Antimicrobial peptidomimetics

Abstract

The present invention relates to peptidomimetics having antibacterial activity, especially against gram-negative bacteria. The peptidomimetics of the present invention have the general formula (I), P 1 -P 2 -P 3 -P 4 -P 5 -P 6 -P 7 -P 8 -P 9 -P 10 -P 11 -P 12 -P 13 -P 14 -P 15 -P 16 (I) and its pharma- ceutically acceptable salts. The present invention also relates to therapeutic uses of peptidomimetics for treating or preventing bacterial infections and diseases associated with bacterial infections, as well as non-therapeutic uses of peptidomimetics for preserving or disinfecting food, cosmetics, pharmaceuticals, or other nutrient-containing materials. In addition, the present invention provides an efficient synthetic process by which these compounds can be made, if desired, in a parallel library format. Furthermore, the peptidomimetics of the present invention exhibit improved antimicrobial activity, low or no hemolysis of red blood cells, and reduced cytotoxicity.

Description

[Technical field]

[0001] The present invention relates to peptidomimetics having antimicrobial activity, in particular against Gram-negative bacteria. The peptidomimetics of the present invention are represented by the general formula (I) as described herein below: P 1 -P 2 -P 3 -P 4 -P 5 -P 6 -P 7 -P 8 -P 9 -P 10 -P 11 -P 12 -P 13 -P 14 -P 15 -P 16 (I) and its pharmaceutically acceptable salts. The present invention also relates to therapeutic uses of peptidomimetics for treating or preventing bacterial infections and diseases associated with bacterial infections, as well as non-therapeutic uses of peptidomimetics for preserving or disinfecting food, cosmetics, pharmaceuticals or other nutrient-containing materials. In addition, the present invention provides an efficient synthetic process by which these compounds can be made in a parallel library-format, if desired. Furthermore, the peptidomimetics of the present invention exhibit improved antimicrobial activity, low or no hemolysis of red blood cells, and reduced cytotoxicity. [Background technology]

[0002] Treatment options for carbapenem-resistant Enterobacteriaceae (CRE) infections are limited. Antibiotics that show more in vitro activity against CRE include colistin, tigecycline, and fosfomycin. However, data on their efficacy and clinical experience are limited. They also have a higher frequency of adverse effects, and resistance emerges rapidly during treatment, with resistance spreading worldwide. Colistin is commonly used to treat CRE infections, but colistin resistance may emerge in CRE-infected patients treated with colistin. Since 2015, transferable plasmid-borne colistin resistance genes (mcr 1-5) have been discovered that can more easily transfer colistin resistance between bacteria, further increasing the risk of spreading colistin resistance (Giamarellou H.et al.,Antimicrob Agents Chemother.2013,57(5),2388-90). Summary of the Invention [Problem to be solved by the invention]

[0003] None of the recently approved antibiotics or antibiotics in late-stage development adequately address CRE. In particular, the novel β-lactam combinations have no activity against metallo-β-lactamase (MBL)-producing organisms. Ceftazidime / avibactam (CAZ-AVI), the most commonly used novel antibiotic against CRE, is not effective against MBL-producing organisms. Furthermore, shortly after the launch of CAZ-AVI, CAZ-AVI-resistant CRE strains have been reported, in which resistance emerged during treatment with CAZ-AVI alone or in combination with other antibiotics. After these concerns were reported, ECDC issued an urgent risk assessment report on this issue on June 12, 2018. Plazomicin, a novel aminoglycoside, carries safety warnings in its prescribing information (nephrotoxicity, ototoxicity, neuromuscular blockade, and adverse effects on the fetus).

[0004] Thus, there is a continuing need to develop antibiotics that can be used to effectively treat CRE infections.

[0005] Thanatin, a 21-residue inducible insect defense peptide (Fehlbaum P. et al., Proc. Natl. Acad. Sci. USA 1996,93,1221-1225), a natural antimicrobial peptide, targets the lipopolysaccharide transport protein LptA of Gram-negative bacteria and inhibits LPS transport and outer membrane (OM) biogenesis (Vetterli SU et al., Sci. Adv. 2018;4:eaau2634). Thanatin is active against carbapenem-resistant Enterobacteriaceae, including pan-drug-resistant strains. These highly resistant bacteria can cause a variety of infections, including complicated urinary tract infections (cUTI), complicated intra-abdominal infections (cIAI), hospital-acquired or ventilator-associated pneumonia (HAP / VAP) or bloodstream infections (BSI). [Means for solving the problem]

