DBip(2-Me)-Bip(2-Et) 19 FA-(GH2)3-DBip-DBip 20 Ha-(CH 2

)

3 -Bip(2-Me)-Bip(2-Me) 21 Ha-(CH 2

)

4 -Bip(2-Me)-Bip(2-Me) 22 Ha-(CH 2

)

5 -Bip(2-Me)-Bip(2-Me) 23 Ha-(CH 2

)

3 -Bip(2-Et)-Bip(2-Me) 24 Ha-(CH 2 )3-Bip(2-Et)-DBip(2-Me) 25 Ha-(CH2)3-Bip(2-Me)-DBip(2-Me) 26 Ha-(C11 2 )-Bip(2-Et)-DBip(2-Et) 27 Ha-(CH 2 )3-Bip(2-Me)-Bip 28 Ha-(CH 2 )3-(N(Me))-DBip(2-Me)-Bip(2-Et) -30- WO 2007/017892 PCT/1N2006/000154 29 Ha-(CH 2

)

3 -(N(Me))-Bip(2-Et)-Bip(2-Me) 30 Ha-(CH 2

)

3 -(N(Me))-DBip-Bip(2-Et) 31 Ha-(GH 2

)

3 -DBip(2-Me)-Bip(2-Et) 32 HA-(CH 2

)

3 -Bip(2-Me)-Bip(2-Me) 33 HA-(CH 2

)

4 -Bip(2-Me)-Bip(2-Me) 34 HA-(C11 2

)

5 -Bip(2-Me)-Bip(2-Me) 35 HA-(CH 2

)

6 -Bip(2-Me)-Bip(2-Me) 36 HA-(CH 2

)

10 -Bip(2-Me)-Bip(2-Me) 37 HA-(CH 2

)

11 -Bip(2-Me)-Bip(2-Me) 38 HA-(CH 2

)

3 -Bip(2-Et)-Bip(2-Me) 39 HA-(CH 2

)

3 -Bip(2-Et)-DBip(2-Et) 40 HA-(CFI 2

)

3 -DBip(2-Me)-DBip(2-Me) 41 HA-(CH 2 )3-DBip(2-Me)-Bip(2-Me) 42 JLA-(CH 2

)

3 -Bip(2-Me)-DBip(,2-Me) 43 HIA-(CH 2

)

3 -Bip(2-Jpr)-Bip(2-Ipr) 44 JIA-(CH 2

)

3 -Bip(2-Ipr)-Bip(2-Me) 45 HA-(CH 2

)

3 -Bip(2-Me)-Bip(2-Jpr) 46 HA-(CH 2

)

4 -Bip(2-Et)-Bip(2-Me) 47 IIA-(CH 2

)

3 -Bip(2-Me)-DBip(2-Et) 48 HA-(CH 2

)

2 -Bip(2-Et)-Bip(2-Me) 49 JIA-(CH 2

)

5 -Bip(2-Et)-Bip(2-Me) 50 HiA-(CH 2

)

6 -Bip(2-Et)-Bip(2-Me) 51 HA-(CH 2

)

2 -Bip(2-Me)-Bip(2-Me) 52 ELA-(CH 2 )-DBip(2-Et)-DBip(2-Me) 53 HA-(CH 2

)

3 -DBip(2-Et)-Bip(2-Me) 54 H-A-(CH 2

)

2 -Bip(2-Me)-DBip(2-Me) 55 HA-(CH 2

)

3 -Bip(2-Et)-Bip(2-Et) 56 HA-(CH 2

)

3 -DBip(2-Et)-DBip(2-Et) 57 HIA-(CH 2

)

3 -DBip(2-Et)-Bip(2-Et) 58 HA-(CH 2

)

3 -DBip(2-Me)-DBip(2-Et) 59 HA-(CH 2

)

3 -Bip(2-Me)-Bip(2-Et) 60 HIA-(CH 2

)

3 -DBip(2-Me)-Bip(2-Et) 61 fIA-(CH 2

)

3 -Bip-Bip -31- WO 2007/017892 PCT/1N2006/000154 62 J{A-(CH 2

)

3 -Bip-DBip 63 HA-(CH 2

)

3 -DBip-DBip 64 HA-(CJJ 2

)

3 -DBip-Bip 65 H-A-(CH 2

)

3 -Bip-Bip(2-Me) 66 HA-(CH 2

)

3 -Bip(2-Me)-Bip 67 HA- (CH 2

)

3 -Bip(2-Et)-Bip 68 HA-(CH 2

)

3 -Bip-Bip(2-Et) 69 HA-.(CH 2

)

3 -Bip(2-Ipr)-DBip(2-Ipr) 70 HA-(CH 2

)

3 -DBip(2-Jpr)-Bip(2-Ipr) 71 HA-(CH 2

)

3 -DBip(2-Ipr)-DBip(2-Ipr) 72 HA-(CH 2

)

3 -Bip(2-Me)-Bip(2-CN) 73 HA-(CH- 2

)

3 -Bip-Bip(2-CN) 74 HA-(CH 2

)

3 -Bip(2-Et)-Bip(2-CN) 75 JIA-(CH 2

)

3 -Bip(2-Ipr)-Bip(2-CN) 76 IIA-(CH 2

)

3 -Bip(2-CN)-Bip(2-Me) 77 HA-(C11 2

)

3 -Bip(2-CN)-Bip 78 I-A-(GH 2

)

3 -Bip(2-CN)-Bip(2-Et) 79 HA-(C11 2

)

3 -Bip(2-CN)-Bip(2-Ipr) 80 HIA-(CH 2

)

3 -Bip(2-CN)-Bip(2-CN) 81 HA-(CH 2

)

2

-F-(GH

2

)

2 -Bip(2-Et)-DBip(2-Et) 82 HIA-(CH 2

)

2 -F-(C11 2

)

2 -Bip(2-Et)-DBip(2-Me) 83 HA-(CH 2

)

5 -Bip(2-Me)-DBip 84 HA-(CH 2

)

3 -Bip(2-Me)-DBip-R 85 IIA-(CI1 2

)

3 -DBip(2-Mc)-DBip 86 HA-(CH 2 )5-Bip(2-Me)-DBip(2-Me) 87 HA-(CH 2

)

5 -DBip(2-Me)-Bip(2-Me) 88 IIA-(CH 2

)

4 -D(Bip)-Bip(2-Et) 89 LIA-(C11 2

)

5 -D(Bip)-Bip(2-Et) 90 HA-(CH 2

)

4 -Bip(2-Me)-DBip(2-Me) 91 H-A-(CH 2 )-Bip(2-Me)-DBip(2-Me) 92 JIA-(CH 2

)

3 -(N(Me))-DBip-Bip(2-Et) 93 H4A-(CH 2

)

4 -DBip(2-Me)-Bip(2-Et) 94 J{A-(CH 2

)

5 -DBip(2-Me)-Bip(2-Et) -32- WO 2007/017892 PCT/IN2006/000154 95 HA-(CH 2

)

3 -(N(Me))-DBip(2-Me)-Bip(2-Et) 96 HA-(CH 2

)

4 -Bip(2-Me)-DBip 97 HA-(CH 2

)

5 -Bip(2-Me)-DBip 98 HA-(CH 2

)

3 -(N(Me))-Bip(2-Et)-Bip(2-Me) 99 HA-(N(Me))-(CH 2

)

3 -DBip(2-Me)-Bip(2-Et) 100 HA-(N(Me))-(CH 2

)

3 -DBip-Bip(2-Et) 101 HA-(N(Me))-(CH 2

)

3 -Bip(2-Et)-Bip(2-Me) 102 HA-(N(Me))-(CH 2

)

3 -Bip(2-Me)-DBip 103 HAE-(CH 2

)

2

-F-(CH

2

)

2 -Bip(2-Et)-DBip(2-Et) 104 HAE-(CH 2

)

2

-F-(CH

2

)

2 -Bip(2-Et)-DBip(2-Me) 105 HAib-(CH 2

)

3 -(N(Me))-Bip(2-Et)-Bip(2-Me) The following compounds can be prepared according to the general processes described above and are included within the scope of the present invention (Tables 7-9) Table 7: S. Sequence No. 1 HA-(CH 2

)

2 -Bip(2'-Et-4'-OMe)-4-(2'-Me-Ph)-3-Pyr-Ala-NH2 2 H-Aib-(CH 2

)

2 -Bip(2'-Et-4'-OMe)-4-(2'-Me-Ph)-3-Pyr-Ala-NH2 3 Ha-(CH 2

)

2 -Bip(2'-Et-4'-OMe)-4-(2'-Me-Ph)-3-Pyr-Ala-NH 2 4 H-(N(Me))A-(CH 2

)

2 -Bip(2'-Et-4'-OMe)-4-(2'-Me-Ph)-3-Pyr-Ala-NH2 5 H-(N(Me))A-(N(Me))-(CH 2

)

2 -Bip(2'-Et-4'-OMe)-4-(2'-Me-Ph)-3-Pyr-Ala

NH

2 6 H-(N(Me))Aib-(N(Me))-(CH 2

)

2 -Bip(2'-Et-4'-OMe)-4-(2t'-Ms-Ph)-3-Pyr Ala-NH 2 7 H-(N(Me))A-(N(Me))-(CH 2

)

2 -(N(Me))-Bip(2'-Et-4'-OMe)-4-(2'-Me-Ph)-3 Pyr-Ala-NH 2 8 H-(N(Me))Aib-(N(Me))-(CH 2

)

2 -(N(Me))-Bip(2'-Et-4'-OMe)-4-(2'-Me-Ph) 3-Pyr-Ala-NH 2 9 H-(N(Me))A-(N(Me))-(CH 2

)

2 -(N(Me))-Bip(2'-Et-4'-OMe)-(N(Me))-4-(2' Me-Ph)-3-Pyr-Ala-NH 2 10 H-(N(Me))Aib-(N(Me))-(CH 2

)

2 -(N(Me))-Bip(2'-Et-4'-OMe)-(N(Me))-4 (2'-Me-Ph)-3-Pyr-Ala-NH 2 -33- WO 2007/017892 PCT/1N2006/000154 11 Des-amino-H-(N(Me))A-(N(Me)).(CH 2

)

2 (N(Me))Bip(2'Et-4'-OMe) (N(Me))-4-(2'-Me-Ph)-3 -Pyr-Ala-NH 2 12 Des-amino-H-(N(Me))Aib-(N(Me))-(CH 2

)

2 (N(Me))Bip(2'-Et-4 -OMe) (N(Me))-4-(2'-Me-Ph)-3 -Pyr-Ala-NH 2 13 H-(N(Me))A-(N(Me))-(CH 2

)

2 -(N(Me))-Bip(2 '-Et-4'-OMe)-(N(Me))-4-(2' Me-Ph)-3-Pyr-Ala-NII-(GH 2

)

6

-CH

3 14 H-(N(Me))Aib-(N(Me))-(CH 2

)

2 -(N(Me))-Bip(2'-Et-4'-OMe)-(N(Me))-4 (2'-Me-Ph)-3-Pyr-Ala-NH-(CH 2

)

6

-CH

3 15 H-(N(Me))A-(N(Me))-(CH 2

)

2 -(N(Me))-Bip(2'-Et-4'-OMe)-(N(Me))4(2 ' Me-Ph)-3-Pyr-Ala-N{-(CH 2 )io-CH 3 16 H-(N(Me))Aib-(N(Me))-(CH 2

)

2 -(N(Me))-Bip(2'Et4'.OMe )-N(Me))4 (2'-Me-Ph)-3-Pyr-Ala-NH-(CH 2 )l-C{ 3 17 CH3-(CH2)6-NH-(N(Me))A-(N(Me))-(CH 2

)

2 -(N(Me))-Bip(2'-Et.4'-OMe) (N(Me))-4-(2'-Me-Ph)-!3-Pyr-Ala-NH-(CH 2

)

6

-CH

3 18 GH3-(CH2)6-NH-(N(Me))Aib-(N(Me))-(CH 2

)

2 -(N(MNe))-Bip(2'.Et.4' -OMe) (N(Me))-4-(2 '-Me-Ph)-3 -Pyr-Ala-NH-(CH 2

)

6

-CJJ

3 1-9 CH3-(CH2)lo-NH-(N(Me))A-(N(Me))-(CH 2

)

2 -(N(Me))-Bip(2'-Et..4'.OMe). (N(Mle))-4-(2'-Me-Ph)-3 -Pyr-Ala-NH-(CH 2

)

6

-CH

3 20 CH3-(CH2)io-NII-(N(Me))Aib-(N(M\e))-(CH 2

)

2 -(N(M\e))-Bip(2 '-Et-4' OMe)-(N(Me))-4-(2'-Me-Ph)-3-Pyr-Ala-NH-(CH 2

)

6

-CH

3 21 HA-(CH 2

)

3 -BiP(2'-Et-4'-OMe)-4-(2' -Me-Ph)-3-Pyr-Ala-NH 2 22 FI-Aib-(CH 2

)

3 -Bip(2 '-Et-4'-OMe)-4-(2 '-Me-Ph)-3-Pyr-Ala-NH 2 23 Ha-(CH 2 )3ip(2 '-Et-4'-OMe)-4-(2 '-Me-Ph)-3-Pyr--Ala-NH 2 24 T-(N(Me))A-(CH 2 1,)3-Bip(2 '-Et-4'-OMe)-4-(2'-Me-Ph)-3-Pyr-Ala-NH 2 25 H-(N(M\e))A-((Me))-(CH 2

)

3 -Bip(2'-Et-4'.-OMe)-4-2 '-Me-Ph)-3-Pyr-Ala Nil 2 26 H-(N(Me))Aib-(N(Me))-(CH 2

)

3 -Bip(2 '-Et-4'-OMe)-4-(2'-Me-Ph)-3-Pyr Ala-NH 2 27 H-(N(Me))A-(N(M\e))-(CH 2

)

3 -(N(Me))-Bip(2 '-Et-4'-OMe)-4-(2 '-Me-Ph)-3 Pyr-Ala-NH 2 28 H-(N(Me))Aib-(N(Me))-(CH 2

)

3 -(N(M\e))-Bip(2' -Et-4'-OMe)-4-(2 '-Me-Ph) 3-Pyr-Ala-NH 2 29 H-(N(Me))A-(N(Me))(CH 2

)

3 -(N(Me))-Bip(2'E 4'OM(e))4-(2'. - 34 - WO 2007/017892 PCT/1N2006/000154 Me-Ph)-3-Pyr-Ala-NH 2 30 H-(N(M\e))Aib-(N(Me))-(CH 2

)

3 -(N(Me))-Bip(2 '-Et-4'-OMe)-(N(Me))-4 (2'-Me-Ph)-3-Pyr-Ala-NJ 2 31 Des-amino-H-(N(Me))A-(N(Me))-(CH 2

)

3 -(N(Me))-Bip(2'-Et-4' -OMe) (N(Me))-4-(2'-Me-Ph)-3 -Pyr-Ala-NH 2 32 Des-amino-H-(N(v~e))Aib-(N(Me))-(CH 2

)

3 -(N(Me))-Bip(2' -Et-4'-OMe) (N(Me))-4-(2'-Me-Ph)-3 -Pyr-Ala-N11 2 33 H-(N(Me))A-(N(Me))-(GH 2

)

3 -{N(Me))-Bip(2' -Et-4'-OMe)-(N(Me))-4-(2' Me-Ph)-3-Pyr-Ala-N{-(CH 2

)

6

-CFI

3 34 H-(N(Me))Aib-(N(Me))-(CH 2

)

3 -(N(Me))-Bip(2'-Et-4'-OMe)-(N(Me))-4 (2 '-Me-Ph)-3-Pyr-Ala-NH-(CH 2

)

6

-CFI

3 Me-Ph)-3-Pyr-Ala-NII-(CH 2 )lo-CH 3 36 H-(N(Me))Aib-(N(Me))-(CH 2

)

3 -(N(Me))-Bip(2'-Et-4'-OMe)-(N(Me))-4 (2'-Me-Ph)-3-Pyr-Ala-NI-(CH 2 )lo-CH 3 37 CH 3

-(CH

2

)

6 -NII-(N(Me))A-(N(Me))-(C14 2

)

3 -(N(Me))-Bip(2'-Et-4'-OMe) (N(Me))-4-(2'-Me-Ph)-3 -Pyr-Ala-NII-(CH 2

)

6

-CH

3 38 CH3-(CH2) 6 -NH-H-(N(Me))Aib-(N(Me))-(CH 2

)

3 -(N(Me))-Bip(2'-Et-4' OMe)-(N(Me))-4-(2'-Me-Ph)-3-Pyr-Ala-NH-(CH 2

)

6

-CI

3 39 CH 3 -(C14 2 )io-NH-H-(N(Me))A-(N(Me))-(CH 2

)

3 -(N(Me))-Bip(2'-Et-4 ' OMe)-(N(Me))-4-(2'-Me-Ph)-3-Pyr-Ala-NH-(C1 2

)

6

-CH

3 40 GH3-(CH 2 )lo-NH-H-(N(Me))Aib-(N(Me))-(CH 2

)

3 -(N(Me))-Bip(2'-Et-4' OMe)-(N(Me))-4-(2'-Me-Ph)-3-Pyr-Ala-NH-(CH 2

)

6

-CH

3 41 JIA-(CH 2

)

4 -Bip(2'-Et-4'-OMe)-4-(2 '-Me-Ph)-3-Pyr-Ala-NH 2 42 J{-Aib-(CH 2

)

2 -Bip(2' -Et-4'-OMe)-4-(2 '-Me-Ph)-3-Pyr-Ala-N- 2 43 H-a-(CH 2

)

4 -Bip(2'-Et-4'-OMe)-4-(2'-Me-Ph)-3-Pyr-Ala-NH 2 44 H-(N(Me))A-(CH 2 1) 4 -Bip(2'-Et-4' -OMe)-4-(2' -Me-Ph)-3 -Pyr-A la-NH-2 45 H-(N(Me))A-(N(Me))-(CH 2

)

4 -Bip(2 '-Et-4' -OMe)-4-(2' -Me-Ph)-3-Pyr-Ala Nil 2 46 H-(N(Me))Aib-(N(Me))-(CH 2

)

4 -Bip(2 '-Et-4' -OMe)-4-(2 '-Me-Ph)-3-Pyr Ala-Nil 2 47 H-(N(M\e))A-(N(Me))-(CH 2

)

4 -(N(Me))-Bip(2 '-Et-4'-OMe)-4-(2 '-Me-Ph)-3 Pyr-Ala-N11 2 -35- WO 2007/017892 PCT/1N2006/000154 48 H-(N(Me))Aib-(N(Me))-(CH 2

)

4 -(N(M~e))-Bip(2 '-Et-4'-OMe)-4-(2'-Me-Ph) 3 -Pyr-Ala-N1 2 49 H-(N(Me))A-(N(Me))-(CH 2

)

4 -(N(Me))-Bip(2 '-Et-4' -OMe)-(N(M~e))-4-(2' Me-Ph)-3-Pyr-Ala-NH 2 50 H-(N(Me))Aib-(N(Me))-(CH 2

)

4 -(N(Me))-Bip(2 '-Et-4'-OMe)-(N(Me))-4 (2' -Me-Ph)-3-Pyr-Ala-NH 2 51 Des-amino-H-(N(Me))A-(N(Me))-(C11 2

)

4 -(N(Me))-Bip(2'-Et-4' -OMe) (N(Me))-4-(2'-Me-Ph)-3 -Pyr-Ala-NH 2 52 Des-amino-H-(N(Me))Aib-(N(Me))-(CFI 2

)

4 -(N(M~e))-Bip(2' -Et-4'-OMe) (N(Me))-4-(2'-Me-Ph)-3 -Pyr-Ala-NH 2 53 H-(N(Me))A-(N(Me))-(CH 2

)

4 -(N(Me))-Bip(2' -Et-4'-OMe)-(N(Me))-4-(2' Me-Ph)-3-Pyr-Ala-NH-(CH 2

)

6

-CH

3 54 H-(N(Me))Aib-(N(Me))-(CH 2

)

4 -(N(Me))-Bip(2'-Et-4'-OMe)-(N(Me))-4 (2'-Me-Ph)-3-Pyr-Ala-NH(CH 2

)

6

-CH

3 55 H-(N(Me))A-(N(M~e))-(CH 2

)

4 -(N(Me))-Bip(2'-Et-4'-OMe)-(N(Me))-4-(2 ' Me-Ph)-3-Pyr-Ala-NH-(CH 2

)

10

-CH

3 56 H-(N(Me))Aib-(N(Me))-(CH 2

)

4 -(N(Me))-Bip(2'-Et-4'-OMe)-(N(Me))-4 (2'-Me-Ph)-3-Pyr-Ala-NH-(CH 2

)

0

-CH

3 57 CH3-(CH 2

)

6 -NH-H-(N(Me))A-(N(Me))-(CH 2

)

4 -(N(Me))-Bip(2' -Et-4' OMe)-(N(Me))-4-(2'-Me-Ph)-3-Pyr-Ala-NH-(CH 2

)

6

-CH

3 58 CH 3

-(CH

2

)

6 -NI-H-(N(Me))Aib-(N(Me))-(CH 2

)

4 -(N(Me))-Bip(2'-Et-4' OMe)-(N(Me))-4-(2'-Me-Ph)-3-Pyr-Ala-NH-(CH 2

)

6

-CH

3 59 C113-(CH 2 )o-NH-H-(N(Me))A-(N(Me))-(CH 2

)

4 -(N(Me))-Bip(2'-Et-4 ' OMe)-(,N(,Me))-4-(2 9 -Me-Ph)-3-Pyr-Al-N-(CH 2

)

6

-CH

3 60 CH3-(CH 2 )lo-NH-H-N(Me))Aib-(N(Me))-(CH 2

)

4 -(N(Me))-Bip(2'-Et-4 ' OMe)-(N(Me))-4-(2'-Me-Ph)-3-Pyr-Ala-NH-(CH 2

)

6 -11 3 61 IIAE-(CH 2

)

2 -Bip(2' -Et-4 '-OMe)-4-(2 '-Me-Ph)-3-Pyr-Ala-NH 2 6 2 H-Aib-E-(CH 2

)

2 -Bip(2' -Et-4'-OMe)-4-(2'-Me-Ph)-3-Pyr-Ala-N1 2 63 HaE-(CH 2

)

2 -Bip(2'-Et-4' -OMe)-4 -(2' -Me-Ph)-3-Pyr-Ala-NH 2 6 4 H-(N(Me))AE-(CH 2

)

