CN101223189A - Novel compounds as GLP-I agonists - Google Patents
Novel compounds as GLP-I agonists Download PDFInfo
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- CN101223189A CN101223189A CNA2006800242771A CN200680024277A CN101223189A CN 101223189 A CN101223189 A CN 101223189A CN A2006800242771 A CNA2006800242771 A CN A2006800242771A CN 200680024277 A CN200680024277 A CN 200680024277A CN 101223189 A CN101223189 A CN 101223189A
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Abstract
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 below: A-X1-S1-Y-S2-X2-B (I).
Description
Invention field
The present invention relates to the novel intermediates, their pharmacological-acceptable salt and the pharmacology composition that comprises them that relate in the compounds, their tautomeric form, their building-up process of general formula (I).
A-X
1-S
1-Y-S
2-X
2-B(I)
Specifically, the present invention relates to novel glucagon-like-peptide-1 (GLP-1) peptide mimics (plan peptide), it works as the GLP-1 receptor stimulant and shows most of biological activity of primary GLP-1.And, these GLP-1 intend peptide proteolysis division (particularly resisting DPP-IV (dipeptidyl peptidase-IV) enzyme) are shown the stability of increase, and can send by invasive and various Noninvasive route of administration (for example oral cavity, nasal cavity, cheek, lung and transdermal administration approach), be used for the treatment of or prevent diabetes and associated conditions.
The invention still further relates to the intermediate of the novelty that relates in the method for preparing general formula (I) compound, their tautomeric form, their pharmacological-acceptable salt, the pharmacology composition that comprises them and their building-up process.
Background of invention
GLP-1 (7-36) acid amides is the product of protogene before the hyperglycemic-glycogenolytic factor, and the ingestion of food of described Proglucagon gene response is come out from intestines L emiocytosis.The physiologic function of GLP-1 has attracted suitable research interest.GLP-1 brings into play multinomial function (pancreotropic hormone function) by stimulating the insulin secretion from pancreatic beta cell in the mode that depends on glucose.GLP-1 has reduced round-robin blood plasma hyperglycemic-glycogenolytic factor concentration (Drucker D.J., Endocrinology, 142,521-527,2001) also by the secretion of glucagon suppression from the α cell.Recently, people have known the character (Nauck, Horm.Metab.Res., 1253-1258,1997) that GLP-1 also shows to be stimulated the growth of β cell, depress appetite, the emptying of postponement stomach and stimulate insulin sensitivity.
Contain in the venom of Gila monster (Heloderma Suspectum) and be called acetate Exenatide (Exendin-4, EX-4) 39 amino acid peptides, its sequence of about 50% is identical with GLP-1, show potent GLP-1R (glucagon-like peptide-1 receptor) agonist activity (Thorens B., Diabetes, 42,1678-1682,1993).In fact, have been found that EX-4 is more effective than primary GLP-1 peptide, because the transformation period of EX-4 is grown (25 minutes, intravenous administration), and the transformation period of GLP-1 is lacked (2-5 minute, intravenous administration).Owing to there are 9 unusual C terminal sequences, so the affinity of Exendin-4 and GLP-1R (Doyle M.E., Regulatory Peptides, 114,153-158,2003) greatly.Therefore, the above-mentioned pharmacological property of GLP-1R agonist makes it become the very ideal therapeutical agent of treatment diabetes.
Primary or synthetic GLP-1 peptide is inactive metabolite by the quick metabolism of proteolytic ferment (for example dipeptidyl peptidase-IV (DPP-IV)), thereby has limited the purposes of GLP-1 as medicine.At present, the multiple analogue of GLP-1 and EX-4 Liraglutide/NN2211 (Novo Nordisk for example; The III phase; WO 1,998 008871), BIM 51077 (Ipsen; The II phase; WO 2,000 034331), CJC-1131 (ConjuChem; The II phase; WO 2,000 069911), ZP-10 (Zealand﹠amp; Aventis; The II phase; WO 2,001 004156) all be in different clinical development in the stage (Nauck M.A., RegulatoryPeptides, 115,13-19,2004).But all these peptides all need to send by the parenteral route of administration, comprise
(Exendin-4, AC 2933; WO 2,001 051078), it puts (Amylin﹠amp recently on market; Lilly).Therefore, be starved of the biologic activity GLP-1 stand-in that exploitation has the beneficial effect curve of expansion.
GLP-1R is 7 membrane-spanning domain G protein binding acceptors (GPCR), is positioned on the cytolemma of pancreatic beta cell.The effector system of GLP-1R is adenylyl-cyclase (AC).The interaction of GLP-1 agonist and GLP-1R causes AC to be activated, and ATP is converted into cAMP.The raising of cAMP level has increased ADP/ATP ratio in the cell, thus trigger cell depolarization (because K
ATPPathway closure).The raising of cAMP level has also activated protein kinase (PK-A﹠amp in the cell; PK-C), it is by opening L type Ca
2+Passage increases Ca in the cell
2+Concentration.Ca in the cell
2+Increase cause Regular Insulin exocytosis in the pancreatic beta cell (Fehmann, H.C., Endocr.Rev., 16,390-410,1995).
Have been found that the interactional general mechanism of peptide part and category-B GPCR at present, be called " two territory " model (Hoare S.R.J., Drug Discovery Today, 10 (6), 417-427,2005).In this pair of domain model, the C end parts of peptide combines with the N territory of acceptor, the regional combination in J territory (film thoroughly) of N end part zone and GPCR.This interaction has activated acceptor, thus signal transmission in the irritation cell.Receptors bind and activation in two independences of Exendin but (Eng J., J.B.C., 272 (34), 21291-21296,1997) take place in the territory in GLP-1 of combining closely.
Prior art
In early days, Bristol-Myers Squibb (BMS), Princeton, NJ (US) has reported people GLP-1 stand-in, its general formula is Xaa1-Xaa11, wherein Xaa1-Xaa9 represents the preceding 1-9 residue of GLP-1 peptide, in some stand-in, Xaa2 represents L-Ala (Ala) or optional with aminoisobutyric acid (Aib) replacement, Xaa6 represents phenylalanine (Phe) or optional with α-Me-Phe (2-F)-OH replacement, combination (the WO 03/033671A2 of Xaa10 and Xaa11 representative replacement or unsubstituted biphenyl group L-Ala (Bip) derivative; US 2004/0127423 A1; WO 2004/094461 A2; US 2006/0004222 A1 and WO2006/014287 A1).
The invention provides the novel GLP-1 peptide mimics (hereinafter referred to as intending peptide) of general formula (I), it works as the GLP-1R agonist and shows most of biologic activity of primary GLP-1 peptide.And, these GLP-1 intend peptide proteolysis division (particularly resisting the DPP-IV enzyme) are shown the stability of increase, therefore, we find amazedly, the transformation period that these GLP-1 intend peptides and increase make its be suitable for treating/alleviate/prevent 1 type and diabetes B, Metabolic disorder, obesity and relevant discomfort.
Summary of the invention
The invention describes one group of novelty that is applicable to the treatment diabetes and intend peptide.These compounds are determined by following general formula (I).Compound of the present invention is applicable to by regulating insulin secretion treatment human body or animal body.Therefore, compound of the present invention is applicable to and treats/alleviate/regulate or prevent 1 type and diabetes B and obesity.
The preferred embodiment for the present invention
Main purpose of the present invention provide be applicable to treat/alleviate/regulate the compounds of the general formula (I) of diabetes, their tautomeric form, the novel intermediates that in their building-up process, relates to, they pharmacological-acceptable salt, they pharmacology acceptable solvent thing and comprise their pharmacology composition or their mixture.
In one embodiment, the compounds that is used to prepare general formula (I), their tautomeric form, their pharmacological-acceptable salt, pharmacology acceptable solvent thing and the pharmacology method for compositions that comprises them are provided.
In another embodiment, the compound that comprises general formula (I), their tautomeric form, their the pharmacology composition of pharmacological-acceptable salt, solvate and their mixture are provided, have comprised normally used pharmacology acceptable carrier, solvent, thinner, vehicle and other media in their manufacturing processed in the described pharmacology composition.
In another embodiment, effective and general formula (I) compound or their pharmacology non-toxicity amount can be accepted composition by the Mammals pharmacology that gives to carry out this kind treatment, and the purposes of compounds of the present invention as antidiabetic is provided.
The abbreviated form that uses
In embodiment and other parts, used following abbreviated form:
The Aib=α-An Jiyidingsuan
ACN or MeCN=acetonitrile
Bip=biphenyl alanine residue
Bip (4-fluro)=4-fluoro-biphenyl alanine residue
Bip (2-Me)=2-methyl biphenyl residue
Bip (2-Et)=2-ethyl biphenyl base residue
Bip (2-CN)=2-nitrile xenyl residue
Bip (2-Ipr)=2-isopropyl biphenyl base residue
Bip (2 '-Et-4 '-OMe)=2 '-ethyl-4 '-methoxyl group-xenyl residue
Bip (2-F)=2-fluoro-xenyl residue
The Bn=benzyl
The Boc=tert-butoxycarbonyl
The But=O-tertiary butyl
CAMP=3 ', 5 '-single adenosine phosphate encircled
The DCM=methylene dichloride
DMF=N, dinethylformamide
The DIPCDI=DIC
The DIPEA=diisopropyl ethyl amine
4-DBF=4-diphenylene-oxide-Phe-OH residue
4-DBT=4-dibenzothiophene-Phe-OH residue
Dihydro-Phen=2-(9, the 10-dihydro-Fei)-L-Ala-OH residue
The Et=ethyl
Et
2The O=diethyl ether
Fmoc=fluorenyl methoxy carbonyl
2-Flu=2-fluorenyl-L-Ala-OH residue
The g=gram
The test of GTT=glucose tolerance
The GLP-1R=glucagon-like peptide-1 receptor
H=hour
The HOBt=hydroxybenzotriazole
HOAT=7-azepine-hydroxybenzotriazole
HBTU=2-(1H-benzotriazole-1-yl)-1,1,3,3-tetramethyl-ammonium hexafluorophosphate
The HPLC=high performance liquid chromatography
The L=liter
The LC/MS=liquid chromatography/mass spectrometry
4-(2 '-Me-Ph)-3-Pyr-Ala=4-(2 '-aminomethyl phenyl)-3-pyridyl alanine residue
The Me=methyl
Min=minute
The ml=milliliter
μ l=microlitre
The mg=milligram
Mmol=rub in the least (that)
Fmol=method rub (that)
The MS=mass spectrum
1-Nap=4-(1-naphthyl)-phenylalanine residue
2-Nap=4-(2-naphthyl)-phenylalanine residue
Phen=2-(phenanthryl)-L-Ala-OH residue
Pbf=pentamethyl-benzo furans-5-alkylsulfonyl
PyBOP=benzotriazole-1-base-oxygen-tripyrrole alkyl-phosphorus hexafluorophosphate
The SPPS=solid-phase peptide is synthetic
Sc=is subcutaneous
TrPh=4-phenyl-biphenyl alanine residue
The TMS=trimethyl silyl
The TIPS=tri isopropyl silane
The TFA=trifluoroacetic acid
TBTU=2-(1H-benzotriazole-1-yl)-1,1,3,3-tetramethyl-ammonium a tetrafluoro borate
The Trt=trityl
(Phe (2-F)=alpha-methyl-2-fluoro-phenylalanine residue of α-Me)
-(N (Me))-=the N-amido linkage that methylates
Represent the D-L-Ala with " a ", D-Bip representative " D "-biphenyl alanine residue
Ip=is endoperitoneal
The GLP-1 peptide sequence=
NH
2-HAEGTFTSDVSSYLEGQAAKEFIAWLVKGR-CONH
2(30 amino acid).30 amino acid of described GLP-1 peptide are as shown in Seq ID 1.
HAEGTFTSDVSSYLEGQAAKEFIAWLVKGR---Seq ID 1
The Exendin-4 sequence=
NH
2-HGEGTFTSDLSKQMEEEAVRLFIEWLKNGGPSSGAPPPS-CONH
2(39 amino acid).39 amino acid of Extendin-4 are as shown in Seq ID 2.
HGEGTFTSDLSKQMEEEAVRLFIEWLKNGGPSSGAPPPS---Seq ID 2
Describe in detail
In the present invention, provide the similar peptide of synthetic GLP-1/plan peptide, it has general formula (I), A-X
1-S
1-Y-S
2-X
2-B (I)
Wherein,
A represents-NH-R
1, R
1Expression: hydrogen; Be selected from straight or branched (C
1-C
15) group of alkyl, for example methyl, ethyl, propyl group, sec.-propyl, normal-butyl, isobutyl-, the tertiary butyl, amyl group, isopentyl, hexyl, heptyl, octyl group, decyl etc.; Comprise amino acid or peptide a kind of, two or three natural amino acid residue; R
3-CO-group, for example (2-hydroxyl-phenyl)-ethanoyl etc.; R
3O-C (O)-group, for example Fmoc group etc.; Has general formula R
3-SO
2-alkylsulfonyl, various can the replacement in these groups, wherein R
3Be selected from: straight or branched (C
1-C
10) alkyl (for example methyl, ethyl, propyl group, sec.-propyl, normal-butyl, isobutyl-, the tertiary butyl, amyl group, isopentyl, hexyl, heptyl, octyl group, decyl etc.), (C
3-C
6) cycloalkyl (for example cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl etc.), be selected from the aryl of phenyl, naphthyl, indanyl, fluorenyl, xenyl etc., be selected from the heteroaryl of pyridyl, thienyl, furyl, imidazolyl, benzofuryl etc., be selected from the aralkyl of benzyl, menaphthyl etc., various can the replacement in these groups;
B represents-COOR
2,-CONHR
2Or CH
2OR
2, R
2Expression: H; Be selected from straight or branched (C
1-C
10) group of alkyl, for example methyl, ethyl, propyl group, sec.-propyl, normal-butyl, isobutyl-, the tertiary butyl, amyl group, isopentyl, hexyl, heptyl, octyl group, decyl etc.; Be selected from the aryl aryl of phenyl, naphthyl, indanyl, fluorenyl, xenyl etc.; Aralkyl, various can the replacement in these groups,
Each S
1And S
2Can be a key independently or represent NH-(CH independently
2)
n-COO-, wherein n=1-9, for example derivative of Padil, alanine, aminobutyric acid, aminovaleric acid, hexosamine, aminoheptylic acid, aminocaprylic acid, amino-nonanoic acid, amino capric acid etc.;
Y represent a key or-CO-,-(CH
2)
m-(m=1-3), O, S ,-CO-NH-,-CO-NR
4, perhaps expression comprises a kind of, the two or three amino acid whose small peptide that is selected from natural or alpha-non-natural amino acid; R wherein
4Expression: H; Be selected from straight or branched (C
1-C
10) group of optional replacement of alkyl; For example methyl, ethyl, propyl group, sec.-propyl, normal-butyl, isobutyl-, the tertiary butyl, amyl group, isopentyl, hexyl, heptyl, octyl group, decyl etc.; Be selected from the aryl of phenyl, naphthyl, indanyl, fluorenyl, xenyl etc.; Prerequisite is:
I) work as S
1-Y-S
2When representing a key,
X
1Be selected from following aminoacid sequence
HAEGTFTSD (Seq ID 3), HAEGTFTSDV (Seq ID 4), HAEGTFTSDVS (Seq ID5), 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), HAEGTFTSDVSSYLEGQAAK (Seq ID 14), HAEGTFTSDVSSYLEGQAAKE (Seq ID 15), HAEGTFTSDVSSYLEGQAAKEF (Seq ID 16), HAEGTFTSDVSSYLEGQAAKEFI (Seq ID 17), in further option, one or more in these amino acid can be replaced by alpha-non-natural amino acid, X
2Be selected from following aminoacid sequence:
GPSSGAPPPS (Seq ID 18) or
KELEKLL (Seq ID 19) or
GPPS (Seq ID 20) or
VKGR(Seq ID 21)；
Ii) work as S
1-Y-S
2When not representing a key,
X
1Be selected from following aminoacid sequence:
HA (Seq ID 22), HAE (Seq ID 23), HAEG (Seq ID 24), HAEGT (SeqID 25), HAEGTF (Seq ID 26), HAEGTFT (Seq ID 27), HAEGTFTS (Seq ID28), HAEGTFTSD (Seq ID 29), in further option, one or more in these amino acid can be replaced by alpha-non-natural amino acid;
X
2Be selected from:
GPSSGAPPPS (Seq ID 18) or
KELEKLL (Seq ID 19) or
GPPS (Seq ID 20) or
VKGR (Seq ID 21) or
Be selected from the dipeptides of the combination of two seed amino acids, form by natural or alpha-non-natural amino acid, has the side chain that comprises aralkyl or heteroaralkyl part, described aralkyl or heteroaralkyl are selected from benzyl, menaphthyl, picolyl, thenyl, furfuryl, imidazoles methyl isoxazole methyl, the quinoline methyl, the cumarone methyl, the thionaphthene methyl, the indoline methyl, indole methyl, the diphenylene-oxide methyl, the dibenzothiophene methyl, the coumaran methyl, the thiaindan methyl, the Thienopyrimidine methyl, the benzoglyoxaline methyl, luxuriant and rich with fragrance methyl, the luxuriant and rich with fragrance methyl of dihydro, fluorene methyl, the diphenylene-oxide methyl, dibenzo thiophenyl methyl etc., various can the choosing wantonly by following group in these groups replaces: (C
1-C
6) alkyl, for example methyl, ethyl, propyl group, sec.-propyl, normal-butyl, isobutyl-, the tertiary butyl, amyl group, isopentyl, hexyl etc.; (C
1-C
6) alkoxyl group, for example methoxyl group, oxyethyl group, propoxy-, butoxy, pentyloxy, hexyloxy; Cyano group; Halogen, for example chlorine, bromine, iodine, fluorine; Hydroxyl; Perhaps be selected from the aryl or the heteroaryl of following optional replacement: phenyl, naphthyl, pyridyl, thienyl, furyl, imidazolyl, isoxazolyl, quinolyl, benzofuryl, benzothienyl, indoline base, indyl, dibenzofuran group, dibenzothiophene base, coumaran base, thiaindan base, Thienopyrimidine base, benzimidazolyl-, phenanthryl, dihydrophenanthrenyl, fluorenyl, dibenzofuran group, dibenzothiophene base etc., stipulate that further these aryl or heteroaryl substituting group can be further randomly by (C
1-C
6) alkyl, (C
1-C
6) alkoxyl group, cyano group, halogen, hydroxyl, aryl or heteroaryl replace.
One preferred embodiment in, described two peptide sequences can comprise and are selected from one or more following amino acid: Bip, Bip (2-methyl), Bip (2-ethyl), Bip (2-sec.-propyl), Bip (2-CN), Bip (2 '-ethyl-4 '-methoxyl group), Bip (4 '-fluorine), Bip (4 '-phenyl), 2-(9,10-dihydro-phenanthryl)-Ala, 2-(phenanthryl)-Ala, 4-(2-naphthyl)-Phe, 4-(1-naphthyl)-Phe, 2-fluorenyl-Ala, 4-diphenylene-oxide-Phe, 4-dibenzothiophene-Phe, 4-(2 '-aminomethyl phenyl)-3-pyridyl L-Ala; Naturally occurring all that 20 seed amino acids of term " natural amino acid " expression.
Term " alpha-non-natural amino acid " expression replaces L-amino acid with corresponding D-amino acid, for example replaces L-Ala with D-Ala, or replaces L-Pro etc. with D-Pro; Perhaps suitable modification is carried out in L-amino acid or D-amino acid, aminoalkyl group acid by following effect:
-alpha-alkyl turns usefulness into, for example uses Alpha-Methyl Ala (Aib) to replace Ala, replaces Phe with Alpha-Methyl Phe, replaces the Bip that replaces with Alpha-Methyl Bip;
-with being selected from (C
1-C
6) alkyl or (C
3-C
6) group of cycloalkyl carries out the N-alkylating;
-side chain is carried out modification, for example use Histidine analogue (for example 1-imidazolyl-L-Ala (II) or deaminizating His) to replace His,
Or replace the phenyl ring of Phe with pyridyl, naphthyl, xenyl;
-on amino acid whose side chain, replace, for example use halogen, (C
1-C
3) alkyl, aryl replace the aromatic amino acid side chain, more particularly is with 2 and 4-halo Phe replacement Phe;
These " alpha-non-natural amino acids " generally can show with following structural table:
R wherein
5Be selected from H, F, (C
1-C
5) alkyl, band R
5The three-dimensional chemical configuration at carbon atom place can be (R) or (S); R
6Be selected from H or (C
1-C
3) alkyl; R
7And R
8Be selected from H, (C independently of one another
1-C
3) alkyl, for example methyl and ethyl or halogen atom, preferably fluorine atom; R
9Expression is selected from (C
1-C
5) group of alkyl, aryl or heteroaryl, aryl or heteroaryl moieties are selected from phenyl, naphthyl, pyridyl, thienyl, furyl, imidazolyl, isoxazolyl, quinolyl, benzofuryl, benzothienyl, indoline base, indyl, dibenzofuran group, dibenzothiophene base, coumaran base, thiaindan base, Thienopyrimidine base, benzimidazolyl-, phenanthryl, dihydrophenanthrenyl, fluorenyl, dibenzofuran group, dibenzo thiophenyl, and various can the choosing wantonly by following group in these groups replaces: (C
1-C
6) alkyl, (C
1-C
6) alkoxyl group, cyano group, halogen, hydroxyl or optional aryl or the heteroaryl that replaces, stipulate that further these aryl or heteroaryl substituting group can further choose quilt (C
1-C
6) alkyl, (C
1-C
6) alkoxyl group, cyano group, halogen, hydroxyl, aryl or heteroaryl replace.