[0006] The present invention encompasses a novel class of peptidomimetics having 16 amino acids or amino acid-derived residues derived from thanatin, which have a narrow antimicrobial spectrum, mainly against Enterobacteriaceae bacteria. Surprisingly, despite having a shorter sequence compared to thanatin, the novel peptidomimetics derived from thanatin exhibit improved antimicrobial activity, low or no hemolysis of red blood cells, and reduced cytotoxicity. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0007] In a first aspect, the present invention provides a compound of general formula (I) P 1 -P 2 -P 3 -P 4 -P 5 -P 6 -P 7 -P 8 -P 9 -P 10 -P11 -P 12 -P 13 -P 14 -P 15 -P 16 (I) (In the formula, P 1 is 2OHVal, Ala, Ala(cPr), Ala(tetrahydropyran-4-yl), Abu, alloIle, betaGly, Cha, Cpa, Cpg, Cyg, Dea, Gly, Hle, Ile, Leu, Met, Nle, OctGly, Sar, tBuGly, tBuAla, Val, Pro, NMeAla, NMeVal or Nva; P 1 wherein the amino group is optionally substituted by a guanidino group (Gua) or a tetramethylguanidino (TMG) group; P 2 ,Hyp; Pro; Pro((4S)F), Pro((4R)F), Pro(4,4F2), Pro((4R)OMe), Pro(3,4 dehydro); P 3 is Ala, Ala(cPr), Ala(tetrahydropyran-4-yl), Abu, alloIle, betaGly, Cha, Cpa, Cpg, Cyg, Dea, Gly, Hle, Ile, Leu, Met, Nle, OctGly, Sar, tBuGly, tBuAla, Val, Pro, NMeAla, NMeVal or Nva; P 4 ,Pra,Abu(4N3); Dab, dap, D Dab, D Dap; Cys, Hcy, NMeCys, Pen, D Cys, D Hcy, D NMeCys, D Pen; Asp, Glu, HgI, D Asp, D Glu or D HgI; P 5are Phe, His, Phe(3OH), Phe(4F), Phe(4OCF3), Trp(6Cl), Tyr(3Cl), Tyr(3F), Tyr(phenyl), Trp, Tyr, 4Thz, Phe(4(4-hydroxyphenoxy)), Phe(4NH2), Tyr(Me), Ntyr, Nphe; Ala, Ala(cPr), Ala(tetrahydropyran-4-yl), Abu, alloIle, betaGly, Cha, Cpa, Cpg, Cyg, Dea, Gly, Hle, Ile, Leu, Met, Nle, OctGly, Sar, tBuGly, tBuAla, Val, Pro, NMeAla, NMeVal, Nva; is alloThr, Cit, Hgn, Hse, Hyp, Leu((3R)OH), Asn, Gln, Ser, Thr, Asp, Glu or Hgl; P 6 are alloThr, Cit, Hgn, Hse, Hyp, Leu((3R)OH), Asn, Gln, Ser, Thr, Asp, Glu, Hgl; Agb, Agp, Dab, Dab(iPr), Dap, Dap(iPr), Har, Lys, Lys(iPr), Narg, Ndab, Nlys, Norn, Orn, Orn(iPr), Pro((4R)guanidine), Pro((4R)NH2), Pro((4S)NH2), Arg, NMeLys; is Ala, Ala(cPr), Ala(tetrahydropyran-4-yl), Abu, alloIle, betaGly, Cha, Cpa, Cpg, Cyg, Dea, Gly, Hle, Ile, Leu, Met, Nle, OctGly, Sar, tBuGly, tBuAla, Val, Pro, NMeAla, NMeVal or Nva; P 7 are alloThr, Cit, Hgn, Hse, Hyp, Leu((3R)OH), Asn, Gln, Ser, Thr, Asp, Glu, Hgl; Ala, Ala(cPr), Ala(tetrahydropyran-4-yl), Abu, alloIle, betaGly, Cha, Cpa, Cpg, Cyg, Dea, Gly, Hle, Ile, Leu, Met, Nle, OctGly, Sar, tBuGly, tBuAla, Val, Pro, NMeAla, NMeVal or Nva; P 8 is Agb, Agp, Dab, Dab(iPr), Dap, Dap(iPr), Har, Lys, Lys(iPr), Narg, Ndab, Nlys, Norn, Orn, Orn(iPr), Pro((4R)guanidine), Pro((4R)NH2), Pro((4S)NH2), Arg or NMeLys; P 9 are Agb, Agp, Dab, Dab(iPr), Dap, Dap(iPr), Har, Lys, Lys(iPr), Narg, Ndab, Nlys, Norn, Orn, Orn(iPr), Pro((4R)guanidine), Pro((4R)NH2), Pro((4S)NH2), Arg, NMeLys; D Dab, D Dab(iPr), D Dap, D Dap(iPr), D Lys, D Lys(iPr), D Orn, D Orn(iPr), D Arg; alloThr, Cit, Hgn, Hse, Hyp, Leu((3R)OH), Asn, Gln, Ser, Thr; D Cit, D Asn, D Gln, D Ser or D Thr; Ala, Ala(cPr), Ala(tetrahydropyran 4-yl), Abu, alloIle, betaGly, Cha, Cpa, Cpg, Cyg, Dea, Gly, Hle, Ile, Leu, Met, Nle, OctGly, Sar, tBuGly, tBuAla, Val, Pro, NMeAla, NMeVal, Nva; D Ala, D Ile, D Leu, D Nle, D Pro or D Val; P 10 is alloThr, Cit, Hgn, Hse, Hyp, Leu((3R)OH), Asn, Gln, Ser or Thr; P 11 teeth, D Dab, D Dab(iPr), D Dap, D Dap(iPr), D Lys, D Lys(iPr), D Orn, D Orn(iPr), D Arg; D Cit, D Asn, D Gln, D Ser or D Thr; P 12 are Agb, Agp, Dab, Dab(iPr), Dap, Dap(iPr), Har, Lys, Lys(iPr), Narg, Ndab, Nlys, Norn, Orn, Orn(iPr), Pro((4R)guanidine), Pro((4R)NH2), Pro((4S)NH2), Arg, NMeLys; alloThr, Cit, Hgn, Hse, Hyp, Leu((3R)OH), Asn, Gln, Ser, Thr; Ala, Ala(cPr), Ala(tetrahydropyran 4-yl), Abu, alloIle, betaGly, Cha, Cpa, Cpg, Cyg, Dea, Gly, Hle, Ile, Leu, Met, Nle, OctGly, Sar, tBuGly, tBuAla, Val, Pro, NMeAla, NMeVal, Nva; Phe, His, Phe(3OH), Phe(4F), Phe(4OCF3), Trp(6Cl), Tyr(3Cl), Tyr(3F), Tyr(phenyl), Trp, Tyr, 4Thz, Phe(4(4hydroxyphenoxy)), Phe(4NH2), Tyr(Me), Ntyr or Nphe; P 13 are Agb, Agp, Dab, Dab(iPr), Dap, Dap(iPr), Har, Lys, Lys(iPr), Narg, Ndab, Nlys, Norn, Orn, Orn(iPr), Pro((4R)guanidine), Pro((4R)NH2), Pro((4S)NH2), Arg, NMeLys; alloThr, Cit, Hgn, Hse, Hyp, Leu((3R)OH), Asn, Gln, Ser, Thr; Ala, Ala(cPr), Ala(tetrahydropyran-4-yl), Abu, alloIle, betaGly, Cha, Cpa, Cpg, Cyg, Dea, Gly, Hle, Ile, Leu, Met, Nle, OctGly, Sar, tBuGly, tBuAla, Val, Pro, NMeAla, NMeVal or Nva; P 14 are Agb, Agp, Dab, Dab(iPr), Dap, Dap(iPr), Har, Lys, Lys(iPr), Narg, Ndab, Nlys, Norn, Orn, Orn(iPr), Pro((4R)guanidine), Pro((4R)NH2), Pro((4S)NH2), Arg, NMeLys; D Dab, D Dab(iPr), D Dap, D Dap(iPr), D Lys, D Lys(iPr), D Orn, D Orn(iPr), D Arg; alloThr, Cit, Hgn, Hse, Hyp, Leu((3R)OH), Asn, Gln, Ser, Thr; D Cit, D Asn,D Gln, D Ser, D Thr; Ala, Ala(cPr), Ala(tetrahydropyran-4-yl), Abu, alloIle, betaGly, Cha, Cpa, Cpg, Cyg, Dea, Gly, Hle, Ile, Leu, Met, Nle, OctGly, Sar, tBuGly, tBuAla, Val, Pro, NMeAla, NMeVal or Nva; D Ala, D Ile, D Leu, D Nle, D Pro, D Val; Phe, His, Phe(3OH), Phe(4F), Phe(4OCF3), Trp(6Cl), Tyr(3Cl), Tyr(3F), Tyr(phenyl), Trp, Tyr, 4Thz, Phe(4(4hydroxyphenoxy)), Phe(4NH2), Tyr(Me), Ntyr, Nphe; D Phe, D His, D Trp or D Tyr; P 15 ,Pra,Abu(4N3); Dab, dap, D Dab, D Dap; Cys, Hcy, NMeCys, Pen, D Cys, D Hcy, D NMeCys, D Pen; Asp, Glu, HgI, D Asp, D Glu or D HgI; P 16 are Phe, His, Phe(3OH), Phe(4F), Phe(4OCF3), Trp(6Cl), Tyr(3Cl), Tyr(3F), Tyr(phenyl), Trp, Tyr, 4Thz, Phe(4(4hydroxyphenoxy)), Phe(4NH2), Tyr(Me), Ntyr, Nphe; Ala, Ala(cPr), Ala(tetrahydropyran-4-yl), Abu, alloIle, betaGly, Cha, Cpa, Cpg, Cyg, Dea, Gly, Hle, Ile, Leu, Met, Nle, OctGly, Sar, tBuGly, tBuAla, Val, Pro, NMeAla, NMeVal, or Nva. A peptidomimetic compound of the formula: If present, P 4 Cys, Hcy, NMeCys or Pen in 15 Cys, Hcy, NMeCys or Pen in the formula (I) is optionally 4 and P 15 or forms a disulfide bridge between If present, P 4 In D Cys, D Hcy, D NMeCys or D Pen and, if present, P 15 In D Cys, D Hcy, D NMeCys or D Pen is optionally 4 and P 15 or forms a disulfide bridge between If present, P 4 Dab or Dap in and, if present, P 15 Asp, Glu or HgI in 4 and P 15 or forming a lactam bridge between If present, P 4 In D Dab or D Dap and, if present, P 15 In D Asp, D Glu or D HgI is optionally 4 and P 15 or forming a lactam bridge between If present, P 4 Asp, Glu or HgI in 15 Dab or Dap in the formula (I) is optionally P 4 and P 15 or forming a lactam bridge between If present, P 4 In D Asp, D Glu or D HgI and, if present, P 15 In D Dab or D Dap is optionally P 4 and P 15 or forming a lactam bridge between If present, P 4 Pra in and, if present, P 15 Abu(4N3) in the formula (I) is optionally 4 and P 15 or forming a 1,2,3-triazole bridge between If present, P 4 Abu(4N3) in and, if present, P 15 Pra in the formula (I) is optionally P 4 and P 15 Forms a 1,2,3-triazole bridge between However, at position P 6 , P 8 , P 9 and P 11 ~P 14 At least five of the seven amino acid residues in D Dab, D Dab(iPr), D Dap, D Dap(iPr), D Lys, D Lys(iPr),D Orn, D Orn(iPr) or D The present invention provides peptidomimetic compounds, or tautomers, rotamers, salts, hydrates or solvates thereof, in which the basic amino acid residue is selected from Arg.