2 -Bip(2 '-Et-4'-OMe)-4-(2 '-Me-Ph)-3-Pyr-Ala-N4 2 65 H-(N(Me))AE-(N(Me))-(CH 2

)

2 -Bip(2 '-Et-4 '-OMe)-4-(2 '-Me-Ph)-3-Pyr Ala-Nfl 2 66 H-(N(Me))Aib-E-(N(Me))-(CJJ 2

)

2 -Bip(2'-Et-4' -OMe)-4-(2 '-Me-Ph)-3-Pyr - 36 - WO 2007/017892 PCT/1N2006/000154 Ala-MI 2 67 TI-(N(Me))AE-((Me))-(CH 2

)

2 (N(Me))Bip(2'Et4'OMe)-4(2 '-Me-Ph) 3 -Pyr-Ala-NFI 2 68 H-(N(Me))Aib-E-(N(Me))-(CH 2

)

2 -(N(Me))-Bip(2 '-Et-4'-OMe)-4-(2 '-Me Ph)-3-Pyr-Ala-N1 2 69 H-(N(Me))AE-(N(Me))-(CH 2

)

2 (N(Me))Bip(2'E4'OMe)((e))-4.(2' Me-Ph)-3-Pyr-Ala-NH 2 70 H-(N(Me))Aib-E-(N(Me))-(CH 2

)

2 -(N(Me))-Bip(2 '-Et-4'-OMe)-(N(Me))-4 (2 '-Me-Ph)-3-Pyr-Ala-N1 2 71 Des-amino-H-QN(Me))AE-(N(Me))(CH 2

)

2 N(Me))Bip(2'Et4'OMe) (N(Me))-4-(2'-Me-Ph)-3 -Pyr-Ala-N1 2 72 Des-amino-H-N(e))Aib-E-(N(Me))(CH 2

)

2 (N(Me))-Bip(2 '-Et-4'-OMe) (N(M~e))-4-(2'-Me-Ph)-3 -Pyr-Ala-N11 2 73 H-(N(Me))AE-(N(Me))-(CH 2

)

2 -(N(Me))-Bip(2' -Et-4'-OMe)-{N(Me))-4-(2' Me-Ph)-3-Pyr-Ala-NH-(CH 2

)

6

-CH

3 (2' -Me-Ph)-3-Pyr-Ala-NH-(CH 2

)

6

..CH

3 75 H-(N(Me))AE-(N(Me))-(CH 2

)

2 -(N(Me))-Bip(2 '-Et-4'-OMe)-(N(Me))-4-(2' Me-Ph)-3-Pyr-Ala-NI-(C 2 )io-CH 3 76 H-(N(Me))AibE-(N(Me))(C

I

2

)

2 N e))Bip(2'Et4'OMe)((e))-4 (2 '-Me-Ph)-3-Pyr-Ala-N--(CH 2 )io-CH 3 (N(Me))-4-(2'-Me-Ph)-3 -Pyr-Ala-NH-(CH 2

)

6

-CH

3 78 C1i3-(C112)6-NI-(N(Me))Aib-E-(N(Me))..(CH 2

)

2 -{N(Me)).Bip(2'.Et.4

'

OMe)-(N(Me))-4-(2'-Me-Ph)-3-Pyr-AlaMIH(CH 2

)

6

-CH

3 79 CH 3

-(CH

2 ) 1o-NII-(N(Me))AE-(N(Me))-(CH- 2

)

2 -(N(Me))-B ip(2'-Et-4 ' OMe)-(N(Me))-4-(2'-Me-Ph)-3-Pyr-AaMIH(CH 2

)

6

-CH

3 80 CH3-(CH2)io-NH(N(Me))AibE(N(Me))(CH 2

)

2 .N1e))-BiP(2 '-Et-4' OMe)-(N(Me))-4-(2' -Me-Ph)-3-Pyr-Ala-NH-(C 2

)

6

-CH

3 81 HAEG-(CH 2

)

2 -Bip(2'-Et-4 '-OMe)-4-(2 '-Me-Ph)-3-Pyr-Ala-NH 2 82 H-Aib-EG-(CH 2

)

2 -Bip(2 '-Et-4 '-OMe)-4-(2 '-Me-Ph)-3- Pyr-Ala-N1 2 83 HaEG-(CH 2

)

2 -Bip(2'-Et-4'-OMe)-4.(2 '-Me-Ph)-3 -Pyr-Ala-N1 2 84 H-(N(Me))AEG-(CH 2

)

2 -Bip(2'-Et-4 '-OMe)-4 -(2' -Me-Ph)-3-Pyr-Ala-N1 2 -37- WO 2007/017892 PCT/1N2006/000154 85 H-(N(Me))AEG-(N(Mle))-(CH 2

)

2 -Bip(2' -Et-4'-OMe)-4-(2' -Me-Ph)-3-Pyr Ala-Nil 2 86 J1-(N(Me))Aib-EG-(N(Me))-(CH 2

)

2 -Bip(2'-Et-4'-OMe)-4-(2'MePh)-3 Pyr-Ala-N{ 2 87 H-(N(Me))AEG- (4(e))-(CH 2

)

2 -(N(Me))-Bip(2'-Et-4'-OMe)-4.2'-Me Ph)-3-Pyr-Ala-NH 2 88 H-(N(Me))Aib-EG-(N(Me))-(CH 2

)

2 -(N(Me))-Bip(2 '-Et-4'-OMe)-4-(2' -Me Ph)-3 -Pyr-Ala-NH 2 89 H-(N(Me))AEG-(N(Me))-(CH 2

)

2 -(N(Me))-Bip(2'-Et-4'-OMe)((Me))-4 (2'-Me-Ph)-3-Pyr-Ala-NH 2 90 H-(N(Me))Aib-EG-(N(Me))-(CH 2

)

2 -(N(Me))-Bip(2'-Et.4'-OMe)-(N(M\e)) 4-(2'-Me-Ph)-3-Pyr-Ala-NH 2 91 Des-amino-H-(N(Me))AEG-(N(Me))-(Cfl 2

)

2 -(N(Me))-Bip(2 '-Et-4' -OMe) (N(Me))-4-(2 '-Me-Ph)-3-Pyr-Ala-NH 2 92 Des-amino-H-(N(Me))Aib-EG-(N(Me))-(CH 2

)

2 -{N(Me))-Bip(2' -Et-4' OMe)-(N(Me))-4-(2'-Me-Ph)-3-Pyr-Ala-N1 2 93 H-(N(Me))AEG-(N(Me))-(CH 2

)

2 -(N(Me))-Bip(2'-Et-4' -OMe)-(N(Me))-4 (2'-Me-Ph)-3-Pyr-Ala-NI-(C1 2

)

6

-CH

3 94 H-(N(Me))Aib-EG-(N(Me))-(CH 2

)

2 -(N(Me))-Bip(2'-Et-4'-OMe)-{N(Me)). 4-(2 '-Me-Ph)-3-Pyr-Ala-NH-(CH 2

)

6

-CH

3 (2 '-Me-Ph)-3-Pyr-Ala-NH-(CH 2

)

10

-CH

3 96 H-(N(Me))Aib-EG-(N(Me))-(CH 2

)

2 -(N(Me))-B3ip(2'-Et-4'-OMe)-(N(Me)). 4-(2 '-Me-Ph)-3-Pyr-Ala-NH-(CH 2

)

0 -C1 3 97 CHk-(GH2)6-NH-(N(Me))AEG-(N(Me))-(CH 2

)

2 -(N(Me))-Bip(2'-Et-4' OMe)-(N(Me))-4-(2'-MC-Ph)-3-Pyr-Ala-NHl-(CH- 2

)

6

-CIH

3 98 CH3-(CJ{ 2

)

6 -NH-(N(Me))Aib-EG-(N(Me))-(CH 2

)

2 (N(Me)).Bip(2'-Et4'. OMe)-(N(Me))-4-(2' -Me-Ph)-3-Pyr-Ala-NH-(CH 2

)

6

-CH

3 OMe)-(N(Me))-4-(2 '-Me-Ph)-3-Pyr-Ala-NI-(CH 2

)

6

-I-

3 100 CH3-(CH2)lo-NH-(N(Me))Aib-EG-(N(Mle))-(CH 2

)

2 -(N(Me))..Bip(2'..Et-4' OMe)-(N(Me))-4-(2'-Me-Ph)-3-Pyr-Ala-NH-(CH 2

)

6

-CH

3 101 HAEGT-(CH 2

)

2 -Bip(2 '-Et-4'-OMe)-4-(2'-Me-Ph)-3-Pyr-Ala-N1 2 - 38 - WO 2007/017892 PCT/1N2006/000154 102 H-Aib-EGT-(CH 2

)

2 -Bip(2'-Et-4'-OMe)-4{2 '-Me-Ph)-3-Pyr-Ala-NEI 2 103 HaEGT-(CH 2

)

2 -Bip(2 '-Et-4'-OMe)-4-(2 '-Me-Ph)-3-Pyr-Ala-N{ 2 104 H-(N(Me))AEGT-(CH 2

)

2 -Bip(2'-Et-4'-OMe)-4-(2'MePh)3-PyrAla-N 2 105 H-(N(Me))AEGT-(N(Me))-(CH 2

)

2 -Bip(2'-Et4' -OMe)-4-(2' -Me-Ph)-3-Pyr Ala-NH 2 106 H-(N(Me))Aib-EGT-(N(Me))-(CH 2

)

2 -Bip(2' -Et-4' -OMe)-4-(2 '-Me-Ph)-3 Pyr-Ala-NH 2 107 H-(N(Me))AEGT-(N(Me))-(CH 2

)

2 -(N(Me))-Bip(2 '-Et-4'-OMe)-4-(2'-Me Ph)-3 -Pyr-Ala-NH 2 108 II-(N(Me))Aib-EGT-(N(Me))-(CH 2

)

2 -(N(Me))-Bip(2 '-Et-4'-OMe)-4-(2 ' Me-Ph) -3 -Pyr-Ala-N11 2 109 H-(N(Me))AEGT-(N(Me))-(C1 2

)

2 -(N(Me))-Bip(2'Et-4'-OMe)-(N(Me))-4 (2'-Me-Ph)-3-Pyr-Ala-N1 2 110 H-c (Mi ))Aib-EGT-(N(Me))-(CH 2

)

2 -(N(Me))-B ip(2'-Et.4'..OMe) (N(Me))-4-(2'-Me-Ph)-3 -Pyr-Ala-NH 2 I1I Des-amino-H-(N(Me))AEGT-(N(Me))(CH 2

)

2 N(Me))Bip(2'Et-4'-OMe) (N(M~e))-4-(2 '-Me-Ph)-3 -Pyr-Ala-NH 2 112 Des-amino-H-(N(Me))Aib-EGT-(N(Me))-(CI 2

)

2 (N(Me))Bip(2'-Et-4' OMe)-(N(Me))-4-(2 '-Me-Ph)-3-Pyr-Ala-N1 2 113 H-(N(Me))A-EGT-(N(Me))-(CH 2

)

2 -(N(Me))-Bip(2 '-Et-4'-OMe)-(N(Me))-4 (2'-Me-Ph)-3-Pyr-Ala-NH-(CH 2

)

6

-CH

3 114 H-(N(Me))Aib-EGT-(N(Me))-(CH- 2

)

2 -(N(~e))-Bip(2'Et-4 '-OMe) (N(Me))-4-(2 '-Me-Ph)-3 -Pyr-Ala-NH-(C1 2

)

6

-CH

3 115 H-(N(Me))AEGT-(N(Me))-(CH 2

)

2 -(N(Me))-Bip(2 '-Et-4'-OMe)-(N(Me))-4 (2'-Me-Ph)-3-Pyr-Ala-NH-(CH 2

)

10

-CH

3 116 H-(N(Me))Aib-EGT-(N(Me))-(C1 2

)

2 -(N(e))-Bip(2'Et-4'-OMe) (N(M\e))-4-(2'-Me-Ph)-3 -Pyr-Ala-NH-(CH 2 )lo-CH 3 117 CH3-(CH2)6-NH-(N(Me))AEGT-(N(Me))-(CH 2

)

2 -(N(Me)).Bip(2'-Et-4' OMe)-(N(Me))-4-(2 '-Me -Ph)-3-Pyr-Ala-NHr-(CH 2

)

6

-GH

3 118 CH3-(CH2)6-NH-(N(Me))Aib-EGT-(N(Me))-(CH 2

)

2 N(Me)).Bip(2'-Et.4' OMe)-(N(Me))-4-(2'-Me-Ph)-3 -Pyr-Ala-NI{-(CH 2

)

6

-CH

3 119 CH3-(CH2)io-NH-(N(Me))AEGT-(N(Me))-(CH 2

)

2 -(N(Me)).Bip(2'.Et.4' OMe)-(N(Me))-4-(2 '-Me-Ph)-3-Pyr-Ala-NH-(CH 2

)

6

-CH

3 -39- WO 2007/017892 PCT/1N2006/000154 120 CH3-(CH2)io-NH-(N(Me))Aib-EGT-(N(Me))-(CH- 2

)

2 -(N(Me))-Bip(2'-Et-4' OMe)-(N(Me))-4-(2 '-Me-Ph)-3-Pyr-Ala-NH-(CH 2

)

6

-CH

3 121 HA-(CH 2

)

3 -Bip(2-Me)-Bip(2-Me)-N1 2 122 H-Aib-(G11 2

)

3 -Bip(2-Me)-Bip(2-Me)-NH 2 123 Ha-(CH 2

)

3 -Bip(2-Me)-Bip(2-Me)-NH 2 124 H-(N(Me))A-(CH 2

)

3 -Bip(2-Me)-Bip(2-Me)-NH 2 125 H-(N(Me))A-(N(Me))-(CH 2

)

3 -Bip(2-Me)-Bip(2-Me)-NH 2 126 H-(N(Me))Aib-(N(Me))-(CH 2

)

3 -Bip(2-Me)-Bip(2-Me)-NA 2 127 H-(f-(Me))A-(N(Me))-(CH 2

)

3 -(N(Me))-Bip(2-Me)-Bip(2-Me)-NH 2 128 H-(N(Me))Aib-(N(Me))-(CH 2

)

3 -(N(Me))-Bip(2-Me)-Bip(2-Me)-N 2 129 H-(N(Me))A-(N(Me))-(CH 2

)

3 -(N(Me))-Bip(2 -Me)-{N(Me))-.Bip(2-Me)N11 2 130 H-(NMe))Aib-(N(Me))-(CH 2

)

3 -{N(Me))-Bip(2-Me)-(N(Me))-Bip(2-Me).

NH

2 131 Des-amino-H-(N(Me))A-(N(Me))-(CH 2

)

3 -(N(Me)>Bip(2Me)-(Nvje)). Bip(2-Me)-N11 2 132 Des-amino-H-(N(Me))Aib-(N(Ne))-(C1 2

)

3 -(N(Me))-.Bip(2-Me)-{N(Me)). Bip(2-Me)-NH 2 133 H-(N(Me))A-(N(Me))-(CH 2

)

3 -(N(Me))-Bip(2-Me)-(N(Me))-Bip(2-Me)NH

(CH

2

)

6

-CH

3 134 H-(N(Me))Aib-(N(Me))-(CH 2

)

3 -(N(Me))-Bip(2-Me)-(N(Me))-Bip(2-Me).

NI{-(CH

2

)

6

-CH

3 135 H-(N(Me))A-(N(Me))-(CH 2

)

3 -(N(Me))-Bip(2-Me)-(N(Me))Bip(2Me)-NH

(CH

2 ) 10

-CH

3 136 H-(N(Mc))Aib-(N(Mc))-(CI 12i)3-(N(Me))-B1ip(2-Me)-(N(MC))-Bip(2-Me)

NH-(CH

2

)

10

-CH

3 1-37 CH3-(CH2) 6 -NII-H-(N(Me))A-(N(Me))-(CH 2

)

3 -(N(Me))-Bip(2-Me) (N(Me))-Bip(2-Me)-N{-(CH 2

)

6

-CH

3 138- CH3-(CH)-NI-H-(N(Me))Aib-(N(Me))-(CH 2

)

3 -(N(Me))Bip(2-Me) (N(Mve))-Bip(2-Me)-NH-(CH 2

)

6

-CH

3 139 CH3-(CF 2 )lo-NH-H-(N(Me))A-(N(Me))-(CH 2

)

3 -(N(Me))-Bip(2-Me) (N(Me))-BiP(2-Me)-NH--(CH 2

)

6

-CH

3 140 CH3-(CH 2 )lo-NH-H-(N(Me))Aib-N(Me))-(CH 2

)

3 - 4(Me))-Bip(2-Me). (N(Me))-Bip(2-Me)-NH-(C1 2

)

6

-CH

3 - 40 - WO 2007/017892 PCT/IN2006/000154 141 HA-(CH 2

)

3 -Bip(2-Et)-Bip(2-Me)-NH2 142 H-Aib-(CH 2

)

3 -Bip(2-Et)-Bip(2-Me)-NH 2 143 Ha-(CH 2

)

3 -Bip(2-Et)-Bip(2-Me)-NH2 144 H-(N(Me))A-(CH 2

)

3 -Bip(2-Et)-Bip(2-Me)-NH2 145 H-(N(Me))A-(N(Me))-(CH 2

)

3 -Bip(2-Et)-Bip(2-Me)-NH2 146 H-(N(Me))Aib-(N(Me))-(CH 2

)

3 -Bip(2-Et)-Bip(2-Me)-NH2 147 H-(N(Me))A-(N(Me))-(CH 2

)

3 -(N(Me))-Bip(2-Et)-Bip(2-Me)-NH 2 148 H-(N(Me))Aib-(N(Me))-(CH 2

)

3 -(N(Me))-Bip(2-Et)-Bip(2-Me)-NH2 149 H-(N(Me))A-(N(Me))-(CH 2

)

3 -(N(Me))-Bip(2-Et)-(N(Me))-Bip(2-Me)-NH 2 150 H-(N(Me))Aib-(N(Me))-(CH 2

)

3 -(N(Me))-Bip(2-Et)-(N(Me))-Bip(2-Me) NH2 151 Des-amino-H-(N(Me))A-(N(Me))-(CH 2

)

3 -(N(Me))-Bip(2-Et)-(N(Me)) Bip(2-Me)-NH 2 152 Des-amino-H-(N(Me))Aib-(N(Me))-(CH 2

)

3 -(N(Me))-Bip(2-Et)-(N(Me)) Bip(2-Me)-NH 2 153 H-(N(Me))A-(N(Me))-(CH 2

)

3 -(N(Me))-Bip(2-Et)-(N(Me))-Bip(2-Me)-NH

(CH

2

)

6

-CH

3 154 H-(N(Me))Aib-(N(Me))-(CH 2

)

3 -(N(Me))-Bip(2-Et)-(N(Me))-Bip(2-Me)

NH-(CH

2

)

6

-CH

3 155 H-(N(Me))A-(N(Me))-(CH 2

)

3 -(N(Me))-Bip(2-Et)-(N(Me))-Bip(2-Me)-NH

(CH

2 )jo-CH3 156 H-(N(Me))Aib-(N(Me))-(CH 2

)

3 -(N(Me))-Bip(2-Et)-(N(Me))-Bip(2-Me)

NH-(CH

2

)

10 -CH3 157 CH3-(OH2)6-NH-H-(N(Mfe))A-(N(Me))-(CH2)3-(N l-e))-Bip(2-Et) (N(Me))-Bip(2-Me)-NH-(CH 2

)

6

-CH

3 158 CH-(CH2)-NH-H-(N(Me))Aib-(N(Me))-(CH 2

)

3 -(N(Me))-Bip(2-Et) (N(Me))-Bip(2-Me)-NH-(CH 2

)

6

-CH

3 159 CH 3

-(CH

2 )io-NH-H-(N(Me))A-(N(Me))-(CH 2

)

3 -(N(Me))-Bip(2-Et) (N(Me))-Bip(2-Me)-NH-(CH 2 )-CH3 160 CH 3

-(CH

2 )io-NH-H-(N(Me))Aib-(N(Me))-(CH 2

)

3 -(N(Me))-Bip(2-Et) (N(Me))-Bip(2-Me)-NH-(CH 2

)

6

-CH

3 Table 8: -41- WO 2007/017892 PCT/1N2006/000154 S. Sequence No. 1 HA-(CH2)2-Bip(2'-Et-4'-OMe)-4-(2'-MePh).3Pyr.Ala.OH 2 H-Aib-(CH 2

)

2 -Bip(2'-Et-4' -OMe)-4-(2 '-Me-Ph)-3-Pyr-Ala-OH 3 Ha-(CH 2

)

2 -Bip(2 '-Et-4'-OMe)-4-(2'-Me-Ph)-3-Pyr-Ala-OH 4 H-(N(Me))A-(CH 2

)

2 -Bip(2'-Et-4' -OMe)-4-(2'-Me-Ph)-3-Pyr-Ala-OH 5 H-(N(Me))A-cN(Me))-(CH 2

)

2 -Bip(2'Et-4'OMe)4(2'MePh)3PyrAla-OH 6 H-(N(Me))Aib-(N(e))-(CH 2

)

2 Bip(2'Et4'OMe)4(2'-Me-Ph)3-PrAa OH 7 H-(N(Me))A-(N(Me))-(CH 2

)

2 -(N(Me))-Bip(2'-Et-4' -OMe)-4-(2 '-Me-Ph)-3 Pyr-Ala-Oli 8 H-(N(Mle))Aib-(N(Me))-(CH 2

)

2 -(N(Me))-Bip(2'..E4'-OMe)-4(2 '-Me-Ph)-3 Pyr-Ala-Oll 9 H-(N(Me))A-(N(Me))-(CH 2

)

2 (N(Me))Bip(2'Et4'rMe)NMe))-4..2'-Me Ph)-3-Pyr-Ala-OH 10 l1-(N(Me))Aib-(N(Me))-(CH 2

)

2 -(N(Me))-Bip(2'Et4'OMe)-(N(Me))-4(2'. Me-Ph)-3-Pyr-Ala-OH 11 Des-amino-H-(N(Me))A-(N(Me))-(CH 2

)

2 -(N(Me))-Bip(2 '-Et-4'-OMe) (N(Me))-4-(2'-Me-Ph)-3 -Pyr-Ala-OH 12 Des-amino-H-(N(Me))Aib-(N(Me))-(d11 2

)

2 Nqvje))-Bip(2' -Et-4'-OMe) (N(Me))-4-(2 '-Me-Ph)-3 -Pyr-Ala-OH 13 H-(N(Me))A-(N(Me))-(CH 2

)