Be used for the Bip analogue tabulation that synthetic GLP-1 intends the Fmoc protection of peptide
Fomc-4-(2 '-aminomethyl phenyl)-3-pyridyl L-Ala-OH, Fmoc-Bip (2 '-Et-4 '-OMe)-OH, Fmoc-Bip (2-CN)-OH
Fmoc-Bip(2-Me)-OH， Fmoc-Bip-OH， Fmoc-Bip(2-Ipr)-OH
Fmoc-Bip (2-Et)-OH, Fmoc-4-(1-naphthyl)-Phe-OH, Fmoc-2-(9,10-dihydro-phenanthryl)-Ala-OH
Fmoc-Bip (4-Ph)-OH, Fmoc-Bip (4-F)-OH, Fmoc-2-(phenanthryl)-Ala-OH
Fmoc-2-fluorenyl-Ala-OH, Fmoc-4-diphenylene-oxide-Phe-OH, Fmoc-4-dibenzothiophene-Phe-OH
The group that suitable substituents includes, but are not limited to following independent use or uses with other moiety combinations: hydroxyl, oxo, halogen, sulfo-, nitro, amino, cyano group, alkyl, haloalkyl, alkoxyl group, halogenated alkoxy, cycloalkyl, aryl, aryloxy, aralkyl, aralkoxy, heteroaryl, heteroaralkyl, heteroaryloxy, assorted aralkoxy, acyl group, acyloxy, carboxylic acid and derivative thereof be ester and acid amides for example;
Following paragraph is described various groups, base and the substituting group that uses in the specification sheets.
Use separately in the literary composition or contain the group of the straight or branched of 1-10 carbon atom, for example methyl, ethyl, n-propyl, sec.-propyl, normal-butyl, sec-butyl, the tertiary butyl, amyl group, tert-pentyl, n-pentyl, n-hexyl, isohexyl, heptyl, octyl group, decyl etc. with term " alkyl " expression that other moiety combinations are used.
Use separately in the literary composition or contain the group of 3-7 carbon atom, as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, suberyl etc. with term " cycloalkyl " expression that other moiety combinations are used.
The aromatic systems that the term " aryl " that uses separately in the literary composition or use with other moiety combinations or " aromatics " expression contain 1,2 or 3 ring, wherein these rings can the side chain mode link together, perhaps these rings can be condensed, for example phenyl, naphthyl, tetralyl, indane, biphenyl etc.
The abovementioned alkyl that term " aralkyl " expression is connected with aryl, for example benzyl, styroyl, menaphthyl etc.The above-mentioned aryl that term " aryloxy " expression is connected with alkoxyl group, for example phenoxy group, naphthyloxy etc. can replace.
The above-mentioned aralkyl moiety that term " aralkoxy " expression is connected with oxygen, for example benzyloxy, benzene oxyethyl group, naphthalene methoxyl group, benzene propoxy-etc. can replace.
Use separately in the literary composition or comprise 1 with term " heteroaryl " or " heteroaromatic " expression that other moiety combinations are used, the aromatic systems of 2 or 3 rings, wherein these rings can the side chain mode link together, perhaps these rings can be condensed, and contain one or more O of being selected from these rings, the heteroatoms of N or S, for example pyridyl, thienyl, furyl, pyrryl oxazolyl, thiazolyl, isothiazolyl, imidazolyl isoxazolyl oxadiazole base, thiadiazolyl group, triazolyl, tetrazyl, benzopyranyl, the chromene ketone group, benzofuryl, benzothienyl, the indoline base, indyl, azaindolyl, azaindole quinoline base, the coumaran base, the thiaindan base, the pyrazolopyrimidine base, the pyrazolopyrimidine ketone group, the azepine quinazolyl, azepine quinazoline ketone group, the pyrido furyl, the pyrido thienyl, the Thienopyrimidine base, the Thienopyrimidine ketone group, quinolyl, pyrimidyl, pyrazolyl, quinazolyl, the quinazoline ketone group, the pyrimidine ketone group, pyridazinyl, triazinyl; benzoxazinyl; benzoxazine ketone group, the benzothiazine base, benzothiazine ketone group; benzoxazolyl, benzothiazolyl, benzimidazolyl-, the benzotriazole base, phthalazinyl, naphthylidinyl, purine radicals, carbazyl, phenothiazinyl phenoxazine etc.
Use separately in the literary composition or represent the above-mentioned heteroaryl that is connected with the straight or branched saturated carbon chains that contains 1-6 carbon atom, for example (2-furyl) methyl, (3-furyl) methyl, (2-thienyl) methyl, (3-thienyl) methyl, (2-pyridyl) methyl, 1-methyl isophthalic acid-(2-pyrimidyl) ethyl etc. with the term " heteroaralkyl " that other moiety combinations are used.Term " heteroaryloxy ", " assorted aralkoxy ", " heterocyclic oxy group " are represented the above-mentioned heteroaryl, heteroaralkyl and the heterocyclic radical that are connected with Sauerstoffatom respectively.
Use separately in the literary composition or contain the group of 1-8 carbon atom with term " acyl group " expression that other moiety combinations are used; for example formyl radical, ethanoyl, propionyl, butyryl radicals, isobutyryl, pentanoyl, caproyl, oenanthyl, benzoyl etc. can replace.
Use separately in the literary composition or with term " carboxylic acid " expression-COOH group that other moiety combinations are used, comprise carboxylic acid derivative for example ester and acid amides.Use separately in the literary composition or with term " ester " expression-COO-group that other moiety combinations are used, comprise that ester moiety wherein is the carboxylic acid derivative of carbalkoxy, for example methoxycarbonyl, ethoxycarbonyl etc. can replace.
Unless other explanation is arranged, otherwise the amino and the carboxyl that use separately in the literary composition or include, but are not limited to as the term " amino acid " that the part of another kind of group is used to connect with identical carbon atom (referring to " α " carbon atom).
Absolute " S " configuration ordinary representation " L " in " α " carbon atom place or native configurations." α " carbon atom place " R " configuration ordinary representation " D " amino acid.When two " alpha-substitution bases " were identical, when for example being hydrogen or methyl, described amino acid was Gly (glycine) or Aib, and is achirality.
Term " receptor modulators " expression plays a role as the GLP-1 acceptor and regulates the compound that downstream signal transmits the ability of incident to change it.The example of receptor modulators comprises agonist, partial agonist, inverse agonist, allosteric potentiators.
Isolating plan peptide is the 3-30 aggressiveness preferably, these peptides and GLP-1 receptors bind and activation GLP-1 acceptor.
According to the present invention, the isolating plan peptide of described synthetic has the ability of simulation GLP-1 peptide biological activity, the preferably agonist activity of GLP-1R.These synthetic peptide GLP-1-1 stand-in of intending show character in the body that needs, thereby make them become the ideal treatment material standed for of oral or parenterai administration.
The invention provides the pharmacology composition that is used singly or in combination general formula (I) compound, and the method for using these compounds is provided.Specifically, the invention provides a kind of pharmacology composition, wherein comprise general formula (I) compound for the treatment of significant quantity separately, perhaps comprise the combination of general formula (I) compound and pharmacological-acceptable carrier.
The method of disposing or delaying diabetes development or outbreak also is provided, described diabetes specifically are type ii diabetes, comprise diabetic complication, comprise retinopathy, neuropathy, ephrosis and wound healing postpone, and associated conditions insulin resistance (the glucose homeostasis is impaired) for example, hyperglycemia, hyperinsulinemia, lipid acid or glycerine level raise in the blood, obesity, hyperlipidemia (comprising hypertriglyceridemia), X syndrome, atherosclerosis and hypertension, in this method, need the Mammals of disposing, the general formula of human therapy significant quantity (I) compound or their combination.
Can use some synthesis paths to prepare the synthetic well-known The compounds of this invention of those skilled in the art of peptide.The version that can use the synthetic known routine techniques of those skilled in the art of following method and peptide or those skilled in the art to understand synthesizes the compound (all symbols are as indicated above) of general formula (I).Described method includes, but are not limited to hereinafter described content.
The chemosynthesis of intending the appropriate variation form that peptide can be by utilizing known various solid phase techniques described in the literary composition prepares, described in these known technologies such as the following document: G.Barany﹠amp; R.B.Merrifield, " The peptides:Analysis, synthesis, Biology "; The 2nd volume " Special methodsin peptide synthesis, Part A ", 3-284 page or leaf, E.Gross﹠amp; J.Meienhofer compiles, Academic Press, New York, 1980; With J.M.Stewart and J.D.Young, " Solid-phasepeptide synthesis " the 2nd edition, Pierce chemical Co., Rockford, IL, 1984.
Preparation the present invention intends the preference policy of peptide to utilize the approach based on the SPPS of Fmoc; wherein use Fmoc (9-fluorenyl-methyl-methoxycarbonyl) group to come the temporary protection alpha-amino group, use simultaneously the unsettled blocking group of acid (for example tertbutyloxycarbonyl (Boc), the tertiary butyl (Bu
t), trityl (Trt)) come the temporary protection amino acid side chain (for example referring to E.Atherton﹠amp; R.C.Sheppard, " TheFluorenylmethoxycarbonyl amino protecting group ", " The peptides:Analysis, synthesis, Biology "; The 9th volume " Special methods in peptidesynthesis, Part C ", 1-38 page or leaf, S.Undenfriend﹠amp; J.Meienhofer compiles, AcademicPress, San Diego, 1987).
The amino acid whose example of the orthogonally protect that in the Fmoc solid-phase peptide building-up process of synthetic plan peptide, uses
Can in mode progressively, go up the synthetic peptide of intending from forming the C-terminal of peptide at insoluble polymer carrier (resin).In one embodiment, by forming acid amides, ester or ehter bond, the C terminal amino acid of peptide is attached on the resin, cause synthetic, thereby finally discharge the peptide that makes with the form of C end acid amides, carboxylic acid or alcohol respectively.
In SPPS based on Fmoc; need carry out the protection (orthogonally protect) of differentiation with all other amino acid whose alpha-amino groups and side chain functionalities (if present) to the C terminal amino acid that uses in synthetic; make and in building-up process, can use suitable alkali (for example 20% piperidine solution) optionally to remove the alpha-amino group blocking group; and peptide is dissociated from resin prematurely, perhaps make the side chain protected group generation deprotection that is generally the unsettled blocking group of acid.
By activating amino acid whose carboxyl, make it become active ester and make itself and the non-sealing alpha-amino group reaction that is attached to N terminal amino acid on the resin, connect amino acid.After each connection and the deprotection steps, with excessive solvent (for example DMF, DCM and diethyl ether) washing peptide acyl-resin.Repeat alpha-amino group deprotection and the process that is connected successively, up to being assembled into the peptide sequence that needs.Use the suitable mixture that dissociates then, (with the restriction side reaction) makes peptide dissociate from resin in the presence of suitable scavenging agent usually, and is accompanied by the deprotection of side chain functionality.The peptide that makes by the reversed-phase HPLC purifying at last.
Synthetic peptide acyl-resin is during as final propeptide, use commercially available crosslinked polystyrene polymer resin (Novabiochem, San Diego, CA).Among the present invention preferred use Fmoc-PAL-PEG-PS resin, 4-(2 '; 4 '-Dimethoxyphenyl-Fmoc-aminomethyl)-phenoxy group ethanoyl-para-methylbenzhydrylamine resin (Fmoc-Rink acid amides mbha resin), chlorination 2-chloro-trityl resin or right-benzyloxy benzylalcohol resin (HMP resin), these resins can connect or not connect the C terminal amino acid.If do not connect the C terminal amino acid, then can be by being connected by the amino acid whose HOBt active ester of resin with DIPCDI reaction formation Fmoc protection.For the situation of 2-chloro-trityl resin, use DIPEA to connect the amino acid of Fmoc protection.For the amino acid whose assembling of the next one, use N end protection the carry out selectivity deprotection of the piperidine solution of 10-20% to peptidyl resin.Each connect and deprotection steps after, wash with DMF, DCM and ether that to remove the excess of ammonia base sour and be connected reagent.Use the HOBt or the HOAT active ester that make by DIPCDI/HOBt or DIPCDI/HOAT respectively to finish follow-up amino acid whose connection.Connect situation of difficult for some; particularly connect hydrophobic amino acid or have the amino acid whose situation of large volume side chain protected, can use efficient linking agent (for example HBTU, PyBOP or TBTU) to realize being connected fully with the combination of additive (for example DIPEA).
General course based on the SPPS of Fmoc:
The synthetic of peptide analogs described in the literary composition can be flowed the peptide synthesis device in batches or continuously and carry out by using.Use one or more methods as known in the art, the non-commercially available amino acid of non-natural that will be present in different positions is attached in the peptide chain.In a kind of approach, use suitable literature method in solution, to prepare the alpha-non-natural amino acid of Fmoc protection.For example, use the Bip analogue of the above-mentioned Fmoc protection of known improved Suzuki cross-connection method (for example Tetrahedron Letter 58,9633-9695,2002) preparation in the document.Use asymmetric Strecker synthetic method to prepare the alpha-methylated amino acid of Fmoc protection, as Org.Letters 3 (8), 1121-1124 is described in 2001.Use for example JOC, 2005,70, the literature method described in the 6918-6920 prepares the methylated amino acid of N-of Fmoc protection.Use the progressively synthetic peptide of the derivative that makes then.Perhaps, use the Synthetic Organic Chemistry method directly on resin, to make up the alpha-non-natural amino acid that needs, form linear peptide chain.
Can use any standard dissociating method of describing in the document the appropriate variation form (for example, referring to D.S.King etc., Int.J.peptide Protein res.36,1990,255-266), corresponding peptide-resin precursor of intending peptide is dissociated and deprotection.The method that the present invention preferably uses is utilized the TFA mixture that dissociates, and carries out in the presence of water, and uses TIPS as scavenging agent.Usually, make peptide acyl-resin TFA/ water/TIPS (94: 3: 3; V: V: V; 10 milliliters/100 milligrams peptidyl resins) at room temperature cultivated 1.5-2 hour in.Remove by filter dissociated resin then, under reduced pressure concentrate or dry TFA solution.Use Et
2The thick peptide that O precipitation or washing make perhaps directly is dissolved in thick peptide again in the acetic acid aqueous solution of DMF or 50%, and carries out purifying with preparation HPLC.
Use preparation HPLC to carry out the plan peptide that purifying need can obtain purity.Thick peptide solution is injected into semipreparative column (Luna 10 μ; C
18100 dusts) in, column dimension is 250 * 50 millimeters, carries out linear gradient elution with the aqueous solution of ACN, and the thick peptide solution and the ACN aqueous solution all use 0.1% TFA to carry out buffering, eluent flow rate is the 15-50 ml/min, and effluent liquid is monitored in 220 nanometers with the PDA detector.Can use electrospray ionization mass spectrum (ES-MS) analysis to determine the structure of the plan peptide of purifying.
After the preparation HPLC purifying, use TFA as counter ion, all peptides that make with the isolated in form of trifluoroacetate.But, for some peptide, make it pass through suitable ion exchange resin bed, preferably, carry out desalting by anionite-exchange resin Dowex SBR P (Cl) or the basic anion exchange resin that is equal to.In some cases, make the TFA counter ion, use the acetic acid,diluted eluant solution, thereby replace the TFA counter ion with acetate ion by suitable ion exchange resin.For the situation of hydrochloride of preparation peptide, in the final stage of the selected peptide of preparation, acetate is handled with the HCl of 4M.The solution that makes is filtered and freeze-drying subsequently by film filter (0.2 micron), make from white to linen HCl salt.Carry out appropriate variation within those skilled in the art's limit of power according to similar techniques and/or to it, can prepare other suitable pharmacological-acceptable salts that the present invention intends peptide.
One preferred embodiment in, the invention provides the method for the active plan peptide of preparation simulation endogenous polypeptide GLP-1R agonist.In another preferred implementation, the polypeptide receptor agonist is GLP-1.
By making up with well-known appropriate excipients, compounds of the present invention can be mixed with suitable pharmacology can accept composition.
Provide the pharmacology composition by routine techniques.The active ingredient that comprises significant quantity in the unit dosage form of preferred composition, i.e. Individual existence or general formula of the present invention (I) compound that exists with array configuration.
According to the effectiveness of concrete application method, specific compound and the concentration of needs, can change or regulate the quantity of active ingredient in pharmacology composition and the unit dosage form thereof (being the compound of general formula of the present invention (I)) widely.The directiveness suggestion be, obtain positive effect, the daily oral dosage of active ingredient is about 0.001-1000 mg/kg body weight/day, preferably is about 0.01-100 mg/kg body weight/day, is most preferably 0.6-20 mg/kg body weight/day.
Utilize the preparation of SPPS approach to intend the general method of peptide:
To intend peptide is assembled on the resin:
Swelling capacity (50-100 milligram) Fmoc-PAL-PEG-PS resin or Fmoc-Rink acid amides mbha resin (charge capacity: 0.5-0.6 rubs in the least/restrains) are 2-10 minute in DMF (1-10 milliliter/100 milligram resin).Use the DMF solution (10-30 milliliter/100 milligram resin) of the piperidines of 10-30% that resin was cultivated 10-30 minute then, remove the Fmoc group on the resin.Filter out the resin of deprotection, and wash (50 milliliters * 4) with DMF, DCM and ether.Resin after the washing was cultivated 5 minutes in fresh distillatory DMF (1 milliliter/100 milligrams resins), in nitrogen atmosphere.In resin, add the amino acid whose DMF solution (the 1-3 equivalent uses HOBt (1-3 equivalent) and DIPCDI (1-2 equivalent) to activate in advance) that is subjected to Fmoc protection of 0.5M, then jolting resin 1-3 hour in nitrogen atmosphere.Whether finish connection with qualitative ninhydrin test monitoring.Connected after first amino acid, with DMF, DCM and diethyl ether washing resin (50 milliliters * 4).For the second amino acid whose connection, at first use the Fmoc protection on piperidine solution pair first amino acid that is connected with resin of 10-20% to carry out deprotection, use suitable linking agent to connect second amino acid of Fmoc protection as mentioned above then.Repeat the circulation of deprotection, washing, connection and washing, up on resin, assembled the peptide chain that needs according to above-mentioned course.
At last, handle with 20% piperidines as mentioned above, make the peptide acyl-resin deprotection that is subjected to the Fmoc protection of above preparation, and wash peptide acyl-resin (50 milliliters * 4) with DMF, DCM and diethyl ether.Under nitrogen pressure resin 10-15 minute of the dry peptide that contains needs, and dissociate/deprotection.
Dissociate and deprotection:
Handle with the TFA mixture that dissociates according to following steps, the plan peptide that needs is dissociated and deprotection from the peptide acyl-resin of their correspondences.In peptide acyl-resin, add the solution (10 milliliters/100 milligrams peptide acyl-resins) of TFA/ water/tri isopropyl silane (95: 2.5: 2.5), stir frequently, make mixture keep room temperature.Filter resin, with dissociating mixture washing and be evaporated to the filtrate that merges dried.The resistates that obtains is dissolved in 10 ml waters, with ether aqueous layer extracted 3 times (using 20 milliliters of ethers) at every turn, at last with the water layer freeze-drying.According to following steps by preparation HPLC with the thick peptide purification that obtains after the freeze-drying:
The preparation HPLC purifying of rough plan peptide:
On Shimadzu LC-8A liquid chromatography, carry out the preparation HPLC purifying.The thick peptide solution that is dissolved in DMF or the water is injected into semipreparative column (Luna 10 μ; C
18100 dusts) in, column dimension is 250 * 50 millimeters, carries out linear gradient elution with the aqueous solution of ACN, and the thick peptide solution and the ACN aqueous solution all use 0.1% TFA to carry out buffering, eluent flow rate is the 15-50 ml/min, effluent is monitored in 220 nanometers with the PDA monitor.Usually use the water-ACN mixture of gradient as 20%-70%, the TFA with 0.1% cushions, and elution time is 50 minutes, and the per minute graded is 1%.The required product collection of wash-out is single 10-20 milliliter part, and the pure plan peptide that obtains by the HPLC part freeze-drying with correspondence is amorphous white powder.