[0008] A preferred embodiment of the first aspect comprises P 1 is Abu, tBuGly, or Val; P 1 wherein the amino group is optionally substituted by a guanidino group (Gua) or a tetramethylguanidino (TMG) group; P 2 But Hyp; Pro; Pro((4S)F), Pro((4R)F), Pro(4,4F2), Pro((4R)OMe) or Pro(3,4 dehydro); P 3 is Hle, Ile, Leu, Cpg, or Nle; P 4 But, Pra, Abu(4N3); Dab, Dap; Cys, Hcy, NMeCys, Pen; Asp, Glu or HgI; P 5 are Phe, His, Phe(3OH), Phe(4F), Phe(4OCF3), Trp(6Cl), Tyr(3Cl), Tyr(3F), Tyr(phenyl), Trp, Tyr, 4Thz, Phe(4(4hydroxyphenoxy)), Phe(4NH2), Tyr(Me), Ntyr, Nphe; Ala, Ala(cPr), Ala(tetrahydropyran-4-yl), Abu, alloIle, Cha, Cpa, Cpg, Cyg, Dea, Hle, Ile, Leu, Met, Nle, OctGly, tBuGly, tBuAla, Val, NMeAla, NMeVal, Nva; alloThr, Cit, Hgn, Hse, Leu((3R)OH), Asn, Gln, Ser, Thr, Asp, Glu, or Hgl; P 6is alloThr, Cit, Hgn, Hse, Leu((3R)OH), Asn, Gln, Ser, Thr, Asp, Glu or Hgl; Agb, Agp, Dab, Dab(iPr), Dap, Dap(iPr), Har, Lys, Lys(iPr), Narg, Ndab, Nlys, Norn, Orn, Orn(iPr), Arg, NMeLys; Ala, Ala(cPr), Ala(tetrahydropyran-4-yl), Abu, alloIle, Cha, Cpa, Cpg, Cyg, Dea, Hle, Ile, Leu, Met, Nle, OctGly, tBuGly, tBuAla, Val, NMeAla, NMeVal or Nva; P 7 is alloThr, Cit, Hgn, Hse, Leu((3R)OH), Asn, Gln, Ser, Thr, Asp, Glu or Hgl; Ala, Ala(cPr), Ala(tetrahydropyran-4-yl), Abu, alloIle, Cha, Cpa, Cpg, Cyg, Dea, Hle, Ile, Leu, Met, Nle, OctGly, tBuGly, tBuAla, Val, NMeAla, NMeVal or Nva; P 8 is Agb, Agp, Har, or Arg; P 9 But, Agb, Agp, Dab, Dab(iPr), Dap, Dap(iPr), Har, Lys, Lys(iPr), Narg, Ndab, Nlys, Norn, Orn, Orn(iPr), Arg, NMeLys; D Dab, D Dab(iPr), D Dap, D Dap(iPr), D Lys, D Lys(iPr), D Orn, D Orn(iPr), D Arg; alloThr, Cit, Hgn, Hse, Leu((3R)OH), Asn, Gln, Ser, Thr; Ala, Ala(cPr), Ala(tetrahydropyran-4-yl), Abu, alloIle, Cha, Cpa, Cpg, Cyg, Dea, Hle, Ile, Leu, Met, Nle, OctGly, tBuGly, tBuAla, Val, NMeAla, NMeVal or Nva; P 10 is Asn, Ser or Thr; P 11 but, D Dab, D Dab(iPr), D Dap, D Dap(iPr), D Lys, D Lys(iPr), D Orn, D Orn(iPr), D Arg; D Cit, D Asn, D Gln, D Ser or D Thr; P 12 But, Agb, Agp, Dab, Dab(iPr), Dap, Dap(iPr), Har, Lys, Lys(iPr), Narg, Ndab, Nlys, Norn, Orn, Orn(iPr), Arg, NMeLys; alloThr, Cit, Hgn, Hse, Leu((3R)OH), Asn, Gln, Ser, Thr; Ala, Ala(cPr), Ala(tetrahydropyran-4-yl), Abu, alloIle, Cha, Cpa, Cpg, Cyg, Dea, Hle, Ile, Leu, Met, Nle, OctGly, tBuGly, tBuAla, Val, NMeAla, NMeVal, Nva; Phe, His, Phe(3OH), Phe(4F), Phe(4OCF3), Trp(6Cl), Tyr(3Cl), Tyr(3F), Tyr(phenyl), Trp, Tyr, 4Thz, Phe(4(4hydroxyphenoxy)), Phe(4NH2), Tyr(Me), Ntyr or Nphe; P 13But, Agb, Agp, Dab, Dab(iPr), Dap, Dap(iPr), Har, Lys, Lys(iPr), Narg, Ndab, Nlys, Norn, Orn, Orn(iPr), Arg, NMeLys; alloThr, Cit, Hgn, Hse, Leu((3R)OH), Asn, Gln, Ser, Thr; Ala, Ala(cPr), Ala(tetrahydropyran-4-yl), Abu, alloIle, Cha, Cpa, Cpg, Cyg, Dea, Hle, Ile, Leu, Met, Nle, OctGly, tBuGly, tBuAla, Val, NMeAla, NMeVal or Nva; P 14 But, Agb, Agp, Dab, Dab(iPr), Dap, Dap(iPr), Har, Lys, Lys(iPr), Narg, Ndab, Nlys, Norn, Orn, Orn(iPr), Arg, NMeLys; D Dab, D Dab(iPr), D Dap, D Dap(iPr), D Lys, D Lys(iPr), D Orn, D Orn(iPr), D Arg; alloThr, Cit, Hgn, Hse, Leu((3R)OH), Asn, Gln, Ser, Thr; Ala, Ala(cPr), Ala(tetrahydropyran-4-yl), Abu, alloIle, Cha, Cpa, Cpg, Cyg, Dea, Hle, Ile, Leu, Met, Nle, OctGly, tBuGly, tBuAla, Val, NMeAla, NMeVal, Nva; Phe, His, Phe(3OH), Phe(4F), Phe(4OCF3), Trp(6Cl), Tyr(3Cl), Tyr(3F), Tyr(phenyl), Trp, Tyr, 4Thz, Phe(4(4hydroxyphenoxy)), Phe(4NH2), Tyr(Me), Ntyr or Nphe; P 15But, Pra, Abu(4N3); Dab, Dap; Cys, Hcy, NMeCys, Pen; Asp, Glu or HgI; P 16 are Phe, His, Phe(3OH), Phe(4F), Phe(4OCF3), Trp(6Cl), Tyr(3Cl), Tyr(3F), Tyr(phenyl), Trp, Tyr, 4Thz, Phe(4(4hydroxyphenoxy)), Phe(4NH2), Tyr(Me), Ntyr, Nphe; A compound which is Ala, Ala(cPr), Ala(tetrahydropyran-4-yl), Abu, alloIle, Cha, Cpa, Cpg, Cyg, Dea, Hle, Ile, Leu, Met, Nle, OctGly, tBuGly, tBuAla, Val, NMeAla, NMeVal or Nva, If present, P 4 Cys, Hcy, NMeCys or Pen in 15 Cys, Hcy, NMeCys or Pen in the formula (I) is optionally 4 and P 15 or forms a disulfide bridge between If present, P 4 Dab or Dap in and, if present, P 15 Asp, Glu or HgI in 4 and P 15 or forming a lactam bridge between If present, P 4 Asp, Glu or HgI in 15 Dab or Dap in the formula (I) is optionally P 4 and P 15 or forming a lactam bridge between If present, P 4 Pra in and, if present, P 15 Abu(4N3) in the formula (I) is optionally 4 and P 15or forming a 1,2,3-triazole bridge between If present, P 4 Abu(4N3) in and, if present, P 15 Pra in the formula (I) is optionally P 4 and P 15 Forms a 1,2,3-triazole bridge between However, at position P 6 , P 8 , P 9 and P 11 ~P 14 At least five of the seven amino acid residues in D Dab, D Dab(iPr), D Dap, D Dap(iPr), D Lys, D Lys(iPr), D Orn, D Orn(iPr) or D or a tautomer, rotamer, salt, hydrate or solvate thereof, wherein the basic amino acid residue is selected from the group consisting of: Arg.

[0009] Another preferred embodiment of the first aspect comprises P 1 is Abu, tBuGly, or Val; P 1 wherein the amino group is optionally substituted by a guanidino group (Gua) or a tetramethylguanidino (TMG) group; P 2 But Hyp; Pro; Pro((4S)F), Pro((4R)F), Pro(4,4F2), Pro((4R)OMe) or Pro(3,4 dehydro); P 3 is Hle, Ile, Leu or Nle; P 4But, Pra, Abu(4N3); Dab, Dap; Cys, Hcy, NMeCys, Pen; Asp, Glu or HgI; P 5 are Phe, His, Phe(3OH), Phe(4F), Phe(4OCF3), Trp(6Cl), Tyr(3Cl), Tyr(3F), Tyr(phenyl), Trp, Tyr, 4Thz, Phe(4(4hydroxyphenoxy)), Phe(4NH2), Tyr(Me), Ntyr, Nphe; Ala, Ala(cPr), Ala(tetrahydropyran-4-yl), Abu, alloIle, Cha, Cpa, Cpg, Cyg, Dea, Hle, Ile, Leu, Met, Nle, OctGly, tBuGly, tBuAla, Val, NMeAla, NMeVal, Nva; alloThr, Cit, Hgn, Hse, Leu((3R)OH), Asn, Gln, Ser, Thr, Asp, Glu, or Hgl; P 6 is alloThr, Cit, Hgn, Hse, Leu((3R)OH), Asn, Gln, Ser, Thr, Asp, Glu or Hgl; Agb, Agp, Dab, Dab(iPr), Dap, Dap(iPr), Har, Lys, Lys(iPr), Narg, Ndab, Nlys, Norn, Orn, Orn(iPr), Arg, NMeLys; Ala, Ala(cPr), Ala(tetrahydropyran-4-yl), Abu, alloIle, Cha, Cpa, Cpg, Cyg, Dea, Hle, Ile, Leu, Met, Nle, OctGly, tBuGly, tBuAla, Val, NMeAla, NMeVal or Nva; P 7 is alloThr, Cit, Hgn, Hse, Leu((3R)OH), Asn, Gln, Ser, Thr, Asp, Glu or Hgl; Ala, Ala(cPr), Ala(tetrahydropyran-4-yl), Abu, alloIle, Cha, Cpa, Cpg, Cyg, Dea, Hle, Ile, Leu, Met, Nle, OctGly, tBuGly, tBuAla, Val, NMeAla, NMeVal or Nva; P 8 is Agb, Agp, Har, or Arg; P 9 But, Agb, Agp, Dab, Dab(iPr), Dap, Dap(iPr), Har, Lys, Lys(iPr), Narg, Ndab, Nlys, Norn, Orn, Orn(iPr), Arg, NMeLys; D Dab, D Dab(iPr), D Dap, D Dap(iPr), D Lys, D Lys(iPr), D Orn, D Orn(iPr), D Arg; alloThr, Cit, Hgn, Hse, Leu((3R)OH), Asn, Gln, Ser, Thr; Ala, Ala(cPr), Ala(tetrahydropyran-4-yl), Abu, alloIle, Cha, Cpa, Cpg, Cyg, Dea, Hle, Ile, Leu, Met, Nle, OctGly, tBuGly, tBuAla, Val, NMeAla, NMeVal or Nva; P 10 is Asn, Ser or Thr; P 11 but, D Dab, D Dab(iPr), D Dap, D Dap(iPr), D Lys, D Lys(iPr), D Orn, D Orn(iPr), D Arg; D Cit, D Asn, DGln, D Ser or D Thr; P 12 But, Agb, Agp, Dab, Dab(iPr), Dap, Dap(iPr), Har, Lys, Lys(iPr), Narg, Ndab, Nlys, Norn, Orn, Orn(iPr), Arg, NMeLys; alloThr, Cit, Hgn, Hse, Leu((3R)OH), Asn, Gln, Ser, Thr; Ala, Ala(cPr), Ala(tetrahydropyran-4-yl), Abu, alloIle, Cha, Cpa, Cpg, Cyg, Dea, Hle, Ile, Leu, Met, Nle, OctGly, tBuGly, tBuAla, Val, NMeAla, NMeVal, Nva; Phe, His, Phe(3OH), Phe(4F), Phe(4OCF3), Trp(6Cl), Tyr(3Cl), Tyr(3F), Tyr(phenyl), Trp, Tyr, 4Thz, Phe(4(4hydroxyphenoxy)), Phe(4NH2), Tyr(Me), Ntyr or Nphe; P 13 But, Agb, Agp, Dab, Dab(iPr), Dap, Dap(iPr), Har, Lys, Lys(iPr), Narg, Ndab, Nlys, Norn, Orn, Orn(iPr), Arg, NMeLys; alloThr, Cit, Hgn, Hse, Leu((3R)OH), Asn, Gln, Ser, Thr; Ala, Ala(cPr), Ala(tetrahydropyran-4-yl), Abu, alloIle, Cha, Cpa, Cpg, Cyg, Dea, Hle, Ile, Leu, Met, Nle, OctGly, tBuGly, tBuAla, Val, NMeAla, NMeVal or Nva; P 14 But, Agb, Agp, Dab, Dab(iPr), Dap, Dap(iPr), Har, Lys, Lys(iPr), Narg, Ndab, Nlys, Norn, Orn, Orn(iPr), Arg, NMeLys; D Dab,D Dab(iPr), D Dap, D Dap(iPr), D Lys, D Lys(iPr), D Orn, D Orn(iPr), D Arg; alloThr, Cit, Hgn, Hse, Leu((3R)OH), Asn, Gln, Ser, Thr; Ala, Ala(cPr), Ala(tetrahydropyran-4-yl), Abu, alloIle, Cha, Cpa, Cpg, Cyg, Dea, Hle, Ile, Leu, Met, Nle, OctGly, tBuGly, tBuAla, Val, NMeAla, NMeVal, Nva; Phe, His, Phe(3OH), Phe(4F), Phe(4OCF3), Trp(6Cl), Tyr(3Cl), Tyr(3F), Tyr(phenyl), Trp, Tyr, 4Thz, Phe(4(4hydroxyphenoxy)), Phe(4NH2), Tyr(Me), Ntyr or Nphe; P 15 But, Pra, Abu(4N3); Dab, Dap; Cys, Hcy, NMeCys, Pen; Asp, Glu or HgI; P 16 are Phe, His, Phe(3OH), Phe(4F), Phe(4OCF3), Trp(6Cl), Tyr(3Cl), Tyr(3F), Tyr(phenyl), Trp, Tyr, 4Thz, Phe(4(4hydroxyphenoxy)), Phe(4NH2), Tyr(Me), Ntyr, Nphe; A compound which is Ala, Ala(cPr), Ala(tetrahydropyran-4-yl), Abu, alloIle, Cha, Cpa, Cpg, Cyg, Dea, Hle, Ile, Leu, Met, Nle, OctGly, tBuGly, tBuAla, Val, NMeAla, NMeVal or Nva, If present, P 4Cys, Hcy, NMeCys or Pen in 15 Cys, Hcy, NMeCys or Pen in the formula (I) is optionally 4 and P 15 or forms a disulfide bridge between If present, P 4 Dab or Dap in and, if present, P 15 Asp, Glu or HgI in 4 and P 15 or forming a lactam bridge between If present, P 4 Asp, Glu or HgI in 15 Dab or Dap in the formula (I) is optionally P 4 and P 15 or forming a lactam bridge between If present, P 4 Pra in and, if present, P 15 Abu(4N3) in the formula (I) is optionally 4 and P 15 or forming a 1,2,3-triazole bridge between If present, P 4 Abu(4N3) in and, if present, P 15 Pra in the formula (I) is optionally P 4 and P 15 Forms a 1,2,3-triazole bridge between However, at position P 6 , P 8 , P 9 and P 11 ~P 14 At least five of the seven amino acid residues in D Dab, D Dab(iPr), D Dap, D Dap(iPr),D Lys, D Lys(iPr), D Orn, D Orn(iPr) or D or a tautomer, rotamer, salt, hydrate or solvate thereof, wherein the basic amino acid residue is selected from the group consisting of: Arg.