2 -(N(Me))Bip(2'Et4'OMe)(Me))-4-{2'-Me Ph)-3-Pyr-Ala-COO-(CH 2

)

6

-CH

3 1i4 1--(N(Me))Aib-(N(Me))-(CH 2

)

2 -(N(Me))Bip(2'Et-4'-OMe)-(N(Me))-4-(2' Me-Ph)-3-Pyr-Ala-COO-(CH 2

)

6

-CH

3 15 H-4N(e))A-(NMe))-(CH 2

)

2 -(N(Me))-Bip(2'Et4'OMe)N(Me))4(2'-Me Ph)-3-Pyr-Ala-COO-(CH 2 )jo-CH 3 1Y6 H-(N(Me))Aib-(N(Me))-(CH 2

)

2 -(N(Me))Bip(2'Et4'OMe)(Ie))4(2

'

Me-Ph)-3-Pyr-Ala-COO-(CH 2 )l-C1 3 17 C1I3-(CH2)6-N1-(N(Me))A-(N(Me))-(CH 2

)

2 -(N(Me)).Bip(2'.Et.4'.OMe). (N(Me))-4-(2'-Me-Ph)-3 -Pyr-Ala-COO-(CH 2

)

6

-CH

3 18 CH3-(CH2)6-NH-(N(Me))Aib-(N(Me))-(CH 2

)

2 -(N(Me))..Bip(2'.Et.4'OMe). (N(Me))-.4-(2' -Me-Ph)-3 -Pyr-Ala-COO-(CH 2

)

6

-CH

3 -42 - WO 2007/017892 PCT/1N2006/000154 19 CH 3

-(CH

2 ) o-NH-(N(Me))A-(N(Me))-(CH 2

)

2 -(N(Me))-Bip(2'-Et-4' -OMe) (N(M~e))-4-(2'-Me-Ph)-3 -Pyr-Ala-COO-(CI 2

)

6

-CH

3 20 CH 3

-(CH

2 )lo-NII-(N(Me))Aib-(N(Me))-(CHI 2

)

2 -(N(Me))-Bip(2 '-Et-4 '-OMe) (N(Me))-4-(2'-Me-Ph)-3 -Pyr-Ala-COO-(CH 2

)

6 -CH3 21 HA-(C11 2

)

3 -Bip(2' -Et-4'-OMe)-4-(2'-Me-Ph)-3-Pyr-Ala-OH 22 IJ-Aib-(CH 2

)

3 -Bip(2' -Et-4' -OMe)-4-(2' -Me-Ph)-3 -Pyr-Ala-OH 23 IHa-(CH 2

)

3 -Bip(2'-Et-4'-OMe)-4-(2'-Me-Ph)-3-Pyr-Ala-OH 24 H-(N(Me))A-(CH 2

)

3 -Bip(2'-Et-4'-OMe)-4-(2 '-Me-Ph)-3-Pyr-Ala-OH 25 H-(N(Me))A-(N(Me))-(C1 2

)

3 -Bip(2 '-Et-4 '-OMe)-4-(2'-Me-Ph)-3-Pyr-Ala-OH 26 H-(N(Me))Aib-(N(Me))-(CH 2

)

3 -Bip(2' -Et-4'-OMe)-4-(2'-Me-Ph)-3-Pyr-Ala OH 27 H-(N(Me))A-(N(Me))-(CH 2

)

3 -(N(Me))-B~p(2'-Et-4'-OMe)-4-(2 '-Me-Ph)-3 Pyr-Ala-Oll 28 T-(N(Me))Aib-(N(Me))-(CH 2

)

3 -(N(Me))-Bip(2'-Et-4'-OMe)-4-(2'-Me-Ph)-3 Pyr-Ala-OH 29 H-(N(Me))A-(N(Me))-(C11 2

)

3 -(N(Me))-BiP(2'-Et-4'-OMe)-(N(Me))-4-(2' -Me Ph)-3-Pyr-Ala-OH 30 H-(N(Me))Aib-(N(Me))-(CH 2

)

3 -(N(Me))-Bip(2 '-Et-4'-OMe)-(N(Me))-4-(2' Me-Ph)-3-Pyr-Ala-OJ1 31 Des-amino-H-(N(Me))A-(N(Me))-(CH 2

)

3 -(N(Me))-Bip(2' -Et-4' -OMe) (N(Me))-4-(2'-Me-Ph)-3 -Pyr-Ala-OLI 32 Des-amino-H-(N(Me))Aib-(N(Me))-(CH 2

)

3 -(N(Mle))-Bip(2'-Et-4 '-OMe) (N(Me))-4-(2'-Me-Ph)-3 -Pyr-Ala-Oll 33 L4-1(N(Me))A-(N(Me))-(CH 2

)

3 -(N(Me))-Bip(2' -Et-.4'-OMe)-(N(Me))-4-(2 '-Me Ph)-3 -Pyr-Ala-COO-(CH 2

)

6

-CH

3 34 H-(N(Me))Aib-(N(Me))-(CH 2

)

3 -(N(Mc))-Bip(2'-Et-4'-OM)-(NMIe)).4-(2' Me-Ph)-3-Pyr-Ala-COO-(GH 2

)

6

-GH

3 35 H-(N(Me))A-(N(Me))-(CH 2

)

3 -(N(Me))-Bip(2'-Et-4 '-OMe)-(N(Me))-4-(2 '-Me Ph)-3 -Pyr-Ala-COO-(CH 2 ) 1 0

-CH

3 36 H-(N(Me))Aib-(N(Me))-(CH 2

)

3 -(N(Me))-Bip(2' -Et-4' -OMe)-(N(Me))-4-(2' Me-Ph)-3-Pyr-Ala-COO-(CH 2 )lo-CH3 37 CH 3

-(CH

2

)

6 -NII-(N(Me))A-(N(Me))-(CH 2 )3-(N(Me))-Bip(2'-Et-4'-OMe) (N(M\e))-4-(2'-Me-Ph)-3 -Pyr-Ala-COO-(CH 2

)

6

-CH

3 - 43 - WO 2007/017892 PCT/1N2006/000154 3 8 CH3-(CJ{2),-NH-H-(N(Me))Aib-(N(Me))-(CJJ 2

)

3 -{N(Me))-.Bip(2' -Et-4 '-OMe) (N(Me))-4-(2' -Me-Ph)-3-Pyr-Ala-COO-(C1 2

)

6

-CH-

3 (N(Me))-4-(2'-Me-Ph)-3-Pyr-Ala-COO-(CH 2

)

6

-CH

3 (N(Me))-4-(2'-Me-Ph)-3 -Pyr-Ala-COO-(CH 2

)

6

-CH

3 41 HA-(CLI2)4-BiP(2'-Et-4'-OMe)-4-(2'-Me-Ph)-3 -Pyr-Ala-OH 42 H-Aib-(C11 2

)

2 -Bip(2 '-Et-4'-OMe)-4-(2 '-Me-Ph)-3 -Pyr-Ala-Oll 43 Ha-(CH 2

)

4 -Bip(2'-Et-4'-OMe)-4-(2 '-Me-Ph)-3-Pyr-Ala--OH 44 H-(N(Me))A-(CH 2

)

4 -Bip(2 '-Et-4'-OMe)-4-(2 '-Me-Ph)-3-Pyr-Ala-OH 45 H-(N(Me))A-(N(Me))-(CH 2

)

4 -Bip(2 '-Et-4'-OMe)-4-(2'-Me-Ph)-3-Pyr-Ala-OHI 46 FI-(N(Me))Aib-(N(Mle))-(CH 2

)

4 -BiP(2 '-Et-4'-OMe)-4-(2'-Me-Ph)-3-Pyr-Ala OH 4-7- H-(N(Me))A(N(Me))-(CH 2

)

4 -N(Me))Bip(2'Et4'OMe)-4(2 '-Me-Ph)-3 Pyr-Ala-OTI 48 H-(N(Me))Aib-(N(Me))(CH 2

)

4 (N(e))Bip(2'Et4'OMe)4.(2'Me-Ph)-3 Pyr-Ala-OTI 49 NM))-NMe)(H )4((e)Bp2-t4-~)((e)4('M Ph)-3-Pyr-Ala-OH Me-Ph)-3-Pyr-Ala-OH 51 Des-amino-H-(N(Me))A-(N(Me))(C} 2

)

4 (N(Me))Bip(2'Et-4'OMe). (N(Me))-4-(2 '-Me-Ph)-3 -Pyr-Ala-OJI 52 iin--NMe)i-NM)-CH)-T(e)Bp('-t4-~) (N(Me))-4-(2 '-Me-Ph)-3 -Pyr-Ala -OH 5 3 'H-{N(Me))A-(N(Mle))-(CH 2

)

4 -(N(Me))..Bip(2' -Et-4' -OMe)-(N(M~e))-4-(2 '-Me- Ph)-3-Pyr-Ala-COO-(H 2

)

6

-CH

3 Me-Ph)-3-Pyr-Ala-COO-(CI 2

)

6

-CH

3 55 H-NM)A((e)(H)-NM))Bp2-t4 ~)((e)4('-Me MPh)-3-Pyr-Ala-COO-(CH 2

)

10

.CH

3 - 44 - WO 2007/017892 PCT/1N2006/000154 (N7(Me))-4-(25-Me-Ph)N3M-Pyr-Ala-COO-(CI 2 )-CI-1 3 Bi('-t-'O~) (N(Me))-4-(2'-Me-Ph)-3 -Pyr-Ala-COO-(GH 2

)

6

-CH

3 598 CH-CI6N--NM)Ab((e)-C24 (e)]i('E-'-OMe)- (N(M~e))-4-(2 '-Me-Ph) -3 -Pyr-Ala-COO-(CH 2

)

6

-CH

3 60 CH-C2i-HH((e)-NM)-C24((e)Bp2-t4-~) (N(Me))-4-(2'-Me-Ph)-3 -Pyr-Ala-COO-(CH 2

)

6

-CH

3 61 H(C 2

)

2 -i( t4-~)-4-(2 '-Me-Ph)-3 -Pyr-Ala-OH-CH)-C4 62 H-AiE-(CH 2

)

2 -Bip(2 '-Et-4'-OMe)-4-(2 '-MePh)-3-Pyr-Aa-OH 6 3 HaE-(CH)2-Bip(2'-Et-4'OMe)42'MePh)3-Pyr-AlaOH 6 4 H-(N(Me'))'A-(C1 2

)

2 -. Bip(2'-Et-4'-OMe)-4-(2 '-Me-Ph)-3-Pyr-Ala-OH 65 H-(N(Me))AE-(N(Me))-(C11 2

)

2 -Bip(2 '-Et-4 '-OMe)-4-(2 '-Me-Ph)-3-Pyr-Ala OH 66 M)AbE-NM)-C22-i('E-1-~)4('M-P)3prAa OH 67 H-(N(Me))AE(NMe))(H 2

)

2 N(Me))Bip(2'Et4'OMe)4(2-MePh)-3 Pyr-Ala-ON 68 H-(N(Me))Aib-E-(N(Me))-(CH 2

)

2 {.(vie))-Bip(2 '-Et-4'-OMe)-4-(2 '-Me-Ph) 3-Pyr-Ala-OH 69 H-(N(Me))AE-(N(Me))-(CH 2 )2(N e))Bip(2'Et4'OMe)(e))-4(2

'

Me-Ph)-3-Pyr-Al -OH 70 H-(N(Me))Aib-E-(N(Me))-(CH 2

)

2 N(M~e))-Bip(2 '-Et-4'-OMe)-(N(Me))-4-(2' Me-Ph)-3-Pyr-Ala-OH 71 Des-atmino-H-(N(Me))AE-(N(Me))j(CH 2

)

2 -{N(Me))-Bip(2 '-Et-4'-OMe) (N(Me))-4-(2 '-Me-Ph)-3 -Pyr-Ala-OH 72Des-aimino-H(N(Me))AibE(N(Me))(CH 2

)

2 (N(Me))Bip(2'Et-4'-OMe) (N(Me))-4-(2 '-Me-Ph)-3-Pyr-Ala-OH 73 H-(N(Me))AE-(N(Me))-(CH 2

)

2 -(N(Me))-Bip(2 '-Et-4'-OMe)-(N(Me))-4-(2' Me-Ph)-3-Pyr-Ala-COO{(CH 2

)

6

-CH

3 Me-Ph)-3-Pyr-Ala-COO-(CH 2

)

6

-CH

3 - 45 - WO 2007/017892 PCT/1N2006/000154 Me-Ph)-3-Pyr-Ala-COO-(C 2 )lo..C 3 76 H-(N(Me))Aib-E-(N(Me))-(CH 2

)

2 -(N(Me))-Bip(2 '-Et-4' -OMe)-(N(Me))-4-(2' Me-Ph)-3-Pyr-Ala-COO-(CJ 2

)

0

-CH

3 77 CH3-(CH2)6-NH-(N(Me))AE-(N(Me))-(CH 2

)

2 (N(Me))-Bip(2'-Et.4' -OMe) (N(Me))-4-(2'-Me-Ph)-3 -Pyr-Ala-COO-(CH 2

)

6

-GJ{

3 7 8 CH3-(CH2)6-N-(N(Me))Aib-E(N(Me))(CH 2

)

2 M\e))Bip(2'Et-4'-OMe) (N(Me))-4-(2'-Me-Ph)-3 -Pyr-Ala-COO-(CH 2

)

6 -C1 3 79 C11 3

-(CH

2 ) io-NH-(N(Me))AE-(N(Me))-(CH 2

)

2 -(N(Me))-B ip(2 '-Et-4 '-OMe) (N(Me))-4-(2'-Me-Ph)-3 -Pyr-Ala-COO-(CH 2

)

6 -C1 3 80 CH3-(CH2)io-NH-(N(M\e))Aib-E-(N(Me))(C 2

)

2 .q%.(Me))Bip(2'..Et-4' -OMe) (N(Me))-4-(2 '-Me-Ph)-3 -Pyr-Ala-COO-(CH 2

)

6

-CH

3 81 HAEG-(CH 2

)

2 -Bip(2 '-Et-4 '-OMe)-4-(2 '-Me-Ph)-3-Pyr-Ala .- OHJ 82 H-Aib-EG-(CH 2

)

2 -Bip(2'-Et-4'-OMe)-4.{2' -Me-Ph)-3-Pyr-Ala-OH 83 HaEG-(CH 2

)

2 -Bip(2' -Et-4 '-OMe)-4-(2 '-Me-Ph)-3 -Pyr-Ala-ON 84H-(N(Me))AEG-(CH 2

)

2 -Bip(2'-Et-4'OMe)-4-(2' -Me-Ph)-3-Pyr-Ala-OHl 85H-(N(Me))AEG-(N(Me))(Ci 2

)

2 Bip(2'E4'..OMe)4-2' -Me-Ph)-3-Pyr-Ala OH 86 HNMe))Aib-EG-(N(Me))-(CH 2

)

2 -Bip(2'Et4'OMe)-4-{2 '-Me-Ph)-3 -Pyr Ala-Oil 87 H-(N(Me))AEG-(N(Me))-(CH 2

)

2 -(N(Me))-Bip(2 '-Et-4'-OMe)-4-(2 '-Me-Ph)-3 Pyr-Ala-OH 8 H-(N(Me))Aib-EG-(N(Me))..(CH 2

)

2 .(N(Me))-Bip(2' -Et-4' -OMe)-4-(2 -'-Me-Ph) 3-Pyr-Ala-OH 89 H-(N(M\e))AEG-(N(Me))-(CH 2

)

2 -(N(Me))-Bip(2 '-Et-4'-OMe)-(N(Me))-4-(2' Me-Ph)-3-Pyr-Ala-OH 90 H-(N(Me))Aib-EG-(N(Me))-(CH 2

)

2 -(N(Me))Bip(2'Et-4'-OMe)-(N(Me))-4 (2'-Me-Ph)-3 -Pyr-Ala-OH 91 Des-amino-H-(N(Me))AEG-(N(Me))(CH 2

)

2 N(Me))-Bip(2 '-Et-4' -OMe) (N(Me))-4-(2'-Me-Ph)-3 -Pyr-Ala-Oll 9 2 Des-amino-H-(N(Me))AibEGN e))-(CH 2

)

2 ((Me))-Bip(2'-Et-4'-OMe) (N(Me))-4-(2'-Me-Ph)-3 -Pyr-Ala-OH 9 3- H-(N(MNe))AEG-(N(Me))-(CH 2

)

2 -(N(Me))-iiP(2 '-Et-4'-OMe)-(N(Me))-4-(2'- Me-Ph)-3-Pyr-Ala-COO-(CH 2

)

6 -Ci{ 3 -46- WO 2007/017892 PCT/1N2006/000154 94 (Me))Ai-yr-AlaMe))-(Cj 2 )2-NM))Bp2CH- 3 O~)((M)- (Me-Ph)-3-Pyr-Ala-COO-(C 2

)C

3 96 H-(N(Me))AibEG-(N(Me))-(CH 2

)

2 .. N(Me))ip(2' -Et-4'-OMe)-(N(Me))-4- ('Me-Ph)-3-Pyr-Ala-Coo{CH 2 ) 0 -C1 3 97 Fl((e)i-G((e)(H)-NMe)Bp2-t4-~)((e)4 (M)4(2'-Me-Ph)-3 -Pyr-Ala-COO-(CH 2 ) -CH 3 98 H3-(CF12)6-NI-(N(Me))AibEG (e))-(C1 2

)

2 N(Me)-Bip(2'Et4'-~) ONMe))-(N(Me h)4-(2~ePhyr-Aa.COO .. (Cj 2

)

6 C 3 O)(N(Me))-4-(2 '-Me-Ph)-3-Pyr-Ala-COO-(CH 2

)

6 -C3 ____ Me))-(e)2'-Me-Ph)3PyrAlaCOOCH 2

)

6

CH

3 10 HeG-(CH 2 e)-Bp2'4'Oe)-4-(2 '-Me-Ph)-3-Pyr-Ala-OH-C2)-H '1 HAibEGT-(CH2) 2 Bip(2'Et4'OMe)4(2'.MePh)3.PyrAaOH 103 HiAiEGT-(CH 2

)

2 -Bip(2 '-Et-4'-OMe)-4-(2 '-Me-Ph)-3-Pyr-Ala-OH 10O4 H-(N(Ne))AEGT-(CH2)2BiP(2'Et4'OMe)4(2'-MePh)3-Pyr-AlaOH 105 H-(N(Me))AEGT-(N(Me))-(CH+ 2

)

2 .Bip(2'Et-4'-OMe)-4-(2 '-Me-Ph)-3-Pyr Ala-OH 106 fl-(N(Me))Aib-EGT-(N(Me))-(C1 2

)

2 -Bip(2'..t-4 '-OMe)-4-(2 '-Me-Ph)-3-Pyr Ala-OH 10O7 l-(N(Me))AEGT-(N(Me))-(CH- 2

)

2 -{N(Me))-Bip(2 '-Et-4' -OMe)-4-(2'-Me-Ph) 3-Pyr-Ala-Oll 108 H-(N(e))Aib-EGT-(N(Me))(CH 2

)

2 (N(Me))Bip(2'Et-4'-OMe)-4-(2 '-Me Ph)-3 -Pyr-Ala-OH 109 H-(N(Me))AEGT-(N(Me))(CH 2

)

2 ((Me))Bip(2'Et4'OMe)((Me))-4(2- Me-Ph)-3-Pyr-Ala-Oj{ 110 H-(N(M~e))Aib-EGT-(N(Me))-(CH- 2

)

2 (N(Me))>Bip(2 '-Et-4' -OMe)-(N(M\e)) -4 111 -h)3Py-laO 112 1 Des-amino-H-(N(Me))AiEGT((Me))(CH 2

)

2 (N(Me))Bip(2'Et4OMe) - 47 - WO 2007/017892 PCT/1N2006/000154 (N(Me))-4-(2 '-Me-Ph)-3 -Pyr-Ala-OH 113 H-(N(Me))AEGT-(N(Me))(CH 2

)

2 (N(Me))Bip(2'Et4'-oMe).{NqMe))-4.2' Me-Ph)-3-Pyr-Ala-COO-(CH 2

)

6

-CH

3 11l4- H-(N(Me))Aib-EGT-(N(Me))-(CH- 2

)

2 -(N(Me))Bip(2'-Et4' -OMe)-(N(Me))-4- (2 '-Me-Ph)-3-Pyr-Ala-COO-(CH 2

)

6 -CJ1 3 11l5 H-(N(Me))AEGT-(N(Me))-(CH 2

)

2 (N(Me))Bip(2'Et4'OMe)(Ne)).4{2

'

Me-Ph)-3-Pyr-Ala-COO-(C1 2 )lo-CH 3 116 H-(N(Me))Aib-EGT-(N(Me))-(CH 2

)

2 (N(Me))Bip(2'Et-4'-OMe)-(N(Me))-4- (2'-Me-Ph)-3-Pyr-Ala-GOO-(CH 2 ) la-Gl 3 117 CH3-(CH2)6-NI-(N(Me))AEGT(N(Me))(H 2

)

2 ((Me))yBip(2'..Et-4'OMe. (N(Me))-4-(2'-Me-Ph)-3 -Pyr-Ala-COO-(CH 2

)

6

-CH

3 118 CH3-(CH2)6-NH-(N(Me))Aib-EGT-(N(Me))..(CH 2

)

2 ..a4(Me))..Bip(2 '-Et-4' O~)((e)4 2-eP)3PrAaCO(H)-H 119q cH3-(cH2)lo-NHl-(N(IMe))AEGT-(N(Me))(C 2

)

2 ( (Me))Bip(2' -Et .- 4'-OMe) (N(Me))-4-(2 '-Me-Ph)-3 -Pyr-Ala-COO-(C1 2

)

6

-CH

3 120 CH3-(CH2)lo-Ni-(N(M\e))Aib-EGT-(N(Me))-(CH 2

)

2 .. (N(Me))..Bip(2'..Et-4'. OMe)-(N(Me))-4-(2'-Me-Ph)-3-Pyr-Ala-COO{(CH 2

)

6

-CH

3 121 HA-(CH 2

)

3 -Bip(2-Me)-Bip(2-Me)-OH 122 il-Aib-(CH 2

)

3 -Bip(2-Me)-Bip(2-Me)-OH 123 Ha-(CH 2

)

3 -Bip(2-Me)-Bip(2-Me)-Ou 1f24 il-(N(Me))A-(CH 2

)

3 -Bip(2-Me)-Bip(2Me)-OH 125 H-(N(Me))A-MNe))-(CH 2 1) 3 -Bip(2Me)B-ip(2-Me)-OH 126 H-(N(M\e))Aib-(N(Me))-(CH 2

)

3 -Bip(2Me)-Bip(2-Me).OH 127 H-(N(Me))A-(N(Me))-(CH 2

)

3 -(N(Mle))Bip(2Me)Bip(2Me)-OH 128 H-(N(Me))Aib-(N(Me))-(CH- 2

)

3 (N(Me))Bip(2Me)Bip(2Me)-OH 129 H-(N(Me))A-(N(Me))-(CH 2

)

3 -(N(Me))-Bip(2-Me)-qS(Me))..Bip(2-Me).OH 130 H-NM)Ab-NM)-C23((e)Bp2M)((e)Bp M)O 131 De-mn--NM)A((e)(H)-NM)-i(-e-NNe)Bp2 Me)-OH 132 Des-amino-H-(N(Me))Aib(N(Me)){CH 2

)

3 -((Me))-Bip(2-Me)-q M1\e)).. Bip(2-Me)-OH 133 H-(N(Me))A-(N(Me))-(CH 2

)

3 -(N(Me))-Bip(2Me)((Me))Bip(2-Me)-COO

(CH

2

)

6

-CH

3 -48- WO 2007/017892 PCT/1N2006/000154 134 JI-(N(Me))Aib-(N(Me))-(CH2)3-(N(Me))Bip(2Me(M\e)Bip(2Me)COO.