The HPLC of the plan peptide of purifying analyzes
Pass through as mentioned above after the preparation HPLC purifying, in Shimadzu LC-10AD analysis mode HPLC system, each peptide is analyzed by analysis mode RP-HPLC.Analyze for the analysis mode HPLC that intends peptide, use Luna 5 μ; C
18100 dusts, be of a size of 250 * 4.6 millimeters pillar, 0.1%TFA and ACN buffer reagent are linear gradient, use the PDA detector to obtain chromatogram in 220 nanometers.
Characterize with mass spectrum
Each peptide is characterized with flow injection pattern or LC/MS pattern with electrospray ionization mass spectrometry (ESI-MS).All are analyzed and all use triple quadrupole bar mass spectrum (API-3000 (MDS-SCIES, Canada)) in positive ion and the negative ion electrospray spray pattern.In mass range, obtain the full scan data with the quadrupole of unit resolution rate work.In all cases, the molecular weight that records of experiment is all in positive and negative 0.5 dalton's scope of the single isotopic molecule amount that calculates.Use Analyst 1.4.1 software to carry out the mass spectrum quantitative Treatment.
Adopt synthetic method and other technique known and their the following GLP-1 plan of the suitable version preparation peptide described in the literary composition.This tabular has shown the various groups of intending peptide, and described plan peptide can be prepared according to the present invention, and expection comprises the conspicuous version of these compounds at least.But, should not think that the content that discloses limits scope of the present invention by any way.
Table 1
| Sequence number | Sequence |
| 1 | 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) 11-GPSSGAPPPS |
| 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) 10-GPSS |
| 14 | HGEGTFTSDLSKQM-(CH 2) 11-GPSS |
| 15 | HGEGTFTSDLSKQME-G-GPSSGAPPPS |
| 16 | HGEGTFTSDLSKQME-(CH 2) 2-GPSSGAPPPS |
| 17 | HGEGTFTSDLSKQME-(CH 2) 3-GPSSGAPPPS |
| 18 | HGEGTFTSDLSKQME-(CH 2) 4-GPSSGAPPPS |
| 19 | HGEGTFTSDLSKQME-(CH 2) 5-GPSSGAPPPS |
| 20 | HGEGTFTSDLSKQME-(CH 2) 6-GPSSGAPPPS |
| 21 | HGEGTFTSDLSKQME-(CH 2) 7-GPSSGAPPPS |
| 22 | HGEGTFTSDLSKQME-(CH 2) 10-GPSSGAPPPS |
| 23 | HGEGTFTSDLSKQME-(CH 2) 11-GPSSGAPPPS |
Table 2:
| Sequence number | Sequence |
| 1 | HAEGTFTSD-(CH 2) 2-VKGR |
| 2 | HAEGTFTSD-(CH 2) 3-VKGR |
| 3 | HAEGTFTSD-(CH 2) 4-VKGR |
| 4 | HAEGTFTSD-(CH 2) 5-VKGR |
| 5 | HAEGTFTSD-(CH 2) 6-VKGR |
| 6 | HAEGTFTSD-(CH 2) 10-VKGR |
| 7 | HAibEGTFTSD-(CH 2) 2-VKGR |
| 8 | HAibEGTFTSD-(CH 2) 3-VKGR |
| 9 | HAibEGTFTSD-(CH 2) 4-VKGR |
| 10 | HAibEGTFTSD-(CH 2) 5-VKGR |
| 11 | HAibEGTFTSD-(CH 2) 6-VKGR |
| 12 | HAibEGTFTSD-(CH 2) 10-VKGR |
Table 3:
| Sequence number | Sequence |
| 1 | HGEGTFTSDLSKQMKELEKLL |
| 2 | HAEGTFTSDKELEKLL |
| 3 | HGEGTFTSDKELEKLL |
| 4 | HAibEGTFTSDGKELEKLL |
| 5 | HGEGTFTSDGKELEKLL |
| 6 | HGEGTFTSDVSKELEKLL |
| 7 | HAEGTFTSDVSKELEKLL |
| 8 | HAEGTFTSDVSEKELEKLL |
| 9 | HAEGTFTSDVSGKELEKLL |
| 10 | HAEGTFTSDVSSYLEKELEKLL |
| 11 | HAEGTFTSDVSSYLEGKELEKLL |
| 12 | HGEGTFTSDVSSYLEGKELEKLL |
| 13 | HaEGTFTSDVSSYLEGKELEKLL |
| 14 | HAibEGTFTSDVSSYLEGKELEKLL |
| 15 | HAEGTFTSDVSSYLEGKELEKLLVKG |
| 16 | HAEGTFTSDVSSYLEPKELEKLL |
| 17 | HAEGTFTSDVSSYLEGQAAKELEKLL |
| 18 | HAEGTFTSDVSSYLEGQAAKEFIKELEKLL |
| 19 | HAibEGTFTSDVSSYLEGQAAKEFIKELEKLL |
| 20 | HAibEGT-(α-Me)Phe(2-F)-TSDVSSYLEGQAAKEFIKELEKLL |
| 21 | Deaminizating-HAibEGT-(Phe (2-F)-TSDVSSYLEGQAAKEFIKELEKLL of α-Me) |
| 22 | HAEGTFTSD-(CH 2) 3-KELEKLL |
| 23 | HAEGTFTSD-(CH 2) 4-KELEKLL |
| 24 | HAEGTFTSD-(CH 2) 5-KELEKLL |
| 25 | HAEGTFTSD-(CH 2) 6-KELEKLL |
| 26 | HA-(CH 2) 3-DVSSYLEGQAAKEFIKELEKLL |
| 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:
| Sequence number | Sequence |
| 1 | HGEGTFTSD-(CH 2) 3-Bip-Bip |
| 2 | HAibEGTFTSD-(CH 2) 3-Bip-Bip |
| 3 | HAibEGT-(α-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-(α-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-(α-Me)-Phe(2-F)-TS-G-Bip(2-Me)-Bip(2-Me) |
| 10 | HAEGTFTS-(CH 2) 2-Bip(2-Me)-Bip(2-Me) |
| 11 | HAibEGTFTS-(CH 2) 2-Bip(2-Me)-Bip(2-Me) |
| 12 | HAibEGT-(α-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-(α-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 | HAibEGT-(α-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) |
| 25 | HAibEGT-(α-Me)-Phe(2-F)-TSD-(CH 2) 2-Bip(2-Me)-Bip(2-Me) |
| 26 | HAEGTFTSD-G-Bip-Bip(2-Me) |
| 27 | HAibEGTFTSD-G-Bip-Bip(2-Me) |
| 28 | HAibEGT-(α-Me)-Phe(2-F)-TSD-G-Bip-Bip(2-Me) |
| 29 | HAEGTFTSD-G-Bip(2-Me)-Bip |
| 30 | HAibEGTFTSD-G-Bip(2-Me)-Bip |
| 31 | HAibEGT-(α-Me)-Phe(2-F)-TSD-G-Bip(2-Me)-Bip |
| 32 | HAEGTFTSD-G-Bip-Bip |
| 33 | HAibEGTFTSD-G-Bip-Bip |
| 34 | HAibEGT-(α-Me)-Phe(2-F)-TSD-G-Bip-Bip |
| 35 | HAEGTFTSD-G-Bip-Bip(2-Et) |
| 36 | HAibEGTFTSD-G-Bip-Bip(2-Et) |
| 37 | HAibEGT-(α-Me)-Phe(2-F)-TSD-G-Bip-Bip(2-Et) |
| 38 | HAEGTFTSD-G-Bip(2-Et)-Bip(2-Et) |
| 39 | HAibEGTFTSD-G-Bip(2-Et)-Bip(2-Et) |
| 40 | HAibEGT-(α-Me)-Phe(2-F)-TSD-G-Bip(2-Et)-Bip(2-Et) |
| 41 | HAEGTFTSD-G-Bip(2-Et)-Bip |
| 42 | HAibEGTFTSD-G-Bip(2-Et)-Bip |
| 43 | HAibEGT-(α-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) |
| 46 | HAibEGT-(α-Me)-Phe(2-F)-TSD-G-Bip(2-Et)-Bip(2-Me) |
| 47 | HAEGTFTSD-G-Bip(2-Me)-Bip(2-Et) |
| 48 | HAibEGTFTSD-G-Bip(2-Me)-Bip(2-Et) |
| 49 | HAibEGT-(α-Me)-Phe(2-F)-TSD-G-Bip(2-Me)-Bip(2-Et) |
| 50 | HGEGTFTSD-G-Bip(2-Me)-Bip(2-Me) |
| 51 | HGEGT-(α-Me)-Phe(2-F)-TSD-G-Bip(2-Me)-Bip(2-Me) |
| 52 | HGEGTFTSD-G-Bip(2-Et)-Bip(2-Et) |
| 53 | HGEGT-(α-Me)-Phe(2-F)-TSD-G-Bip(2-Et)-Bip(2-Et) |
| 54 | HGEGTFTSD-(CH 2) 3-Bip(2-Me)-Bip(2-Me) |
| 55 | HGEGT-(α-Me)-Phe(2-F)-TSD-(CH 2) 3-Bip(2-Me)-Bip(2-Me) |
| 56 | HGEGTFTSD-(CH 2) 4-Bip(2-Me)-Bip(2-Me) |
| 57 | HGEGT-(α-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-(α-Me)-Phe(2-F)-TSD-(CH 2) 5-Bip(2-Me)-Bip(2-Me) |
| 60 | HGEGTFTSD-(CH 2) 6-Bip(2-Me)-Bip(2-Me) |
| 61 | HGEGT-(α-Me)-Phe(2-F)-TSD-(CH 2) 6-Bip(2-Me)-Bip(2-Me) |
| 62 | HGEGTFTSD-(CH 2) 10-Bip(2-Me)-Bip(2-Me) |
| 63 | HGEGT-(α-Me)-Phe(2-F)-TSD-(CH 2) 10-Bip(2-Me)-Bip(2-Me) |
| 64 | HGEGTFTSD-(CH 2) 3-Bip(2-Et)-Bip(2-Et) |
| 65 | HGEGT-(α-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-(α-Me)-Phe(2-F)-TSD-(CH 2) 4-Bip(2-Et)-Bip(2-Et) |
| 68 | HGEGTFTSD-(CH 2) 5-Bip(2-Et)-Bip(2-Et) |
| 69 | HGEGT-(α-Me)-Phe(2-F)-TSD-(CH 2) 5-Bip(2-Et)-Bip(2-Et) |
| 70 | HGEGTFTSD-(CH 2) 6-Bip(2-Et)-Bip(2-Et) |
| 71 | HGEGT-(α-Me)-Phe(2-F)-TSD-(CH 2) 6-Bip(2-Et)-Bip(2-Et) |
| 72 | HGEGTFTSD-(CH 2) 10-Bip(2-Et)-Bip(2-Et) |
| 73 | HGEGT-(α-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-(α-Me)-Phe(2-F)-TSD-(CH 2) 11-Bip(2-Et)-Bip(2-Et) |
| 76 | HGEGTFTS-(CH 2) 3-Bip(2-Me)-Bip(2-Me) |
| 77 | HGEGT-(α-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-(α-Me)-Phe(2-F)-TS-(CH 2) 4-Bip(2-Me)-Bip(2-Me) |
| 80 | HGEGTFTS-(CH 2) 5-Bip(2-Me)-Bip(2-Me) |
| 81 | HGEGT-(α-Me)-Phe(2-F)-TS-(CH 2) 5-Bip(2-Me)-Bip(2-Me) |
| 82 | HGEGTFTS-(CH 2) 6-Bip(2-Me)-Bip(2-Me) |
| 83 | HGEGT-(α-Me)-Phe(2-F)-TS-(CH 2) 6-Bip(2-Me)-Bip(2-Me) |
| 84 | HGEGTFTS-(CH 2) 10-Bip(2-Me)-Bip(2-Me) |
| 85 | HGEGT-(α-Me)-Phe(2-F)-TS-(CH 2) 10-Bip(2-Me)-Bip(2-Me) |
| 86 | HGEGTFTS-(CH 2) 11-Bip(2-Me)-Bip(2-Me) |
| 87 | HGEGT-(α-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) |
| 89 | HGEGT-(α-Me)-Phe(2-F)-TS-(CH 2) 3-Bip(2-Et)-Bip(2-Et) |
| 90 | HGEGT-(α-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-(α-Me)-Phe(2-F)-TS-(CH 2) 4-Bip(2-Et)-Bip(2-Et) |
| 93 | HGEGTFTS-(CH 2) 5-Bip(2-Et)-Bip(2-Et) |
| 94 | HGEGT-(α-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-(α-Me)-Phe(2-F)-TS-(CH 2) 6-Bip(2-Et)-Bip(2-Et) |
| 97 | HGEGTFTS-(CH 2) 10-Bip(2-Et)-Bip(2-Et) |
| 98 | HGEGT-(α-Me)-Phe(2-F)-TS-(CH 2) 10-Bip(2-Et)-Bip(2-Et) |
| 99 | HGEGTFTS-(CH 2) 11-Bip(2-Et)-Bip(2-Et) |
| 100 | HGEGT-(α-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-(α-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-(α-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-(α-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-(α-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-(CH 2) 2-Bip(2-Et)-Bip(2-Et) |
| 112 | HAibEGT-(α-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 | HAibEGTF-(CH 2) 2-Bip(2-Me)-Bip(2-Et) |
| 115 | HAibEGT-(α-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-(α-Me)-Phe(2-F)-TSD-G-TrPh-TrPh |
| 119 | HAibEGT-(α-Me)-Phe(2-F)-(CH 2) 2-TrPh-TrPh |
| 120 | HAibEG-(CH 2) 2-TrPh-TrPh |
| 121 | HAibE-(CH 2) 2-TrPh-TrPh |
| 122 | HAib-(CH 2) 3-TrPh-TrPh |
| 123 | HAEGTFTSD-G-Nap-Nap |
| 124 | HAibEGTFTSD-G-Nap-Nap |
| 125 | HAibEGT-(α-Me)-Phe(2-F)-TSD-G-Nap-Nap |
| 126 | HAEGTFTSD-G-Bip(2-F)-Bip(2-F) |
| 127 | HAibEGTFTSD-G-Bip(2-F)-Bip(2-F) |
| 128 | HAibEGT-(α-Me)-Phe(2-F)-TSD-G-Bip(2-F)-Bip(2-F) |
| 129 | HAEGTFTSD-G-Bip(2’-Et-4’-OMe)-4-(2’-Me-Ph)-3-Pyr-Ala |
| 130 | HAibEGTFTSD-G-Bip(2’-Et-4’-OMe)-4-(2’-Me-Ph)-3-Pyr-Ala |
| 131 | HAibEGT-(α-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 | HAibEGTFTSD-(CH 2) 2-Bip(2’-Et-4’-OMe)-4-(2’-Me-Ph)-3-Pyr- Ala |
| 134 | HAibEGT-(α-Me)-Phe(2-F)-TSD-(CH 2) 2-Bip(2’-Et-4’-OMe)-4-(2’- Me-Ph)-3-Pyr-Ala |
| 135 | HAEGTFTS-(CH 2) 2-Bip(2’-Et-4’-OMe)-4-(2’-Me-Ph)-3-Pyr-Ala |
| 136 | HAibEGTFTS-(CH 2) 2-Bip(2’-Et-4’-OMe)-4-(2’-Me-Ph)-3-Pyr-Ala |
| 137 | HAibEGT-(α-Me)-Phe(2-F)-TS-(CH 2) 2-Bip(2’-Et-4’-OMe)-4-(2’- Me-Ph)-3-Pyr-Ala |
| 138 | HAEGTFT-(CH 2) 2-Bip(2’-Et-4’-OMe)-4-(2’-Me-Ph)-3-Pyr-Ala |
| 139 | HAibEGTFT-(CH 2) 2-Bip(2’-Et-4’-OMe)-4-(2’-Me-Ph)-3-Pyr-Ala |
| 140 | HAibEGT-(α-Me)-Phe(2-F)-T-(CH 2) 2-Bip(2’-Et-4’-OMe)-4-(2’- Me-Ph)-3-Pyr-Ala |
| 141 | HAEGTF-(CH 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 | HAibEGT-(α-Me)-Phe(2-F)-(CH 2) 2-Bip(2’-Et-4’-OMe)-4-(2’-Me- Ph)-3-Pyr-Ala |
| 144 | HAEGT-(CH 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 | HAEG-(CH 2) 2-Bip(2’-Et-4’-OMe)-4-(2’-Me-Ph)-3-Pyr-Ala |
| 147 | HAibEG-(CH 2) 2-Bip(2’-Et-4’-OMe)-4-(2’-Me-Ph)-3-Pyr-Ala |
| 148 | HAEG-(CH 2) 3-Bip(2’-Et-4’-OMe)-4-(2’-Me-Ph)-3-Pyr-Ala |
| 149 | HAibEG-(CH 2) 3-Bip(2’-Et-4’-OMe)-4-(2’-Me-Ph)-3-Pyr-Ala |
Table 5:
| Sequence number | Sequence |
| 1 | HAEGT-(CH 2) 2-Bip(2-Me)-Bip(2-Me) |
| 2 | HGEGT-(CH 2) 3-Bip(2-Me)-Bip(2-Me) |
| 3 | HGEGT-(CH 2) 4-Bip(2-Me)-Bip(2-Me) |
| 4 | HGEGT-(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 | HAEGT-(CH 2) 2-DBip(2-Me)-Bip(2-Me) |
| 8 | HaEGT-(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 | HGEG-(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 | HAEG-(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-Me)-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 | HAE-(CH 2) 3-Bip(2-Me)-DBip(2-Me) |
| 21 | HAE-(CH 2) 2-D-Bip(2-Me)-Bip(2-Me) |
| 22 | HAE-(CH 2) 3-D-Bip(2-Me)-Bip(2-Me) |
| 23 | HAE-(CH 2) 4-D-Bip(2-Me)-Bip(2-Me) |
| 24 | HAE-(CH 2) 4-Bip(2-Me)-DBip(2-Me) |
| 25 | HAE-(CH 2) 5-D-Bip(2-Me)-Bip(2-Me) |
| 26 | HAE-(CH 2) 3-Bip(2-Et)-Bip(2-Me) |
| 27 | HAE-(CH 2) 2-Bip(2-Me)-Bip(2-Me) |
Table 6:
| Sequence number | Sequence |
| 1 | H-(CH 2) 3-Bip(2-Me)-Bip(2-Me) |
| 2 | H-(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 | H-(CH 2) 4-Bip(2-Et)-Bip(2-Me) |
| 6 | H-(CH 2) 5-Bip(2-Et)-Bip(2-Me) |
| 7 | H-(CH 2) 6-Bip(2-Et)-Bip(2-Me) |
| 8 | H-(CH 2) 10-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) 5-DBip(2-Me)-DBip(2-Me) |
| 12 | HG-(CH 2) 3-Bip(2-Me)-Bip(2-Me) |
| 13 | HG-(CH 2) 4-Bip(2-Me)-Bip(2-Me) |
| 14 | HG-(CH 2) 3-Bip(2-Et)-Bip(2-Me) |
| 15 | HG-(CH 2) 4-Bip(2-Et)-Bip(2-Me) |
| 16 | HG-(CH 2) 3-Bip(2-Et)-DBip(2-Me) |
| 17 | HG-(CH 2) 3-Bip(2-Me)-DBip(2-Me) |
| 18 | FA-(CH 2) 3-DBip(2-Me)-Bip(2-Et) |
| 19 | FA-(CH 2) 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-(CH 2) 3-Bip(2-Me)-DBip(2-Me) |
| 26 | Ha-(CH 2) 3-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) |
| 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-(CH 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-(CH 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-(CH 2) 3-DBip(2-Me)-DBip(2-Me) |
| 41 | HA-(CH 2) 3-DBip(2-Me)-Bip(2-Me) |
| 42 | HA-(CH 2) 3-Bip(2-Me)-DBip(2-Me) |
| 43 | HA-(CH 2) 3-Bip(2-Ipr)-Bip(2-Ipr) |
| 44 | HA-(CH 2) 3-Bip(2-Ipr)-Bip(2-Me) |
| 45 | HA-(CH 2) 3-Bip(2-Me)-Bip(2-Ipr) |
| 46 | HA-(CH 2) 4-Bip(2-Et)-Bip(2-Me) |
| 47 | HA-(CH 2) 3-Bip(2-Me)-DBip(2-Et) |
| 48 | HA-(CH 2) 2-Bip(2-Et)-Bip(2-Me) |
| 49 | HA-(CH 2) 5-Bip(2-Et)-Bip(2-Me) |
| 50 | HA-(CH 2) 6-Bip(2-Et)-Bip(2-Me) |
| 51 | HA-(CH 2) 2-Bip(2-Me)-Bip(2-Me) |
| 52 | HA-(CH 2) 3-DBip(2-Et)-DBip(2-Me) |
| 53 | HA-(CH 2) 3-DBip(2-Et)-Bip(2-Me) |
| 54 | HA-(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 | HA-(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 | HA-(CH 2) 3-DBip(2-Me)-Bip(2-Et) |
| 61 | HA-(CH 2) 3-Bip-Bip |
| 62 | HA-(CH 2) 3-Bip-DBip |
| 63 | HA-(CH 2) 3-DBip-DBip |
| 64 | HA-(CH 2) 3-DBip-Bip |
| 65 | HA-(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-Ipr)-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 | HA-(CH 2) 3-Bip(2-Ipr)-Bip(2-CN) |
| 76 | HA-(CH 2) 3-Bip(2-CN)-Bip(2-Me) |
| 77 | HA-(CH 2) 3-Bip(2-CN)-Bip |
| 78 | HA-(CH 2) 3-Bip(2-CN)-Bip(2-Et) |
| 79 | HA-(CH 2) 3-Bip(2-CN)-Bip(2-Ipr) |
| 80 | HA-(CH 2) 3-Bip(2-CN)-Bip(2-CN) |
| 81 | HA-(CH 2) 2-F-(CH 2) 2-Bip(2-Et)-DBip(2-Et) |
| 82 | HA-(CH 2) 2-F-(CH 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 | HA-(CH 2) 3-DBip(2-Me)-DBip |
| 86 | HA-(CH 2) 5-Bip(2-Me)-DBip(2-Me) |
| 87 | HA-(CH 2) 5-DBip(2-Me)-Bip(2-Me) |
| 88 | HA-(CH 2) 4-D(Bip)-Bip(2-Et) |
| 89 | HA-(CH 2) 5-D(Bip)-Bip(2-Et) |
| 90 | HA-(CH 2) 4-Bip(2-Me)-DBip(2-Me) |
| 91 | HA-(CH 2) 5-Bip(2-Me)-DBip(2-Me) |
| 92 | HA-(CH 2) 3-(N(Me))-DBip-Bip(2-Et) |
| 93 | HA-(CH 2) 4-DBip(2-Me)-Bip(2-Et) |
| 94 | HA-(CH 2) 5-DBip(2-Me)-Bip(2-Et) |
| 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 compound of general method preparation that can as described above, these compounds are included within the scope of the invention and (show 7-9)
Table 7:
| Sequence number | Sequence |
| 1 | HA-(CH 2) 2-Bip(2’-Et-4’-OMe)-4-(2’-Me-Ph)-3-Pyr-Ala-NH 2 |
| 2 | H-Aib-(CH 2) 2-Bip(2’-Et-4’-OMe)-4-(2’-Me-Ph)-3-Pyr-Ala-NH 2 |
| 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-NH 2 |
| 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-(2’-Me-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 |
| 11 | Deaminizating-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 | Deaminizating-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-NH-(CH 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-NH-(CH 2) 10-CH 3 |
| 16 | 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) 10-CH 3 |
| 17 | CH 3-(CH 2) 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 | CH 3-(CH 2) 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-NH-(CH 2) 6-CH 3 |
| 19 | CH 3-(CH 2) 10-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 |
| 20 | CH 3-(CH 2) 10-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-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 | H-Aib-(CH 2) 3-Bip(2’-Et-4’-OMe)-4-(2’-Me-Ph)-3-Pyr-Ala-NH 2 |
| 23 | Ha-(CH 2) 3-Bip(2’-Et-4’-OMe)-4-(2’-Me-Ph)-3-Pyr-Ala-NH 2 |
| 24 | H-(N(Me))A-(CH 2) 3-Bip(2’-Et-4’-OMe)-4-(2’-Me-Ph)-3-Pyr-Ala-NH 2 |
| 25 | H-(N(Me))A-(N(Me))-(CH 2) 3-Bip(2’-Et-4’-OMe)-4-(2’-Me-Ph)-3-Pyr-Ala- NH 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(Me))-(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(Me))-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’-Et-4’-OMe)-(N(Me))-4-(2’- Me-Ph)-3-Pyr-Ala-NH 2 |
| 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-NH 2 |
| 31 | Deaminizating-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 | Deaminizating-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 |
| 33 | 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-(CH 2) 6-CH 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-CH 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-NH-(CH 2) 10-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-NH-(CH 2) 10-CH 3 |
| 37 | CH 3-(CH 2) 6-NH-(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-(CH 2) 6-CH 3 |
| 38 | CH 3-(CH 2) 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-CH 3 |
| 39 | CH 3-(CH 2) 10-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-(CH 2) 6-CH 3 |
| 40 | CH 3-(CH 2) 10-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 | HA-(CH 2) 4-Bip(2’-Et-4’-OMe)-4-(2’-Me-Ph)-3-Pyr-Ala-NH 2 |
| 42 | H-Aib-(CH 2) 2-Bip(2’-Et-4’-OMe)-4-(2’-Me-Ph)-3-Pyr-Ala-NH 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) 4-Bip(2’-Et-4’-OMe)-4-(2’-Me-Ph)-3-Pyr-Ala-NH 2 |
| 45 | H-(N(Me))A-(N(Me))-(CH 2) 4-Bip(2’-Et-4’-OMe)-4-(2’-Me-Ph)-3-Pyr-Ala- NH 2 |
| 46 | H-(N(Me))Aib-(N(Me))-(CH 2) 4-Bip(2’-Et-4’-OMe)-4-(2’-Me-Ph)-3-Pyr- Ala-NH 2 |
| 47 | H-(N(Me))A-(N(Me))-(CH 2) 4-(N(Me))-Bip(2’-Et-4’-OMe)-4-(2’-Me-Ph)-3- Pyr-Ala-NH 2 |
| 48 | H-(N(Me))Aib-(N(Me))-(CH 2) 4-(N(Me))-Bip(2’-Et-4’-OMe)-4-(2’-Me-Pb)- 3-Pyr-Ala-NH 2 |
| 49 | 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 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 | Deaminizating-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 2 |
| 52 | Deaminizating-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 |
| 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(Me))-(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) 10-CH 3 |
| 57 | CH 3-(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-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-CH 3 |
| 59 | CH 3-(CH 2) 10-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 |
| 60 | CH 3-(CH 2) 10-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-CH 3 |
| 61 | HAE-(CH 2) 2-Bip(2’-Et-4’-OMe)-4-(2’-Me-Ph)-3-Pyr-Ala-NH 2 |