[0010] A more preferred embodiment of the first aspect comprises P 1 are Abu, tBuGly, and Val; P 1 wherein the amino group is optionally substituted by a guanidino group (Gua) or a tetramethylguanidino (TMG) group; P 2 But Hyp; Pro; Pro((4S)F), Pro((4R)F), Pro(4,4F2), Pro((4R)OMe) or Pro(3,4 dehydro); P 3 is Cpg or Ile; P 4 But, Dab, Dap; Cys, Pen; Asp or Glu; P 5 is Phe, His, Phe(3OH), Phe(4F), Phe(4OCF3), Trp(6Cl), Tyr(3Cl), Tyr(3F), Tyr(phenyl), Trp, Tyr, 4Thz, Phe(4(4hydroxyphenoxy)), Phe(4NH2), Tyr(Me), Ntyr or Nphe; Ala, Ala(cPr), Ala(tetrahydropyran-4-yl), Abu, alloIle, Cha, Cpa, Cpg, Cyg, Dea, Hle, Ile, Leu, Met, Nle, OctGly, tBuGly, tBuAla, Val, NMeAla, NMeVal, Nva; alloThr, Cit, Hgn, Hse, Leu((3R)OH), Asn, Gln, Ser, Thr, Asp, Glu, or Hgl; P 6is alloThr, Cit, Hgn, Hse, Leu((3R)OH), Asn, Gln, Ser, Thr, Asp, Glu, Hgl; Agb, Agp, Dab, Dab(iPr), Dap, Dap(iPr), Har, Lys, Lys(iPr), Narg, Ndab, Nlys, Norn, Orn, Orn(iPr), Arg, NMeLys; Ala, Ala(cPr), Ala(tetrahydropyran - 4 - yl), Abu, alloIle, Cha, Cpa, Cpg, Cyg, Dea, Hle, Ile, Leu, Met, Nle, OctGly, tBuGly, tBuAla, Val, NMeAla, NMeVal or Nva; P 7 is alloThr, Cit, Hgn, Hse, Leu((3R)OH), Asn, Gln, Ser, Thr, Asp, Glu, Hgl; Ala, Ala(cPr), Ala(tetrahydropyran - 4 - yl), Abu, alloIle, Cha, Cpa, Cpg, Cyg, Dea, Hle, Ile, Leu, Met, Nle, OctGly, tBuGly, tBuAla, Val, NMeAla, NMeVal or Nva; P 8 is Arg; P 9 is Agb, Agp, Dab, Dab(iPr), Dap, Dap(iPr), Har, Lys, Lys(iPr), Narg, Ndab, Nlys, Norn, Orn, Orn(iPr), Arg, NMeLys; D Dab, D Dab(iPr), D Dap, D Dap(iPr), D Lys, D Lys(iPr), D Orn, D Orn(iPr), D Arg; alloThr, Cit, Hgn, Hse, Leu((3R)OH), Asn, Gln, Ser, Thr; Ala, Ala(cPr), Ala(tetrahydropyran-4-yl), Abu, alloIle, Cha, Cpa, Cpg, Cyg, Dea, Hle, Ile, Leu, Met, Nle, OctGly, tBuGly, tBuAla, Val, NMeAla, NMeVal or Nva; P 10 is Asn, Ser or Thr; P 11 but, D Dab, D Dab(iPr), D Dap, D Dap(iPr), D Lys, D Lys(iPr), D Orn, D Orn(iPr), D Arg; D Cit, D Asn, D Gln, D Ser or D Thr; P 12 But, Agb, Agp, Dab, Dab(iPr), Dap, Dap(iPr), Har, Lys, Lys(iPr), Narg, Ndab, Nlys, Norn, Orn, Orn(iPr), Arg, NMeLys; alloThr, Cit, Hgn, Hse, Leu((3R)OH), Asn, Gln, Ser, Thr; Ala, Ala(cPr), Ala(tetrahydropyran-4-yl), Abu, alloIle, Cha, Cpa, Cpg, Cyg, Dea, Hle, Ile, Leu, Met, Nle, OctGly, tBuGly, tBuAla, Val, NMeAla, NMeVal, Nva; Phe, His, Phe(3OH), Phe(4F), Phe(4OCF3), Trp(6Cl), Tyr(3Cl), Tyr(3F), Tyr(phenyl), Trp, Tyr, 4Thz, Phe(4(4hydroxyphenoxy)), Phe(4NH2), Tyr(Me), Ntyr or Nphe; P 13But, Agb, Agp, Dab, Dab(iPr), Dap, Dap(iPr), Har, Lys, Lys(iPr), Narg, Ndab, Nlys, Norn, Orn, Orn(iPr), Arg, NMeLys; alloThr, Cit, Hgn, Hse, Leu((3R)OH), Asn, Gln, Ser, Thr; Ala, Ala(cPr), Ala(tetrahydropyran-4-yl), Abu, alloIle, Cha, Cpa, Cpg, Cyg, Dea, Hle, Ile, Leu, Met, Nle, OctGly, tBuGly, tBuAla, Val, NMeAla, NMeVal or Nva; P 14 But, Agb, Agp, Dab, Dab(iPr), Dap, Dap(iPr), Har, Lys, Lys(iPr), Narg, Ndab, Nlys, Norn, Orn, Orn(iPr), Arg, NMeLys; D Dab, D Dab(iPr), D Dap, D Dap(iPr), D Lys, D Lys(iPr), D Orn, D Orn(iPr), D Arg; alloThr, Cit, Hgn, Hse, Leu((3R)OH), Asn, Gln, Ser, Thr; Ala, Ala(cPr), Ala(tetrahydropyran-4-yl), Abu, alloIle, Cha, Cpa, Cpg, Cyg, Dea, Hle, Ile, Leu, Met, Nle, OctGly, tBuGly, tBuAla, Val, NMeAla, NMeVal, Nva; Phe, His, Phe(3OH), Phe(4F), Phe(4OCF3), Trp(6Cl), Tyr(3Cl), Tyr(3F), Tyr(phenyl), Trp, Tyr, 4Thz, Phe(4(4hydroxyphenoxy)), Phe(4NH2), Tyr(Me), Ntyr or Nphe; P 15 But, Dab, Dap; Cys, Pen; Asp or Glu; P 16 are Phe, His, Phe(3OH), Phe(4F), Phe(4OCF3), Trp(6Cl), Tyr(3Cl), Tyr(3F), Tyr(phenyl), Trp, Tyr, 4Thz, Phe(4(4hydroxyphenoxy)), Phe(4NH2), Tyr(Me), Ntyr, Nphe; A compound which is Ala, Ala(cPr), Ala(tetrahydropyran-4-yl), Abu, alloIle, Cha, Cpa, Cpg, Cyg, Dea, Hle, Ile, Leu, Met, Nle, OctGly, tBuGly, tBuAla, Val, NMeAla, NMeVal or Nva, If present, P 4 Cys or Pen in the formula (I) and, if present, P 15 Cys or Pen in the formula (I) is optionally P 4 and P 15 or forms a disulfide bridge between If present, P 4 Dab or Dap in and, if present, P 15 Asp or Glu in the formula (I) is optionally 4 and P 15 or forming a lactam bridge between If present, P 4 Asp or Glu in 15 Dab or Dap in the formula (I) is optionally P 4 and P 15 forming a lactam bridge between However, at position P 6 , P 8 , P 9 and P 11 ~P 14At least five of the seven amino acid residues in D Dab, D Dab(iPr), D Dap, D Dap(iPr), D Lys, D Lys(iPr), D Orn, D Orn(iPr) or D or a tautomer, rotamer, salt, hydrate or solvate thereof, wherein the basic amino acid residue is selected from the group consisting of: Arg.