(CH

2

)

6

-CH

3 135 H-(N(Me))A-(N(Me))-(CH 2 )3-(N(Me))-Bip(2Me)(Me))-Bip(2-Me)CO0

(GH

2

)

10

-CH

3 136 H-(N(Me))Aib-(N(Me))-(CH 2

)

3 -(N(Me))-Bip(2Me)(N(Me))Bip(2Me)C00

(CH

2 )lo-C11 3 137 CH3-(CH2)6-NH-H-(N(Me))A-(N(Me))-(CH 2

)

3 -(N(Me))-Bip(2.Me)-{N(Me)). BiP(2-Me)-COO-(CH 2

)

6

-CH

3 138 CH3-(C112)6-NH-H-(N(Me))Aib-(N(Me))-(CH 2

)

3 -(N(Me))Bip(2-Me).(N(Me)). B ip(2.-Me)-COO{CH 2

)

6

-GH

3 139 CH3-(CH2)lo-NH-1-(N(Me))A-(N(Me))-(CH 2

)

3 -(N(Me))..Bip(2..Me)iyN(Me)). Bip(2-Me)-C00-(CH 2

)

6

-CH

3 140 CH3-(CII2)1o-IH-H-(N(Me))Aib-(N(M\e))-(CH 2

)

3 -(N(Me))-Bip(2.Me) 11 F(CJJ))-Bip(2-e)-Bip-(C2-M)-OJ 1i42 H-A-(CH 2

)

3 -Bip(2-Et)-Bip(2-Me)-OH 1T432 H-A-(CH 2

)

3 -Bip(2-Et)-Bip(2-Me)-OH 144 LI(NM)-(C FI 2

)

3 -Bip(2-Et)-Bip(2-Me)-OH 145 H-(N(Me))A(N)-(CH 2

)

3 -Bip(2-Et)-Bip(2 Me) o11 146 H-(N(Me))Ai-(N(Me))-(CH 2

)

3 -Bip(2-EtBip(2Me)0H 147 H-(N(Me))Ai-(N(Me))-(GH 2

)

3 -B(ME)Bip(2-et)i(2OH 148 H-(N(M4e))A-(N(Me))-(CI 2

)

3 -(N(Me))Bip(2Et)Bip(2.Me)OH 149 H-(N(Me))Ai-(N(Me))-(CH 2

)

3 -(N(Me))-Bip(2-Et)-(.{NM)).ip2M)0 150 H-(N(Me))A-(N(e))-(CH 2

)

3 -(N(Me))Bip(2Et)(N(e))Bip(2Me)OH 1f51 Des-amino-1I-(N(Mle))A-(N(Me))-(CH 2

)

3 (N(Me))-Bip(2-Et)-{N(Me))-Bip(2 Me)-OH 152 Des-amino-H-(N(Me))Aib-(N(Me))(CH 2

)

3 \4e))Bip(2Et)IN4e))-Bip(2. Me)-OH 1T53 H-(N(Me))A-(N(Me))-(CH 2

)

3 (N(M4e))-Bip(2Et)..((Me)).Bip(2Me)-COO.

(CH

2

)

6

-CH

3 154 H-(N(Me))Aib-(N(Me))-(CH 2

)

3 -(N(Me))-Bip(2Et)(N(Me))Bip(2-Me)-COO.

(CI{

2

)

6

-CH

3 - 49 - WO 2007/017892 PCT/IN2006/000154

(CH

2

)

10

-CH

3 156 H-(N(Me))Aib-(N(Me))-(CH 2

)

3 -(N(Me))-Bip(2-Et)-(N(Me))-Bip(2-Me)-COO

(CH

2

)

10 -CH3 157 CH3-(CH2)6-NH-H-(N(Me))A-(N(Me))-(CH 2

)

3 -(N(Me))-Bip(2-Et)-(N(Me)) Bip(2-Me)-COO-(CH 2

)-CH

3 158 CH3-(CH2)6-NH-H-(N(Me))Aib-(N(Me))-(CH 2

)

3 -(N(Me))-Bip(2-Et)-(N(Me)) Bip(2-Me)-COO-(CH 2

)

6

-CH

3 159 CH 3

-(CH

2 )1o-NH-H-(N(Me))A-(N(Me))-(CH 2

)

3 -(N(Me))-Bip(2-Et)-(N(Me)) Bip(2-Me)-COO-(CH 2

)

6

-CH

3 160 CH3-(CH2)1-NH-H-(N(Me))Aib-(N(Me))-(CH 2

)

3 -(N(Me))-Bip(2-Et)-(N(Me)) Bip(2-Me)-COO-(CH 2

)-CH

3 Table 9: S. Sequence No. 1 HA-(CH 2

)

3 -DVSSYLEGQAAKEFIKELEKLL 2 HAib-(CH 2

)

3 -DVSSYLEGQAAKEFIKELEKLL 3 HAibEGTFTSDVSSYLEGQ-(CH 2

)

2 -KELEKLL 4 HAibEGTFTSDVSSYLEGQ-(CH 2

)

3 -KELEKLL 5 HAibEGTFTSDVSSYLE-(CH 2

)

2 -FIKELEKLL 6 HAibEGT-(c-Me)Phe(2-F)-TSDVSSYLE-(CH 2

)

2 -FIKELEKLL 7 HAib-(CH 2

)

3

-VSSYLE-(CH

2

)

2 -FIKELEKLL 8 HAib-(C1 2

)

3

-VSSYLE-(CH

2

)

3 -FIKELEKLL 9 HAib-(CH 2

)

3

-YLE-(CH

2

)

3 -FIKELEKLL 10 HAib-(CH 2 )4-YLE-(CH 2

)

3 -FIKELEKLL 11 HAib-(CH 2

)

4

-YL-(CH

2

)

3 -FIKELEKLL 12 HAib-(CH 2

)

4

-Y-(CH

2

)

3 -FIKELEKLL 13 HAib-(CH 2

)

4 -FIKELEKLL 14 H4Aib-(CH 2

)

5 -FIKELEKLL 15 HAib-(CH 2

)

6 -FIKELEKLL 16 HAib-(CH 2

)

8 -FIKELEKLL 17 HAib-(CH 2

)

3

-VSSYLEGQ-(CH

2

)

3 -KELEKLL 18 HAib-(CH 2

)

3

-VSSYLEG-(CH

2

)

3 -KELEKLL - 50 - WO 2007/017892 PCT/IN2006/000154 19 HAib-(CH 2 )3-VSSYLE-(CH 2

)

4 -KELEKLL 20 HAib-(CH 2

)

3

-SSYLE-(CH

2

)

4 -KELEKLL 21 HAib-(CH 2

)

3

-SYLE-(CH

2

)

4 -KELEKLL 22 HAib-(CH 2

)

3

-YLE-(CH

2

)

4 -KELEKLL 23 HAib-(CH 2

)

3

-YL-(CH

2

)

4 -KELEKLL 24 HAib-(CH 2

)

3

-Y-(CH

2

)

4 -KELEKLL 25 HAib-(CH 2 )s-KELEKLL 26 HAib-(CH 2

)

6 -KELEKLL 27 HAib-(CH 2 )8-KELEKLL The peptidomimetics prepared as described above were tested for GLP-1 agonist activity in vitro using the cAMP cell-based assay described below. The GLP-1 mimetic peptide analog stimulated cAMP production in a dose response manner and the 5 corresponding EC 50 value were determined for some of the selected peptidomimetics, which are active in vitro at 10 to 100 nM range. The ECso value of EX-4 was used as a positive control. Cyclic AMP determination The GLP-1 receptor is a G-protein coupled receptor. GLP-1 (7-36)-amide, the 10 biologically active form, binds to the GLP-1 receptor and through signal transduction causes activation of adenylate cyclase and raises intracellular cAMP levels. To monitor agonism of peptide compounds in stimulating the GLP-1 receptor, adenyl cyclase activity was monitored by assaying for cellular cAMP levels. cAMP assay: 15 Stably transfected CHO/HGLPlR cells were assayed for cAMP generation in a semi high throughput platform using DiscoverX cAMP kit with Exendin-4 as a positive control. The activity of NCEs was determined as % Exendin-4 activity at 0.01pM concentration. The positive compounds were further validated for cAMP generation using indirect cAMP ELISA kit (R & D systems) The activity of the compounds was expressed as fmol cAMP/pg of protein. 20 EC 50 values of some of the representative compounds (I to IV) are shown in Figure 1. Demonstration of in vivo efficacy of compounds: The in- vivo glucose lowering properties of some of the representative compounds in animal models is described below. This test was used to examine in vivo efficacy of compounds of the present invention on blood glucose at hyperglycemia. The 25 intra peritoneal glucose tolerance test (IPGTT) was performed in overnight fasted Swiss Albino Mice (SAM), weighing 25-30 g. Mice were given glucose load of 1.5g/ -51- WO 2007/017892 PCT/IN2006/000154 Kg/ 10 ml and blood was collected at different time intervals, via retroorbital plexus. Test compounds (peptidomimetics) were dissolved in an appropriate vehicle at a concentration in nmol/ ml equivalent to the dose that was to be administered in nmol / kg, so that each mouse would receive the same volume / weight of dosing solution. 5 Blood samples were drawn prior to Vehicle/Test compound/Glucose load (0 minute) and then at 15 min, 30 min, 60 min and 120 min. Vehicle/Test compound was administered 15 minutes prior to glucose load, via intra-peritoneal route of administration. Blood samples were centrifuged and the obtained serum was stored at 20' C for analysis. Test compounds were examined along with a reference (positive 10 control) and a vehicle control, with n = 6 animals per group. Glucose was determined by the GOD/POD method from serum. The mean value of duplicate results was calculated. The absolute values of glucose in serum levels were calculated using MS Excel software. The 0-minute base line corrected line graph were plotted using Graphpad prism software (ver 3.0). Area under the Curve (AUC) and Base line corrected area under the 15 curve (BCAUC) were calculated and analyzed by performing One way ANOVA followed by Dunnett's post test using Graphpad prism software (ver 3.0). - Using above experimental protocol, in vivo glucose lowering properties of some of the selected compounds, which showed in vitro EC 50 , in CHO-GLP-1R cAMP assay, in the range of 1-50 nM range were determined. In Table 10, the in vivo glucose 20 lowering potencies (ED 5 o in IPGTT SAM model) of selected four representative compounds (Comp. I, II, III & IV) were given. Table 10: In vivo potencies of compound I to IV (EDo), in IPGTT SAM Model Comp. ED 50 in IPGTT SAM Model (n 6) I 1 jtmole /kg II 500 nM /Kg III 250 nM /kg IV 100 nM /Kg -52- WO 2007/017892 PCT/IN2006/000154 Several compounds of the present invention were screened in vivo, using other animal models, such as ob/ob, db/db and C57 and they showed in vivo efficacy and potency in varying degrees. Utilities: 5 The present invention provides novel GLP-1 peptide mimics, with a preference for mimicking GLP-l, such that the compounds of the present invention have agonist activity for the GLP-1 receptor. Further, many of the GLP peptide mimics of the present invention exhibit increased stability to proteolytic cleavage as compared to GLP-1 native sequences. 10 Accordingly, the compounds of the present invention can be administered to mammals, preferably humans, for the treatment of a variety of conditions and disorders, including, but not limited to, treating or delaying the progression or onset of diabetes (preferably type II, impaired glucose tolerance, insulin resistance and diabetic complications, such as nephropathy, retinopathy, neuropathy and cataracts), 15 hyperglycemia, hyperinsulinemia, hypercholesterolemia, elevated blood levels of free fatty acids or glycerol, hyperlipidemia, hypertriglyceridemia, obesity, wound healing, tissue ischemia, atherosclerosis, hypertension, intestinal diseases (such as necrotizing enteritis, microvillus inclusion disease or celic disease). The compound of the present invention may also be utilized to increase the blood levels of high density lipoprotein 20 (HDL). In addition, the conditions, diseases collectively referenced to as 'Syndrome X' or metabolic syndrome as detailed in Johannsson J., Clin. Endocrinol. Metab., 82, 727 34,1997, may be treated employing the compounds of the invention. The compounds of the present invention may optionally be used in combination with suitable DPP-IV 25 inhibitors for the treatment of some of the above disease states either by administering the compounds sequentially or as a formulation containing the compounds of the present invention along with a suitable DPP-IV inhibitors. No adverse effects were observed for any of the mentioned compounds of invention. The compounds of the present invention showed good glucose serum 30 lowering activity in the experimental animals 'used. These compounds are used for the testing/ prophylaxis of diseases caused by hyperinsulinaemia, hyperglycemia such as NIDDM, metabolic disorders and obesity since such diseases are inter-linked to each other. - 53 -

Claims (14)

1. An isolated polypeptide having a sequence of Formula (I), including its tautomers, solvates and pharmaceutically acceptable salts A-Xr- Sr-Y-S 2 -X 2 -B (I) 5 wherein, A represents -NH-R 1 , wherein R 1 represents hydrogen, groups selected from linear or branched (C-C 15 ) alkyl chain, an amino acid or peptide containing one, two or three natural amino acid residues, R 3 -CO- group, R 3 0-C(O)- group, a sulfonyl group of formula R 3 -SO 2 -, each of these groups may be substituted; R 3 is selected from linear or 10 branched (C-C 10 ) alkyl, (C 3 -C 6 ) cycloalkyl, aryl, heteroaryl, arylalkyl groups, each of these groups may be substituted; B represents -COOR 2 , -CONHR 2 or CH 2 OR 2 , R 2 represents H, groups selected from linear or branched (C-C 10 ) alkyl, aryl groups selected from phenyl, napthyl, indanyl, fluorenyl, biphenyl groups, aralkyl group, wherein the aryl groups are as defined 15 earlier, each of these groups may be substituted; each of Si and S2 may independently be a bond or independently represents a group ' NH-(CH 2 )n-COO-', where, n=1-9; Y represents a bond or -CO-, -(CH 2 )m- (m = 1-3), '0', 'S', -CO-NH-, -CO-NR-, or represents a short peptide containing one or two or three amino acids selected from 20 natural or non-natural amino acids; where R 4 represents H, optionally substituted groups selected from linear or branched (C-C10) alkyl or aryl groups selected from phenyl, napthyl, indanyl, fluorenyl, biphenyl groups; with the proviso that when S-Y S2 represents a bond, X 1 is selected from the following amino acid sequences 25 HAEGTFTSD, HAEGTFTSDV, HAEGTFTSDVS, HAEGTFTSDVSS, HAEGTFTSDVSSY, HAEGTFTSDVSSYL, HAEGTFTSDVSSYLE, HAEGTFTSDVSSYLEG, HAEGTFTSDVSSYLEGQ, HAEGTFTSDVSSYLEGQA, HAEGTFTSDVSSYLEGQAA, HAEGTFTSDVSSYLEGQAAK, HAEGTFTSDVSSYLEGQAAKE, HAEGTFTSDVSSYLEGQAAKEF, 30 HAEGTFTSDVSSYLEGQAAKEFI, with the further option that one or more of these amino acids may be replaced by unnatural amino acids, and X 2 is selected from the following amino acid sequences GPSSGAPPPS or KELEKLL or -54- WO 2007/017892 PCT/IN2006/000154 GPPS or VKGR; and when S-Y-S 2 does not represent a bond X 1 is selected from the following amino acid sequences 5 HA, HAE, HAEG, HAEGT, HAEGTF, HAEGTFT, HAEGTFTS, HAEGTFTSD with the further option that one or more of these amino acids may be replaced by unnatural amino acids; X 2 is selected from GPSSGAPPPS or 10 KELEKLL or GPPS or VKGR or a dipeptide, selected from combination of two amino acids consisting of natural or unnatural amino acids, having a side chain containing an arylalkyl or heterorylalkyl 15 moieties selected from benzyl, napthylmethyl, pyridylmethyl, thienylmethyl, furylmethyl, imidazolylmethyl, isooxazolylmethyl, quinolylmethyl, benzofuranylmethyl, benzothienylmethyl, indolinylmethyl, indolylmethyl, dibenzofuranylmethyl, dibenzothienylmethyl, benzodihydrofuranylmethyl, benzodihydrothienylmethyl, thienopyrimidylmethyl, benzimidazolylmethyl, 20 phenanthrenylmethyl, dihydrophenanthrenylnethyl, fluorenylmethyl, dibenzofuranylmethyl, dibenzothiophenyl methyl groups, where each of these groups may be optionally substituted with (C-C 6 )alkyl, (C-C5)alkoxy, cyano, halo, hydroxy or optionally substituted aryl or heteroaryl groups, with the further provision that such aryl or heteroaryl substituents may further be optionally substituted with (C-C 6 )alkyl, 25 (CI-C 6 )alkoxy, cyano, halo, hydroxy or aryl or heteroaryl groups.

2. A compound as claimed in claim 1 wherein the non-natural amino acids are represented by the general formula (Ha) R 8 R R 7 Re- OH 5 R 5 0 30 (Ia) - 55 - WO 2007/017892 PCT/IN2006/000154 wherein R 5 is selected from H, F, (G 1 -C 5 ) alkyl, the stereochemical configuration at the carbon bearing R 5 may be (R) or (S); R 6 is selected from H or (CI-C 3 ) alkyl; each of R 7 and R 8 is independently selected from H, (C-C 2 ) alkyl or halogen atom, preferably fluorine atom; R 9 represents groups, selected from (C-C 5 ) alkyl, aryl or 5 heteroryl moieties selected from phenyl, napthyl, pyridyl, thienyl, furyl, imidazolyl, isooxazolyl, quinolyl, benzofuranyl, benzothienyl, indolinyl, indolyl, dibenzofuranyl, dibenzothienyl, benzodihydrofuranyl, benzodihydrothienyl, thienopyrimidyl, benzimidazolyl, phenanthrenyl, dihydrophenanthrenyl, fluorenyl, dibenzofuranyl, dibenzothiophenyl groups, where each of these groups may be 10 optionally substituted with (C-C 6 ) alkyl, (C-C 6 ) alkoxy, cyano, halo, hydroxy or optionally substituted aryl or heteroaryl groups, with the further provision that such aryl or heteroaryl substituents may further be optionally substituted with (C C 6 )alkyl, (C-C 6 )alkoxy, cyano, halo, hydroxy or aryl or heteroaryl groups. 15

3. The isolated peptide as claimed in claim 1, wherein the dipeptide representing X 2 is preferably selected from Bip, Bip(2-Me), Bip(2-Et), Bip(2-Ipr), Bip(2-CN), Bip(2' Et-4'-OMe), Bip(4'-fluoro), Bip(4'-Phenyl), 2-(9, 1 0-Dihydro-phenanthrenyl] -Ala, 2-(Phenanthrenyl)-Ala, 4-(2-Naphthyl)-Phe, 4-(1-Naphthyl)-Phe, 2-Fluorenyl-Ala,

4-dibenzofuran-Phe, 4-dibenzothiophene-Phe, 4-(2'-methylphenyl)-3-pyridylalanine 20 groups. 4. The isolated peptide as claimed in claim 1, wherein the substituents are selected from hydroxyl, oxo, halo, thio, nitro, amino, cyano, alkyl, haloalkyl, alkoxy, haloalkoxy, cycloalkyl, aryl, aryloxy, aralkyl, aralkoxy, heteroaryl, heteroaralkyl, 25 heteroaryloxy, heteroaralkoxy, acyl, acyloxy, carboxylic acid and its derivatives selected from esters and amides.