| 62 | H-Aib-E-(CH 2) 2-Bip(2’-Et-4’-OMe)-4-(2’-Me-Ph)-3-Pyr-Ala-NH 2 |
| 63 | HaE-(CH 2) 2-Bip(2’-Et-4’-OMe)-4-(2’-Me-Ph)-3-Pyr-Ala-NH 2 |
| 64 | H-(N(Me))AE-(CH 2) 2-Bip(2’-Et-4’-OMe)-4-(2’-Me-Ph)-3-Pyr-Ala-NH 2 |
| 65 | H-(N(Me))AE-(N(Me))-(CH 2) 2-Bip(2’-Et-4’-OMe)-4-(2’-Me-Ph)-3-Pyr- Ala-NH 2 |
| 66 | H-(N(Me))Aib-E-(N(Me))-(CH 2) 2-Bip(2’-Et-4’-OMe)-4-(2’-Me-Ph)-3-Pyr- Ala-NH 2 |
| 67 | H-(N(Me))AE-(N(Me))-(CH 2) 2-(N(Me))-Bip(2’-Et-4’-OMe)-4-(2’-Me-Ph)- 3-Pyr-Ala-NH 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-NH 2 |
| 69 | 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 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-NH 2 |
| 71 | Deaminizating-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 2 |
| 72 | Deaminizating-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-NH 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 |
| 74 | 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-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-NH-(CH 2) 10-CH 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-NH-(CH 2) 10-CH 3 |
| 77 | CH 3-(CH 2) 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-NH-(CH 2) 6-CH 3 |
| 78 | CH 3-(CH 2) 6-NH-(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-NH-(CH 2) 6-CH 3 |
| 79 | CH 3-(CH 2) 10-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-NH-(CH 2) 6-CH 3 |
| 80 | CH 3-(CH 2) 10-NH-(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-NH-(CH 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-NH 2 |
| 83 | HaEG-(CH 2) 2-Bip(2’-Et-4’-OMe)-4-(2’-Me-Ph)-3-Pyr-Ala-NH 2 |
| 84 | H-(N(Me))AEG-(CH 2) 2-Bip(2’-Et-4’-OMe)-4-(2’-Me-Ph)-3-Pyr-Ala-NH 2 |
| 85 | H-(N(Me))AEG-(N(Me))-(CH 2) 2-Bip(2’-Et-4’-OMe)-4-(2’-Me-Ph)-3-Pyr- Ala-NH 2 |
| 86 | H-(N(Me))Aib-EG-(N(Me))-(CH 2) 2-Bip(2’-Et-4’-OMe)-4-(2’-Me-Ph)-3- Pyr-Ala-NH 2 |
| 87 | 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 |
| 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)-(N(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(Me))- 4-(2’-Me-Ph)-3-Pyr-Ala-NH 2 |
| 91 | Deaminizating-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-NH 2 |
| 92 | Deaminizating-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 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-NH-(CH 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 |
| 95 | 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-NH-(CH 2) 10-CH 3 |
| 96 | 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) 10-CH 3 |
| 97 | CH 3-(CH 2) 6-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-NH-(CH 2) 6-CH 3 |
| 98 | CH 3-(CH 2) 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-NH-(CH 2) 6-CH 3 |
| 99 | CH 3-(CH 2) 10-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-NH-(CH 2) 6-CH 3 |
| 100 | CH 3-(CH 2) 10-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-NH-(CH 2) 6-CH 3 |
| 101 | HAEGT-(CH 2) 2-Bip(2’-Et-4’-OMe)-4-(2’-Me-Ph)-3-Pyr-Ala-NH 2 |
| 102 | H-Aib-EGT-(CH 2) 2-Bip(2’-Et-4’-OMe)-4-(2’-Me-Ph)-3-Pyr-Ala-NH 2 |
| 103 | HaEGT-(CH 2) 2-Bip(2’-Et-4’-OMe)-4-(2’-Me-Ph)-3-Pyr-Ala-NH 2 |
| 104 | H-(N(Me))AEGT-(CH 2) 2-Bip(2’-Et-4’-OMe)-4-(2’-Me-Ph)-3-Pyr-Ala-NH 2 |
| 105 | H-(N(Me))AEGT-(N(Me))-(CH 2) 2-Bip(2’-Et-4’-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 | H-(N(Me))Aib-EGT-(N(Me))-(CH 2) 2-(N(Me))-Bip(2’-Et-4’-OMe)-4-(2’- Me-Ph)-3-Pyr-Ala-NH 2 |
| 109 | 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 |
| 110 | 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 |
| 111 | Deaminizating-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 |
| 112 | Deaminizating-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 |
| 113 | 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) 6-CH 3 |
| 114 | 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-(CH 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))-(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 |
| 117 | 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-NH-(CH 2) 6-CH 3 |
| 118 | CH 3-(CH 2) 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-NH-(CH 2) 6-CH 3 |
| 119 | CH 3-(CH 2) 10-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 |
| 120 | CH 3-(CH 2) 10-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)-NH 2 |
| 122 | H-Aib-(CH 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)-NH 2 |
| 127 | H-(N(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)-NH 2 |
| 129 | H-(N(Me))A-(N(Me))-(CH 2) 3-(N(Me))-Bip(2-Me)-(N(Me))-Bip(2-Me)-NH 2 |
| 130 | H-(N(Me))Aib-(N(Me))-(CH 2) 3-(N(Me))-Bip(2-Me)-(N(Me))-Bip(2-Me)- NH 2 |
| 131 | Deaminizating-H-(N (Me)) A-(N (Me))-(CH 2) 3-(N(Me))-Bip(2-Me)-(N(Me))- Bip(2-Me)-NH 2 |
| 132 | Deaminizating-H-(N (Me)) Aib-(N (Me))-(CH 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)- NH-(CH 2) 6-CH 3 |
| 135 | H-(N(Me))A-(N(Me))-(CH 2) 3-(N(Me))-Bip(2-Me)-(N(Me))-Bip(2-Me)-NH- (CH 2) 10-CH 3 |
| 136 | H-(N(Me))Aib-(N(Me))-(CH 2) 3-(N(Me))-Bip(2-Me)-(N(Me))-Bip(2-Me)- NH-(CH 2) 10-CH 3 |
| 137 | CH 3-(CH 2) 6-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 |
| 138 | CH 3-(CH 2) 6-NH-H-(N(Me))Aib-(N(Me))-(CH 2) 3-(N(Me))-Bip(2-Me)- (N(Me))-Bip(2-Me)-NH-(CH 2) 6-CH 3 |
| 139 | CH 3-(CH 2) 10-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 | CH 3-(CH 2) 10-NH-H-(N(Me))Aib-(N(Me))-(CH 2) 3-(N(Me))-Bip(2-Me)- (N(Me))-Bip(2-Me)-NH-(CH 2) 6-CH 3 |
| 141 | HA-(CH 2) 3-Bip(2-Et)-Bip(2-Me)-NH 2 |
| 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)-NH 2 |
| 144 | H-(N(Me))A-(CH 2) 3-Bip(2-Et)-Bip(2-Me)-NH 2 |
| 145 | H-(N(Me))A-(N(Me))-(CH 2) 3-Bip(2-Et)-Bip(2-Me)-NH 2 |
| 146 | H-(N(Me))Aib-(N(Me))-(CH 2) 3-Bip(2-Et)-Bip(2-Me)-NH 2 |
| 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)-NH 2 |
| 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)- NH 2 |
| 151 | Deaminizating-H-(N (Me)) A-(N (Me))-(CH 2) 3-(N(Me))-Bip(2-Et)-(N(Me))- Bip(2-Me)-NH 2 |
| 152 | Deaminizating-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) 10-CH 3 |
| 156 | H-(N(Me))Aib-(N(Me))-(CH 2) 3-(N(Me))-Bip(2-Et)-(N(Me))-Bip(2-Me)- NH-(CH 2) 10-CH 3 |
| 157 | CH 3-(CH 2) 6-NH-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 |
| 158 | CH 3-(CH 2) 6-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) 10-NH-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 |
| 160 | CH 3-(CH 2) 10-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:
| Sequence number | Sequence |
| 1 | HA-(CH 2) 2-Bip(2’-Et-4’-OMe)-4-(2’-Me-Ph)-3-Pyr-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-(N(Me))-(CH 2) 2-Bip(2’-Et-4’-OMe)-4-(2’-Me-Ph)-3-Pyr-Ala-OH |
| 6 | H-(N(Me))Aib-(N(Me))-(CH 2) 2-Bip(2’-Et-4’-OMe)-4-(2’-Me-Ph)-3-Pyr-Ala- 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-OH | |
| 8 | H-(N(Me))Aib-(N(Me))-(CH 2) 2-(N(Me))-Bip(2’-Et-4’-OMe)-4-(2’-Me-Ph)-3- Pyr-Ala-OH |
| 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-OH |
| 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-OH |
| 11 | Deaminizating-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 | Deaminizating-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-OH |
| 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-COO-(CH 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-COO-(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-COO-(CH 2) 10-CH 3 |
| 16 | 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-COO-(CH 2) 10-CH 3 |
| 17 | CH 3-(CH 2) 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-COO-(CH 2) 6-CH 3 |
| 18 | CH 3-(CH 2) 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 |
| 19 | CH 3-(CH 2) 10-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-COO-(CH 2) 6-CH 3 |
| 20 | CH 3-(CH 2) 10-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 |
| 21 | HA-(CH 2) 3-Bip(2’-Et-4’-OMe)-4-(2’-Me-Ph)-3-Pyr-Ala-OH |
| 22 | H-Aib-(CH 2) 3-Bip(2’-Et-4’-OMe)-4-(2’-Me-Ph)-3-Pyr-Ala-OH |
| 23 | Ha-(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))-(CH 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))-Bip(2’-Et-4’-OMe)-4-(2’-Me-Ph)-3- Pyr-Ala-OH |
| 28 | H-(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))-(CH 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-OH |
| 31 | Deaminizating-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-OH |
| 32 | Deaminizating-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-OH |
| 33 | 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) 6-CH 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-COO-(CH 2) 6-CH 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) 10-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) 10-CH 3 |
| 37 | CH 3-(CH 2) 6-NH-(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 |
| 38 | CH 3-(CH 2) 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-COO-(CH 2) 6-CH 3 |
| 39 | CH 3-(CH 2) 10-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-COO-(CH 2) 6-CH 3 |
| 40 | CH 3-(CH 2) 10-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-COO-(CH 2) 6-CH 3 |
| 41 | HA-(CH 2) 4-Bip(2’-Et-4’-OMe)-4-(2’-Me-Ph)-3-Pyr-Ala-OH |
| 42 | H-Aib-(CH 2) 2-Bip(2’-Et-4’-OMe)-4-(2’-Me-Ph)-3-Pyr-Ala-OH |
| 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-OH |
| 46 | H-(N(Me))Aib-(N(Me))-(CH 2) 4-Bip(2’-Et-4’-OMe)-4-(2’-Me-Ph)-3-Pyr-Ala- |
| OH | |
| 47 | H-(N(Me))A-(N(Me))-(CH 2) 4-(N(Me))-Bip(2’-Et-4’-OMe)-4-(2’-Me-Ph)-3- Pyr-Ala-OH |
| 48 | H-(N(Me))Aib-(N(Me))-(CH 2) 4-(N(Me))-Bip(2’-Et-4’-OMe)-4-(2’-Me-Ph)-3- Pyr-Ala-OH |
| 49 | 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-OH |
| 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-OH |
| 51 | Deaminizating-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-OH |
| 52 | Deaminizating-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-OH |
| 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-COO-(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-COO-(CH 2) 6-CH 3 |
| 55 | 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-COO-(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-COO-(CH 2) 10-CH 3 |
| 57 | CH 3-(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-COO-(CH 2) 6-CH 3 |
| 58 | CH 3-(CH 2) 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 |
| 59 | CH 3-(CH 2) 10-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-COO-(CH 2) 6-CH 3 |
| 60 | CH 3-(CH 2) 10-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 |
| 61 | HAE-(CH 2) 2-Bip(2’-Et-4’-OMe)-4-(2’-Me-Ph)-3-Pyr-Ala-OH |
| 62 | H-Aib-E-(CH 2) 2-Bip(2’-Et-4’-OMe)-4-(2’-Me-Ph)-3-Pyr-Ala-OH |
| 63 | HaE-(CH 2) 2-Bip(2’-Et-4’-OMe)-4-(2’-Me-Ph)-3-Pyr-Ala-OH |
| 64 | H-(N(Me))AE-(CH 2) 2-Bip(2’-Et-4’-OMe)-4-(2’-Me-Ph)-3-Pyr-Ala-OH |
| 65 | H-(N(Me))AE-(N(Me))-(CH 2) 2-Bip(2’-Et-4’-OMe)-4-(2’-Me-Ph)-3-Pyr-Ala- |
| OH | |
| 66 | H-(N(Me))Aib-E-(N(Me))-(CH 2) 2-Bip(2’-Et-4’-OMe)-4-(2’-Me-Ph)-3-Pyr-Ala- OH |
| 67 | H-(N(Me))AE-(N(Me))-(CH 2) 2-(N(Me))-Bip(2’-Et-4’-OMe)-4-(2’-Me-Ph)-3- Pyr-Ala-OH |
| 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-OH |
| 69 | 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-OH |
| 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-OH |
| 71 | Deaminizating-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-OH |
| 72 | Deaminizating-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-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 |
| 74 | 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-(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-COO-(CH 2) 10-CH 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-(CH 2) 10-CH 3 |
| 77 | CH 3-(CH 2) 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-CH 3 |
| 78 | CH 3-(CH 2) 6-NH-(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-(CH 2) 6-CH 3 |
| 79 | CH 3-(CH 2) 10-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-CH 3 |
| 80 | CH 3-(CH 2) 10-NH-(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-(CH 2) 6-CH 3 |
| 81 | HAEG-(CH 2) 2-Bip(2’-Et-4’-OMe)-4-(2’-Me-Ph)-3-Pyr-Ala-OH |
| 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-OH |
| 84 | H-(N(Me))AEG-(CH 2) 2-Bip(2’-Et-4’-OMe)-4-(2’-Me-Ph)-3-Pyr-Ala-OH |
| 85 | H-(N(Me))AEG-(N(Me))-(CH 2) 2-Bip(2’-Et-4’-OMe)-4-(2’-Me-Ph)-3-Pyr-Ala- OH |
| 86 | H-(N(Me))Aib-EG-(N(Me))-(CH 2) 2-Bip(2’-Et-4’-OMe)-4-(2’-Me-Ph)-3-Pyr- Ala-OH |
| 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 |
| 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-OH |
| 89 | 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 |
| 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 | Deaminizating-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 |
| 92 | Deaminizating-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 |
| 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-COO-(CH 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-COO-(CH 2) 6-CH 3 |
| 95 | 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-(CH 2) 10-CH 3 |
| 96 | 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) 10-CH 3 |
| 97 | CH 3-(CH 2) 6-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-(CH 2) 6-CH 3 |
| 98 | CH 3-(CH 2) 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 |
| 99 | CH 3-(CH 2) 10-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-(CH 2) 6-CH 3 |
| 100 | CH 3-(CH 2) 10-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 |
| 101 | HAEGT-(CH 2) 2-Bip(2’-Et-4’-OMe)-4-(2’-Me-Ph)-3-Pyr-Ala-OH |
| 102 | H-Aib-EGT-(CH 2) 2-Bip(2’-Et-4’-OMe)-4-(2’-Me-Ph)-3-Pyr-Ala-OH |
| 103 | HaEGT-(CH 2) 2-Bip(2’-Et-4’-OMe)-4-(2’-Me-Ph)-3-Pyr-Ala-OH |
| 104 | H-(N(Me))AEGT-(CH 2) 2-Bip(2’-Et-4’-OMe)-4-(2’-Me-Ph)-3-Pyr-Ala-OH |
| 105 | H-(N(Me))AEGT-(N(Me))-(CH 2) 2-Bip(2’-Et-4’-OMe)-4-(2’-Me-Ph)-3-Pyr- Ala-OH |
| 106 | H-(N(Me))Aib-EGT-(N(Me))-(CH 2) 2-Bip(2’-Et-4’-OMe)-4-(2’-Me-Ph)-3-Pyr- Ala-OH |
| 107 | H-(N(Me))AEGT-(N(Me))-(CH 2) 2-(N(Me))-Bip(2’-Et-4’-OMe)-4-(2’-Me-Ph)- 3-Pyr-Ala-OH |
| 108 | H-(N(Me))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-(N(Me))-Bip(2’-Et-4’-OMe)-(N(Me))-4-(2’- Me-Ph)-3-Pyr-Ala-OH |
| 110 | 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 |
| 111 | Deaminizating-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 |
| 112 | Deaminizating-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 |
| 113 | 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 |
| 114 | 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-COO-(CH 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-COO-(CH 2) 10-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-COO-(CH 2) 10-CH 3 |
| 117 | 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 |
| 118 | CH 3-(CH 2) 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-COO-(CH 2) 6-CH 3 |
| 119 | CH 3-(CH 2) 10-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 |
| 120 | CH 3-(CH 2) 10-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-(CH 2) 6-CH 3 | |
| 121 | HA-(CH 2) 3-Bip(2-Me)-Bip(2-Me)-OH |
| 122 | H-Aib-(CH 2) 3-Bip(2-Me)-Bip(2-Me)-OH |
| 123 | Ha-(CH 2) 3-Bip(2-Me)-Bip(2-Me)-OH |
| 124 | H-(N(Me))A-(CH 2) 3-Bip(2-Me)-Bip(2-Me)-OH |
| 125 | H-(N(Me))A-(N(Me))-(CH 2) 3-Bip(2-Me)-Bip(2-Me)-OH |
| 126 | H-(N(Me))Aib-(N(Me))-(CH 2) 3-Bip(2-Me)-Bip(2-Me)-OH |
| 127 | H-(N(Me))A-(N(Me))-(CH 2) 3-(N(Me))-Bip(2-Me)-Bip(2-Me)-OH |
| 128 | H-(N(Me))Aib-(N(Me))-(CH 2) 3-(N(Me))-Bip(2-Me)-Bip(2-Me)-OH |
| 129 | H-(N(Me))A-(N(Me))-(CH 2) 3-(N(Me))-Bip(2-Me)-(N(Me))-Bip(2-Me)-OH |
| 130 | H-(N(Me))Aib-(N(Me))-(CH 2) 3-(N(Me))-Bip(2-Me)-(N(Me))-Bip(2-Me)-OH |
| 131 | Deaminizating-H-(N (Me)) A-(N (Me))-(CH 2) 3-(N(Me))-Bip(2-Me)-(N(Me))- Bip(2-Me)-OH |
| 132 | Deaminizating-H-(N (Me)) Aib-(N (Me))-(CH 2) 3-(N(Me))-Bip(2-Me)-(N(Me))- Bip(2-Me)-OH |
| 133 | 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 |
| 134 | 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 |
| 135 | H-(N(Me))A-(N(Me))-(CH 2) 3-(N(Me))-Bip(2-Me)-(N(Me))-Bip(2-Me)-COO- (CH 2) 10-CH 3 |
| 136 | H-(N(Me))Aib-(N(Me))-(CH 2) 3-(N(Me))-Bip(2-Me)-(N(Me))-Bip(2-Me)-COO- (CH 2) 10-CH 3 |
| 137 | CH 3-(CH 2) 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 | CH 3-(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 |
| 139 | CH 3-(CH 2) 10-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 |
| 140 | CH 3-(CH 2) 10-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 |
| 141 | HA-(CH 2) 3-Bip(2-Et)-Bip(2-Me)-OH |
| 142 | H-Aib-(CH 2) 3-Bip(2-Et)-Bip(2-Me)-OH |
| 143 | Ha-(CH 2) 3-Bip(2-Et)-Bip(2-Me)-OH |
| 144 | H-(N(Me))A-(CH 2) 3-Bip(2-Et)-Bip(2-Me)-OH |
| 145 | H-(N(Me))A-(N(Me))-(CH 2) 3-Bip(2-Et)-Bip(2-Me)-OH |
| 146 | H-(N(Me))Aib-(N(Me))-(CH 2) 3-Bip(2-Et)-Bip(2-Me)-OH |
| 147 | H-(N(Me))A-(N(Me))-(CH 2) 3-(N(Me))-Bip(2-Et)-Bip(2-Me)-OH |
| 148 | H-(N(Me))Aib-(N(Me))-(CH 2) 3-(N(Me))-Bip(2-Et)-Bip(2-Me)-OH |
| 149 | H-(N(Me))A-(N(Me))-(CH 2) 3-(N(Me))-Bip(2-Et)-(N(Me))-Bip(2-Me)-OH |
| 150 | H-(N(Me))Aib-(N(Me))-(CH 2) 3-(N(Me))-Bip(2-Et)-(N(Me))-Bip(2-Me)-OH |
| 151 | Deaminizating-H-(N (Me)) A-(N (Me))-(CH 2) 3-(N(Me))-Bip(2-Et)-(N(Me))- Bip(2-Me)-OH |
| 152 | Deaminizating-H-(N (Me)) Aib-(N (Me))-(CH 2) 3-(N(Me))-Bip(2-Et)-(N(Me))- Bip(2-Me)-OH |
| 153 | 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 |
| 154 | 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 |
| 155 | H-(N(Me))A-(N(Me))-(CH 2) 3-(N(Me))-Bip(2-Et)-(N(Me))-Bip(2-Me)-COO- (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-CH 3 |
| 157 | CH 3-(CH 2) 6-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 |
| 158 | CH 3-(CH 2) 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) 10-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 | CH 3-(CH 2) 10-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 |