[0011] Another more preferred embodiment of the first aspect comprises P 1 are Abu, tBuGly, and Val; P 1 wherein the amino group is optionally substituted by a guanidino group (Gua) or a tetramethylguanidino (TMG) group; P 2 But Hyp; Pro; Pro((4S)F), Pro((4R)F), Pro(4,4F2), Pro((4R)OMe) or Pro(3,4 dehydro); P 3 But, Ile; P 4 But, Dab, Dap; Cys, Pen; Asp or Glu; P 5 is Phe, His, Phe(3OH), Phe(4F), Phe(4OCF3), Trp(6Cl), Tyr(3Cl), Tyr(3F), Tyr(phenyl), Trp, Tyr, 4Thz, Phe(4(4hydroxyphenoxy)), Phe(4NH2), Tyr(Me), Ntyr or Nphe; Ala, Ala(cPr), Ala(tetrahydropyran-4-yl), Abu, alloIle, Cha, Cpa, Cpg, Cyg, Dea, Hle, Ile, Leu, Met, Nle, OctGly, tBuGly, tBuAla, Val, NMeAla, NMeVal, Nva; alloThr, Cit, Hgn, Hse, Leu((3R)OH), Asn, Gln, Ser, Thr, Asp, Glu, or Hgl; P 6 is alloThr, Cit, Hgn, Hse, Leu((3R)OH), Asn, Gln, Ser, Thr, Asp, Glu, Hgl; Agb, Agp, Dab, Dab(iPr), Dap, Dap(iPr), Har, Lys, Lys(iPr), Narg, Ndab, Nlys, Norn, Orn, Orn(iPr), Arg, NMeLys; Ala, Ala(cPr), Ala(tetrahydropyran-4-yl), Abu, alloIle, Cha, Cpa, Cpg, Cyg, Dea, Hle, Ile, Leu, Met, Nle, OctGly, tBuGly, tBuAla, Val, NMeAla, NMeVal or Nva; P 7 is alloThr, Cit, Hgn, Hse, Leu((3R)OH), Asn, Gln, Ser, Thr, Asp, Glu, Hgl; Ala, Ala(cPr), Ala(tetrahydropyran-4-yl), Abu, alloIle, Cha, Cpa, Cpg, Cyg, Dea, Hle, Ile, Leu, Met, Nle, OctGly, tBuGly, tBuAla, Val, NMeAla, NMeVal or Nva; P 8 Wherein, is Arg; P 9 But, Agb, Agp, Dab, Dab(iPr), Dap, Dap(iPr), Har, Lys, Lys(iPr), Narg, Ndab, Nlys, Norn, Orn, Orn(iPr), Arg, NMeLys; D Dab, D Dab(iPr), DDap, D Dap(iPr), D Lys, D Lys(iPr), D Orn, D Orn(iPr), D Arg; alloThr, Cit, Hgn, Hse, Leu((3R)OH), Asn, Gln, Ser, Thr; Ala, Ala(cPr), Ala(tetrahydropyran-4-yl), Abu, alloIle, Cha, Cpa, Cpg, Cyg, Dea, Hle, Ile, Leu, Met, Nle, OctGly, tBuGly, tBuAla, Val, NMeAla, NMeVal or Nva; P 10 is Asn, Ser or Thr; P 11 but, D Dab, D Dab(iPr), D Dap, D Dap(iPr), D Lys, D Lys(iPr), D Orn, D Orn(iPr), D Arg; D Cit, D Asn, D Gln, D Ser or D Thr; P 12 But, Agb, Agp, Dab, Dab(iPr), Dap, Dap(iPr), Har, Lys, Lys(iPr), Narg, Ndab, Nlys, Norn, Orn, Orn(iPr), Arg, NMeLys; alloThr, Cit, Hgn, Hse, Leu((3R)OH), Asn, Gln, Ser, Thr; Ala, Ala(cPr), Ala(tetrahydropyran-4-yl), Abu, alloIle, Cha, Cpa, Cpg, Cyg, Dea, Hle, Ile, Leu, Met, Nle, OctGly, tBuGly, tBuAla, Val, NMeAla, NMeVal, Nva; Phe, His, Phe(3OH), Phe(4F), Phe(4OCF3), Trp(6Cl), Tyr(3Cl), Tyr(3F), Tyr(phenyl), Trp, Tyr, 4Thz, Phe(4(4hydroxyphenoxy)), Phe(4NH2), Tyr(Me), Ntyr or Nphe; P 13 But, Agb, Agp, Dab, Dab(iPr), Dap, Dap(iPr), Har, Lys, Lys(iPr), Narg, Ndab, Nlys, Norn, Orn, Orn(iPr), Arg, NMeLys; alloThr, Cit, Hgn, Hse, Leu((3R)OH), Asn, Gln, Ser, Thr; Ala, Ala(cPr), Ala(tetrahydropyran-4-yl), Abu, alloIle, Cha, Cpa, Cpg, Cyg, Dea, Hle, Ile, Leu, Met, Nle, OctGly, tBuGly, tBuAla, Val, NMeAla, NMeVal or Nva; P 14 But, Agb, Agp, Dab, Dab(iPr), Dap, Dap(iPr), Har, Lys, Lys(iPr), Narg, Ndab, Nlys, Norn, Orn, Orn(iPr), Arg, NMeLys; D Dab, D Dab(iPr), D Dap, D Dap(iPr), D Lys, D Lys(iPr), D Orn, D Orn(iPr), D Arg; alloThr, Cit, Hgn, Hse, Leu((3R)OH), Asn, Gln, Ser, Thr; Ala, Ala(cPr), Ala(tetrahydropyran-4-yl), Abu, alloIle, Cha, Cpa, Cpg, Cyg, Dea, Hle, Ile, Leu, Met, Nle, OctGly, tBuGly, tBuAla, Val, NMeAla, NMeVal, Nva; Phe, His, Phe(3OH), Phe(4F), Phe(4OCF3), Trp(6Cl), Tyr(3Cl), Tyr(3F), Tyr(phenyl), Trp, Tyr, 4Thz, Phe(4(4hydroxyphenoxy)), Phe(4NH2), Tyr(Me), Ntyr or Nphe; P 15 But, Dab, Dap; Cys, Pen; Asp or Glu; P 16 are Phe, His, Phe(3OH), Phe(4F), Phe(4OCF3), Trp(6Cl), Tyr(3Cl), Tyr(3F), Tyr(phenyl), Trp, Tyr, 4Thz, Phe(4(4hydroxyphenoxy)), Phe(4NH2), Tyr(Me), Ntyr, Nphe; A compound which is Ala, Ala(cPr), Ala(tetrahydropyran-4-yl), Abu, alloIle, Cha, Cpa, Cpg, Cyg, Dea, Hle, Ile, Leu, Met, Nle, OctGly, tBuGly, tBuAla, Val, NMeAla, NMeVal or Nva, If present, P 4 Cys or Pen in the formula (I) and, if present, P 15 Cys or Pen in the formula (I) is optionally P 4 and P 15 or forms a disulfide bridge between If present, P 4 Dab or Dap in and, if present, P 15 Asp or Glu in the formula (I) is optionally 4 and P 15 or forming a lactam bridge between If present, P 4 Asp or Glu in 15 Dab or Dap in the formula (I) is optionally P 4 and P 15 forming a lactam bridge between However, at position P 6 , P8 , P 9 and P 11 ~P 14 At least five of the seven amino acid residues in D Dab, D Dab(iPr), D Dap, D Dap(iPr), D Lys, D Lys(iPr), D Orn, D Orn(iPr) or D or a tautomer, rotamer, salt, hydrate or solvate thereof, wherein the basic amino acid residue is selected from the group consisting of: Arg.