5. The isolated polypeptide of claim 1, wherein the isolated polypeptide is a compound selected from 30 HGEGTFTSD-(CH 2 ) 3 -GPSSGAPPPS HGEGTFTSD-(CH 2 ) 4 -GPSSGAPPPS HGEGTFTSD-(CH 2 ) 5 -GPSSGAPPPS HGEGTFTSD-(CH 2 ) 6 -GPSSGAPPPS HGEGTFTSD-(CH 2 ) 7 -GPSSGAPPPS - 56 - WO 2007/017892 PCT/IN2006/000154 HGEGTFTSD-(CH 2 ) 10 -GPSSGAPPPS HGEGTFTSD-(CH 2 )ii-GPSSGAPPPS HGEGTFTSDLSKQM-(CH 2 ) 3 -GPSS HGEGTFTSDLSKQM-(CH 2 ) 4 -GPSS 5 HGEGTFTSDLSKQM-(CH 2 ) 5 -GPSS HGEGTFTSDLSKQM-(CH 2 ) 6 -GPSS HGEGTFTSDLSKQM-(CH 2 ) 7 -GPSS HGEGTFTSDLSKQM-(CH 2 ) 10 -GPSS HGEGTFTSDLSKQM-(CH2)u -GPSS 10 HGEGTFTSDLSKQME-G-GPSSGAPPPS HGEGTFTSDLSKQME-(CH 2 ) 2 -GPSSGAPPPS HGEGTFTSDLSKQME-(CH 2 ) 3 -GPSSGAPPPS HGEGTFTSDLSKQME-(CH 2 ) 4 -GPSSGAPPPS HGEGTFTSDLSKQME-(CH 2 ) 5 -GPSSGAPPPS 15 HGEGTFTSDLSKQME-(CH 2 ) 6 -GPSSGAPPPS HGEGTFTSDLSKQME-(CH 2 )7-GPSSGAPPPS HGEGTFTSDLSKQME-(CH 2 ) 10 -GPSSGAPPPS HGEGTFTSDLSKQME-(CH 2 )u 1 -GPSSGAPPPS HAEGTFTSD-(CH 2 ) 2 -VKGR 20 HAEGTFTSD-(CH 2 ) 3 -VKGR HAEGTFTSD-(CH 2 ) 4 -VKGR LAEGTFTSD-(CH 2 ) 5 -VKGR HAEGTFTSD-(CH2) 6 -VKGR HAEGTFTSD-(CH 2 ) 10 -VKGR 25 HAibEGTFTSD-(CH 2 )2-VKGR HAibEGTFTSD-(CH 2 ) 3 -VKGR HAibEGTFTSD-(CH 2 ) 4 -VKGR HAibEGTFTSD-(CH 2 ) 5 -VKGR HAibEGTFTSD-(CH 2 ) 6 -VKGR 30 HAibEGTFTSD-(CH 2 )1o-VKGR HGEGTFTSDLSKQMKELEKLL HAEGTFTSDKELEKLL HGEGTFTSDKELEKLL HAibEGTFTSDGKELEKLL -57- WO 2007/017892 PCT/IN2006/000154 HGEGTFTSDGKELEKLL HGEGTFTSDVSKELEKLL HAEGTFTSDVSKELEKLL HAEGTFTSDVSEKELEKLL 5 HAEGTFTSDVSGKELEKLL HAEGTFTSDVSSYLEKELEKLL HAEGTFTSDVSSYLEGKELEKLL HGEGTFTSDVSSYLEGKELEKLL HaEGTFTSDVSSYLEGKELEKLL 10 HAibEGTFTSDVSSYLEGKELEKLL HAEGTFTSDVSSYLEGKELEKLLVKG HAEGTFTSDVSSYLEPKELEKLL HAEGTFTSDVSSYLEGQAAKELEKLL HAEGTFTSDVSSYLEGQAAKEFIKELEKLL 15 HAibEGTFTSDVSSYLEGQAAKEFIKELEKLL HAibEGT-(a-Me)Phe(2-F)-TSDVSSYLEGQAAKEFIKELEKLL Des-amino-HAibEGT-(a-Me)Phe(2-F)-TSDVSSYLEGQAAKEFIKELEKLL HAEGTFTSD-(CH 2 ) 3 -KELEKLL HAEGTFTSD-(CH 2 ) 4 -KELEKLL 20 HAEGTFTSD-(CH 2 ) 5 -KELEKLL HAEGTFTSD-(CH 2 ) 6 -KELEKLL HA-(CH 2 ) 3 -DVSSYLEGQAAKEFIKELEKLL HAib-(CH 2 ) 3 -DVSSYLEGQAAKEFIKELEKLL HAibEGTFTSDVSSYLEGQ-(CH 2 ) 2 -KELEKLL 25 HAibEGTFTSDVSSYLEGQ-(CH 2 ) 3 -KELEKLL HAibEGTFTSDVSSYLE-(CH 2 ) 2 -FIKELEKLL HGEGTFTSD-(CH 2 ) 3 -Bip-Bip HAibEGTFTSD-(CH 2 ) 3 -Bip-Bip HAibEGT-(a-Me)-Phe(2-F)-TSD-(CH2) 3 -Bip-Bip 30 HAEGTFTSD-G-Bip(2-Me)-Bip(2-Me) HAibEGTFTSD-G-Bip(2-Me)-Bip(2-Me) HAibEGT-(a-Me)-Phe(2-F)-TSD-G-Bip(2-Me)-Bip(2-Me) HAEGTFTS-G-Bip(2-Me)-Bip(2-Me) HAibEGTFTS-G-Bip(2-Me)-Bip(2-Me) -58- WO 2007/017892 PCT/1N2006/000154 HAibEGT-(c-Me)-Phe(2-F)-TS-G-Bip(2-Me)-Bip(2-Me) IIAEGT'FTS-(CH 2 ) 2 -Bip(2-Me)-Bip(2-Me) HlAibEGTFTS-(CH 2 ) 2 -Bip(2-Me)-Bip(2-Me) HAibEGT-(a-Me)-Phe(2-F)-TS-(CH 2 ) 2 -Bip(2-Me)-Bip(2-Me) 5 HAEGTFT-(CLL 2 ) 2 -Bip(2-Me)-Bip(2-Me) HAibEGTFT-(C11 2 ) 2 -Bip(2-Me)-Bip(2-Me) HAibEGT-(ct-Me)-Phe(2-F)-T-(CH 2 ) 2 -Bip(2-Me)-Bip(2-Me) HAEGTF-(C11 2 ) 2 -Bip(2-Me)-Bip(2-Me) IIAibEGTF-(CH 2 ) 2 -Bip(2-Me)-Bip(2-Me) 10 HAibEGT-(c&Me)-Phe(2-F)-(CH 2 ) 2 -Bip(2-Me)-Bip(2-Me) HAEGT-(C11 2 ) 2 -Bip(2-Me)-Bip(2-Me) HAibEGT-(CH 2 ) 2 -Bip(2-Me)-Bip(2-Me) IIAEG-(CLI 2 ) 2 -Bip(2-Me)-Bip(2-Me) HAibEG-(CH 2 ) 2 -B ip(2-Me)-Bip(2-Me) 15 HAEGTFTSD-(CFI 2 ) 2 -Bip(2-Me)-Bip(2-Me) FIAibEGTFTSD-(CH 2 ) 2 -Bip(2-Me)-Bip(2-Me) HAibEGT-(ox-Me)-Phe(2-IF)-TSD-(CH 2 ) 2 -Bip(2-Me)-Bip(2-Me) HAEGTFTSD-G-Bip-Bip(2-Me) T{AibEGTFTSD-G-Bip-Bip(2-Me) 20 FIAibEGT-(cic-Me)-Phe(2-F)-TSD-G-Bip-Bip(2-Me) JIAEGTFTSD-G-Bip(2-Me)-Bip HAibEGTFTSD-G-Bip(2-Me)-Bip HAibEGT-(cc-Me)-Phe(2-F)-TSD-G-Bip(2-Me)-Bip JIAEGTFTSD-G-Bip-Bip HAibEGTFTSD-G-Bip-Bip 25 FIAibEGT-(ca-Me)-Phe(2-F)-TSD-G-Bip-Bip HAEGTFTSD-G-Bip-Bip(2-Et) HAibEGTFTSD-G-Bip-Bip(2-Et) IIAibEGT-(cc-Me)-Phe(2-F)-TSD-G-Bip-Bip(2-Et) T{AEGTFTSD-G-Bip(2-Et)-Bip(2-Et) 30 HAibEGTFTSD-G-Bip(2-Et)-Bip(2-Et) HAibEGT-(cic-Me)-Phe(2-F)-TSD-G-Bip(2-Et)-Bip(2-Et) L{AEGTFTSD-G-Bip(2-Et)-Bip HAibEGTFTSD-G-Bip(2-Et)-Bip -59- WO 2007/017892 PCT/1N2006/000154 HAibEGT-(a-Me)-Phe(2-F)-TSD-G-Bip(2-Et)-Bip LIAEGTFTSD-G-Bip(2-Et)-Bip(2-.Me) HAibEGTFTSD-G-Bip(2-.Et)-Bip(2-.Me) HAibEGT-(a-.Me)-Phe(2F)SDGBip(2-Et)-Bip(2-Me) 5 HAEGTFTSD-G-Bip(2-Me)Bip(2-Et) HAibEGTFTSD-G-Bip(2-Me)-Bip(2-Et) JIAibEGT-(a-Me)-Phe(2-F)TSD-G-Bip(2-Me)-Bip(2.Et) HGEGTFTSD-G-Bip(2-Me)..Bip(2-Me) HGEGT-(o-Me)-Phe(2-F)-TSD-GBip(2-Me)-Bip(2-Me) 10 HGEGTFTSD-G-Bip(2-Et)-.Bip(2-Et) HGEGTFTSD-(CH 2 ) 3 -Bip(2-Me)-.Bip(2..Me) JIGEGT-(c -Me)-Phe(2-F)-TSD-(CH 2 ) 3 Bip(2-Me)-Bip(2-Me) H 6 EGTFTSD-(CH 2 ) 4 -Bip(2Me)-Bip(2-Me) 15 HGEGT-(cc-Me)-Phe(2-F)-TSD..(CH 2 ) 4 -Bip(2-Me)-Bip(2-Me) HGEGTFTSD-(CH 2 ) 5 -Bip(2-Me)-Bip(2.Me) HGG-aM)Pe2F-S-(H)-i(-e-i(-e HGEGTFTSD-(C{ 2 ) 6 -Bip(2-Me)-Bip(2-.Me) HGG-c-e-h(-)-S-C26Bp2M)Bip(2-Me) 20 HGEGTFTSD-(C1 2 )o-Bip(2.Me)-Bip(2-.Me) JIGEGT-(a-Me)-Phe(2-F)TSD-(CH 2 )lo 0 Bip(2Me).Bip(2-Me) HGTE TFTSD-(CH1 2 )3-Bip(2-.Et)-Bip(2.Et) 25 HGEGT-(oa-Me)-Phe(2-.Fy.TSD.(Cj 2 )-Bip(2Et)Bip(2-Et) HGEGTFTSD-(CH 2 )4-Bip(2-Et)-Bip(2-Et) 25 HGEGTk-(a-Me)-Phe(2-P}..TSD-(CH 2 )4-.Bip(2-Et)-.B ip(2-Et) HGEGTFTSD-(CH 2 )5-Bip(2-Et)-Bip(2.Et) HGEGT-(o-Me)-Phe(2-F)TSD-CH 2 )5Bip(2Et)-Bip(2-Et) 30 HGEGTFTSD-(CH 2 )6-.Bip(2Et)Bip(2Et) HGEGT-(ca-Me)-Phe(2-F)-TSD-(CH 2 )6 -Bip(2-Et)-Bip(2-Et) 30HGEGTFTSD-(C1 2 ) 1 -Bip(2-Et)-Bip(2-Et) HGGTTS-(H2. -ipE)-B(2.. Et)B p2 t -60- WO 2007/017892 PCT/1N2006/000154 I4GEGTFTS-(C11 2 ) 3 -Bip(2-Me)-Bip(2-Me) HGEGT-(a-Me)-Phe(2-F)-TS-(CH 2 ) 3 -Bip(2-Me)Bip(2-Me) HGEGTFTS-(CH 2 ) 4 -Bip(2-Me)-Bip(2..Me) HGEGT-(cx-Me)-Phe(2-F)-TS-(CH 2 ) 4 -Bip(2-Me)Bip(2-Me) 5 HGEGTFTS-(CH 2 )5-Bip(2-Me)-Bip(2-Me) HGEGT-(ox-Me)-Phe(2-F)-TS-(CH- 2 ) 5 -Bip(2..Me)-Bip(2-.Me) HGEGTFTS-(C11 2 ) 6 -Bip(2-Me)-Bip(2-Me) HGEGT-(ca-Me)-Phe(2-F)-TS-(CH 2 ) 6 -Bip(2Me)Bip(2-Me) JIGEGTFTS-(CH 2 )lo-Bip(2-Me)-Bip(2-Me) 10 HGEGT-(oc-Me)-Phe(2-F)-TS-(CH 2 )io-Bip(2-Mey.-Bip(2-Me) HGEGTTS-(CH 2 ) 1 i-Bip(2-Me)-Bip(2-Me) HGEGT-(a-Me)-Phe(2-F)-TS-(CH 2 )1iBip(2-Me)-.Bip(2-Me) HGEGTFTS-(CH 2 ) 3 -Bip(2-Et)-Bip(2-Et) HGEGT-(cx-Me)-Phe(2-F)-TS-(CH 2 ) 3 -Bip(2-Et)-Bip(2-.Et) 15 HGEGT-(ox-Me)-Phe(2-F)-TS-(CFL 2 ) 4 .- Bip(2-Et).Bip(2.Et) HGEGTFTS-(C11 2 ) 4 -Bip(2-Et)-Bip(2-Et) HGEGTFTS-(CJJ 2 )5-Bip(2-Et)-Bip(2-Et) HGEGT-(a-Me)-Phe(2-F)-TS-(CH 2 ) 5 -Bip(2Et)-Bip(2-.Et) 20 HGEGTFTS-(C11 2 ) 6 -Bip(2-Et)-Bip(2-Et) HGEGT-(ca-Me)-Phe(2-F)-TS-(CH 2 ) 6 -Bip(2-Et).Bip(2.Et) H-GEGTFTS-(CI11 2 )lo-Bip(2-Et)-Bip(2-Et) HGEGT-(a-Me)-Phe(2-F)-TS-(CH 2 )lo-Bip(2-Et)-Bip(2-.Et) HGEGTFTS-(CH 2 ) 11 -Bip(2-Et)-Bip(2-Et) 25 HGEGT-(c-Me)-Phe(2-)-TS-(CH 2 ) 11 -Bip(2-Et)-Bip(2-Et) JJGEGTFTS-(CH 2 ) 2 -Bip(2-Me)-Bip(2-Me) HGEGT-(c-Me)-Phe(2-F)-TS-(CH 2 ) 2 -Bip(2.Me).Bip(2-Me) HGEGTFTS-(CH 2 ) 2 -Bip(2-Et)-Bip(2-Et) HGEGT-(c-Me)-Phe(2-F)-TS-(CH 2 ) 2 -Bip(2-Et)-Bip(2-Et) 30 JIAEGTFTS-(CH 2 ) 2 -Bip(2-Et)-Bip(2-Et) HAibEGTFTS-(CH 2 ) 2 -Bip(2-Et)-Bip(2-Et) JIAibEGT-(c&Me)-Phe(2-F)-TS-(d11 2 ) 2 Bip(2-Et)..Bip(2-Et) FIGEGTFTSD-(CH 2 ) 2 -Bip(2-Et)-Bip(2- Et) -61- WO 2007/017892 PCT/1N2006/000154 HGEGT-(cx-Me)-Phe(2-F)-TSD-(C 2 ) 2 -. Bip(2-Et).Bip(2.Et) IIAEGTFTSD-(CH 2 ) 2 -Bip(2-Et)-Bip(2-Et) HAibEGTFTSD-(CH 2 ) 2 -Bip(2-Et)-Bip(2-Et) 5 AiEGT-(GcM)Pe2)TD(H 2 ) 2 -Bip(2-Me)-Bip(2-Et) 5 HAEGTF-(CH 2 ) 2 -Bip(2-Me)-Bip(2-Et) HAibEGT-(a-Me)-Phe(2-F)(CH 2 ) 2 -Bip(2-.Me)..Bip(2-Et) HAEGTFTSD-G-TrPh-TrPh IAibEGTFTSD-G-TrPh-TrPh 10 HAibEGT-(a-Me)-Phe(2-F)-TSD-GTrPhTrPh HAibEGT-(cx-Me)-Phe(2-F)-(CH 2 ) 2 -.TrPhTrPh HAibEG-(C11 2 ) 2 -TrPh-TrPh HAibE-(CH 2 ) 2 -TrPh-TrPh H-Aib-(CH 2 ) 3 -TrPh-TrPh 15 HAEGTFTSD-G-Nap-Nap HAibEGTFTSD-G-Nap-Nap HAibEGT-(w.-Me)-Phe(2-F)-TSD-G..Nap..Nap JIAEGTFTSD-G-Bip(2-F)-Bip(2-F) FIAibEGTFTSD-G-Bip(2-F)-Bip(2-F) 20 AibEGT-(ca-Me)-Phe(2-F)-TSD-GBip(2F)-Bip(2-F) HAEGTFTSD-G-Bip(2' -Et-4'-OMe)-4-(2'-Me-Ph)-3-Pyr-Ala HAibEGTFTSD-G-Bip(2 '-Et-4'-OMe)-4-(2'-Me-.Ph)-3-Pyr-Ala H-AibEGT-(ca-Me)-Phe(2-F)-TSD-G-Bip(2 '-Et-4 '-OMe)-4-(2' -Me-Ph)-3 -Pyr-Ala HAEGTFTSD-(CLI 2 ) 2 -Bip(2 '-Et-4' -OMe)-4-(2'-Me-Ph)-3-Pyr-Ala 25 HAibEGTFTSD-(C{ 2 ) 2 -Bip(2 '-Et-4'-OMe)-4-(2' -Me-Ph)-3-Pyr-Ala HAibEGT-(cc-Me)-Phe(2-F)-TSD-(CH 2 ) 2 -. Bip(2'..Et-4'.OMe)..4-(2 '-Me-Ph)-3-Pyr Ala HAEGTFTS-(CH 2 ) 2 -Bip(2 '-Et-4' -OMe)-4-(2'-Me-Ph)-3-Pyr-Ala HAibEGTFTS-(CH 2 ) 2 -Blp(2' -Et-4 '-OMe)-4-(2'-Me-Ph)-3-Pyr-Ala 30 HAibEGT-(cx-Me)-Phe(2-F)-TS-(CH 2 ) 2 -Bip(2'..Et.4'-OMe).4{2 '-Me-Ph)-3-Pyr Ala HAEGTFT-(CFI 2 ) 2 -Bip(2' -Et-4 '-OMe)-4-(2'-Me-Ph)-3-Pyr-Ala HAibEGTFT-(CH 2 ) 2 -Bip(2'-Et-4' -OMe)-4-(2 '-Me-Ph)-3-Pyr-Ala - -62- WO 2007/017892 PCT/1N2006/000154 HAibEGT-(ca-Me)-Phe(2-F)-T-(CH 2 ) 2 Bip(2'Et4'OMe).4(2 '-Me-Ph)-3-Pyr-Ala HAEGTF-(C1 2 ) 2 -Bip(2 '-Et-4'-OMe)-4-(2 '-Me-Ph)-3-Pyr-Ala HAibEGTF-(CH 2 ) 2 -Bip(2'.Et-4'-OMe)-4-(2 '-Me-Ph)-3-Pyr-Ala HAibEGT-(ca-Me)-Phe(2-F)-(CH 2 ) 2 -Bip(2 '-Et-4'-OMe)-4-(2'-Me-Ph)-3-Pyr-Ala 5 JIAEGT-(CH 2 ) 2 -Bip(2 '-Et-4'-OMe)-4-(2'-Me-Ph)-3-Pyr-Ala JJAibEGT-(CH 2 ) 2 -Bip(2' -Et-4' -OMe)-4-(2'-.Me-Ph)-3-Pyr-Ala HAEG-(CH 2 ) 2 -Bip(2 '-Et-4'-OMe)-4-(2'-Me-Ph)-3-Pyr-Ala H-AibEG-(CH 2 ) 2 -Bip(2 '-Et-4 '-OMe)-4-(2'-Me-Ph)-3-Pyr-Ala HAEG-(CH 2 ) 3 -Bip(2' -Et-4'-OMe)-4-(2'-Me-Ph)-3-Pyr-Ala 10 H-AibEG-(CH 2 ) 3 -Bip(2'-Et-4' -OMe)-4-(2 '-Me-Ph)-3-Pyr-Ala HAEGT-(CH 2 ) 2 -Bip(2-Me)-Bip(2-Me) HGEGT-(CH 2 ) 3 -Bip(2-Me)-Bip(2-Me) HGEGT-(CH 2 ) 4 -Bip(2-Me)-Bip(2-Me) HGEGT-(CH 2 )5-Bip(2..Me)-Bip(2-Me) 15 HGEGT-(CH 2 ) 6 -Bip(2-Me)-Bip(2-Me) ,HAEGT-(CH 2 ) 2 -Bip(2-Me)-DBip(2-Me) HAEGT-(CH 2 ) 2 -DBip(2-Me)-Bip(2-Me) HaEGT-(CH 2 ) 2 -Bip(2-Me)-Bip(2-Me) HGEG-(C11 2 ) 3 -Bip(2-Me)-Bip(2-Me) 20 HAEG-(CLI 2 ) 3 -Bip(2-Me)-Bip(2-Me) HGEG-(C11 2 ) 4 -Bip(2-Me)-Bip(2-Me) HGEG-(CFI 2 )5-Bip(2-Me)-Bip(2-Me) HGEG-(CH 2 ) 6 -Bip(2--Me)-Bip(2-Me) HAEG-(CH 2 ) 3 -Bip(2-Et)-Bip(2-Me) 25 HAEG-(CH2) 3 -Bip(2-Mey.-DBip(2-Me) {A-EG-(CH 2 ) 4 -Bip(2-Me)-DBip(2-Me) HAEG-(CH 2 )5-Bip(2-Me)-DBip(2.Me) FIGEG-(CH 2 )5-DBip(2-Me)-Bip(2-Me) HAE-(CH 2 ) 3 -Bip(2-Me)-Bip(2-Me) 30 I{AE-(CH 2 ) 3 -Bip(2-Me)-DBip(2-Me) T{AE-(CH 2 ) 2 -D-Bip(2-Me)-Bip(2-Me) HAE-(CH5 2 ) 3 -D-Bip(2-Me)-Bip(2-Me) LAE-(CI{ 2 ) 4 -D-Bip(2-Me)-Bip(2-Me) HAE-(GH 2 ) 4 -Bip(2-Me)-DBip(2-Me) - 63 - WO 2007/017892 PCT/1N2006/000154 HAE-(CH 2 ) 5 -D-Bip(2-Me)-Bip(2-Me) HAE-(CH 2 ) 3 -Bip(2-Et)-Bip(2-Me) HAE-(CH 2 ) 2 -Bip(2-Me)-Bip(2-Me) H-(CHr 2 ) 3 -Bip(2-Me)-Bip(2-Me) 5 H-(C112) 4 -Bip(2-Me)-Bip(2-Me) H-(CH 2 ) 5 -Bip(2-Me)-Bip(2-Me) H-(CH 2 ) 3 -Bip(2-Et)-Bip(2-Me) H-(C11 2 ) 4 -Bip(2-Et)-Bip(2-Me) H-(CTI 2 )5-Bip(2-Et)-Bip(2-Me) 10 TI-(CH 2 ) 6 -Bip(2-Et)-Bip(2-Me) H-(CFI 2 )io-Bip(2-Et)-Bip(2-Me) H-(CH2)5-Bip(2-Me)-DBip(2-Me) H-(C112)5-DBip(2-Me)-Bip(2-Me) H.-(CH 2 )s-DBip(2-Me)-DBip(2-Me) 15 ]JG-(CH2) 3 -Bip(2-Me)-Bip(2-Me) HG-(CH 2 ) 4 -Bip(2-Me)-Bip(2-Me) NIG-(CH 2 ) 3 -Bip(2-Et)-Bip(2-Me) HG-(CH 2 ) 4 -Bip(2-Et)-Bip(2-Me) HG-(CH 2 ) 3 -Bip(2-Et)-DBip(2-Me) 20 HG-(CH 2 ) 3 -Bip(2-Me)-DBip(2-Me) FA-(CH 2 ) 3 -DBip(2-Me)-Bip(2-Et) FA-(CH 2 ) 3 -DBip-Dbip Ha-(CH 2 ) 3 -Bip(2-Me)-Bip(2-Me) Ha-(CH 2 ) 4 -Bip(2-Me)-Bip(2-Me) 25 Ha-(CH 2 ) 5 -Bip(2-Me)-Bip(2-Me) Ha-(CH 2 ) 3 -Bip(2-Et)-Bip(2-Me) Ha-(CJJ2) 3 -Bip(2-Et)-DBip(2-Me) JHa-(CH 2 ) 3 -Bip(2-Me)-DBip(2-Me) Ha-(GH 2 ) 3 -Bip(2-Et)-DBip(2-Et) 30 Ha-(CH 2 ) 3 -Bip(2-Me)-Bip Ha-(CT{ 2 ) 3 -(N(Me))-DBip(2-Me)-Bip(2-Et) Ha-(CH 2 ) 3 -(N(Me))-Bip(2-Et)-Bip(2-Me) Ha-(CH 2 ) 3 -(N(Me))-DBip-Bip(2-Et) FHa-(CH 2 ) 3 -DBip(2-Me)-Bip(2-Et) -64 - WO 2007/017892 PCT/1N2006/000154 HA-(CH 2 ) 3 -Bip(2-Me)-Bip(2-Me) HA-(CH 2 ) 4 -Bip(2-Me)-Bip(2-Me) HA-(CH 2 ) 5 -Bip(2-Me)-Bip(2-Me) HA-(CH 2 ) 6 -Bip(2-Me)-Bip(2-Me) 5 I{A-(C11 2 )io-Bip(2-Me)-Bip(2-Me) HA-(CH 2 ) 1 i-Bip(2-Me)-Bip(2-Me) HA-(CH 2 ) 3 -Bip(2-Et)-Bip(2-Me) HA-(CH 2 ) 3 -Bip(2-Et)-DBip(2-Et) HA-(CFI 2 ) 3 -DBip(2-Me)-DBip(2-Me) 10 LLA-(GH 2 ) 3 -DBip(2-Me)-Bip(2-Me) HA-(GH 2 ) 3 -Bip(2-Me)-DBip(2-Me) HA-(CJI 2 ) 3 -Bip(2-Jpr)-Bip(2-Ipr) HIA-(CH 2 ). 3 -Bip(2-Ipr)-Bip(2-Me) HA-(C11 2 ) 3 -Bip(2-Me)-Bip(2-Ipr) 15 HA-(CH 2 ) 4 -Bip(2-Et)-Bip(2-Me) H-A-(CH 2 ) 3 -Bip(2-Me)-DBip(2-Et) HA-(GTI 2 ) 2 -Bip(2-Et)-Bip(2-Me) HA-(CJJ 2 ) 5 -Bip(2-Et)-Bip(2-Me) H-A-(CH 2 ) 6 -Bip(2-Et)-Bip(2-Me) 20 HA-(CH 2 ) 2 -Bip(2-Me)-Bip(2-Me) JIA-(CH 2 )3-DBip(2-Et)-DBip(2-Me) HA-(C11 2 ) 3 -DBip(2-Et)-Bip(2-Me) H-A-(CH- 2 ) 2 -Bip(2-Me)-DBip(2-Me) JIA-(CH 2 ) 3 -Bip(2-Et)-Bip(2-Et) 25 HA-(C11 2 ) 3 -DBip(2-Et)-DBip(2-Et) HA-(CFI 2 ) 3 -DBip(2-Et)-Bip(2-Et) JIA-(G14 2 ) 3 -DBip(2-Me)-DBip(2-Et) HA-(CFI 2 ) 3 -Bip(2-Me)-Bip(2-Et) HA-(CH 2 ) 3 -DBip(2-Me)-Bip(2-Et) 30 HA-(CH 2 ) 3 -Bip-Bip HA-(CH 2 ) 3 -Bip-D-Bip ,HA-(CH 2 ) 3 -DBip-D-Bip i4A-(GH 2 ) 3 -DBip-Bip HA7-{C1 2 ) 3 -Bip-Bip(2-Me) - 65 - WO 2007/017892 PCT/1N2006/000154 JIA-(CH 2 ) 3 -Bip(2-Me)-Bip HA-(CH 2 ) 3 -Bip(2-Et).-Bip IIA-(CH 2 ) 3 -Bip-Bip(2-Et) HA-(CH 2 ) 3 -Bip(2-Ipr)-DBip(2-Ipr) 5 HA-(CH 2 ) 3 -DBip(2-Ipr)-Bip(2-Ipr) HA-(CH 2 ) 3 -DBip(2-Ipr)-DBip(2-Jpr) HA-(CH 2 ) 3 -Bip(2-Me)-Bip(2-CN) HA-(CH 2 ) 3 -Bip-Bip(2-CN) HA-(CH 2 ) 3 -Bip(2-Et)-Bip(2-CN) 10 HA-(CH 2 ) 3 -Bip(2-Ipr)-Bip(2-cN) HA-(CH 2 ) 3 -Bip(2-CN)-Bip(2-Me) HA-(CH 2 ) 3 -Bip(2-CN)-Bip HA-(CH 2 ) 3 -BiP(2-CN)-Bip(2-Et) HA-(CH 2 )3-Bip(2-CN)-Bip(2-Ipr) 15 FIA-(CH 2 ) 3 -BiP(2-CN)-Bip(2-CN) HA-(CH 2 ) 2 -F-(CH 2 ) 2 -Bip(2-Et)-DBip(2-Et) JIA-(CH 2 ) 2 -F-(CH 2 ) 2 -Bip(2-Et)-DBip(2-Me) H-A-(CH 2 ) 5 -Bip(2-Me)-DBip HA-(CH 2 ) 3 -Bip(2-Me)-DBip-R 20 LIA-(CH 2 )-DIip(2-Me)-DBip HA-(CH 2 ) 5 -Bip(2-Me)-DBip(2-Me) HA-(CH 2 )5-DBip(2-Me)-Bip(2-Me) HA-(CH 2 ) 4 -D(Bip)-Bip(2-Et) HA-(CH 2 ) 5 -D(Bip)-Bip(2-Et) 25 HA-(CH 2 ) 4 -Bip(2-Me)-DBip(2-Me) TIA-(CH 2 ) 5 -Bip(2-Me)-DBip(2-Me) HA-(CH 2 ) 3 -(N(Me))-DBip-Bip(2-Ei) HA-(CH 2 ) 4 -DBip(2-Me)-Bip(2-Et) HA-(CH 2 )5-DBip(2-Me)-Bip(2-Et) 30 H-A-(CH 2 ) 3 -(N(Me))-DBip(2-Me)-Bip(2-Et) HA-(CH 2 ) 4 -Bip(2-Me)-DBip RA-(CH 2 ) 5 -Bip(2-Me)-DBip HA-(CH 2 ) 3 -(N(Me))-Bip(2-Et)-Bip(2-Me) HA-(N(Me))-(CH 2 ) 3 -DBip(2-Me)-Bip(2-Et) - 66 - WO 2007/017892 PCT/1N2006/000154 IIA-{N(Me))-(CH 2 ) 3 -DBip-Bip(2-Et) HA-(N(Me))-(CH 2 ) 3 -Bip(2-Et)-Bip(2-Me) HA-(N(Me))-(G11 2 ) 3 -Bip(2-Me)-DBip HAE-(CH 2 ) 2 -F-(CH 2 ) 2 -Bip(2-Et)-DBip(2.Et) 5 LIAE-(C112)2-F-(CH 2 ) 2 -Bip(2-Et)-DBip(2..Me)