Table 9:
| Sequence number | Sequence |
| 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-(α-Me)Phe(2-F)-TSDVSSYLE-(CH 2) 2-FIKELEKLL |
| 7 | HAib-(CH 2) 3-VSSYLE-(CH 2) 2-FIKELEKLL |
| 8 | HAib-(CH 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 | HAib-(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 |
| 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) 5-KELEKLL |
| 26 | HAib-(CH 2) 6-KELEKLL |
| 27 | HAib-(CH 2) 8-KELEKLL |
Test the external GLP-1 agonist activity of the plan peptide of preparation as mentioned above by following assay method based on the cAMP cell.The generation that GLP-1 simulating peptide analogue has stimulated cAMP in the dose response mode has been determined corresponding EC for some selected plan peptides
50Value, described selected plan peptide is an external activity within the 10-100nM scope.Use the EC of EX-4
50Value contrasts as forward.
Determining of cyclic amp
The GLP-1 acceptor is to connect the proteic acceptor of G.GLP-1 (7-36)-acid amides (biologically active form) connects the GLP-1 acceptor, and makes by signal transduction and to improve intracellular cAMP level by the adenylate cyclase enzyme activation.Stimulate the agonism of GLP-1 acceptor in order to monitor peptide compounds, monitor the adenyl cyclase activity by the cAMP level of assay cell.
The cAMP chemical examination:
Use DiscoverX cAMP test kit, use Exendin-4 to contrast as forward, the cAMP generation to the CHO/HGLP1R cell of stable transfection on half format high throughput platform is chemically examined.Account for the activity that the active per-cent form of Exendin-4 is determined NCE during with 0.01 μ M concentration.Use indirect cAMP ELISA test kit (R﹠amp; D system) further confirms the cAMP generation of forward compound.Represent the activity of compound with the rub form of cAMP/ micrograms of protein of method.The EC of some representative compounds (I-IV)
50Value representation is in Fig. 1.
The proof that the internal strength of chemical combination object is imitated:
Below describe some representative compounds and reduce character for glucose in the body of animal model.Use this to test and check that The compounds of this invention is to effect in the body of the blood sugar of hyperglycemia.Switzerland white mouse (SAM) to fasting a whole night of body weight 25-30 gram carries out intraperitoneal glucose tolerance test (IPGTT).Give the glucose of white mouse 1.5 gram/kilograms/10 milliliters of dosage, with different time at interval from back eye socket plexus vasculosus blood sample collection.Test compounds (plan peptide) is dissolved in the appropriate carriers, concentration (rub to receive/milliliter is a unit) and dosage (rub to receive/kilogram is a unit) and be equivalent, make each white mouse accept the solution of same dose (volume/weight).
Before loading carrier/test compounds/glucose, take a blood sample when (0 minute), 15 minutes thereafter, 30 minutes, 60 minutes and 120 minutes.Before loading glucose 15 minutes, give carrier/test compounds by the intraperitoneal route of administration.Blood sample is carried out centrifugal, the serum that obtains is stored under-20 ℃ for analysis.Use reference (forward contrast) and vehicle Control, test compounds is investigated every group of n=6 animal.Determine glucose in the serum by the GOD/POD method.Calculate repeatedly the mean value of reproducible results.Use the abswolute level value of glucose in the MS Excel computed in software serum.Use the line chart of Graphpad Prism software (3.0 editions) drafting with baseline correction in 0 minute.By carry out that One-way ANOVA calculates and analytic curve (AUC) under area and curve (BCAUC) under through the area of baseline correction, use GraphpadPrism software (3.0 editions) to carry out checking behind the Dunnett then.
Use above-mentioned experiment rules, determined that the interior glucose of body of some selected compounds reduces character, the external EC that shows in CHO-GLP-1R cAMP chemical examination
50Within the 1-50nM scope.Provided in table 10 that glucose reduces the effectiveness (ED in the IPGTT SAM model in the body of selected 4 kinds of representative compounds (Compound I, II, III and IV)
50).
Table 10: in IPGTT SAM model, render a service (ED in the body of Compound I-IV
50)
| Compound | ED in the IPGTT SAM model 50(n＝6) |
| I | 1μM/Kg |
| II | 500nM/Kg |
| III | 250nM/Kg |
| IV | 100nM/Kg |
Use other animal models for example ob/ob, db/db and C57 some compounds of the present invention are carried out screening in the body, they show effect and effectiveness in various degree the body.
Practicality:
The invention provides novel GLP-1 peptide mimics, preferably can simulate GLP-1, so that compound of the present invention has agonist activity for the GLP-1 acceptor. And, to compare with the primary sequence of GLP-1, many GLP peptide mimicses of the present invention dissociate for proteolysis and show the stability of raising.
Therefore, can give Mammals (preferred people) The compounds of this invention, be used for the treatment of various illnesss and uncomfortable disease, include, but are not limited to treat or delay the development of diabetes or outbreak (type ii diabetes preferably, impaired glucose tolerance, insulin resistance diabetes and diabetic complication, ephrosis for example, retinopathy, neuropathy and cataract), hyperglycemia, hyperinsulinemia, hypercholesterolemia, free lipid acid or glycerol content raise in the blood, hyperlipidaemia, hypertriglyceridemia, obesity, wound healing [slowly], the tissue local ischemic, atherosclerosis, vascular hypertension, enteropathy (necrotic enteritis for example, microvillus inclusion body disease or coeliac disease).Compound of the present invention can also be used to improve the level of blood middle-high density lipoprotein (HDL).
In addition, use compound of the present invention to treat to be referred to as the illness and the disease of " X syndrome " or metabolism syndrome (seeing Johannsson J. for details, Clin.Endocrinol.Metab., 82,727-34,1997).Compound of the present invention can be randomly to use with the array configuration of suitable DPP-IV inhibitor, treat in the above-mentioned illness some by the mode that gives compound or preparation, comprise compound of the present invention and suitable DPP-IV inhibitor in the described preparation.
All do not observe retroaction for any compound of the present invention.Compound of the present invention shows good glucose serum for the laboratory animal of using and reduces active.These compounds are used for the disease that test/prevention is caused by hyperinsulinemia, hyperglycemia (for example NIDDM), metabolism disorder and obesity, because these diseases all have internal connection each other.
Sequence table
＜110〉Cardila Health Nursing Co., Ltd. (Cadila Healthcare Limited)
The Bradley Jebb still the Rye, Lip river (Lohray, Braj, Bhushan)
The Wei Diyabushangluo Rye (Lohray, Vidya, Bhushan)
La Jieshi H Bach Ka Er (Bahekar, Rajesh, H)
＜120〉as the compounds of GLP-I agonist
<130>CHL-558-645
<160>29
<170>PatentIn version 3.3
<210>1
<211>30
<212>PRT
＜213〉artificial sequence (Artificial Sequence)
<220>
＜223〉this protein is synthetic (This protein was synthetically generated)
<400>1
His Ala Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
1 5 10 15
Gln Ala Ala Lys Glu Phe Ile Ala Trp Leu Val Lys Gly Arg
20 25 30
<210>2
<211>39
<212>PRT
＜213〉Gila monster (Heloderma Suspectum)
<400>2
His Gly Glu Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Met Glu Glu
1 5 10 15
Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser
20 25 30
Ser Gly Ala Pro Pro Pro Ser
35
<210>3
<211>9
<212>PRT
＜213〉artificial sequence (Artificial Sequence)
<220>
＜223〉this protein is synthetic (This protein was synthetically generated)
<400>3
His Ala Glu Gly Thr Phe Thr Ser Asp
1 5
<210>4
<211>10
<212>PRT
＜213〉artificial sequence (Artificial Sequence)
<220>
＜223〉this aminoacid sequence is synthetic (This amino acid sequence was artificially generated)
<400>4
His Ala Glu Gly Thr Phe Thr Ser Asp Val
1 5 10
<210>5
<211>11
<212>PRT
＜213〉artificial sequence (Artificial Sequence)
<220>
＜223〉this aminoacid sequence is synthetic (This amino acid sequence was artificially generated)
<400>5
His Ala Glu Gly Thr Phe Thr Ser Asp Val Ser
1 5 10
<210>6
<211>12
<212>PRT
＜213〉artificial sequence (Artificial Sequence)
<220>
＜223〉this aminoacid sequence is synthetic (This amino acid sequence was artificially generated)
<400>6
His Ala Glu Gly Thr Phe Thr Ser Asp Val Ser Ser
1 5 10
<210>7
<211>13
<212>PRT
＜213〉artificial sequence (Artificial Sequence)
<220>
＜223〉this aminoacid sequence is synthetic (This amino acid sequence was artificially generated)
<400>7
His Ala Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr
1 5 10
<210>8
<211>14
<212>PRT
＜213〉artificial sequence (Artificial Sequence)
<220>
＜223〉this aminoacid sequence is synthetic (This amino acid sequence was artificially generated)
<400>8
His Ala Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu
1 5 10
<210>9
<211>15
<212>PRT
＜213〉artificial sequence (Artificial Sequence)
<220>
＜223〉this aminoacid sequence is synthetic (This amino acid sequence was artificially generated)
<400>9
His Ala Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu
1 5 10 15
<210>10
<211>16
<212>PRT
＜213〉artificial sequence (Artificial Sequence)
<220>
＜223〉this aminoacid sequence is synthetic (This amino acid sequence was artificially generated)
<400>10
His Ala Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
1 5 10 15
<210>11
<211>17
<212>PRT
＜213〉artificial sequence (Artificial Sequence)
<220>
＜223〉this aminoacid sequence is synthetic (This amino acid sequence was artificially generated)
<400>11
His Ala Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
1 5 10 15
Gln
<210>12
<211>18
<212>PRT
＜213〉artificial sequence (Artificial Sequence)
<220>
＜223〉this aminoacid sequence is synthetic (This amino acid sequence was artificially generated)
<400>12
His Ala Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
1 5 10 15
Gln Ala
<210>13
<211>19
<212>PRT
＜213〉artificial sequence (Artificial Sequence)
<220>
＜223〉this aminoacid sequence is synthetic (This amino acid sequence was artificially generated)
<400>13
His Ala Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
1 5 10 15
Gln Ala Ala
<210>14
<211>20
<212>PRT
＜213〉artificial sequence (Artificial Sequence)
<220>
＜223〉this aminoacid sequence is synthetic (This amino acid sequence was artificially generated)
<400>14
His Ala Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
1 5 10 15
Gln Ala Ala Lys
20
<210>15
<211>21
<212>PRT
＜213〉artificial sequence (Artificial Sequence)
<220>
＜223〉this aminoacid sequence is synthetic (This amino acid sequence was artificially generated)
<400>15
His Ala Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
1 5 10 15
Glh Ala Ala Lys Glu
20
<210>16
<2U>22
<212>PRT
＜213〉artificial sequence (Artificial Sequence)
<220>
＜223〉this aminoacid sequence is synthetic (This amino acid sequence was artificially generated)
<400>16
His Ala Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
1 5 10 15
Gln Ala Ala Lys Glu Phe
20
<210>17
<211>23
<212>PRT
＜213〉artificial sequence (Artificial Sequence)
<220>
＜223〉this aminoacid sequence is synthetic (This amino acid sequence was artificially generated)
<400>17
His Ala Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
1 5 10 15
Gln Ala Ala Lys Glu Phe Ile
20
<210>18
<211>10
<212>PRT
＜213〉artificial sequence (Artificial Sequence)
<220>
＜223〉this aminoacid sequence is synthetic (This amino acid sequence was artificially generated)
<400>18
Gly Pro Ser Ser Gly Ala Pro Pro Pro Ser
1 5 10
<210>19
<211>7
<212>PRT
＜213〉artificial sequence (Artificial Sequence)
<220>
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<400>19
Lys Glu Leu Glu Lys Leu Leu
1 5
<210>20
<211>4
<212>PRT
＜213〉artificial sequence (Artificial Sequence)
<220>
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<400>20
Gly Pro Pro Ser
1
<210>21
<211>4
<212>PRT
＜213〉artificial sequence (Artificial Sequence)
<220>
＜223〉this aminoacid sequence is synthetic (This amino acid sequence was artificially generated)
<400>21
Val Lys Gly Arg
1
<210>22
<211>2
<212>PRT
＜213〉artificial sequence (Artificial Sequence)
<220>
＜223〉this aminoacid sequence is synthetic (This amino acid sequence was artificially generated)
<400>22
His Ala
1
<210>23
<211>3
<212>PRT
＜213〉artificial sequence (Artificial Sequence)
<220>
＜223〉this aminoacid sequence is synthetic (This amino acid sequence was artificially generated)
<400>23
His Ala Glu
1
<210>24
<211>4
<212>PRT
＜213〉artificial sequence (Artificial Sequence)
<220>
＜223〉this aminoacid sequence is synthetic (This amino acid sequence was artificially generated)
<400>24
His Ala Glu Gly
1
<210>25
<211>5
<212>PRT
＜213〉artificial sequence (Artificial Sequence)
<220>
＜223〉this aminoacid sequence is synthetic (This amino acid sequence was artificially generated)
<400>25
His Ala Glu Gly Thr
1 5
<210>26
<211>6
<212>PRT
＜213〉artificial sequence (Artificial Sequence)
<220>
＜223〉this aminoacid sequence is synthetic (This amino acid sequence was artificially generated)
<400>26
His Ala Glu Gly Thr Phe
1 5
<210>27
<210>7
<212>PRT
＜213〉artificial sequence (Artificial Sequence)
<220>
＜223〉this aminoacid sequence is synthetic (This amino acid sequence was artificially generated)
<400>27
His Ala Glu Gly Thr Phe Thr
1 5
<210>28
<211>8
<212>PRT
＜213〉artificial sequence (Artificial Sequence)
<220>
＜223〉this aminoacid sequence is synthetic (This amino acid sequence was artificially generated)
<400>28
His Ala Glu Gly Thr Phe Thr Ser
1 5
<210>29
<211>9
<212>PRT
＜213〉artificial sequence (Artificial Sequence)
<220>
＜223〉this aminoacid sequence is synthetic (This amino acid sequence was artificially generated)
<400>29
His Ala Glu Gly Thr Phe Thr Ser Asp
1 5
Claims (14)
1. isolating plan peptide, the sequence that it has general formula (I) comprises its tautomer, solvate and pharmacological-acceptable salt
A-X
1-S
1-Y-S
2-X
2-B(I)
Wherein,
A represents-NH-R
1, R
1Expression: hydrogen is selected from straight or branched (C
1-C
15) group of alkyl chain, comprise amino acid or peptide a kind of, two or three natural amino acid residue, R
3-CO-group, R
3O-C (O)-group, general formula R
3-SO
2-alkylsulfonyl, various can the replacement in these groups; R
3Be selected from: straight or branched (C
1-C
10) alkyl, (C
3-C
6) cycloalkyl, aryl, heteroaryl, aralkyl, various can the replacement in these groups;
B represents-COOR
2,-CONHR
2Or CH
2OR
2, R
2Expression: H is selected from straight or branched (C
1-C
10) group of alkyl, be selected from the aryl of phenyl, naphthyl, indanyl, fluorenyl, xenyl, aralkyl, aryl wherein as hereinbefore defined, various can the replacement in these groups;
Each S
1And S
2Can be a key independently or represent NH-(CH independently
2)
n-COO-, wherein n=1-9;
Y represent a key or-CO-,-(CH
2)
m-(m=1-3), O, S ,-CO-NH-,-CO-NR
4-, perhaps expression comprises a kind of, the two or three amino acid whose small peptide that is selected from natural or alpha-non-natural amino acid; R wherein
4Expression: H is selected from straight or branched (C
1-C
10) group of optional replacement of alkyl, perhaps be selected from the aryl of phenyl, naphthyl, indanyl, fluorenyl, xenyl; Prerequisite is to work as S
1-Y-S
2When representing a key,
X
1Be selected from following aminoacid sequence
HAEGTFTSD, HAEGTFTSDV, HAEGTFTSDVS, HAEGTFTSDVSS, HAEGTFTSDVSSY, HAEGTFTSDVSSYL, HAEGTFTSDVSSYLE, HAEGTFTSDVSSYLEG, HAEGTFTSDVSSYLEGQ, HAEGTFTSDVSSYLEGQA, HAEGTFTSDVSSYLEGQAA, HAEGTFTSDVSSYLEGQAAK, HAEGTFTSDVSSYLEGQAAKE, HAEGTFTSDVSSYLEGQAAKEF, HAEGTFTSDVSSYLEGQAAKEFI, in further option, one or more in these amino acid can be replaced by alpha-non-natural amino acid, X
2Be selected from following aminoacid sequence:
GPSSGAPPPS or
KELEKLL or
GPPS or
VKGR；
Work as S
1-Y-S
2When not representing a key,
X
1Be selected from following aminoacid sequence:
HA, HAE, HAEG, HAEGT, HAEGTF, HAEGTFT, HAEGTFTS, HAEGTFTSD, in further option, one or more in these amino acid can be replaced by alpha-non-natural amino acid;
X
2Be selected from:
GPSSGAPPPS or
KELEKLL or
GPPS or
VKGR or
Be selected from the dipeptides of the combination of two seed amino acids, form by natural or alpha-non-natural amino acid, has the side chain that comprises aralkyl or heteroaralkyl part, described aralkyl or heteroaralkyl are selected from benzyl, menaphthyl, picolyl, thenyl, furfuryl, imidazoles methyl isoxazole methyl, the quinoline methyl, the cumarone methyl, the thionaphthene methyl, the indoline methyl, indole methyl, the diphenylene-oxide methyl, the dibenzothiophene methyl, the coumaran methyl, the thiaindan methyl, the Thienopyrimidine methyl, the benzoglyoxaline methyl, luxuriant and rich with fragrance methyl, the luxuriant and rich with fragrance methyl of dihydro, fluorene methyl, the diphenylene-oxide methyl, dibenzo thiophenyl methyl etc., various can the choosing wantonly by following group in these groups replaces: (C
1-C
6) alkyl, (C
1-C
6) alkoxyl group, cyano group, halogen, hydroxyl, perhaps optional aryl or the heteroaryl that replaces stipulates that further these aryl or heteroaryl substituting group can be further randomly by (C
1-C
6) alkyl, (C
1-C
6) alkoxyl group, cyano group, halogen, hydroxyl, aryl or heteroaryl replace.