[0012] A further embodiment of the first aspect comprises P 1 is 2OHVal, Ala, Ala(cPr), Ala(tetrahydropyran-4-yl), Abu, alloIle, betaGly, Cha, Cyg, Dea, Gly, Ile, Leu, Nle, Sar, tBuGly, tBuAla, Val, Pro, NMeAla, NMeVal or Nva; P 1 wherein the amino group is optionally substituted by a guanidino group (Gua) or a tetramethylguanidino (TMG) group; P 2 But Hyp; Pro; Pro((4S)F), Pro((4R)F), Pro(4,4F2), Pro((4R)OMe), Pro(3,4 dehydro); P 3 is Ala, Ala(cPr), Ala(tetrahydropyran-4-yl), Abu, alloIle, betaGly, Cha, Cpg, Cyg, Dea, Gly, Ile, Leu, Nle, Sar, tBuGly, tBuAla, Val, Pro, NMeAla, NMeVal or Nva; P4 But, Pra, Abu(4N3); Dab, Dap; Cys, Hcy, NMeCys, Pen; Asp, Glu or HgI; P 5 are Phe, His, Phe(3OH), Phe(4F), Trp(6Cl), Trp, Tyr, 4Thz, Phe(4(4hydroxyphenoxy)), Phe(4NH2), Tyr(Me), Ntyr, and Nphe; Ala, Ala(cPr), Ala(tetrahydropyran 4yl), Abu, alloIle, betaGly, Cha, Cyg, Dea, Gly, Ile, Leu, Nle, Sar, tBuGly, tBuAla, Val, Pro, NMeAla, NMeVal, Nva; alloThr, Cit, Hgn, Hse, Hyp, Leu((3R)OH), Asn, Gln, Ser, Thr, Asp, Glu, or Hgl; P 6 is alloThr, Cit, Hgn, Hse, Hyp, Leu((3R)OH), Asn, Gln, Ser, Thr, Asp, Glu, Hgl; Agb, Agp, Dab, Dab(iPr), Dap, Dap(iPr), Lys, Lys(iPr), Narg, Ndab, Nlys, Norn, Orn, Orn(iPr), Pro((4R)NH2), Arg, NMeLys; Ala, Ala(cPr), Ala(tetrahydropyran-4-yl), Abu, alloIle, betaGly, Cha, Cyg, Dea, Gly, Ile, Leu, Nle, Sar, tBuGly, tBuAla, Val, Pro, NMeAla, NMeVal or Nva; P 7 is alloThr, Cit, Hgn, Hse, Hyp, Leu((3R)OH), Asn, Gln, Ser, Thr, Asp, Glu, Hgl; Ala, Ala(cPr), Ala(tetrahydropyran-4-yl), Abu, alloIle, betaGly, Cha, Cyg, Dea, Gly, Ile, Leu, Nle, Sar, tBuGly, tBuAla, Val, Pro, NMeAla, NMeVal or Nva; P 8 is Agb, Agp, Dab, Dab(iPr), Dap, Dap(iPr), Lys, Lys(iPr), Narg, Ndab, Nlys, Norn, Orn, Orn(iPr), Pro((4R)NH2), Arg, or NMeLys; P 9 is Agb, Agp, Dab, Dab(iPr), Dap, Dap(iPr), Lys, Lys(iPr), Narg, Ndab, Nlys, Norn, Orn, Orn(iPr), Pro((4R)NH2), Arg, NMeLys; D Dab, D Dab(iPr), D Dap, D Dap(iPr), D Lys, D Lys(iPr), D Orn, D Orn(iPr), D Arg; alloThr, Cit, Hgn, Hse, Hyp, Leu((3R)OH), Asn, Gln, Ser, Thr; D Cit, D Asn, D Ser; Ala, Ala(cPr), Ala(tetrahydropyran 4yl), Abu, alloIle, betaGly, Cha, Cyg, Dea, Gly, Ile, Leu, Nle, Sar, tBuGly, tBuAla, Val, Pro, NMeAla, NMeVal, Nva; D Ala, D Val or D Ile; P 10 are alloThr, Cit, Hgn, Hse, Hyp, Leu((3R)OH), Asn, Gln, Ser, and Thr; P 11 is D Dab, D Dab(iPr), D Dap, D Dap(iPr), D Lys, D Lys(iPr), D Orn, D Orn(iPr), D Arg; D Cit, D Asn or D Ser; P 12 is Agb, Agp, Dab, Dab(iPr), Dap, Dap(iPr), Lys, Lys(iPr), Narg, Ndab, Nlys, Norn, Orn, Orn(iPr), Pro((4R)NH2), Arg, NMeLys; alloThr, Cit, Hgn, Hse, Hyp, Leu((3R)OH), Asn, Gln, Ser, Thr; Ala, Ala(cPr), Ala(tetrahydropyran-4-yl), Abu, alloIle, betaGly, Cha, Cyg, Dea, Gly, Ile, Leu, Nle, Sar, tBuGly, tBuAla, Val, Pro, NMeAla, NMeVal, Nva; Phe, His, Phe(3OH), Phe(4F), Trp(6Cl), Trp, Tyr, 4Thz, Phe(4-(4-hydroxyphenoxy)), Phe(4NH2), Tyr(Me), Ntyr or Nphe; P 13 is Agb, Agp, Dab, Dab(iPr), Dap, Dap(iPr), Lys, Lys(iPr), Narg, Ndab, Nlys, Norn, Orn, Orn(iPr), Pro((4R)NH2), Arg, NMeLys; alloThr, Cit, Hgn, Hse, Hyp, Leu((3R)OH), Asn, Gln, Ser, Thr; Ala, Ala(cPr), Ala(tetrahydropyran-4-yl), Abu, alloIle, betaGly, Cha, Cyg, Dea, Gly, Ile, Leu, Nle, Sar, tBuGly, tBuAla, Val, Pro, NMeAla, NMeVal or Nva; P 14 is Agb, Agp, Dab, Dab(iPr), Dap, Dap(iPr), Lys, Lys(iPr), Narg, Ndab, Nlys, Norn, Orn, Orn(iPr), Pro((4R)NH2), Arg, NMeLys; D Dab, D Dab(iPr), D Dap, D Dap(iPr), D Lys, D Lys(iPr), D Orn, D Orn(iPr), D Arg; alloThr, Cit, Hgn, Hse, Hyp, Leu((3R)OH), Asn, Gln, Ser, Thr; D Cit, D Asn or D Ser; Ala, Ala(cPr), Ala(tetrahydropyran 4yl), Abu, alloIle, betaGly, Cha, Cyg, Dea, Gly, Ile, Leu, Nle, Sar, tBuGly, tBuAla, Val, Pro, NMeAla, NMeVal, Nva; D Ala, D Val, D Ile; Phe, His, Phe(3OH), Phe(4F), Trp(6Cl), Trp, Tyr, 4Thz, Phe(4(4hydroxyphenoxy)), Phe(4NH2), Tyr(Me), Ntyr, Nphe or D Tyr; P 15 But, Pra, Abu(4N3); Dab, Dap; Cys, Hcy, NMeCys, Pen; Asp, Glu or HgI; P 16 are Phe, His, Phe(3OH), Phe(4F), Trp(6Cl), Trp, Tyr, 4Thz, Phe(4(4hydroxyphenoxy)), Phe(4NH2), Tyr(Me), Ntyr, and Nphe; 1. A compound which is Ala, Ala(cPr), Ala(tetrahydropyran-4-yl), Abu, alloIle, betaGly, Cha, Cyg, Dea, Gly, Ile, Leu, Nle, Sar, tBuGly, tBuAla, Val, Pro, NMeAla, NMeVal or Nva, If present, P 4 Cys, Hcy, NMeCys or Pen in 15 Cys, Hcy, NMeCys or Pen in the formula (I) is optionally 4 and P 15 or forms a disulfide bridge between If present, P 4 Dab or Dap in and, if present, P 15 Asp, Glu or HgI in 4 and P 15 or forming a lactam bridge between If present, P 4 Asp, Glu or HgI in 15 Dab or Dap in the formula (I) is optionally P 4 and P 15 or forming a lactam bridge between If present, P 4 Pra in and, if present, P 15 Abu(4N3) in the formula (I) is optionally 4 and P 15 or forming a 1,2,3-triazole bridge between If present, P 4 Abu(4N3) in and, if present, P 15 Pra in the formula (I) is optionally P 4 and P15 Forms a 1,2,3-triazole bridge between However, at position P 6 , P 8 , P 9 and P 11 ~P 14 At least five of the seven amino acid residues in D Dab, D Dab(iPr), D Dap, D Dap(iPr), D Lys, D Lys(iPr), D Orn, D Orn(iPr) or D or a tautomer, rotamer, salt, hydrate or solvate thereof, wherein the basic amino acid residue is selected from the group consisting of: Arg.