6. The isolated polypeptide of claim 1 wherein the isolated polypeptide is a compound selected from 10 HA-(CH 2 ) 2 -Bip(2'-Et-4 '-OMe)-4-(2 '-Me-Ph)-3 -Pyr-Ala-N- 2 H-Aib-(CH 2 ) 2 -Bip(2 '-Et-4'-OMe)-4-(2 '-Me-Ph)-3 -Pyr-Ala-NH 2 IHa-(CH 2 ) 2 -Bip(2'-Et-4 '-OMe)-4-(2'-Me-Ph)-3-Pyr-Ala-N1 2 H-(N(Me))A-(C11 2 ) 2 -Bip(2'-Et-4' -OMe)-4-(2 '-Me-Ph)-3-Pyr-Ala-N{ 2 H-(N(M\e))A-(N(Me))-(CH 2 ) 2 -Bip(2 '-Et-4'-OMe)-4-(2'-Me-Ph)-3-Pyr.Ala-N 2 15 H-(N(Me))Aib-(N(Me))-(C11 2 ) 2 -Bip(2'Et-4'-OMe)-4-(2'-Me-Ph)-3 -Pyr-Ala-NH 2 H-(N(Me))A-(N(Me))-(CH 2 ) 2 N(Me))Bip(2'E4'..oMe)-4-(2 '-Me-Ph)-3 -Pyr Ala-NH 2 H-(N(Me))Aib-(N(Me))(CH 2 ) 2 (Me))Bip(2'Et4'OMe)4.(2'MePh)3-Pyr Ala-NH 2 20 H-vN(e))A-(N(Me))-(CH 2 ) 2 -(N(Me))Bip(2'-Et-4'-OMe)-(N(Me))-4-(2'-Me-Ph) 3-Pyr-Ala-N11 2 H-(N(Me))Aib-(N(Me))-(CH- 2 ) 2 -(N(Me))-Bip(2 '-Et-4' -OMe)-(N(M~e))-4-(2' -Me Ph)-3-Pyr-Ala-NH 2 25 (2'-Me-Ph)-3 -Pyr-Ala-NH 2 Des-amino-JIN(e)Aib-Ab(N(Me))CH 2 ) 2 Ie))Bip(2'-Et-4'-OMe,)-(N(Me)) 4-(2 '-Me-Ph)-3-Pyr-Ala-NH 2 3-Pyr-Ala-NJI-(C1 2 ) 6 -CH 3 30 H-(N(Me))Aib-(N(Me))(CH 2 ) 2 (N(Me))Bip(2'Et-4'.OMe)-q IvJe))4(21-Me Ph)-3-Pyr-Ala-NH-(CI 2 ) 6 -CH 3 H-((Me))A-(N(Me))-(CH 2 ) 2 -(N(Me))Bip(2'Et-4'-OMe)-(N(Me))-4-(2'-Me-Ph) 3-Pyr-Ala-NH-(11 2 ) 10 -CJ{ 3 - 67 - WO 2007/017892 PCT/1N2006/000154 H-(N(Me))Aib-(N(Me))-(CH 2 ) 2 -(N(Me))Bip(2'Et4'OMe)-{N(Me))-4{2 '-Me Ph)-3-Pyr-Ala-NH-(GH 2 ) 10 -CH 3 CH-C26N-NM)A((e)(H)2((e)Bp2-t4-~)((e) 4-(2 '-Me-Ph)-3-Pyr-Ala-NH-(C1 2 ) 6 -CH 3 5 CH3-(CH2)6-NH-(NMe))Aib-(N(Me))-(CH 2 ) 2 -{N(M\e))>Bip(2'.Et.4' -OMe) (N(Me))-4-(2 '-Me-Ph)-3-Pyr-Ala-N{-(C{ 2 ) 6 -CH- 3 C (e)-- '- Me )-3 rA-NIIe)-(CH 2 )2-cH 3 ))BP2'E-'-~) 10 (N(M\e))-4-(2 '-Me-Ph)-3-Pyr-Ala-N-H-(CH 2 ) 6 -CH 3 H-(CH 2 ) 3 -Bip(2' -Et-4'-O N(Me)-4-(2)2'-Me-Ph)-3i-Pyr-Ala-NIHe) 10a-(C11)-Bp2t4Oe)-4-(2' -Me-Ph)-3 -Pyr-Ala-N11 2 H)6CH H-N)A-(C LI 2 ) 3 -Bip(2' -Et-4' -OMe)-4-(2 '-Me-Ph)-3-Pyr-Ala-NH 2 15 H-(N(Me))A-N)-(CH 2 )-Bip(2'-Et-4'.OMe) 4..(2 '-Me-Ph)-3-Pyr-Aa-N 11 2 15H-(N(Me))Ai-(N(Me))-(CH 2 ) 3 -Bip(2'.Et4 '-OMe)-4-(2'-Me-Ph)-3 -Pyr-Aa-NH 2 H-(N(Me))Ai-(N(e))-(CH 2 ) 3 (N)-Bip(2 '-Et-4'-OMe)-4-(2'-Me-Ph)-3-Pyr--H Ala-NH 2 H-(N(M\e))Aib-((Me))-(CH 2 ) 3 (N(Me))Bip(2'Et4'OMe)42'-Me.Ph)3-Pyr 20 Ala-NH 2 H-(l (Me))A-(N(Me))-(CH 2 ) 3 -(N(Me))-B ip(2'-Et-4'-OMe)-(N(Me))-4-{2 '-Me-Ph) 3-Pyr-Ala-N- 2 H-(NG\4e))Aib-(N(Me))-(CH 2 ) 3 -(N(Me))-Bip(2 '-Et-4'-ome)-(N(Me))-4-(2 '-Me Ph)-3 -Pyr-Ala-NH 2 25 Des-arnino-H-(N(Me))A(N(Me))(CL 2 ) 3 {NMe)Bip(2'Et4'-Oe).(N(Me))-4 (2'-Me-Ph)-3-Pyr-Ala-NH 2 Des-a mino-H-(N(Me))Aib(N(Me))(CH 2 ) 3 (N(Me))Bip(2'Et-4'OMe)-N(Me)). 4-(2'-Me-Ph)-3-Pyr-Ala-NH 2 30 3 -Pyr-Ala-NH-(CH 2 ) 6 -C- 3 L-(N(Me))Aib-(N(e))-(CH 2 )-(N(Me))-Bip(2'Et4'OMe)(N(Me))-4..2'-Me Ph)-3 -Pyr-Ala-NTJ-(CH 2 ) 6 -CH 3 H-(N(Mle))A-(N(Me))-(CH 2 ) 3 -(N(Me))-Bip(2'Et4'-OMe){1(vMe))4(2 '-Me-Ph) 3-Pyr-Ala-NI-(CH 2 ) 10 -d11 3 - 68 - WO 2007/017892 PCT/1N2006/000154 L-(N(Me))Aib-(N(Me))-(CH 2 ) 3 -(N(Me))-Bip(2'E4'O~e)(e))4-2'-Me Ph)-3 -Pyr-Ala-NH-(CH 2 ) 10 -CH 3 CH3-(CL2)6-NH-(Me))A-(N(Me))-(CH 2 ) 3 (N(Me))Bip(2'Et4'-O1e).(Me)) 4-(2 '-Me-Ph)-3-Pyr-Ala-NH-(CH 2 ) 6 -CH 3 5 CH3-(CH2)6-NH-H-(N(Mle))Aib(N(Me))-(CH 2 ) 3 ((Me)>Bip(2'-Et.4'-OMe) (N(Me))-4-(2 '-Me-Ph)-3-Pyr-Ala-NH-(CH 2 ) 6 -CH 3 (NMe--(C 2 '-N-e-h()-3P Al-NH14-(C 2 )-H 3 ))Bp2'E-'-~ 10 (N(Me))-4-(2 '-Me-Ph)-3-Pyr-Ala-NH-(CH 2 ) 6 -CH 3 H-C2l-HH((e)i-NM)-(CH2)-2)Me)-Bip(2'-Et-4'-OMe)-4-2-eP)3-y-l-H 10Ai-(C 2 ) -BpEt4O)-4-(2 '-Me-Ph)-3 -Pyr-Ala-N11 2 H)6CH -A-(CH2)4-Bip(2'-Et4'-OMe)-4-(2'-MePh)3-Pyr-Ala-NH 2 H-(N(e)-(C 2 ) 4 -Bip(2'-Et-4' -OMe)-4-(2 '-Me-Ph)-3-Pyr-Ala-N - 2 15 H-(N(Me))A-(N(Me))-(CH 2 ) 4 -Bi(2'-e-Ph'--Py-e)4( 2'phpy.Aa.H H-(N(Me))A-M)-(CH 2 ) 4 -Bip(2 '-Et-4'-OMe)-4-(2' -Me-Ph)-3-Pyr-Ala-N 11 2 15H-(N(Me))A-(N(Me))-(CH 2 ) 4 (N)-Bip(2' -Et-4' -OMe)-4-(2'-Me-Ph)-3-Pyr-H H-NM)Ab((e)(H)-i('E-'O e--2-eP)3PrAla-NH 2 H-(N(Me))Ai-(N(Me))-(CH 2 ) 4 -(N(Me))-Bip(2 '-Et-4'-OMe)-4-(2'-Me-Ph)-3-Pyr 20Ala-NH 2 20PAla-N 1 2 H-(N(Me))Ai-(N (Me))-(CH 2 ) 4 -(N (Me))-B ip(2'-Et-4'-OMe)-(N (Me))-4-(2 '-Me-) P3 -Pyr-Ala-N1 2 ('ePh)-3-Pyr-Ala-NH 2 25 Des-amino-J-(N(Me))Ab(N(Me))(CH 2 ) 4 (Ie))Bip(2'-Et-4'OMe).{N(Me))-4 4(2' -Me-Ph)-3-Pyr-Aa-NH 2 H-(N(Me))A-(N(Me))-(CH 2 ) 4 ((Me))Bip(2'Et-4'-OMe)-(N(Me))-4-(2 '-Me-Ph) 30 3-Pyr-Ala-NH-(GH 2 ) 6 -CH 3 H-(N(Me))Aib-(N(Me))-(CH 2 ) 4 (N(Me))-Bip(2 '-Et-4'-OMe)-(N(Me))-4-(2 '-Me Ph)-3-Pyr-Ala-NII-(CH 2 ) 6 -CH 3 3-Pyr-Ala-N{.{CH 2 ) 10 ..C 3 - 69 - WO 2007/017892 PCT/1N2006/000154 H-(N(Me))Aib-(N(Me))-(CH 2 ) 4 -(N(Me))-Bip(2'-Et-4' -OMe)-(N(Me))-4-(2' -Me Ph)-3 -Pyr-Ala-NI-(C1 2 )lo-CH 3 CH3-(C112)6-NH-H-(N(Me))A-(N(Me))-(CL{ 2 ) 4 -. (N(Mle)).Bip(2 '-Et-4' -OMe) (N(Me))-4-(2 '-Me-Ph) -3 -Pyr-Ala-NJI-(CH 2 ) 6 -CH 3 5 CH3-(CH2)6-NH-H-(N(Me))Aib-(N(Me))-(CH 2 ) 4 -(N(NMe))..Bip(2'.Et-4 '-OMe) ,(N(Me))-4-(2 '-Me-Ph)-3-Pyr-Ala-NII-(CH 2 ) 6 -CH 3 CH3-(CH2)lo-NH-H-(N(Me))A-(N(Me))-(CH 2 ) 4 -. (N(Me))..Bip(2'.Et4 '-OMe) (N(Me))-4-(2 '-Me-Ph)-3-Pyr-Ala-N{-(CH 2 ) 6 -CH 3 10 (N(Me))-4-(2 '-Me-Ph)-3-Pyr-Ala-NH-(CH 2 ) 6 -CH 3 J{AE-(C11 2 ) 2 -Bip(2 '-Et-4 '-OMe)-4-(2 '-Me-Ph)-3-Pyr-Ala-N1 2 H-Aib-E-(CJ{ 2 ) 2 -Bip(2' -Et-4'-OMe)-4-(2 '-Me-Ph)-3-Pyr-Ala-NH 2 FHaE-(C11 2 ) 2 -Bip(2' -Et-4'-OMe)-4-(2 '-Me-Ph)-3-Pyr-Ala-NH 2 H-(N(Me))AE-(CH2) 2 -Bip(2'-Et-4'-OMe)-4-.(2'MePh)3Pyr-Ala-H 2 15 H-(N(Me))AE-(N(Me))-(C1 2 ) 2 -Bip(2 '-Et-4 '-OMe)-4-(2 '-Me-Ph)-3 -Pyr-Ala-N-H 2 H-(N(Me))Aib-E-(N(Mle))-(CH 2 ) 2 -Bip(2'-Et-4 '-OMe)-4-(2'-Me-Ph)-3-Pyr-Ala Nil 2 Ala-MI 2 20 H-(N\4e))Aib-E-(N(Me))-CH 2 ) 2 -N(Me))-Bip(2 '-Et-4'-OMe)-4-(2' -Me-Ph)-3 Pyr-Ala-NH 2 JI-(N(Me))AE-(N(Me))-(CH 2 ) 2 -(N(Me))-Bip(2 '-Et-4'-OMe)-(N(Me))-4-(2 '-Me Ph)-3-Pyr-Ala-NH 2 H-(N(Me))Aib-E-(N(Me))-(CH 2 ) 2 -(N(Me))-Bip(2 '-Et-4'-OMe)-(N(Me))-4-(2 '-Me 25 Ph)-3 -Pyr-Ala-N11 2 4-(2'-Me-Ph)-3-Pyr-Ala-NH 2 Des-arnino-H-(N(Me))Aib-E(N(Me)(CH 2 ) 2 (Me))ip(2'-Et4'-OMe) (N(Me))-4-(2 '-Me-Ph)-3 -Pyr-Ala-NH 2 30 H-(N(Me))AE-(N(Me))-(CH 2 ) 2 -(N(Me))-Bip(2' -Et-4'-OMe)-(N(Me))-4-(2'-Me Ph)-3 -Pyr-Ala-N{-(CH 2 ) 6 -CH 3 H-(N(Me))Aib-E-(N(Me))-(CH 2 ) 2 -{N(Me))-.Bip(2 '-Et-4'-OMe)-(N(Me))-4-(2'-Me Ph)-3 -Pyr-Ala-N{-(CH 2 ) 6 -CH 3 - 70 - WO 2007/017892 PCT/1N2006/000154 II-(N(Me))AE-(N(Me))-(CH 2 ) 2 -(N(Me))Bip(2'Et-4'-OMe)-(N(Me))-4-(2' -Me Ph)-3 -Pyr-Ala-NH-(CH 2 ) 10 -CH 3 H-(N(Me))Aib-E-(N(Me))-(CH 2 ) 2 -(N(Mle))-Bip(2 '-Et-4'-OMe)-(N(Me))-4-(2'-Me Ph)-3-Pyr-Ala-N{-(C1 2 ) 10 -C 3 5 C 1 I3-(CH2)6-NH-(N(Me))AE-(N(Me))-(CH2) 2 .{N(Me)).Bip(2'-Et.4'OMe) (N(Me))-4-(2 '-Me-Ph)-3 -Pyr-Ala-NII-(CH 2 ) 6 -CFI 3 CH3-(CH2)6-NH-N)Aib-E-b(N(Me))(CH 2 ) 2 (e))-Bip(2'.Et-4 '-OMe) (N(M\e))-4-(2 '-Me-Ph)-3 -Pyr-Ala-NII-(CH 2 ) 6 -CH 3 10 C)o-H(N(Me))-4( -eP)3PrA-NHM)-(CH 2 )-H 3 ))Bp2'E-'-~) 10(N(Me))-4-(2 '-Me-Ph)-3-Pyr-Ala-NII-(CH 2 ) 6 -CHr 3 HAE(C)z-i( -t4-~)-4-(2'-Me-Ph)-3 -Pyr-Ala-NH 2 C2)-H H-AiEG-(CH2)2Bip(2'Et4'OMe)-(2'MePh).3PyrAa.N 2 15HAiEG-(CI2)2-Bip(2'-Et-4'-OMe)4(2'Me-Ph)3-Pyrla.. 2 15 H-(()EG-(CH 2 ) 2 -Bip(2 '-Et-4'-OMe)-4-(2' -Me-Ph)-3-Pyr-Ala-NH 2 H-(N(Me))AEG(N(e))ip 2 ) 2 -4'Bip-(2'-MeP)(234Ph>3pyrAaa N H-((Me))AibEG-(N(Me))(CH 2 ) 2 Bip(2'Et4'OMe)42'MePh)3-Pyr-Ala-H NH 2 20 H-(N(Me))AEG(N(Me)(CH 2 ) 2 N(Me))Bip(2'Et-4'-OMe)-4-(2'-Me-Ph)-3-Pyr Ala-NH 2 H-(N(Me))Aib-EG-(N(Me))-(CH 2 ) 2 .. (N(Me))>Bip(2 '-Et-4'-OMe)-4-(2 '-Me-Ph) -3 Pyr-Ala-NI{ 2 H-(N(Me))AEG-(N(Me))(CH 2 ) 2 (N(Me))Bip(2'Et4'O~e) Ne))-4(2 '-Me 25 Ph)-3-Pyr-Ala-NA 2 Me-Ph)-3-Pyr-Ala-N1 2 De-mn--NM)AG((e)-C22 (e)Bp2-t4-OMe) (N(Me))-4-(2 '-Me-Ph)-3-Pyr-Ala-NH 2 30 Des-arnino-H-(Ni Me))Aib-EG-(N(Me))-(CH 2 ) 2 {N(Me))Bip(2'-Et-4'-OMe) (N(Me))-4-(2 '-Me-Ph)-3-Pyr-Ala-N1 2 H-(N(Me))AEG-(N(Mle))-(CH 2 ) 2 (N(Me))Bip(2'.Et-4'-OMe)-(N(Me))-4-(2'-Me Ph)-3-Pyr-Ala-NH-(CH 2 ) 6 -CH 3 - 71 - WO 2007/017892 PCT/1N2006/000154 Me-Ph)-3-Pyr-Ala-NI-(CH 2 ) 6 -CH 3 I{-(N(Me))AEG-(N(Me))-(CH 2 ) 2 N(Me))Bip(2't4'O~e)((Me))-4(2 '-Me Ph)-3 -Pyr-Ala-NH-(C1 2 ) 10 -CH 3 5 TI-(N(Me))Aib-EG-(N(Me))-(CH 2 ) 2 -{N(Me))-Bip(2 '-Et-4 '-OMe)-(N(Me))-4-(2 ' Me-Ph)-3-Pyr-Ala-NH-(CH 2 )lo..d1 3 CH3-(CH2)6-NH-(N(Me))AEG-(N(Me))-(CH 2 ) 2 -{(NjMe)).Bip(2 '-Et-4'-OMe) (N(Me))-4-(2 '-Me-Ph)-3 -Pyr-Ala-N{-(CH 2 ) 6 -G11 3 CH3-(CH2)6-NH-(N(Me))Aib-EG-(N(Me))-(CH 2 ) 2 -{N(Me)).Bip(2 '-Et-4 '-OMe) 10 (N(Me))-4-(2 '-Me-Ph) -3 -Pyr-Ala-N{-(C1 2 ) 6 -CH 3 CH3-(CH2)io-NI-(N(Me))AEG(N(Me))(CH 2 ) 2 .(Me))-Bip(2'.Et-4 '-OMe) (N(Me))-4-(2 '-Me-Ph)-3 -Pyr-Ala-NH-(CJ 2 ) 6 -CH 3 CH-C2l-H((e)i-G((e)(H)-NNe)Bp2-t4-~) (N(Me))-4-(2 '-Me-Ph)-3 -Pyr-Ala-NII-(CH 2 ) 6 -CH 3 15 HLAEGT-(CH 2 ) 2 -Bip(2'-Et-4'-OMe)-4.(2 '-Me-Ph)-3-Pyr-Ala-NFJ 2 H-Aib-EGT-(CH 2 ) 2 -Bip(2'-Et-4'.OMe)..4-(2' -Me-Ph)-3-Pyr-Ala-NH 2 HaEGT-(CH 2 ) 2 -Bip(2' -Et-4'-OMe)-4-(2'-Me-Ph)-3-Pyr.Ala.NEI 2 H-(N(Me))AEGT-(CH 2 ) 2 -Bip(2 '-Et-4 '-OMe)-4-(2 '-Me-Ph)-3 -Pyr-Ala-NFI 2 H-(N(Me))AEGT-(N(Mle))-(CH 2 ) 2 -Bip(2 '-Et-4'-OMe)-4-(2'-Me-Ph)-3-Pyr.Ala. 20 NHl 2 NH2~ Pyr-Ala-N{ 2 25 H-(N(Me))Aib-EGT-(N(Me))-(CH 2 y,..(N(Me))..Bip(2'..Et4 '-OMe)-4-(2 '-Me-Ph)-3 Pyr-Ala-NH 2 H-(N(Me))AEGT-(N(Me))-(CH 2 ) 2 -{N(Me)).Bip(2 '-Et-4'-OMe)-(N(Me))-4-(2' -Me Ph)-3 -Pyr-Ala-NH 2 30 Me-Ph)-3-Pyr-Ala-NH 2 Des-amino-H-(N(Me))AEGT(N(Me))>{CH 2 ) 2 {Nq\e))Bip(2'-Et-4'-OMe) (N(Me))-4-(2 '-Me-Ph)-3-Pyr-Ala-NH 2 Des-amino-H-(N(Me))Aib-EGT-(N(Me))(CH 2 ) 2 -{N(Me))-Bip(2' -Et-4' -OMe) (N(Me))-4-(2 '-Me-Ph) -3 -Pyr-Ala-NH 2 -72 - WO 2007/017892 PCT/1N2006/000154 PH-3-Pyr-)Aa-N-(N11 2 )).CH2)-N4)-i('E-'Oe-NM)--2-e MPh)-3-Pyr-Ala-NH(CH 2 ) 6 CH 3 5 H-(N(Me))AiEGT(N(Me))-(CH 2 ) 2 N(e))Bip( 2 '-Et-4'-OMe)-(N(Me))-4-(2 MPh)-3-Pyr-Ala-NH-(CH 2 )-CH 3 5H-(N(Me))AbEGT(N(Me))-(CH 2 ) 2 -{I(.4 (e))Bip(2 '-Et-4' -OMe)-(N(Me))-4-(2 MPh)-3-Pyr-Aa-II(CH 2 ) 10 CH 3 1 (NM)-2-Me-Ph)-3-Pyr-Aa-N II(CH 2 ) 6 Cll 3 3 CH3-(CH2)6NI1-(N(Me))AEGT(N(Me))(CH 2 ) 2 N(Me))Bip( 2 '-Et-4'-OMe) 10(N(Me))-4-(2 '-Me-Ph)-3 -Pyr-Ala-NII-(CH 2 ) 6 -CH 3 CH-C26N-NM)AbET NM)-C22((e)Bp2-Et-4' -OMe) (N(Me))-4-(2 '-Me-Ph)-3 -Pyr-Ala-NFI-(CH 2 ) 6 -CH 3 15 C2ioN-NM))ET((e)-C22-NM)-ip2-t4-OMe) (N(Me))-4-(2 '-Me-Ph)-3 -Pyr-Ala-NH-(CH 2 ) 6 -CH 3 HA-(CH2)3-Bip(2-Me)-Bip(2.Me).M{ 2 H-Aib-(GH2.) 3 -Bip(2-Me).Bip(2.Me).NH 2 Ha-(CH 2 ) 3 -Bip(2-Me)-Bip(2-Me)-NHJ 2 20 H-(N(Me))A-(CH 2 ) 3 -Bip(2..Me)Bip(2-Me)-NH 2 H-(N(M\e))A-(N(Me))-(CH 2 ) 3 Bip(2Me)-Bip(2..Me)-NH H-(N(Me))Aib-(N(Me))..{CH 2 ) 3 Bip(2Me)-Bip(2-Me)-NH2 H-(N(Me))A-(N (Me))-(CH2) 3 -(N(Me))Bip(2Me)Bip(2-Me)-NHj 2 Fl-(N(Me))Aib(N(Me))(CH 2 ) 3 (N(Me))Bip(2Me)Bip(2Me)-NH2 NH 2 30 Me)-NH 2 H(H 2 )- l)-C2)-NM)-i(2M)((\e)-i(-e-H (CH 2 ) 6 -CH 3 - 73 - WO 2007/017892 PCT/1N2006/000154 H-NM)A((e)(H)-NM)-i(-e-NM)-i(-e-H (CH 2 )lo-CH 3 (C11 2 )lo-GH 3 BiP(2-Me)-NJI-(C1 2 ) 6 -CH 3 CH-C26N--NM)Ab((e)-C23((e)Bp2M)((e) BiP(2-Me)-NH-(C1 2 ) 6 -CH 3 CH-C2i-HH((e)-NM)-C23((e)Bp2M)((e) 10 BiP(2-Me)-NH-(CH 2 ) 6 -CH 3 BiP(2-Me)-NII-(CH 2 ) 6 -CH 3 HA.-(CH 2 ) 3 -Bip(2-Et)-Bip(2-Me)-Ni 2 H-Aib-(CH 2 ) 3 -Bip(2-Et)-Bip(2.Me).N{ 2 15 Ha-(CH2)3-Bip(2-Et)-Bip(2-Me)-NH 2 H-(N(Me))A-(CH 2 ) 3 -Bip(2-Et)-.Bip(2-Me)-NH 2 .H-(N(Me))A-(N(Me))-(CH 2 ) 3 -Bip(-Et))Bip(2-et)Bip2e 20 H-(N(Me))Aib-(N(Me))-(CH 2 ) 3 Bip(-Et)-Bip(2-et)Bip(2Me H- 4 (Me))A-(N(Me))-(CH 2 ) 3 -(N(Me)).Bip(2Et)-Bip(2Me)-Nip2M) H Nil 2 25 Des-amino-H-(N(e))Aib(N(Me))(CH 2 ) 3 (N(Me))Bip(2Et)(N(e))-Bip(2 Me)-NH 2 CH 3 30 (CH 2 ) 6 -CH 3 CIT 3 H-(N(M\e))Aib-(N(Me))-(CH 2 ) 3 ..{N(Me)).Bip(2Et).