2. compound as claimed in claim 1 is characterized in that, described alpha-non-natural amino acid is represented by general formula (IIa):
R wherein
5Be selected from H, F, (C
1-C
5) alkyl, band R
5The three-dimensional chemical configuration at carbon atom place can be (R) or (S); R
6Be selected from H or (C
1-C
3) alkyl; R
7And R
8Be selected from H, (C independently of one another
1-C
2) alkyl or halogen atom, preferably fluorine atom; R
9Expression is selected from (C
1-C
5) group of alkyl, aryl or heteroaryl, aryl or heteroaryl moieties are selected from phenyl, naphthyl, pyridyl, thienyl, furyl, imidazolyl, isoxazolyl, quinolyl, benzofuryl, benzothienyl, indoline base, indyl, dibenzofuran group, dibenzothiophene base, coumaran base, thiaindan base, Thienopyrimidine base, benzimidazolyl-, phenanthryl, dihydrophenanthrenyl, fluorenyl, dibenzofuran group, dibenzo thiophenyl, and various can the choosing wantonly by following group in these groups replaces: (C
1-C
6) alkyl, (C
1-C
6) alkoxyl group, cyano group, halogen, hydroxyl or optional aryl or the heteroaryl that replaces, stipulate that further these aryl or heteroaryl substituting group can further choose quilt (C
1-C
6) alkyl, (C
1-C
6) alkoxyl group, cyano group, halogen, hydroxyl, aryl or heteroaryl replace.
3. the isolating peptide described in claim 1 is characterized in that X
2The dipeptides of expression is preferably selected from Bip, Bip (2-methyl), Bip (2-ethyl), Bip (2-sec.-propyl), Bip (2-CN), Bip (2 '-Et-4 '-methoxyl group), Bip (4 '-fluorine), Bip (4 '-phenyl), 2-(9,10-dihydro-phenanthryl)-Ala, 2-(phenanthryl)-Ala, 4-(2-naphthyl)-Phe, 4-(1-naphthyl)-Phe, 2-fluorenyl-Ala, 4-diphenylene-oxide-Phe, 4-dibenzothiophene-Phe, 4-(2 '-aminomethyl phenyl)-3-pyridyl L-Ala.
4. the isolating peptide described in claim 1; it is characterized in that described substituting group is selected from hydroxyl, oxo, halogen, sulfo-, nitro, amino, cyano group, alkyl, haloalkyl, alkoxyl group, halogenated alkoxy, cycloalkyl, aryl, aryloxy, aralkyl, aralkoxy, heteroaryl, heteroaralkyl, heteroaryloxy, assorted aralkoxy, acyl group, acyloxy, carboxylic acid and derivative thereof for example ester and acid amides.
5. isolated polypeptide as claimed in claim 1 is characterized in that, described isolated polypeptide is to be selected from following compound.
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
HGEGTFTSD-(CH
2)
10-GPSSGAPPPS
HGEGTFTSD-(CH
2)
11-GPSSGAPPPS
HGEGTFTSDLSKQM-(CH
2)
3-GPSS
HGEGTFTSDLSKQM-(CH
2)
4-GPSS
HGEGTFTSDLSKQM-(CH
2)
5-GPSS
HGEGTFTSDLSKQM-(CH
2)
6-GPSS
HGEGTFTSDLSKQM-(CH
2)
7-GPSS
HGEGTFTSDLSKQM-(CH
2)
10-GPSS
HGEGTFTSDLSKQM-(CH
2)
11-GPSS
HGEGTFTSDLSKQME-G-GPSSGAPPPS
HGEGTFTSDLSKQME-(CH
2)
2-GPSSGAPPPS
HGEGTFTSDLSKQME-(CH
2)
3-GPSSGAPPPS
HGEGTFTSDLSKQME-(CH
2)
4-GPSSGAPPPS
HGEGTFTSDLSKQME-(CH
2)
5-GPSSGAPPPS
HGEGTFTSDLSKQME-(CH
2)
6-GPSSGAPPPS
HGEGTFTSDLSKQME-(CH
2)
7-GPSSGAPPPS
HGEGTFTSDLSKQME-(CH
2)
10-GPSSGAPPPS
HGEGTFTSDLSKQME-(CH
2)
11-GPSSGAPPPS
HAEGTFTSD-(CH
2)
2-VKGR
HAEGTFTSD-(CH
2)
3-VKGR
HAEGTFTSD-(CH
2)
4-VKGR
HAEGTFTSD-(CH
2)
5-VKGR
HAEGTFTSD-(CH
2)
6-VKGR
HAEGTFTSD-(CH
2)
10-VKGR
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
HAibEGTFTSD-(CH
2)
10-VKGR
HGEGTFTSDLSKQMKELEKLL
HAEGTFTSDKELEKLL
HGEGTFTSDKELEKLL
HAibEGTFTSDGKELEKLL
HGEGTFTSDGKELEKLL
HGEGTFTSDVSKELEKLL
HAEGTFTSDVSKELEKLL
HAEGTFTSDVSEKELEKLL
HAEGTFTSDVSGKELEKLL
HAEGTFTSDVSSYLEKELEKLL
HAEGTFTSDVSSYLEGKELEKLL
HGEGTFTSDVSSYLEGKELEKLL
HaEGTFTSDVSSYLEGKELEKLL
HAibEGTFTSDVSSYLEGKELEKLL
HAEGTFTSDVSSYLEGKELEKLLVKG
HAEGTFTSDVSSYLEPKELEKLL
HAEGTFTSDVSSYLEGQAAKELEKLL HAEGTFTSDVSSYLEGQAAKEFIKELEKLI
HAibEGTFTSDVSSYLEGQAAKEFIKELEKLL
HAibEGT-(α-Me)Phe(2-F)-TSDVSSYLEGQAAKEFIKELEKLL
Deaminizating-HAibEGT-(Phe (2-F)-TSDVSSYLEGQAAKEFIKELEKLL of α-Me)
HAEGTFTSD-(CH
2)
3-KELEKLL
HAEGTFTSD-(CH
2)
4-KELEKLL
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
HAibEGTFTSDVSSYLEGQ-(CH
2)
3-KELEKLL
HAibEGTFTSDVSSYLE-(CH
2)
2-FIKELEKLL
HGEGTFTSD-(CH
2)
3-Bip-Bip
HAibEGTFTSD-(CH
2)
3-Bip-Bip
HAibEGT-(α-Me)-Phe(2-F)-TSD-(CH
2)
3-Bip-Bip
HAEGTFTSD-G-Bip(2-Me)-Bip(2-Me)
HAibEGTFTSD-G-Bip(2-Me)-Bip(2-Me)
HAibEGT-(α-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)
HAibEGT-(α-Me)-Phe(2-F)-TS-G-Bip(2-Me)-Bip(2-Me)
HAEGTFTS-(CH
2)
2-Bip(2-Me)-Bip(2-Me)
HAibEGTFTS-(CH
2)
2-Bip(2-Me)-Bip(2-Me)
HAibEGT-(α-Me)-Phe(2-F)-TS-(CH
2)
2-Bip(2-Me)-Bip(2-Me)
HAEGTFT-(CH
2)
2-Bip(2-Me)-Bip(2-Me)
HAibEGTFT-(CH
2)
2-Bip(2-Me)-Bip(2-Me)
HAibEGT-(α-Me)-Phe(2-F)-T-(CH
2)
2-Bip(2-Me)-Bip(2-Me)
HAEGTF-(CH
2)
2-Bip(2-Me)-Bip(2-Me)
HAibEGTF-(CH
2)
2-Bip(2-Me)-Bip(2-Me)
HAibEGT-(α-Me)-Phe(2-F)-(CH
2)
2-Bip(2-Me)-Bip(2-Me)
HAEGT-(CH
2)
2-Bip(2-Me)-Bip(2-Me)
HAibEGT-(CH
2)
2-Bip(2-Me)-Bip(2-Me)
HAEG-(CH
2)
2-Bip(2-Me)-Bip(2-Me)
HAibEG-(CH
2)
2-Bip(2-Me)-Bip(2-Me)
HAEGTFTSD-(CH
2)
2-Bip(2-Me)-Bip(2-Me)
HAibEGTFTSD-(CH
2)
2-Bip(2-Me)-Bip(2-Me)
HAibEGT-(α-Me)-Phe(2-F)-TSD-(CH
2)
2-Bip(2-Me)-Bip(2-Me)
HAEGTFTSD-G-Bip-Bip(2-Me)
HAibEGTFTSD-G-Bip-Bip(2-Me)
HAibEGT-(α-Me)-Phe(2-F)-TSD-G-Bip-Bip(2-Me)
HAEGTFTSD-G-Bip(2-Me)-Bip
HAibEGTFTSD-G-Bip(2-Me)-Bip
HAibEGT-(α-Me)-Phe(2-F)-TSD-G-Bip(2-Me)-Bip
HAEGTFTSD-G-Bip-Bip HAibEGTFTSD-G-Bip-Bip
HAibEGT-(α-Me)-Phe(2-F)-TSD-G-Bip-Bip
HAEGTFTSD-G-Bip-Bip(2-Et)
HAibEGTFTSD-G-Bip-Bip(2-Et)
HAibEGT-(α-Me)-Phe(2-F)-TSD-G-Bip-Bip(2-Et)
HAEGTFTSD-G-Bip(2-Et)-Bip(2-Et)
HAibEGTFTSD-G-Bip(2-Et)-Bip(2-Et)
HAibEGT-(α-Me)-Phe(2-F)-TSD-G-Bip(2-Et)-Bip(2-Et)
HAEGTFTSD-G-Bip(2-Et)-Bip
HAibEGTFTSD-G-Bip(2-Et)-Bip
HAibEGT-(α-Me)-Phe(2-F)-TSD-G-Bip(2-Et)-Bip
HAEGTFTSD-G-Bip(2-Et)-Bip(2-Me)
HAibEGTFTSD-G-Bip(2-Et)-Bip(2-Me)
HAibEGT-(α-Me)-Phe(2-F)-TSD-G-Bip(2-Et)-Bip(2-Me)
HAEGTFTSD-G-Bip(2-Me)-Bip(2-Et)
HAibEGTFTSD-G-Bip(2-Me)-Bip(2-Et)
HAibEGT-(α-Me)-Phe(2-F)-TSD-G-Bip(2-Me)-Bip(2-Et)
HGEGTFTSD-G-Bip(2-Me)-Bip(2-Me)
HGEGT-(α-Me)-Phe(2-F)-TSD-G-Bip(2-Me)-Bip(2-Me)
HGEGTFTSD-G-Bip(2-Et)-Bip(2-Et)
HGEGT-(α-Me)-Phe(2-F)-TSD-G-Bip(2-Et)-Bip(2-Et)
HGEGTFTSD-(CH
2)
3-Bip(2-Me)-Bip(2-Me)
HGEGT-(α-Me)-Phe(2-F)-TSD-(CH
2)
3-Bip(2-Me)-Bip(2-Me)
HGEGTFTSD-(CH
2)
4-Bip(2-Me)-Bip(2-Me)
HGEGT-(α-Me)-Phe(2-F)-TSD-(CH
2)
4-Bip(2-Me)-Bip(2-Me)
HGEGTFTSD-(CH
2)
5-Bip(2-Me)-Bip(2-Me)
HGEGT-(α-Me)-Phe(2-F)-TSD-(CH
2)
5-Bip(2-Me)-Bip(2-Me)
HGEGTFTSD-(CH
2)
6-Bip(2-Me)-Bip(2-Me)
HGEGT-(α-Me)-Phe(2-F)-TSD-(CH
2)
6-Bip(2-Me)-Bip(2-Me)
HGEGTFTSD-(CH
2)
10-Bip(2-Me)-Bip(2-Me)
HGEGT-(α-Me)-Phe(2-F)-TSD-(CH
2)
10-Bip(2-Me)-Bip(2-Me)
HGEGTFTSD-(CH
2)
3-Bip(2-Et)-Bip(2-Et)
HGEGT-(α-Me)-Phe(2-F)-TSD-(CH
2)
3-Bip(2-Et)-Bip(2-Et)
HGEGTFTSD-(CH
2)
4-Bip(2-Et)-Bip(2-Et)
HGEGT-(α-Me)-Phe(2-F)-TSD-(CH
2)
4-Bip(2-Et)-Bip(2-Et)
HGEGTFTSD-(CH
2)
5-Bip(2-Et)-Bip(2-Et)
HGEGT-(α-Me)-Phe(2-F)-TSD-(CH
2)
5-Bip(2-Et)-Bip(2-Et)
HGEGTFTSD-(CH
2)
6-Bip(2-Et)-Bip(2-Et)
HGEGT-(α-Me)-Phe(2-F)-TSD-(CH
2)
6-Bip(2-Et)-Bip(2-Et)
HGEGTFTSD-(CH
2)
10-Bip(2-Et)-Bip(2-Et)
HGEGT-(α-Me)-Phe(2-F)-TSD-(CH
2)
10-Bip(2-Et)-Bip(2-Et)
HGEGTFTSD-(CH
2)
11-Bip(2-Et)-Bip(2-Et)
HGEGT-(α-Me)-Phe(2-F)-TSD-(CH
2)
11-Bip(2-Et)-Bip(2-Et)
HGEGTFTS-(CH
2)
3-Bip(2-Me)-Bip(2-Me)
HGEGT-(α-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-(α-Me)-Phe(2-F)-TS-(CH
2)
4-Bip(2-Me)-Bip(2-Me)
HGEGTFTS-(CH
2)
5-Bip(2-Me)-Bip(2-Me)
HGEGT-(α-Me)-Phe(2-F)-TS-(CH
2)
5-Bip(2-Me)-Bip(2-Me)
HGEGTFTS-(CH
2)
6-Bip(2-Me)-Bip(2-Me)
HGEGT-(α-Me)-Phe(2-F)-TS-(CH
2)
6-Bip(2-Me)-Bip(2-Me)
HGEGTFTS-(CH
2)
10-Bip(2-Me)-Bip(2-Me)
HGEGT-(α-Me)-Phe(2-F)-TS-(CH
2)
10-Bip(2-Me)-Bip(2-Me)
HGEGTFTS-(CH
2)
11-Bip(2-Me)-Bip(2-Me)
HGEGT-(α-Me)-Phe(2-F)-TS-(CH
2)
11-Bip(2-Me)-Bip(2-Me)
HGEGTFTS-(CH
2)
3-Bip(2-Et)-Bip(2-Et)
HGEGT-(α-Me)-Phe(2-F)-TS-(CH
2)
3-Bip(2-Et)-Bip(2-Et)
HGEGT-(α-Me)-Phe(2-F)-TS-(CH
2)
4-Bip(2-Et)-Bip(2-Et)
HGEGTFTS-(CH
2)
4-Bip(2-Et)-Bip(2-Et)
HGEGT-(α-Me)-Phe(2-F)-TS-(CH
2)
4-Bip(2-Et)-Bip(2-Et)
HGEGTFTS-(CH
2)
5-Bip(2-Et)-Bip(2-Et)
HGEGT-(α-Me)-Phe(2-F)-TS-(CH
2)
5-Bip(2-Et)-Bip(2-Et)
HGEGTFTS-(CH
2)
6-Bip(2-Et)-Bip(2-Et)
HGEGT-(α-Me)-Phe(2-F)-TS-(CH
2)
6-Bip(2-Et)-Bip(2-Et)
HGEGTFTS-(CH
2)
10-Bip(2-Et)-Bip(2-Et)
HGEGT-(α-Me)-Phe(2-F)-TS-(CH
2)
10-Bip(2-Et)-Bip(2-Et)
HGEGTFTS-(CH
2)
11-Bip(2-Et)-Bip(2-Et)
HGEGT-(α-Me)-Phe(2-F)-TS-(CH
2)
11-Bip(2-Et)-Bip(2-Et)
HGEGTFTS-(CH
2)
2-Bip(2-Me)-Bip(2-Me)
HGEGT-(α-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-(α-Me)-Phe(2-F)-TS-(CH
2)
2-Bip(2-Et)-Bip(2-Et)
HAEGTFTS-(CH
2)
2-Bip(2-Et)-Bip(2-Et)
HAibEGTFTS-(CH
2)
2-Bip(2-Et)-Bip(2-Et)
HAibEGT-(α-Me)-Phe(2-F)-TS-(CH
2)
2-Bip(2-Et)-Bip(2-Et)
HGEGTFTSD-(CH
2)
2-Bip(2-Et)-Bip(2-Et)
HGEGT-(α-Me)-Phe(2-F)-TSD-(CH
2)
2-Bip(2-Et)-Bip(2-Et)
HAEGTFTSD-(CH
2)
2-Bip(2-Et)-Bip(2-Et)
HAibEGTFTSD-(CH
2)
2-Bip(2-Et)-Bip(2-Et)
HAibEGT-(α-Me)-Phe(2-F)-TSD-(CH
2)
2-Bip(2-Et)-Bip(2-Et)
HAEGTF-(CH
2)
2-Bip(2-Me)-Bip(2-Et)
HAibEGTF-(CH
2)
2-Bip(2-Me)-Bip(2-Et)
HAibEGT-(α-Me)-Phe(2-F)-(CH
2)
2-Bip(2-Me)-Bip(2-Et)
HAEGTFTSD-G-TrPh-TrPh
HAibEGTFTSD-G-TrPh-TrPh
HAibEGT-(α-Me)-Phe(2-F)-TSD-G-TrPh-TrPh
HAibEGT-(α-Me)-Phe(2-F)-(CH
2)
2-TrPh-TrPh
HAibEG-(CH
2)
2-TrPh-TrPh
HAibE-(CH
2)
2-TrPh-TrPh
HAib-(CH
2)
3-TrPh-TrPh
HAEGTFTSD-G-Nap-Nap
HAibEGTFTSD-G-Nap-Nap
HAibEGT-(α-Me)-Phe(2-F)-TSD-G-Nap-Nap
HAEGTFTSD-G-Bip(2-F)-Bip(2-F)
HAibEGTFTSD-G-Bip(2-F)-Bip(2-F)
AibEGT-(α-Me)-Phe(2-F)-TSD-G-Bip(2-F)-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
HAibEGT-(α-Me)-Phe(2-F)-TSD-G-Bip(2’-Et-4’-OMe)-4-(2’-Me-Ph)-3-Pyr-Ala
HAEGTFTSD-(CH
2)
2-Bip(2’-Et-4’-OMe)-4-(2’-Me-Ph)-3-Pyr-Ala
HAibEGTFTSD-(CH
2)
2-Bip(2’-Et-4’-OMe)-4-(2’-Me-Ph)-3-Pyr-Ala
HAibEGT-(α-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-Bip(2’-Et-4’-OMe)-4-(2’-Me-Ph)-3-Pyr-Ala
HAibEGT-(α-Me)-Phe(2-F)-TS-(CH
2)
2-Bip(2’-Et-4’-OMe)-4-(2’-Me-Ph)-3-Pyr-Ala
HAEGTFT-(CH
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
HAibEGT-(α-Me)-Phe(2-F)-T-(CH
2)
2-Bip(2’-Et-4’-OMe)-4-(2’-Me-Ph)-3-Pyr-Ala
HAEGTF-(CH
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-(α-Me)-Phe(2-F)-(CH
2)
2-Bip(2’-Et-4’-OMe)-4-(2’-Me-Ph)-3-Pyr-Ala
HAEGT-(CH
2)
2-Bip(2’-Et-4’-OMe)-4-(2’-Me-Ph)-3-Pyr-Ala
HAibEGT-(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
HAibEG-(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
HAibEG-(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)
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-(CH
2)
3-Bip(2-Me)-Bip(2-Me)
HAEG-(CH
2)
3-Bip(2-Me)-Bip(2-Me)
HGEG-(CH
2)
4-Bip(2-Me)-Bip(2-Me)
HGEG-(CH
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)
HAEG-(CH
2)
3-Bip(2-Me)-DBip(2-Me)
HAEG-(CH
2)
4-Bip(2-Me)-DBip(2-Me)
HAEG-(CH
2)
5-Bip(2-Me)-DBip(2-Me)
HGEG-(CH
2)
5-DBip(2-Me)-Bip(2-Me)
HAE-(CH
2)
3-Bip(2-Me)-Bip(2-Me)
HAE-(CH
2)
3-Bip(2-Me)-DBip(2-Me)
HAE-(CH
2)
2-D-Bip(2-Me)-Bip(2-Me)
HAE-(CH
2)
3-D-Bip(2-Me)-Bip(2-Me)
HAE-(CH
2)
4-D-Bip(2-Me)-Bip(2-Me)
HAE-(CH
2)
4-Bip(2-Me)-DBip(2-Me)
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-(CH
2)
3-Bip(2-Me)-Bip(2-Me)
H-(CH
2)
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-(CH
2)
4-Bip(2-Et)-Bip(2-Me)
H-(CH
2)
5-Bip(2-Et)-Bip(2-Me)
H-(CH
2)
6-Bip(2-Et)-Bip(2-Me)
H-(CH
2)
10-Bip(2-Et)-Bip(2-Me)
H-(CH
2)
5-Bip(2-Me)-DBip(2-Me)
H-(CH
2)
5-DBip(2-Me)-Bip(2-Me)
H-(CH
2)
5-DBip(2-Me)-DBip(2-Me)
HG-(CH
2)
3-Bip(2-Me)-Bip(2-Me)
HG-(CH
2)
4-Bip(2-Me)-Bip(2-Me)
HG-(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)
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)
Ha-(CH
2)
5-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-Me)
Ha-(CH
2)
3-Bip(2-Me)-DBip(2-Me)
Ha-(CH
2)
3-Bip(2-Et)-DBip(2-Et)
Ha-(CH
2)
3-Bip(2-Me)-Bip
Ha-(CH
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)
Ha-(CH
2)
3-DBip(2-Me)-Bip(2-Et)
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)
HA-(CH
2)
10-Bip(2-Me)-Bip(2-Me)
HA-(CH
2)
11-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-(CH
2)
3-DBip(2-Me)-DBip(2-Me)
HA-(CH
2)
3-DBip(2-Me)-Bip(2-Me)
HA-(CH
2)
3-Bip(2-Me)-DBip(2-Me)
HA-(CH
2)
3-Bip(2-Ipr)-Bip(2-Ipr)
HA-(CH
2)
3-Bip(2-Ipr)-Bip(2-Me)
HA-(CH
2)
3-Bip(2-Me)-Bip(2-Ipr)
HA-(CH
2)
4-Bip(2-Et)-Bip(2-Me)
HA-(CH
2)
3-Bip(2-Me)-DBip(2-Et)
HA-(CH
2)
2-Bip(2-Et)-Bip(2-Me)
HA-(CH
2)
5-Bip(2-Et)-Bip(2-Me)
HA-(CH
2)
6-Bip(2-Et)-Bip(2-Me)
HA-(CH
2)
2-Bip(2-Me)-Bip(2-Me)
HA-(CH
2)
3-DBip(2-Et)-DBip(2-Me)
HA-(CH
2)
3-DBip(2-Et)-Bip(2-Me)
HA-(CH
2)
2-Bip(2-Me)-DBip(2-Me)
HA-(CH
2)
3-Bip(2-Et)-Bip(2-Et)
HA-(CH
2)
3-DBip(2-Et)-DBip(2-Et)
HA-(CH
2)
3-DBip(2-Et)-Bip(2-Et)
HA-(CH
2)
3-DBip(2-Me)-DBip(2-Et)
HA-(CH
2)
3-Bip(2-Me)-Bip(2-Et)
HA-(CH
2)
3-DBip(2-Me)-Bip(2-Et)
HA-(CH
2)
3-Bip-Bip
HA-(CH
2)
3-Bip-D-Bip
HA-(CH
2)
3-DBip-D-Bip
HA-(CH
2)
3-DBip-Bip
HA-(CH
2)
3-Bip-Bip(2-Me)
HA-(CH
2)
3-Bip(2-Me)-Bip
HA-(CH
2)
3-Bip(2-Et)-Bip
HA-(CH
2)
3-Bip-Bip(2-Et)
HA-(CH
2)
3-Bip(2-Ipr)-DBip(2-Ipr)
HA-(CH
2)
3-DBip(2-Ipr)-Bip(2-Ipr)
HA-(CH
2)
3-DBip(2-Ipr)-DBip(2-Ipr)
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)
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)
HA-(CH
2)
3-Bip(2-CN)-Bip(2-CN)
HA-(CH
2)
2-F-(CH
2)
2-Bip(2-Et)-DBip(2-Et)
HA-(CH
2)
2-F-(CH
2)
2-Bip(2-Et)-DBip(2-Me)
HA-(CH
2)
5-Bip(2-Me)-DBip
HA-(CH
2)
3-Bip(2-Me)-DBip-R
HA-(CH
2)
3-DBip(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)
HA-(CH
2)
4-Bip(2-Me)-DBip(2-Me)
HA-(CH
2)
5-Bip(2-Me)-DBip(2-Me)