[0013] Yet another embodiment of the first aspect comprises P 1 is 2OHVal, Ala, Ala(cPr), Ala(tetrahydropyran-4-yl), Abu, alloIle, betaGly, Cha, Cyg, Dea, Gly, Ile, Leu, Nle, Sar, tBuGly, tBuAla, Val, Pro, NMeAla, NMeVal or Nva; P 1 wherein the amino group is optionally substituted by a guanidino group (Gua) or a tetramethylguanidino (TMG) group; P 2 But Hyp; Pro; Pro((4S)F), Pro((4R)F), Pro(4,4F2), Pro((4R)OMe), Pro(3,4 dehydro); P 3is Ala, Ala(cPr), Ala(tetrahydropyran-4-yl), Abu, alloIle, betaGly, Cha, Cyg, Dea, Gly, Ile, Leu, Nle, Sar, tBuGly, tBuAla, Val, Pro, NMeAla, NMeVal or Nva; P 4 But, Pra, Abu(4N3); Dab, Dap; Cys, Hcy, NMeCys, Pen; Asp, Glu or HgI; P 5 are Phe, His, Phe(3OH), Phe(4F), Trp(6Cl), Trp, Tyr, 4Thz, Phe(4(4hydroxyphenoxy)), Phe(4NH2), Tyr(Me), Ntyr, and Nphe; Ala, Ala(cPr), Ala(tetrahydropyran 4yl), Abu, alloIle, betaGly, Cha, Cyg, Dea, Gly, Ile, Leu, Nle, Sar, tBuGly, tBuAla, Val, Pro, NMeAla, NMeVal, Nva; alloThr, Cit, Hgn, Hse, Hyp, Leu((3R)OH), Asn, Gln, Ser, Thr, Asp, Glu, or Hgl; P 6 is alloThr, Cit, Hgn, Hse, Hyp, Leu((3R)OH), Asn, Gln, Ser, Thr, Asp, Glu, Hgl; Agb, Agp, Dab, Dab(iPr), Dap, Dap(iPr), Lys, Lys(iPr), Narg, Ndab, Nlys, Norn, Orn, Orn(iPr), Pro((4R)NH2), Arg, NMeLys; Ala, Ala(cPr), Ala(tetrahydropyran-4-yl), Abu, alloIle, betaGly, Cha, Cyg, Dea, Gly, Ile, Leu, Nle, Sar, tBuGly, tBuAla, Val, Pro, NMeAla, NMeVal or Nva; P 7is alloThr, Cit, Hgn, Hse, Hyp, Leu((3R)OH), Asn, Gln, Ser, Thr, Asp, Glu, Hgl; is Ala, Ala(cPr), Ala(tetrahydropyran-4-yl), Abu, alloIle, betaGly, Cha, Cyg, Dea, Gly, Ile, Leu, Nle, Sar, tBuGly, tBuAla, Val, Pro, NMeAla, NMeVal or Nva; P 8 is Agb, Agp, Dab, Dab(iPr), Dap, Dap(iPr), Lys, Lys(iPr), Narg, Ndab, Nlys, Norn, Orn, Orn(iPr), Pro((4R)NH2), Arg or NMeLys; P 9 is Agb, Agp, Dab, Dab(iPr), Dap, Dap(iPr), Lys, Lys(iPr), Narg, Ndab, Nlys, Norn, Orn, Orn(iPr), Pro((4R)NH2), Arg, NMeLys; D Dab, D Dab(iPr), D Dap, D Dap(iPr), D Lys, D Lys(iPr), D Orn, D Orn(iPr), D Arg; alloThr, Cit, Hgn, Hse, Hyp, Leu((3R)OH), Asn, Gln, Ser, Thr; D Cit, D Asn, D Ser; Ala, Ala(cPr), Ala(tetrahydropyran-4-yl), Abu, alloIle, betaGly, Cha, Cyg, Dea, Gly, Ile, Leu, Nle, Sar, tBuGly, tBuAla, Val, Pro, NMeAla, NMeVal, Nva; D Ala, D Val or D Ile; P 10 are alloThr, Cit, Hgn, Hse, Hyp, Leu((3R)OH), Asn, Gln, Ser, and Thr; P 11 but, D Dab, D Dab(iPr), D Dap, D Dap(iPr), D Lys, D Lys(iPr), D Orn, D Orn(iPr), D Arg; D Cit, D Asn or D Ser; P 12 is Agb, Agp, Dab, Dab(iPr), Dap, Dap(iPr), Lys, Lys(iPr), Narg, Ndab, Nlys, Norn, Orn, Orn(iPr), Pro((4R)NH2), Arg, NMeLys; alloThr, Cit, Hgn, Hse, Hyp, Leu((3R)OH), Asn, Gln, Ser, Thr; Ala, Ala(cPr), Ala(tetrahydropyran 4yl), Abu, alloIle, betaGly, Cha, Cyg, Dea, Gly, Ile, Leu, Nle, Sar, tBuGly, tBuAla, Val, Pro, NMeAla, NMeVal, Nva; Phe, His, Phe(3OH), Phe(4F), Trp(6Cl), Trp, Tyr, 4Thz, Phe(4(4hydroxyphenoxy)), Phe(4NH2), Tyr(Me), Ntyr or Nphe; P 13 is Agb, Agp, Dab, Dab(iPr), Dap, Dap(iPr), Lys, Lys(iPr), Narg, Ndab, Nlys, Norn, Orn, Orn(iPr), Pro((4R)NH2), Arg, NMeLys; alloThr, Cit, Hgn, Hse, Hyp, Leu((3R)OH), Asn, Gln, Ser, Thr; Ala, Ala(cPr), Ala(tetrahydropyran-4-yl), Abu, alloIle, betaGly, Cha, Cyg, Dea, Gly, Ile, Leu, Nle, Sar, tBuGly, tBuAla, Val, Pro, NMeAla, NMeVal or Nva; P 14 is Agb, Agp, Dab, Dab(iPr), Dap, Dap(iPr), Lys, Lys(iPr), Narg, Ndab, Nlys, Norn, Orn, Orn(iPr), Pro((4R)NH2), Arg, NMeLys; D Dab, D Dab(iPr), D Dap, D Dap(iPr), D Lys, D Lys(iPr), D Orn, D Orn(iPr), D Arg; alloThr, Cit, Hgn, Hse, Hyp, Leu((3R)OH), Asn, Gln, Ser, Thr; D Cit, D Asn or D Ser; Ala, Ala(cPr), Ala(tetrahydropyran 4yl), Abu, alloIle, betaGly, Cha, Cyg, Dea, Gly, Ile, Leu, Nle, Sar, tBuGly, tBuAla, Val, Pro, NMeAla, NMeVal, Nva; D Ala, D Val, D Ile; Phe, His, Phe(3OH), Phe(4F), Trp(6Cl), Trp, Tyr, 4Thz, Phe(4(4hydroxyphenoxy)), Phe(4NH2), Tyr(Me), Ntyr, Nphe or D Tyr; P 15 But, Pra, Abu(4N3); Dab, Dap; Cys, Hcy, NMeCys, Pen; Asp, Glu or HgI; P 16 are Phe, His, Phe(3OH), Phe(4F), Trp(6Cl), Trp, Tyr, 4Thz, Phe(4(4hydroxyphenoxy)), Phe(4NH2), Tyr(Me), Ntyr, and Nphe; 1. A compound which is Ala, Ala(cPr), Ala(tetrahydropyran-4-yl), Abu, alloIle, betaGly, Cha, Cyg, Dea, Gly, Ile, Leu, Nle, Sar, tBuGly, tBuAla, Val, Pro, NMeAla, NMeVal or Nva, If present, P 4 Cys, Hcy, NMeCys or Pen in 15 Cys, Hcy, NMeCys or Pen in the formula (I) is optionally 4 and P 15 or forms a disulfide bridge between If present, P 4 Dab or Dap in and, if present, P 15 Asp, Glu or HgI in 4 and P 15 or forming a lactam bridge between If present, P 4 Asp, Glu or HgI in 15 Dab or Dap in the formula (I) is optionally P 4 and P 15 or forming a lactam bridge between If present, P 4 Pra in and, if present, P 15 Abu(4N3) in the formula (I) is optionally 4 and P 15 or forming a 1,2,3-triazole bridge between If present, P 4 Abu(4N3) in and, if present, P 15Pra in the formula (I) is optionally P 4 and P 15 Forms a 1,2,3-triazole bridge between However, at position P 6 , P 8 , P 9 and P 11 ~P 14 At least five of the seven amino acid residues in D Dab, D Dab(iPr), D Dap, D Dap(iPr), D Lys, D Lys(iPr), D Orn, D Orn(iPr) or D or a tautomer, rotamer, salt, hydrate or solvate thereof, wherein the basic amino acid residue is selected from the group consisting of: Arg.