(Nqve))Bip(2Me)-NH (CH 2 ) 10 -CH 3 - 74 - WO 2007/017892 PCT/1N2006/000154 CH-C26N--NM)A((\e)(H23((e)Bp2E)((e)Bp2 Me)-NH-(CH 2 ) 6 -CH 3 Bip(2-Me)-NH-(CH 2 ) 6 -GH 3 5 CH-C2i-HH((e)-NM)-C23((e)Bp2E)((\e)Bp2 Me)-NII-(CH 2 ) 6 -CH 3 Bip(2-Me)-NH-(CH 2 ) 6 -CH 3 HA-(CH 2 ) 2 -Bip(2 '-Et-4 '-OMe)-4-(2'-Me-Ph)-3-Pyr-A'la.OH 10 JI-Aib-(CH 2 ) 2 -Bip(2 '-Et-4'-OMe)-4-(2 '-Me-Ph)-3 -Pyr-Ala-OFI Ha-(CH 2 ) 2 -Bip(2'-Et-4'-OMe)4(2 '-Me-Ph)-3 -Pyr-Ala-OFI 'H-(N(Me))A-(CH 2 ) 2 -Bip(2' -Et-4' -OMe)-4-(2'-Me-Ph)-3-Pyr-Ala-OH H-(N(Me))A-(N(Me))-(CH 2 ) 2 -Bip(2 '-Et-4' -OMe)-4-(2 '-Me-Ph)-3-Pyr-Ala-OH 15 H-(N(Me))A-(N(Me))-(CH 2 ) 2 -(N)Bip(2' Et4' ' -OMe)-4-(2 '-Me-Ph)-3-Pyr-O Ala-OH H-( 'N(Me))Aib-(N(Me))-(CH 2 ) 2 -{N(Me))-Bip(2'..E-4 '-OMe)-4-(2 '-Me-Ph)-3-Pyr Ala-OH 20 3-Pyr-Ala-OFI Ph)-3-Pyr-Ala-OH. Des-amino-H-(N(Me))A(N(e))(CH 2 ) 2 y(Me))Bip(2'-Et-4'-OMe)-(N(Me))-4 (2 '-Me-Ph)-3-Pyr-Ala-OH 25 De-mn--NM)Ab((e)(H)2((e)Bp2-t4-~)((e) 4-(2 '-Me-Ph)-3-Pyr-Ala-OH H-(N(M\e))A-(N(Me))-(CH- 2 ) 2 -<N(Me))-Bip(2 '-Et-4'-OMe)-(N(Me))-4-(2 '-Me-Ph) 3-Pyr-Ala-COO-(CH 2 ) 6 -CH- 3 30 Ph)-3 -Pyr-Ala-COO-(CH 2 ) 6 -CH 3 3-Pyr-Ala-COO-(CH 2 )1O.CH 3 Ph)-3-Pyr-Ala-COO(CH 2 ) 10 -CH 3 - 75 - WO 2007/017892 PCT/1N2006/000154 4-(2'-Me-Ph)-3-Pyr-Ala-COO-(C 2 ) 6 .CH 3 CH-C26N-NM)Ab((e)(C22((e)Bp2-t4-~) (N(Me))-4-(2 '-Me-Ph)-3-Pyr-Ala-COO-(CH 2 ) 6 -CH 3 5 CF[ 3 -(CH 2 ) oN-NM)A((e)(H)2((e)Bp2-t4-~) (N(Me))-4-(2'-Me-Ph)-3 -Pyr-Ala-COO-(CH 2 ) 6 -CH 3 (N(Me))-4-(2 '-Me-Ph)-3-Pyr-Ala-COO-(CH 2 ) 6 -CH 3 JIA-(CH 2 ) 3 -Bip(2 '-Et-4 '-OMe)-4-(2' -Me-Ph)-3 -Pyr-Ala-OH 10 H-Aib-(CH 2 ) 3 -Bip(2 '-Et-4'-OMe)-4-(2 '-Me-Ph)-3-Pyr-Ala-OH Ha-(CH 2 ) 3 -Bip(2'-Et-4' -OMe)-4-(2'-Me-Ph)-3-Pyr-Ala-OH H-(N(Me))A-(C1 2 ) 3 -Bip(2 '-Et-4 '-OMe)-4-(2 '-Me-Ph)-3-Pyr-Ala-OH H-(N(Me))A-(N(Mle))-(G11 2 ) 3 -Bip(2 '-Et-4'-OMe)-4-(2'-Me-Ph)-3-Pyr-Ala-OH H-{N(Me))Aib-(N(Me))-(CH 2 ) 3 -Bip(2 '-Et-4 '-OMe)-4-(2'-Me-Ph)-3-Pyr-Ala-cjn 15 H-(N(Me))A-(N(Me))-(CH 2 ) 3 -(N(Me))-Bip(2 '-Et-4'-OMe)-4-(2 '-Me-Ph)-3 -Pyr Ala-OH H-(N(Me))Aib-(N(Me))-(CH 2 ) 3 -{1 Me))-Bip(2 '-Et-4 '-OMe)-4-(2'-Me-Ph)-3-Pyr Ala-OH H-(N(Me))A-(N(Me))-(d11 2 ) 3 (N(Me))-Bip(2 '-Et-4' -OMe)-(N(Me))-4-(2 '-Me-Ph) 20 3-Pyr-Ala-OH Ph)-3-Pyr-Ala-OH Des-amino-H-(N(Me))A(N(Me))(H 2 ) 3 Ne))-Bip('Et-4'OMe)-q,(Me))-4 (2'-Me-Ph)-3-Pyr-Ala-OH 4-(2 '-Me-Ph)-3-Pyr-Ala-OH 3-Pyr-Ala-COO-(CH 2 ) 6 -C1 3 30 Ph)-3 -Pyr-Ala-COO-(CH 2 ) 6 -CH 3 H-N14)A((Ne)(H)-NMe)Bp2-t4 ~)((e)4('-Me-Ph) 3-Pyr-Ala-COO-(C1 2 )io-C11 3 Ph)-3-Pyr-Ala-COO..(CH 2 ) 1 0 -C11 3 - 76 - WO 2007/017892 PCT/1N2006/000154 4-(2 '-Me-Ph)-3-Pyr-Ala-COO-(CHj 2 ) 6 -CH 3 5 -C26NHH((e)Ab((e)-C23 (M)-i('-Et-4'-OMe) (N(Me))-4-(2'-Me-Ph)-3 -Pyr-Ala-COO-(CI 2 ) 6 -CHi 3 (N(Me))-4-(2 '-Me-Ph)-3 -Pyr-Ala-COO-(CH 2 ) 6 -C 3 H-C2i-HH((e)i-NM)-(CH2)J 2 ) 4 e)-Bip(2 '-Et-4-OMe)-4-2-eP)3pr~O 10 H-Alb 4-( 2 2 Bp2-t4Oe--'-Me-Ph)-3-3 -Pyr-Ala-OH6-CH HA-(CHI 2 ) 4 -Bip(2 '-Et-4'-OMe)-4-(2 '-Me-Ph)-3 -Pyr-Ala-OH H-(N(Me))A-(CH2)4Bip(2'Et4'OMe)4(2'MePh)-3-PrAla-OH H-(N(Me))A-(N(Me))-(CH- 2 ) 4 Bip(2'Et-4'-OMe)-4-(2'-Me-Ph)-3-Pyr-Ala-OH H-(N(Me))Aib-(N(Me))-(CH- 2 ) 4 -Bip(2 '-Et-4'-OMe)-4-(2'-Me-Ph)-3 -Pyr-Ala-Gil Ala-Oil Ala-OH H-(N(Me))Ai-(N(Me))-(CF 2 ) 4 (N(e))Bp(2 '-Et-4 '-OMe)-(N(Me))-4-(2 '-Me- Ph-3-Pyr-Ala-OH (2'-M-P-l---la 25 Des-amino-H-(N(Me))Ai(N(Me)).(CH 2 ) 4 qv(e))Bip(2 '-Et-4'-OMe)-(N(Me)) 4(2 '-Me-Ph)-3-Pyr-Ala-OH 4-2-P)3-Pyr-Ala-CO-CO 6 CH il-(N(Me))A-(N(Me))-(GH 2 ) 4 .(N(e)).Bip(2' -Et-4'-OMe)-(N(Me))-4-(2 '-Me-) 30 P3-Pyr-Ala-COO-(CH 2 ) 6 -C 3 Jl-(N(Me))Ai-(N(Me))-(CH 2 ) 4 -(N(Me))Bip(2 '-Et-4'-OMe)-(N(Me))-4-(2 '-Me-) 30 P3-Pyr-Ala- OO-(CH 2 )-C 3 H-(N(Me))Ai-(N(Me))-(CH 2 ) 4 (Me))Bip(2'Et4' -OMe)-(N(Me))-4-(2'-Me-) Ph)-3 -Pyr-Ala-COO-(CH 2 ) 10 -d11 3 - 77 - WO 2007/017892 PCT/1N2006/000154 (N(Me))-4-(2 '-Me-Ph)-3 -Pyr-Ala-COO-(CJ 2 ) 6 -CH 3 CH3-(CH2)6-NH-H-(N(Me))Aib-(N(Me))-(CH 2 ) 4 -{N(Me)).Bip(2'.Et-4 '-OMe) (N(Me))-4-(2 '-Me-Ph)-3-Pyr-Ala-COO-(CH 2 ) 6 -CH 3 5 CH3-(CH2)o-NI-H(N(Me))A(N(Me)>CH 2 ) 4 (Me))Bip(2'-Et-4'-OMe) (N(Me))-4-(2 '-Me-Ph) -3 -Pyr-Ala-COO-(CH 2 ) 6 -CH 3 (N(Me))-4-(2'-Me-Ph)-3-Pyr-Aa-COO..{CH 2 ) 6 -CH 3 HAE-(C11 2 ) 2 -Bip(2'-Et-4 '-OMe)-4-(2 '-Me-Ph)-3-Pyr-Ala-OH 10 H-Aib-E-(CH 2 ) 2 -Bip(2' -Et-4 '-OMe)-4-(2 '-Me-Ph)-3-Pyr-Ala-OH HaE-(C11 2 ) 2 -Bip(2' -Et-4'-OMe)-4-(2' -Me-Ph)-3-Pyr-Ala-OH H-(N(M~e))AE-(CH 2 ) 2 -Bip(2'-Et-4'-OMe)-4{2 '-Me-Ph)-3-Pyr-Ala-OH H-(N(Me))AE-(N(Me))-(C1 2 ) 2 -Bip(2' -Et-4 '-OMe)-4-(2'-Me-Ph)-3 -Pyr-Ala-OH H-(N(Me))Aib-E-(N(Me))-(CH 2 ) 2 -Bip(2'E4'OMe)4(2'Me-Ph)-3-Pyr-Ala-OH 15 JI-(N(Me))AE-(N(Me))-(CH 2 ) 2 (N(Me))Bip(2'Et4'OMe)4(2'Me-ph)-3-Pr Ala-OH Pyr-Ala-OH H-(N(Me))AE-(N(Me))-(CH 2 ) 9 .(N(Me))Bip(2'-Et-4' -OMe)-(N( Me))-4-(2' -Me 20 Ph)-3 -Pyr-Ala-OH H-(N(Me))Aib-E-(N(Me))-(CH- 2 ) 2 -<N(M\e))-Bip(2' -Et-4' -OMe)-(N(Me))-4-(2 '-Me Ph)-3-Pyr-Ala-OH 4-(2 '-Me-Ph) -3 -Pyr-Ala-OH 25 Des-amino-H-(N(M~e))Aib-E(N\4e))-(CH 2 ) 2 -{N(Me))-Bip(2' -Et-4' -OMe) (N(Me))-4-(2 '-Me-Ph)-3-Pyr-Ala-OH H-(N(Me))AE-(N(Me))-(CH 2 ) 2 (N(Me))-Bip(2' -Et-4'-OMe)-(N(Me))-4-(2 '-Me Ph)-3 -Pyr-Ala-COO-(CH 2 ) 6 -CH 3 H-(N(Me))Aib-E-(N(Me)).(CH 2 ) 2 -{N(lMe))..Bip(2' -Et-4'-OMe)-(N(M~e))-4-(2'-Me 30 Ph)-3-Pyr-Ala-COO-(CH 2 ) 6 -CH 3 H-(N(NMe))AE-(N(Me))-(CH 2 ) 2 (N(Me))-Bip(2 '-Et-4'-OMe)-(N(Me))-4-(2 '-Me Ph)-3-Pyr-Ala-COO-(CH- 2 ) 10 -CH 3 H-(N(Me))Aib-E (N(Me)(CH 2 ) 2 ((Me))-Bip(2'-Et.4' -OMe)-(N(Me))-4-(2 '-Me Ph)-3-Pyr-Ala-COO-(C1 2 )j 0 ..CH 3 - 78 - WO 2007/017892 PCT/1N2006/000154 C -()-H(N(Me))-4( -eP)3PrAa-COOe-(C11 2 )2-CJ()-Bi1 3 E-4-~) (N(Me))-4-(2 '-Me-Ph)-3-Pyr-Ala-COO-(11 2 ) 6 -C1 3 5CH3-(CH2)l-NH-(N(Me))AE-(N(Me))-(CH 2 ) 2 -(N(Me))Bip(2'-Et4'OMe) (N(Me))-4-(2 '-Me-Ph)-3-Pyr-Ala-COO-(GH 2 ) 6 -CH 3 5GC13-(CH2)lo-NH-(N(Me))AiE-(N(Me))-(CH 2 ) 2 -(N(Me)Bip(2 '-Et-4 '-OMe) (N(Me))-4-(2 '-Me-Ph)-3-Pyr-Ala-COO-(CH 2 ) 6 -C1 3 HEG 2i-H-NM)Ab--NM)-(CH2)2-NM)-Bip(2'-Et-4'-OMe)-4('MPh3.yrlaO 10 HAibeG-C) 2 Bp2-t4-~)-4-(2'-Me-Ph)-3-Pr.PyrCO-(laOHCH HAEG-(C1 2 ) 2 -Bip(2' -Et-4 '-OMe)-4-(2 '-Me-Ph)-3-Pyr-Ala-OH 10H-(N(e)EG-(C1 2 ) 2 -Bip(2'-Et-4'-OMe)-4-(2' -Me-Ph)-3-Pyr-Ala-OH H-(N(Me))AEG-(N(Me))-(CH 2 ) 2 -Bip(2'Et4'OMe)4(2'MePh)3-Pyr-AlaOH H-(N(Me))Aib-EG-(N(Me))(CH 2 ) 2 Bip(2'Et4'OMe)4(2'MePh-3-Pyr-Ala 15 OH H-(N(Me))AEG-(N(Me))-(CH 2 ) 2 -(N(Me))-Bip(2' -Et-4'-OMe)-4-(2'-Me-Ph)-3-Pyr Ala-Oil H-(N(Me))Aib-EG-(N(NMe))-(CH 2 ) 2 -(N(Me))Bip(2'Et4'OMe)-4(2 '-Me-Ph)-3 Pyr-Ala-OH 20 H-(N(Me))AEG-(N(Me))-(CH 2 ) 2 -{N(Me))-Bip(2' -Et-4'-OMe)-(N(Me))-4-(2 '-Me Ph)-3 -Pyr-Ala-OH Me-Ph)-3-Pyr-Ala-OH Des-arnino-H-(N(Me))A-EG-(N(Me))-(CFI 2 ) 2 (N(Me))>Bip(2 '-Et-4'-OMe) 25 (N(Me))-4-(2'-Me-Ph)-3-Pyr-Ala-OH Des-amino-H-(N(Me))AibEG((Me))-(CH 2 ) 2 -(Nvje))-Bip(2' -Et-4 '-OMe) (N(Me))-4-(2 '-Me-Ph)-3 -Pyr-Ala-OHr H-(N(Me))AEG-(N(Me))-(CH 2 ) 2 -(N(Mle))-Bip(2'..Et-4' -OMe)-(N(Me))-4-(2' -Me Ph)-3 -Pyr-Ala-COO-(CH 2 ) 6 -CH 3 30 H-(N(Me))Aib-EG-(N(Me))-(CH 2 ) 2 -(N(Me))-Bip(2 '-Et-4'-OMe)-(N(Me))-4-(2 ' Me-Ph)-3-Pyr-Ala-COO(CT{ 2 ) 6 -CH 3 H-(N(Me))AEG-(N(Me))-(CH- 2 ) 2 -(N(Me))-Bip(2 '-Et-4'-OMe)-(N(Me))-4-(2' -Me Ph)-3-Pyr-Ala-COO-(C1 2 )lo.C1 3 - 79 - WO 2007/017892 PCT/1N2006/000154 H-(N(Me))Aib-EG-(N(Me))-(CH 2 ) 2 -(N(Me))-Bip(2'-Et-4'-OMe)-(N(Me))-4-(2' Me-Ph)-3-Pyr-Ala-COO-(CH 2 )io-CH 3 CH-C26N-NM)AG((e)(C22((e)Bp2-t4-~) (N(Me))-4-(2 '-Me-Ph) -3 -Pyr-Ala-COO-(CH 2 ) 6 -CH 3 5 CH3-(CH2)6-NH-(N(Me))Aib-EG-(N(Me))-(CH 2 ) 2 -(N(Me))-Bip(2 '-Et-4 '-OMe) (N(Me))-4-(2 '-Me-Ph)-3 -Pyr-Ala-COO-(CH 2 ) 6 -CH 3 CH 3 -(CH 2 ) io-NH-(N(Me))AEG-(N(Me))-(CH 2 ) 2 -(N(Me))-Bip(2'-Et-4 '-OMe) (N(Me))-4-(2 '-Me-Ph)-3 -Pyr-Ala-COO-(GH 2 ) 6 -CH 3 GH3-(CH2)io-NH-(N(Me))Aib-EG-(N(Me))-(CH 2 ) 2 -(N(Me))-Bip(2'-Et-4' -OMe) 10 (N(Me))-4-(2 '-Me-Ph)-3 -Pyr-Ala-COO-(CH 2 ) 6 -CH 3 HAEGT-(CH2) 2 -Bip(2'-Et-4'-OMe)-4-(2'-Me-Ph)-3-Pyr-Ala-OH H-Aib-EGT-(CH 2 ) 2 -Bip(2' -Et-4'-OMe)-4-(2 '-Me-Ph)-3-Pyr-Ala-OH HaEGT-(CH 2 ) 2 -Bip(2 '-Et-4'-OMe)-4-(2'-Me-Ph)-3-Pyr-Ala-OH H-(N(Me))AEGT-(CH 2 ) 2 -Bip(2'-Et-4'-OMe)-4-(2 '-Me-Ph)-3 -Pyr-Ala-OH 15 Jr-(N(Me))AEGT-(N(Me))-(CH 2 ) 2 -Bip(2'-Et-4'-OMe)-4-(2' -Me-Ph)-3-Pyr-Ala OH H-(N(Me))Aib-EGT-(N(Me))-(CH 2 ) 2 -Bip(2 '-Et-4'-OMe)-4-(2 '-Me-Ph)-3-Pyr-Ala OH H-(N(Me))AEGT-(N(Me))-(CH 2 ) 2 -(N(Me))-Bip(2 '-Et-4' -OMe)-4-(2' -Me-Ph)-3 20 Pyr-Ala-Oll H-(N(Me))Aib-EGT-(N(Me))-(CH 2 ) 2 -(N(Me))-Bip(2'-Et-4' -OMe)-4-(2'-Me-Ph)-3 Pyr-Ala-Oll H-(N(Me))AEGT-(N(Me))-(CH 2 ) 2 -(N(Me))-Bip(2'-Et-4'-OMe)-(N(e))4(2'-Me Ph)-3 -Pyr-Ala-OH 25 H-(N(Me))Aib-EGT-(N(Me))-(CH 2 ) 2 -(N(Me))-Bip(2'-Et-4' -OMe)-(N(Me))-4-(2 ' Me-Ph)-3-Pyr-Ala-OH Des-amino-H-(N(Me))AEGT-(N(Me))-(CH 2 ) 2 -(N(Me))-Bip(2'-Et.4 '-OMe) (N(Me))-4-(2 '-Me-Ph)-3 -Pyr-Ala-OH Des-amino-H-(N(Me))Aib-EGT-(N(Me))-(CH 2 ) 2 -(N(Me))-Bip(2'-Et-4'.OMe) 30 (N(Me))-4-(2 '-Me-Ph)-3 -Pyr-Ala-OH H-(N(Me))AEGT-(N(Me))-(CH 2 ) 2 -(N(Me))-Bip(2 '-Et-4'-OMe)-(N(Me))-4-(2'-Me Ph)-3-Pyr-Ala-COO-(CH 2 ) 6 -CH 3 H-(N(Me))Aib-EGT-(N(Me))-(G ,H 2 ) 2 -(N(Me))-Bip(2' -Et-4' -OMe)-(N(Me))-4-(2 ' Me-Ph)-3 -Pyr-Ala-COO-(GH 2 ) 6 -CH 3 - 80 - WO 2007/017892 PCT/1N2006/000154 H-(N(M\e))AEGT-(N(Me))-(GH 2 ) 2 -(N(Me))-Bip(2 '-Et-4'-OMe)-(N(Me))-4 -(2' -Me Ph)-3-Pyr-Ala-COO-(CH 2 )lo-CH 3 H-(N(Me))Aib-EGT-(N(Me))-(C11 2 ) 2 -(N(Me))-Bip(2' -Et-4' -OMe)-(N(Me))-4-(2 ' Me-Ph)-3-Pyr-Ala-COO-(CH 2 )lo-CH 3 5 CH 3 -(CH 2 ) 6 -NH-(N(Me))AEGT-(N(Me))-(CH 2 ) 2 -{N(Me))-Bip(2 '-Et-4'-OMe) (N(Me))-4-(2'-Me-Ph)-3-Pyr-Ala-COO-(CH 2 ) 6 -CH 3 CH3-(CH 2 ) 6 -NII-(N(Me))Aib-EGT-(N(Me))-(CH 2 ) 2 -(N(Me))-Bip(2 '-Et-4'-OMe) (N(Me))-4-(2 '-Me-Ph)-3 -Pyr-Ala-COO-(CH 2 ) 6 -CLI 3 CH3-(CH 2 )io-NH-(N(Me))AEGT-(N(Me))-(CH 2 ) 2 -(N(Me))-Bip(2' -Et-4' -OMe) 10 (N(Me))-4-(2'-Me-Ph)-3 -Pyr-Ala-COO-(CH 2 ) 6 -CJJ 3 C113-(CH 2 )o-NH-(N(Me))Aib-EGT-(N(Me))-(CH 2 ) 2 -(N(Me))-Bip(2'-Et-4' -OMe) (N(Me))-4-(2 '-Me-Ph)-3-Pyr-Ala-COO-(CI 2 ) 6 -CH 3 HA-(CH 2 ) 3 -Bip(2-Me)-Bip(2-Me)-OH H-Aib-(CH 2 ) 3 -Bip(2-Me)-Bip(2-Me)-OH 15 Ha-(CJJ 2 ) 3 -Bip(2-Me)-Bip(2-Me)-OH H-(N(Me))A-(C11 2 ) 3 -Bip(2-Me)-Bip(2-Me)-OH H-(N(Me))A-(N(Me))-(CH 2 ) 3 -Bip(2-Me)-Bip(2-Me)-OH H-(N(Me))Aib-(N(M\e))-(CH 2 ) 3 -Bip(2-Me)-Bip(2-Me)-OH H-(N(Me))A-(N(Me))-(CH 2 ) 3 -(N(Me))-Bip(2-Me)-Bip(2-Me)-OH 20 H-(N(Mle))Aib-(N(Me))-(C11 2 ) 3 -(N(Me))-Bip(2-Me)-Bip(2-Me)-OH H-(N(Mle))A-(N(Me))-(CH 2 ) 3 -(N(Me))-Bip(2-Me)-(N(Me))-Bip(2-Me)-OH H-(N(Me))Aib-(N(Me))-(CH 2 ) 3 -(N(Me))-Bip(2-Me)-(N(Me))-Bip(2-Me)-OH Des-amino-H-(N(Me))A-(N(Me))-(CJI 2 ) 3 -(N(Me))-Bip(2-Me)-(N(Me))-Bip(2-Me) OH 25 Des-amino-JJ-(N(Me))Aib-(N(M\e))-(CH 2 ) 3 -(N(Me))-Bip(2-Me)-(N(Me))-Bip(2 Me)-OH H-(N(Me))A-(N(Me))-(CH 2 ) 3 -(N(Me))-Bip(2-Me)-(N(Mle))-Bip(2-Me)-COO (CH 2 ) 6 -GH 3 H-(N(Me))Aib-(N(Me))-(C11 2 ) 3 -(N(Me))-Bip(2-Me)7(N(M\e))-Bip(2-Me)-COO 30 (C11 2 ) 6 -CH 3 H-(N(Me))A-(N(Me))-(CH 2 ) 3 -(N(Me))-Bip(2-Me)-(N(Me))-Bip(2-Me)-COO (CH 2 )lo-CH 3 H-(N(Me))Aib-(N(Ivle))-(CH 2 ) 3 -(N(Me))-Bip(2-Me)-(N(Me))-Bip(2-Me)-CO (CH 2 )lo-GH 3 - 81 - WO 2007/017892 PCT/1N2006/000154 CH3-(CH2)6-NH-H-(N(Me))A-(N(Me))-(CH 2 ) 3 -(N(Me))-Bip(2-Me)-(N(Me)) Bip(2-Me)-COO-(CH 2 ) 6 -GH 3 CH3-(CH 2 ) 6 -NH-H-(N(Me))Aib-(N(Me))-(CH 2 ) 3 -(N(Me))-Bip(2-Me)-(N(Me)) Bip(2-Me)-COO-(CH 2 ) 6 -CH 3 5 CH3-(CH 2 )Io-NH-H-(N(Me))A-(N(Me))-(CJI 2 ) 3 -(N(Me))-Bip(2-Me)-(N(Me)) Bip(2-Me)-COO-(CH 2 ) 6 -CH 3 CH3-(CH2)lo-NII-H-(§N(Me))Aib-(N(Me))-(CH 2 ) 3 -(N(Me))-Bip(2-Me)-(N(Me)) Bip(2-Me)-COO-(CH 2 ) 6 -CH 3 HA-(CH 2 ) 3 -Bip(2-Et)-Bip(2-Me)-OH 10 H-Aib-(CH 2 ) 3 -Bip(2-Et)-Bip(2-Me)-OH Ha-(CH 2 ) 3 -Bip(2-Et)-Bip(2-Me)-OL{ H-(N(Me))A-(CH 2 ) 3 -Bip(2-Et)-Bip(2-Me)-OH IH-(N(Me))A-(N(Me))-(CH 2 ) 3 -Bip(2-Et)-Bip(2-Me)-OH H-(N(Me))Aib-(N(Me))-(CH 2 ) 3 -Bip(2-Et)-Bip(2-Me)-OH 15 H-(N(Me))A-(N(Me))-(CH 2 ) 3 -(N(Me))-Bip(2-Et)-Bip(2-Me)-OHi H-(N(M\e))Aib-(N(Me))-(CH 2 ) 3 -(N(Me))-Bip(2-Et)-Bip(2-Me)-OH H-((Me))Ab-(N(Me))-(CH 2 ) 3 -(N(e))-Bip(2-Et)-(N(Me))Bip(2Me)cH 2HNM)AbNMe)(H)-NM)-i2-t-NM)-ip2M)O Des-amino-H-(N(M\e))Ai-(N(Me))-(CH 2 ) 3 -(N(Me))-Bip(2-Et)(N(Me))Bip(2-Me) Me)-OH (CH 2 ) 6 -C11 3 25 H-(N(Me))Aib-(N(Me))-(CH 2 ) 3 -(N(Me))-Bip(2-Et)-(N(Me))-Bip(2Me)COO. (CH 2 ) 6 -CFI 3 (Gil 2 ) 10 -CH 3 H-(N(Me))Aib-(N(Me))-(CH 2 ) 3 -(N(Me))-Bip(2-Et)-(N(Me))-Bip(2-Me).COO. 30 (CH 2 ) 10 -CH 3 MC O-(CH 2 ) 6 -H 3 (e)-NM)-C23((e)Bp2E)((e)Bp2 BpMe)-COO-(C I 2 ) 6 -CH 3 - 82- WO 2007/017892 PCT/1N2006/000154 Me)-COO-(CH 2 ) 6 -CH 3 BiP(2-Me)-COO-(CH 2 ) 6 -C 3 5 HA-(CH2)3-DVSSYLEGQAAKEFIKELEKLL HAib-(CH2)3-DVSSYLEGQAAKEFIKELEKLL HAibEGTFTSDVSSYLEGQ-(CH 2 ) 2 ..KELEKLL HAibEGTFTSDVSSYLEGQ-(CH 2 ) 3 KLEKLL HAibEGTFTSDVS SYLE-(CH 2 ) 2 -FIKELEKLL 10 H~ibEGT-(cc-Me)Phe(2-F).TSDVSSYLE-(CH 2 ) 2 -FIELEKLL IIAib-(C11 2 ) 3 -VS SYLE-(CH 2 ) 2 -FJKELEKLL J{Aib-(C11 2 ) 3 -VS SY-LE-(CH 2 ) 3 -FIKELEKLL IIAib-(CH2)3-YLE-(CH 2 ) 3 .FIKELEKLL T{Aib-(CH2)4-YLE-(CH2) 3 ..FIKELEKLL 15 LIAib-(CH2) 4 -YL-(CH 2 ) 3 .TJKELEKILL IIAib-(CH2)4-y-(CH 2 ) 3 -FIKELEKLL HAib-(C11 2 ) 4 -FJIKELEKLL HlAib-(CH 2 ) 5 -FIKELEKLL RAib-(CH 2 ) 6 -FIKELEKLL 20 JIAib-(CH 2 )8-FIKELEKLL J{Aib-(CH2)3 -VS SYLEGQ-(CH 2 ) 3 -. KELEKLL JIAib-(CH2)3 -VS SYLEG-(CH2) 3 -. KELEKLL J{Aib-(CH 2 ) 3 -VS SYLE-(C11 2 ) 4 -KELEKL H7Aib-(CH2)3-SSYLE-(CH 2 ) 4 4-IELEKLL 25 HAib-(CH2)3-SYLE-(CH 2 ) 4 -KELEKLL JJAib-(CH2)3-YLE-(CH 2 ) 4 ..KELEKLL HAib-(CH2) 3 -YL-(CH 2 ) 4 -KELEKcLL HAib-(CH2)3-y-(CH 2 ) 4 ..KELEKLL HAib-(CH 2 )5-KELEKLL 30 J{Aib-(CH 2 ) 6 -KELEKLL J{Aib-(C11 2 )8-KELEKLL. - 83 - WO 2007/017892 PCT/IN2006/000154