HA-(CH
2)
3-(N(Me))-DBip-Bip(2-Et)
HA-(CH
2)
4-DBip(2-Me)-Bip(2-Et)
HA-(CH
2)
5-DBip(2-Me)-Bip(2-Et)
HA-(CH
2)
3-(N(Me))-DBip(2-Me)-Bip(2-Et)
HA-(CH
2)
4-Bip(2-Me)-DBip
HA-(C
H2)
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)
HA-(N(Me))-(CH
2)
3-DBip-Bip(2-Et)
HA-(N(Me))-(CH
2)
3-Bip(2-Et)-Bip(2-Me)
HA-(N(Me))-(CH
2)
3-Bip(2-Me)-DBip
HAE-(CH
2)
2-F-(CH
2)
2-Bip(2-Et)-DBip(2-Et)
HAE-(CH
2)
2-F-(CH
2)
2-Bip(2-Et)-DBip(2-Me)
HAib-(CH
2)
3-(N(Me))-Bip(2-Et)-Bip(2-Me)
6. isolated polypeptide as claimed in claim 1 is characterized in that, described isolated polypeptide is to be selected from following compound.
HA-(CH
2)
2-Bip(2’-Et-4’-OMe)-4-(2’-Me-Ph)-3-Pyr-Ala-NH
2
H-Aib-(CH
2)
2-Bip(2’-Et-4’-OMe)-4-(2’-Me-Ph)-3-Pyr-Ala-NH
2
Ha-(CH
2)
2-Bip(2’-Et-4’-OMe)-4-(2’-Me-Ph)-3-Pyr-Ala-NH
2
H-(N(Me))A-(CH
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-Bip(2’-Et-4’-OMe)-4-(2’-Me-Ph)-3-Pyr-Ala-NH
2
H-(N(Me))Aib-(N(Me))-(CH
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’-Et-4’-OMe)-4-(2’-Me-Ph)-3-Pyr-Ala-NH
2
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
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
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
Deaminizating-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
Deaminizating-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
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-(CH
2)
6-CH
3
H-(N(Me))Aib-(N(Me))-(CH
2)
2-(N(Me))-Bip(2’-Et-4’-OMe)-(N(Me))-4-(2’-Me-Pb)-3-Pyr-Ala-NH-(CH
2)
6-CH
3
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-(CH
2)
10-CH
3
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)
10-CH
3
CH
3-(CH
2)
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
CH
3-(CH
2)
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-NH-(CH
2)
6-CH
3
CH
3-(CH
2)
10-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
CH
3-(CH
2)
10-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-NH-(CH
2)
6-CH
3
HA-(CH
2)
3-Bip(2’-Et-4’-OMe)-4-(2’-Me-Ph)-3-Pyr-Ala-NH
2
H-Aib-(CH
2)
3-Bip(2’-Et-4’-OMe)-4-(2’-Me-Ph)-3-Pyr-Ala-NH
2
Ha-(CH
2)
3-Bip(2’-Et-4’-OMe)-4-(2’-Me-Ph)-3-Pyr-Ala-NH
2
H-(N(Me))A-(CH
2)
3-Bip(2’-Et-4’-OMe)-4-(2’-Me-Ph)-3-Pyr-Ala-NH
2
H-(N(Me))A-(N(Me))-(CH
2)
3-Bip(2’-Et-4’-OMe)-4-(2’-Me-Ph)-3-Pyr-Ala-NH
2
H-(N(Me))Aib-(N(Me))-(CH
2)
3-Bip(2’-Et-4’-OMe)-4-(2’-Me-Ph)-3-Pyr-Ala-NH
2
H-(N(Me))A-(N(Me))-(CH
2)
3-(N(Me))-Bip(2’-Et-4’-OMe)-4-(2’-Me-Ph)-3-Pyr-Ala-NH
2
H-(N(Me))Aib-(N(Me))-(CH
2)
3-(N(Me))-Bip(2’-Et-4’-OMe)-4-(2’-Me-Ph)-3-Pyr-Ala-NH
2
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
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
Deaminizating-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
Deaminizating-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
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-(CH
2)
6-CH
3
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
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-(CH
2)
10-CH
3
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)
10-CH
3
CH3-(CH
2)
6-NH-(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-(CH
2)
6-CH
3
CH
3-(CH
2)
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-CH
3
CH
3-(CH
2)
10-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-(CH
2)
6-CH
3
CH
3-(CH
2)
10-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
HA-(CH
2)
4-Bip(2’-Et-4’-OMe)-4-(2’-Me-Ph)-3-Pyr-Ala-NH
2
H-Aib-(CH
2)
2-Bip(2’-Et-4’-OMe)-4-(2’-Me-Ph)-3-Pyr-Ala-NH
2
H-a-(CH
2)
4-Bip(2’-Et-4’-OMe)-4-(2’-Me-Ph)-3-Pyr-Ala-NH
2
H-(N(Me))A-(CH
2)
4-Bip(2’-Et-4’-OMe)-4-(2’-Me-Ph)-3-Pyr-Ala-NH
2
H-(N(Me))A-(N(Me))-(CH
2)
4-Bip(2’-Et-4’-OMe)-4-(2’-Me-Ph)-3-Pyr-Ala-NH
2
H-(N(Me))Aib-(N(Me))-(CH
2)
4-Bip(2’-Et-4’-OMe)-4-(2’-Me-Ph)-3-Pyr-Ala-NH
2
H-(N(Me))A-(N(Me))-(CH
2)
4-(N(Me))-Bip(2’-Et-4’-OMe)-4-(2’-Me-Ph)-3-Pyr-Ala-NH
2
H-(N(Me))Aib-(N(Me))-(CH
2)
4-(N(Me))-Bip(2’-Et-4’-OMe)-4-(2’-Me-Ph)-3-Pyr-Ala-NH
2
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
2
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
Deaminizating-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
2
Deaminizating-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
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
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
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)
10-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-NH-(CH
2)
10-CH
3
CH
3-(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
CH
3-(CH
2)
6-NH-H-(N(Me))Aib-(N(Me))-(CH
2)
4-(N(Me))-Bip(2’-Et-4’-OMe)-(N(Me))-4-(2’-Me-Pb)-3-Pyr-Ala-NH-(CH
2)
6-CH
3
CH
3-(CH
2)
10-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
CH
3-(CH
2)
10-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-CH
3
HAE-(CH
2)
2-Bip(2’-Et-4’-OMe)-4-(2’-Me-Ph)-3-Pyr-Ala-NH
2
H-Aib-E-(CH
2)
2-Bip(2’-Et-4’-OMe)-4-(2’-Me-Ph)-3-Pyr-Ala-NH
2
HaE-(CH
2)
2-Bip(2’-Et-4’-OMe)-4-(2’-Me-Ph)-3-Pyr-Ala-NH
2
H-(N(Me))AE-(CH
2)
2-Bip(2’-Et-4’-OMe)-4-(2’-Me-Ph)-3-Pyr-Ala-NH
2
H-(N(Me))AE-(N(Me))-(CH
2)
2-Bip(2’-Et-4’-OMe)-4-(2’-Me-Ph)-3-Pyr-Ala-NH
2
H-(N(Me))Aib-E-(N(Me))-(CH
2)
2-Bip(2’-Et-4’-OMe)-4-(2’-Me-Ph)-3-Pyr-Ala-NH
2
H-(N(Me))AE-(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-E-(N(Me))-(CH
2)
2-(N(Me))-Bip(2’-Et-4’-OMe)-4-(2’-Me-Ph)-3-Pyr-Ala-NH
2
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
2
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-NH
2
Deaminizating-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
2
Deaminizating-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-NH
2
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
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-NH-(CH
2)
6-CH
3
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)
10-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-NH-(CH
2)
10-CH
3
CH
3-(CH
2)
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-NH-(CH
2)
6-CH
3
CH
3-(CH
2)
6-NH-(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-NH-(CH
2)
6-CH
3
CH
3-(CH
2)
10-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-NH-(CH
2)
6-CH
3
CH
3-(CH
2)
10-NH-(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-NH-(CH
2)
6-CH
3
HAEG-(CH
2)
2-Bip(2’-Et-4’-OMe)-4-(2’-Me-Ph)-3-Pyr-Ala-NH
2
H-Aib-EG-(CH
2)
2-Bip(2’-Et-4’-OMe)-4-(2’-Me-Ph)-3-Pyr-Ala-NH
2
HaEG-(CH
2)
2-Bip(2’-Et-4’-OMe)-4-(2’-Me-Ph)-3-Pyr-Ala-NH
2
H-(N(Me))AEG-(CH
2)
2-Bip(2’-Et-4’-OMe)-4-(2’-Me-Ph)-3-Pyr-Ala-NH
2
H-(N(Me))AEG-(N(Me))-(CH
2)
2-Bip(2’-Et-4’-OMe)-4-(2’-Me-Ph)-3-Pyr-Ala-NH
2
H-(N(Me))Aib-EG-(N(Me))-(CH
2)
2-Bip(2’-Et-4’-OMe)-4-(2’-Me-Ph)-3-Pyr-Ala-NH
2
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-NH
2
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-NH
2
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
2
Deaminizating-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-NH
2
Deaminizating-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
2
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-NH-(CH
2)
6-CH
3
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
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-NH-(CH
2)
10-CH
3
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)
10-CH
3
CH
3-(CH
2)
6-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-NH-(CH
2)
6-CH
3
CH
3-(CH
2)
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-NH-(CH
2)
6-CH
3
CH
3-(CH
2)
10-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-NH-(CH
2)
6-CH
3
CH
3-(CH
2)
10-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-NH-(CH
2)
6-CH
3
HAEGT-(CH
2)
2-Bip(2’-Et-4’-OMe)-4-(2’-Me-Ph)-3-Pyr-Ala-NH
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-NH
2
H-(N(Me))AEGT-(CH
2)
2-Bip(2’-Et-4’-OMe)-4-(2’-Me-Ph)-3-Pyr-Ala-NH
2
H-(N(Me))AEGT-(N(Me))-(CH
2)
2-Bip(2’-Et-4’-OMe)-4-(2’-Me-Ph)-3-Pyr-Ala-NH
2
H-(N(Me))Aib-EGT-(N(Me))-(CH
2)
2-Bip(2’-Et-4’-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)-4-(2’-Me-Ph)-3-Pyr-Ala-NH
2
H-(N(Me))Aib-EGT-(N(Me))-(CH
2)
2-(N(Me))-Bip(2’-Et-4’-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
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
Deaminizating-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
Deaminizating-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
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)
6-CH
3
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-(CH
2)
6-CH
3
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
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-(CH
2)
10-CH
3
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-NH-(CH
2)
6-CH
3
CH
3-(CH
2)
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-NH-(CH
2)
6-CH
3
CH
3-(CH
2)
10-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
CH
3-(CH
2)
10-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
HA-(CH
2)
3-Bip(2-Me)-Bip(2-Me)-NH
2
H-Aib-(CH
2)
3-Bip(2-Me)-Bip(2-Me)-NH
2
Ha-(CH
2)
3-Bip(2-Me)-Bip(2-Me)-NH
2
H-(N(Me))A-(CH
2)
3-Bip(2-Me)-Bip(2-Me)-NH
2
H-(N(Me))A-(N(Me))-(CH
2)
3-Bip(2-Me)-Bip(2-Me)-NH
2
H-(N(Me))Aib-(N(Me))-(CH
2)
3-Bip(2-Me)-Bip(2-Me)-NH
2
H-(N(Me))A-(N(Me))-(CH
2)
3-(N(Me))-Bip(2-Me)-Bip(2-Me)-NH
2
H-(N(Me))Aib-(N(Me))-(CH
2)
3-(N(Me))-Bip(2-Me)-Bip(2-Me)-NH
2
H-(N(Me))A-(N(Me))-(CH
2)
3-(N(Me))-Bip(2-Me)-(N(Me))-Bip(2-Me)-NH
2
H-(N(Me))Aib-(N(Me))-(CH
2)
3-(N(Me))-Bip(2-Me)-(N(Me))-Bip(2-Me)-NH
2
Deaminizating-H-(N (Me)) A-(N (Me))-(CH
2)
3-(N (Me))-Bip (2-Me)-(N (Me))-Bip (2-Me)-NH
2
Deaminizating-H-(N (Me)) Aib-(N (Me))-(CH
2)
3-(N (Me))-Bip (2-Me)-(N (Me))-Bip (2-Me)-NH
2
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
H-(N(Me))Aib-(N(Me))-(CH
2)
3-(N(Me))-Bip(2-Me)-(N(Me))-Bip(2-Me)-NH-(CH
2)
6-CH
3
H-(N(Me))A-(N(Me))-(CH
2)
3-(N(Me))-Bip(2-Me)-(N(Me))-Bip(2-Me)-NH-(CH
2)
10-CH
3
H-(N(Me))Aib-(N(Me))-(CH
2)
3-(N(Me))-Bip(2-Me)-(N(Me))-Bip(2-Me)-NH-(CH
2)
10-CH
3
CH
3-(CH
2)
6-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
CH
3-(CH
2)
6-NH-H-(N(Me))Aib-(N(Me))-(CH
2)
3-(N(Me))-Bip(2-Me)-(N(Me))-Bip(2-Me)-NH-(CH
2)
6-CH
3
CH
3-(CH
2)
10-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
CH
3-(CH
2)
10-NH-H-(N(Me))Aib-(N(Me))-(CH
2)
3-(N(Me))-Bip(2-Me)-(N(Me))-Bip(2-Me)-NH-(CH
2)
6-CH
3
HA-(CH
2)
3-Bip(2-Et)-Bip(2-Me)-NH
2
H-Aib-(CH
2)
3-Bip(2-Et)-Bip(2-Me)-NH
2
Ha-(CH
2)
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(2-Et)-Bip(2-Me)-NH
2
H-(N(Me))Aib-(N(Me))-(CH
2)
3-Bip(2-Et)-Bip(2-Me)-NH
2
H-(N(Me))A-(N(Me))-(CH
2)
3-(N(Me))-Bip(2-Et)-Bip(2-Me)-NH
2
H-(N(Me))Aib-(N(Me))-(CH
2)
3-(N(Me))-Bip(2-Et)-Bip(2-Me)-NH
2
H-(N(Me))A-(N(Me))-(CH
2)
3-(N(Me))-Bip(2-Et)-(N(Me))-Bip(2-Me)-NH
2
H-(N(Me))Aib-(N(Me))-(CH
2)
3-(N(Me))-Bip(2-Et)-(N(Me))-Bip(2-Me)-NH
2
Deaminizating-H-(N (Me)) A-(N (Me))-(CH
2)
3-(N (Me))-Bip (2-Et)-(N (Me))-Bip (2-Me)-NH
2
Deaminizating-H-(N (Me)) Aib-(N (Me))-(CH
2)
3-(N (Me))-Bip (2-Et)-(N (Me))-Bip (2-Me)-NH
2
H-(N(Mc))A-(N(Mc))-(CH
2)
3-(N(Me))-Bip(2-Et)-(N(Me))-Bip(2-Me)-NH-(CH
2)
6-CH
3
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
H-(N(Me))A-(N(Me))-(CH
2)
3-(N(Me))-Bip(2-Et)-(N(Me))-Bip(2-Me)-NH-(CH
2)
10-CH
3
H-(N(Me))Aib-(N(Me))-(CH
2)
3-(N(Me))-Bip(2-Et)-(N(Me))-Bip(2-Me)-NH-(CH
2)
10-CH
3
CH3-(CH
2)
6-NH-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
CH
3-(CH
2)
6-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
CH
3-(CH
2)
10-NH-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
CH
3-(CH
2)
10-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
HA-(CH
2)
2-Bip(2’-Et-4’-OMe)-4-(2’-Me-Ph)-3-Pyr-Ala-OH
H-Aib-(CH
2)
2-Bip(2’-Et-4’-OMe)-4-(2’-Me-Ph)-3-Pyr-Ala-OH
Ha-(CH
2)
2-Bip(2’-Et-4’-OMe)-4-(2’-Me-Ph)-3-Pyr-Ala-OH
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
H-(N(Me))Aib-(N(Me))-(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-(N(Me))-Bip(2’-Et-4’-OMe)-4-(2’-Me-Ph)-3-Pyr-Ala-OH
H-(N(Me))Aib-(N(Me))-(CH
2)
2-(N(Me))-Bip(2’-Et-4’-OMe)-4-(2’-Me-Ph)-3-Pyr-Ala-OH
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
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-OH
Deaminizating-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
Deaminizating-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-OH
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-COO-(CH
2)
6-CH
3
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-COO-(CH
2)
6-CH
3
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-COO-(CH
2)
10-CH
3
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-COO-(CH
2)
10-CH
3
CH
3-(CH
2)
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-COO-(CH
2)
6-CH
3
CH
3-(CH
2)
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
CH
3-(CH
2)
10-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-COO-(CH
2)
6-CH
3
CH
3-(CH
2)
10-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
HA-(CH
2)
3-Bip(2’-Et-4’-OMe)-4-(2’-Me-Ph)-3-Pyr-Ala-OH
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-(CH
2)
3-Bip(2’-Et-4’-OMe)-4-(2’-Me-Ph)-3-Pyr-Ala-OH
H-(N(Me))A-(N(Me))-(CH
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-OH
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-(N(Me))-Bip(2’-Et-4’-OMe)-4-(2’-Me-Ph)-3-Pyr-Ala-OH
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-OH
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-OH
Deaminizating-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-OH
Deaminizating-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-OH
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)
6-CH
3
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)
6-CH
3
H-(N(Me))A-(N(Me))-(CH
2)
3-(N(Me))-Bip(2’-Et4’-OMe)-(N(Me))-4-(2’-Me-Ph)-3-Pyr-Ala-COO-(CH
2)
10-CH
3
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)
10-CH
3
CH
3-(CH
2)
6-NH-(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
CH
3-(CH
2)
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-COO-(CH
2)
6-CH
3
CH
3-(CH
2)
10-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-COO-(CH
2)
6-CH
3
CH
3-(CH
2)
10-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-COO-(CH
2)
6-CH
3
HA-(CH
2)
4-Bip(2’-Et-4’-OMe)-4-(2’-Me-Ph)-3-Pyr-Ala-OH
H-Aib-(CH
2)
2-Bip(2’-Et-4’-OMe)-4-(2’-Me-Ph)-3-Pyr-Ala-OH
Ha-(CH
2)
4-Bip(2’-Et-4’-OMe)-4-(2’-Me-Ph)-3-Pyr-Ala-OH
H-(N(Me))A-(CH
2)
4-Bip(2’-Et-4’-OMe)-4-(2’-Me-Ph)-3-Pyr-Ala-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-OH
H-(N(Me))A-(N(Me))-(CH
2)
4-(N(Me))-Bip(2’-Et-4’-OMe)-4-(2’-Me-Ph)-3-Pyr-Ala-OH
H-(N(Me))Aib-(N(Me))-(CH
2)
4-(N(Me))-Bip(2’-Et-4’-OMe)-4-(2’-Me-Ph)-3-Pyr-Ala-OH
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-OH
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-OH
Deaminizating-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-OH
Deaminizating-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-OH
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-COO-(CH
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-COO-(CH
2)
6-CH
3
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-COO-(CH
2)
10-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-COO-(CH
2)
10-CH
3
CH
3-(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-COO-(CH
2)
6-CH
3
CH
3-(CH
2)
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
CH
3-(CH
2)
10-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-COO-(CH
2)
6-CH
3
CH
3-(CH
2)
10-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
HAE-(CH
2)
2-Bip(2’-Et-4’-OMe)-4-(2’-Me-Ph)-3-Pyr-Ala-OH
H-Aib-E-(CH
2)
2-Bip(2’-Et-4’-OMe)-4-(2’-Me-Ph)-3-Pyr-Ala-OH
HaE-(CH
2)
2-Bip(2’-Et-4’-OMe)-4-(2’-Me-Ph)-3-Pyr-Ala-OH
H-(N(Me))AE-(CH
2)
2-Bip(2’-Et-4’-OMe)-4-(2’-Me-Ph)-3-Pyr-Ala-OH
H-(N(Me))AE-(N(Me))-(CH
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’-Et-4’-OMe)-4-(2’-Me-Ph)-3-Pyr-Ala-OH
H-(N(Me))AE-(N(Me))-(CH
2)
2-(N(Me))-Bip(2’-Et-4’-OMe)-4-(2’-Me-Ph)-3-Pyr-Ala-OH
H-(N(Me))Aib-E-(N(Me))-(CH
2)
2-(N(Me))-Bip(2’-Et-4’-OMe)-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-OH
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-OH
Deaminizating-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-OH
Deaminizating-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-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(Me))-Bip(2’-Et-4’-OMe)-(N(Me))-4-(2’-Me-Ph)-3-Pyr-Ala-COO-(CH
2)
6-CH
3
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)
10-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-COO-(CH
2)
10-CH
3
CH
3-(CH
2)
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-CH
3
CH
3-(CH
2)
6-NH-(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-(CH
2)
6-CH
3
CH
3-(CH
2)
10-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-CH
3
CH
3-(CH
2)
10-NH-(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-(CH
2)
6-CH
3
HAEG-(CH
2)
2-Bip(2’-Et-4’-OMe)-4-(2’-Me-Ph)-3-Pyr-Ala-OH
H-Aib-EG-(CH
2)
2-Bip(2’-Et-4’-OMe)-4-(2’-Me-Ph)-3-Pyr-Ala-OH
HaEG-(CH
2)
2-Bip(2’-Et-4’-OMe)-4-(2’-Me-Ph)-3-Pyr-Ala-OH
H-(N(Me))AEG-(CH
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’-Et-4’-OMe)-4-(2’-Me-Ph)-3-Pyr-Ala-OH
H-(N(Me))Aib-EG-(N(Me))-(CH
2)
2-Bip(2’-Et-4’-OMe)-4-(2’-Me-Ph)-3-Pyr-Ala-OH
H-(N(Me))AEG-(N(Me))-(CH
2)
2-(N(Me))-Bip(2’-Et-4’-OMe)-4-(2’-Me-Ph)-3-Pyr-Ala-OH
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
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
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
Deaminizating-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
Deaminizating-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
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-(CH
2)
6-CH
3
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)
6-CH
3
H-(N(Me))AEG-(N(Me))-(CH
2)
2-(N(Me))-Bip(2’-Et4’-OMe)-(N(Me))-4-(2’-Me-Ph)-3-Pyr-Ala-COO-(CH
2)
10-CH
3
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)
10-CH
3
CH
3-(CH
2)
6-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-(CH
2)
6-CH
3
CH
3-(CH
2)
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)10-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-(CH
2)
6-CH
3
CH
3-(CH
2)
10-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
HAEGT-(CH
2)
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
H-(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-Pyr-Ala-OH
H-(N(Me))Aib-EGT-(N(Me))-(CH
2)
2-(N(Me))-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)-(N(Me))-4-(2’-Me-Ph)-3-Pyr-Ala-OH
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
Deaminizating-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
Deaminizating-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
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))-(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))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)
10-CH
3
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-COO-(CH
2)
10-CH
3
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
CH
3-(CH
2)
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-COO-(CH
2)
6-CH
3
CH
3-(CH
2)
10-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
CH
3-(CH
2)
10-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-(CH
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
Ha-(CH
2)
3-Bip(2-Me)-Bip(2-Me)-OH
H-(N(Me))A-(CH
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(Me))-(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
H-(N(Me))Aib-(N(Me))-(CH
2)
3-(N(Me))-Bip(2-Me)-Bip(2-Me)-OH
H-(N(Me))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
Deaminizating-H-(N (Me)) A-(N (Me))-(CH
2)
3-(N (Me))-Bip (2-Me)-(N (Me))-Bip (2-Me)-OH
Deaminizating-H-(N (Me)) Aib-(N (Me))-(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(Me))-Bip(2-Me)-COO-(CH
2)
6-CH
3
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
H-(N(Me))A-(N(Me))-(CH
2)
3-(N(Me))-Bip(2-Me)-(N(Me))-Bip(2-Me)-COO-(CH
2)
10-CH
3
H-(N(Me))Aib-(N(Me))-(CH
2)
3-(N(Me))-Bip(2-Me)-(N(Me))-Bip(2-Me)-COO-(CH
2)
10-CH
3
CH
3-(CH
2)
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
CH
3-(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
CH
3-(CH
2)
10-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
CH
3-(CH
2)
10-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
HA-(CH
2)
3-Bip(2-Et)-Bip(2-Me)-OH
H-Aib-(CH
2)
3-Bip(2-Et)-Bip(2-Me)-OH
Ha-(CH
2)
3-Bip(2-Et)-Bip(2-Me)-OH
H-(N(Me))A-(CH
2)
3-Bip(2-Et)-Bip(2-Me)-OH
H-(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
H-(N(Me))A-(N(Me))-(CH
2)
3-(N(Me))-Bip(2-Et)-Bip(2-Me)-OH
H-(N(Me))Aib-(N(Me))-(CH
2)
3-(N(Me))-Bip(2-Et)-Bip(2-Me)-OH
H-(N(Me))A-(N(Me))-(CH
2)
3-(N(Me))-Bip(2-Et)-(N(Me))-Bip(2-Me)-OH
H-(N(Me))Aib-(N(Me))-(CH
2)
3-(N(Me))-Bip(2-Et)-(N(Me))-Bip(2-Me)-OH
Deaminizating-H-(N (Me)) A-(N (Me))-(CH
2)
3-(N (Me))-Bip (2-Et)-(N (Me))-Bip (2-Me)-OH
Deaminizating-H-(N (Me)) Aib-(N (Me))-(CH
2)
3-(N (Me))-Bip (2-Et)-(N (Me))-Bip (2-Me)-OH
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
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
H-(N(Me))A-(N(Me))-(CH
2)
3-(N(Me))-Bip(2-Et)-(N(Me))-Bip(2-Me)-COO-(CH
2)
10-CH
3
H-(N(Me))Aib-(N(Me))-(CH
2)
3-(N(Me))-Bip(2-Et)-(N(Me))-Bip(2-Me)-COO-(CH
2)
10-CH
3
CH
3-(CH
2)
6-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
CH
3-(CH
2)
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
CH
3-(CH
2)
10-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
CH
3-(CH
2)10-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
HA-(CH
2)
3-DVSSYLEGQAAKEFIKELEKLL
HAib-(CH
2)
3-DVSSYLEGQAAKEFIKELEKLL
HAibEGTFTSDVSSYLEGQ-(CH
2)
2-KELEKLL
HAibEGTFTSDVSSYLEGQ-(CH
2)
3-KELEKLL
HAibEGTFTSDVSSYLE-(CH
2)
2-FIKELEKLL
HAibEGT-(α-Me)Phe(2-F)-TSDVSSYLE-(CH
2)
2-FIKELEKLL
HAib-(CH
2)
3-VSSYLE-(CH
2)
2-FIKELEKLL
HAib-(CH
2)
3-VSSYLE-(CH
2)
3-FIKELEKLL
HAib-(CH
2)
3-YLE-(CH
2)
3-FIKELEKLL
HAib-(CH
2)
4-YLE-(CH
2)
3-FIKELEKLL
HAib-(CH
2)
4-YL-(CH
2)
3-FIKELEKLL
HAib-(CH
2)
4-Y-(CH
2)
3-FIKELEKLL
HAib-(CH
2)
4-FIKELEKLL
HAib-(CH
2)
5-FIKELEKLL
HAib-(CH
2)
6-FIKELEKLL
HAib-(CH
2)
8-FIKELEKLL
HAib-(CH
2)
3-VSSYLEGQ-(CH
2)
3-KELEKLL
HAib-(CH
2)
3-VSSYLEG-(CH
2)
3-KELEKLL
HAib-(CH
2)
3-VSSYLE-(CH
2)
4-KELEKLL
HAib-(CH
2)
3-SSYLE-(CH
2)
4-KELEKLL
HAib-(CH
2)
3-SYLE-(CH
2)
4-KELEKLL
HAib-(CH
2)
3-YLE-(CH
2)
4-KELEKLL
HAib-(CH
2)
3-YL-(CH
2)
4-KELEKLL
HAib-(CH
2)
3-Y-(CH
2)
4-KELEKLL
HAib-(CH
2)
5-KELEKLL
HAib-(CH
2)
6-KELEKLL
HAib-(CH
2)
8-KELEKLL
7. pharmacology composition, it comprises the compound described in claim 1-6 and one or more suitable pharmacological-acceptable carriers according to the preparation of method described in the literary composition.
8. the compound described in claim 1-7 or its pharmacology composition is characterized in that, have the ability of simulation GLP-1 biologic activity, are more preferably the ability of simulation GLP-1R agonist activity.
9. as each described compound among the claim 1-7 or its pharmacology composition, it is characterized in that, be suitable for treating or prevent the GLP-1R peptide to play the disease of pathology function.
10. one kind is prevented or treats by hyperlipidaemia, hypercholesterolemia, hyperglycemia, hyperinsulinemia, free lipid acid or glycerine level raise in the blood, hypertriglyceridemia, wound healing postpones, obesity, impaired glucose tolerance, Leptin resistance, insulin resistance, the method of the disease that the diabetic complication of ephrosis, retinopathy, neuropathy and cataract and so on causes, it comprises the compound of each described general formula (I) in the above claim of the effective and non-toxicity amount of patient that needs prevention or treatment.
11. method according to any one of the preceding claims, it is characterized in that described disease is the I type i diabetes, impaired glucose tolerance, hyperlipemia, vascular hypertension, obesity, atherosclerosis, hyperlipidaemia, coronary artery disease, cardiovascular discomfort, and insulin resistance is the other diseases of potential pathology mechanism.
12. medicine that is used for the treatment of/alleviates each described disease situation in the above claim, it is characterized in that, comprise needing the patient that treats/alleviate such as compound and pharmacological-acceptable carrier, thinner, vehicle or the solvate of the general formula (I) described in the claim 1-7.
13. medicine that is used for the treatment of/alleviates each described disease situation in the above claim, it is characterized in that, comprise needing patient such as the compound of the general formula (I) described in the claim 1-7 and the suitable DPP IV inhibitor for the treatment of/alleviating.
14. the compound of independent use according to any one of the preceding claims or the general formula (I) that is used in combination with suitable DPP IV inhibitor, their pharmacology composition, and the medicine that comprises them is as the application that is applicable to the medicine of each described disease in the above claim of treatment.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IN558/MUM/2005 | 2005-05-05 | ||
| IN558MU2005 | 2005-05-05 | ||
| IN645/MUM/2005 | 2005-05-31 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN101223189A true CN101223189A (en) | 2008-07-16 |
Family
ID=39632377
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNA2006800242771A Pending CN101223189A (en) | 2005-05-05 | 2006-05-04 | Novel compounds as GLP-I agonists |
Country Status (2)
| Country | Link |
|---|---|
| CN (1) | CN101223189A (en) |
| ZA (1) | ZA200709471B (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102414220A (en) * | 2009-05-01 | 2012-04-11 | 霍夫曼-拉罗奇有限公司 | Insulinotropic peptide synthesis using solid and solution phase combination techniques |
| CN111423506A (en) * | 2019-11-08 | 2020-07-17 | 成都奥达生物科技有限公司 | G L P-1 compound |
-
2006
- 2006-05-04 CN CNA2006800242771A patent/CN101223189A/en active Pending
- 2006-05-04 ZA ZA200709471A patent/ZA200709471B/en unknown
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102414220A (en) * | 2009-05-01 | 2012-04-11 | 霍夫曼-拉罗奇有限公司 | Insulinotropic peptide synthesis using solid and solution phase combination techniques |
| CN111423506A (en) * | 2019-11-08 | 2020-07-17 | 成都奥达生物科技有限公司 | G L P-1 compound |
| CN111423506B (en) * | 2019-11-08 | 2023-06-27 | 成都奥达生物科技有限公司 | GLP-1 compound |
Also Published As
| Publication number | Publication date |
|---|---|
| ZA200709471B (en) | 2009-03-25 |
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