7. A pharmaceutical composition comprising compounds as claimed in claims 1-6 prepared according to the processes described herein and a suitable pharmaceutically acceptable carrier(s).

8. The compounds or their pharmaceutical compositions as claimed in claims 1-7, 5 which possess the ability to mimic the biological activity of GLP-1, more preferably mimic the GLP-1R agonist activity.

9. The compounds or their pharmaceutical compositions as claimed in any of the claims 1-7, useful for the treatment or prevention of diseases wherein GLP-1R peptide plays a patho-physiological function.

10 10. A method of preventing or treating diseases caused by hyperlipidaemia, hypercholesteremia, hyperglycemia, hyperinsulinemia, elevated blood levels of free fatty acids or glycerol, hypertriglyceridemia, wound healing, obesity, impaired glucose tolerance, leptin resistance, insulin resistance, diabetic complications, such as nephropathy, retinopathy, neuropathy and cataracts, comprising administering an 15 effective, non-toxic amount of compound of formula (I) as defined in any preceding claims to a patient in need thereof.

11. The method according to any preceding claims, wherein the disease is type 2 diabetes, impaired glucose tolerance, dyslipidaemia, hypertension, obesity, atherosclerosis, hyperlipidaemia, coronary artery disease, cardiovascular disorders 20 and other diseases wherein insulin resistance is the underlying pathophysiological mechanism.

12. A medicine for treating/reducing any of the disease conditions described in any preceding claims which comprises administering a compound of formula (I), as defined in claims 1-7 and a pharmaceutically acceptable carrier, diluent, excipients 25 or solvate to a patient in need thereof.

13. A medicine for treating/reducing any of the disease conditions described in any preceding claims which comprises administering a compound of formula (I), as defined in claims 1-7 in combination with a suitable DPP IV inhibitor, to a patient in need thereof. 30

14. Use of compounds of formula (I), alone or in combination with suitable DPP IV inhibitors, their pharmaceutical compositions and medicines containing them as defined in any previous claims as a medicament suitable for the treatment of diseases mentioned in any of the aforesaid claims. - 84 -