[0014] A preferred embodiment of a further embodiment of the first aspect comprises P 1 is Abu, tBuGly, or Val; P 1 wherein the amino group is optionally substituted by a guanidino group (Gua) or a tetramethylguanidino (TMG) group; P 2 But Hyp; Pro; Pro((4S)F), Pro((4R)F), Pro(4,4F2), Pro((4R)OMe) or Pro(3,4 dehydro); P 3 is Ile, Leu, Cpg, or Nle; P 4 But, Pra, Abu(4N3); Dab, Dap; Cys, Hcy, NMeCys, Pen; Asp, Glu or HgI; P 5 are Phe, His, Phe(3OH), Phe(4F), Trp(6Cl), Trp, Tyr, 4Thz, Phe(4(4hydroxyphenoxy)), Phe(4NH2), Tyr(Me), Ntyr, and Nphe; Ala, Ala(cPr), Ala(tetrahydropyran-4-yl), Abu, alloIle, Cha, Cyg, Dea, Ile, Leu, Nle, tBuGly, tBuAla, Val, NMeAla, NMeVal, Nva; alloThr, Cit, Hgn, Hse, Leu((3R)OH), Asn, Gln, Ser, Thr, Asp, Glu, or Hgl; P 6 is alloThr, Cit, Hgn, Hse, Leu((3R)OH), Asn, Gln, Ser, Thr, Asp, Glu, Hgl; Agb, Agp, Dab, Dab(iPr), Dap, Dap(iPr), Lys, Lys(iPr), Narg, Ndab, Nlys, Norn, Orn, Orn(iPr), Arg, NMeLys; Ala, Ala(cPr), Ala(tetrahydropyran-4-yl), Abu, alloIle, Cha, Cyg, Dea, Ile, Leu, Nle, tBuGly, tBuAla, Val, NMeAla, NMeVal or Nva; P 7 is alloThr, Cit, Hgn, Hse, Leu((3R)OH), Asn, Gln, Ser, Thr, Asp, Glu, Hgl; Ala, Ala(cPr), Ala(tetrahydropyran-4-yl), Abu, alloIle, Cha, Cyg, Dea, Ile, Leu, Nle, tBuGly, tBuAla, Val, NMeAla, NMeVal or Nva; P 8 is Agb, Agp or Arg; P 9But, Agb, Agp, Dab, Dab(iPr), Dap, Dap(iPr), Lys, Lys(iPr), Narg, Ndab, Nlys, Norn, Orn, Orn(iPr), Arg, NMeLys; D Dab, D Dab(iPr), D Dap, D Dap(iPr), D Lys, D Lys(iPr), D Orn, D Orn(iPr), D Arg; alloThr, Cit, Hgn, Hse, Leu((3R)OH), Asn, Gln, Ser, Thr; Ala, Ala(cPr), Ala(tetrahydropyran-4-yl), Abu, alloIle, Cha, Cyg, Dea, Ile, Leu, Nle, tBuGly, tBuAla, Val, NMeAla, NMeVal or Nva; P 10 is Asn, Ser or Thr; P 11 but, D Dab, D Dab(iPr), D Dap, D Dap(iPr), D Lys, D Lys(iPr), D Orn, D Orn(iPr), D Arg; D Cit, D Asn or D Ser; P 12 But, Agb, Agp, Dab, Dab(iPr), Dap, Dap(iPr), Lys, Lys(iPr), Narg, Ndab, Nlys, Norn, Orn, Orn(iPr), Arg, NMeLys; alloThr, Cit, Hgn, Hse, Leu((3R)OH), Asn, Gln, Ser, Thr; Ala, Ala(cPr), Ala(tetrahydropyran-4-yl), Abu, alloIle, Cha, Cyg, Dea, Ile, Leu, Nle, tBuGly, tBuAla, Val, NMeAla, NMeVal, Nva; Phe, His, Phe(3OH), Phe(4F), Trp(6Cl), Trp, Tyr, 4Thz, Phe(4(4-hydroxyphenoxy)), Phe(4NH2), Tyr(Me), Ntyr or Nphe; P 13 is Agb, Agp, Dab, Dab(iPr), Dap, Dap(iPr), Lys, Lys(iPr), Narg, Ndab, Nlys, Norn, Orn, Orn(iPr), Arg, NMeLys; alloThr, Cit, Hgn, Hse, Leu((3R)OH), Asn, Gln, Ser, Thr; Ala, Ala(cPr), Ala(tetrahydropyran-4-yl), Abu, alloIle, Cha, Cyg, Dea, Ile, Leu, Nle, tBuGly, tBuAla, Val, NMeAla, NMeVal, Nva; P 14 is Agb, Agp, Dab, Dab(iPr), Dap, Dap(iPr), Lys, Lys(iPr), Narg, Ndab, Nlys, Norn, Orn, Orn(iPr), Arg, NMeLys; D Dab, D Dab(iPr), D Dap, D Dap(iPr), D Lys, D Lys(iPr), D Orn, D Orn(iPr), D Arg; alloThr, Cit, Hgn, Hse, Leu((3R)OH), Asn, Gln, Ser, Thr; Ala, Ala(cPr), Ala(tetrahydropyran-4-yl), Abu, alloIle, Cha, Cyg, Dea, Ile, Leu, Nle, tBuGly, tBuAla, Val, NMeAla, NMeVal, Nva; Phe, His, Phe(3OH), Phe(4F), Trp(6Cl), Trp, Tyr, 4Thz, Phe(4(4hydroxyphenoxy)), Phe(4NH2), Tyr(Me), Ntyr or Nphe; P 15 But, Pra, Abu(4N3); Dab, Dap; Cys, Hcy, NMeCys, Pen; Asp, Glu or HgI; P 16 are Phe, His, Phe(3OH), Phe(4F), Trp(6Cl), Trp, Tyr, 4Thz, Phe(4(4hydroxyphenoxy)), Phe(4NH2), Tyr(Me), Ntyr, and Nphe; A compound which is Ala, Ala(cPr), Ala(tetrahydropyran-4-yl), Abu, alloIle, Cha, Cyg, Dea, Ile, Leu, Nle, tBuGly, tBuAla, Val, NMeAla, NMeVal or Nva, If present, P 4 Cys, Hcy, NMeCys or Pen in 15 Cys, Hcy, NMeCys or Pen in the formula (I) is optionally 4 and P 15 or forms a disulfide bridge between If present, P 4 Dab or Dap in and, if present, P 15 Asp, Glu or HgI in 4 and P 15 or forming a lactam bridge between If present, P 4 Asp, Glu or HgI in 15 Dab or Dap in the formula (I) is optionally P 4 and P 15 or forming a lactam bridge between If present, P 4 Pra in and, if present, P15 Abu(4N3) in the formula (I) is optionally 4 and P 15 or forming a 1,2,3-triazole bridge between If present, P 4 Abu(4N3) in and, if present, P 15 Pra in the formula (I) is optionally P 4 and P 15 Forms a 1,2,3-triazole bridge between However, at position P 6 , P 8 , P 9 and P 11 ~P 14 At least five of the seven amino acid residues in D Dab, D Dab(iPr), D Dap, D Dap(iPr), D Lys, D Lys(iPr), D Orn, D Orn(iPr) or D or a tautomer, rotamer, salt, hydrate or solvate thereof, wherein the basic amino acid residue is selected from the group consisting of: Arg.

[0015] Another preferred embodiment of the further embodiment of the first aspect comprises P 1 is Abu, tBuGly, or Val; P 1 wherein the amino group is optionally substituted by a guanidino group (Gua) or a tetramethylguanidino (TMG) group; P 2 But Hyp; Pro; Pro((4S)F), Pro((4R)F), Pro(4,4F2), Pro((4R)OMe) or Pro(3,4 dehydro); P3 is Ile, Leu or Nle; P 4 But, Pra, Abu(4N3); Dab, Dap; Cys, Hcy, NMeCys, Pen; Asp, Glu or HgI; P 5 are Phe, His, Phe(3OH), Phe(4F), Trp(6Cl), Trp, Tyr, 4Thz, Phe(4(4hydroxyphenoxy)), Phe(4NH2), Tyr(Me), Ntyr, and Nphe; Ala, Ala(cPr), Ala(tetrahydropyran-4-yl), Abu, alloIle, Cha, Cyg, Dea, Ile, Leu, Nle, tBuGly, tBuAla, Val, NMeAla, NMeVal, Nva; alloThr, Cit, Hgn, Hse, Leu((3R)OH), Asn, Gln, Ser, Thr, Asp, Glu, or Hgl; P 6 is alloThr, Cit, Hgn, Hse, Leu((3R)OH), Asn, Gln, Ser, Thr, Asp, Glu, Hgl; Agb, Agp, Dab, Dab(iPr), Dap, Dap(iPr), Lys, Lys(iPr), Narg, Ndab, Nlys, Norn, Orn, Orn(iPr), Arg, NMeLys; Ala, Ala(cPr), Ala(tetrahydropyran-4-yl), Abu, alloIle, Cha, Cyg, Dea, Ile, Leu, Nle, tBuGly, tBuAla, Val, NMeAla, NMeVal or Nva; P 7 is alloThr, Cit, Hgn, Hse, Leu((3R)OH), Asn, Gln, Ser, Thr, Asp, Glu, Hgl; Ala, Ala(cPr), Ala(tetrahydropyran-4-yl), Abu, alloIle, Cha, Cyg, Dea, Ile, Leu, Nle, tBuGly, tBuAla, Val, NMeAla, NMeVal or Nva; P 8 is Agb, Agp or Arg; P 9 But, Agb, Agp, Dab, Dab(iPr), Dap, Dap(iPr), Lys, Lys(iPr), Narg, Ndab, Nlys, Norn, Orn, Orn(iPr), Arg, NMeLys; D Dab, D Dab(iPr), D Dap, D Dap(iPr), D Lys, D Lys(iPr), D Orn, D Orn(iPr), D Arg; alloThr, Cit, Hgn, Hse, Leu((3R)OH), Asn, Gln, Ser, Thr; Ala, Ala(cPr), Ala(tetrahydropyran-4-yl), Abu, alloIle, Cha, Cyg, Dea, Ile, Leu, Nle, tBuGly, tBuAla, Val, NMeAla, NMeVal or Nva; P 10 is Asn, Ser or Thr; P 11 but, D Dab, D Dab(iPr), D Dap, D Dap(iPr), D Lys, D Lys(iPr), D Orn, D Orn(iPr), D Arg; D Cit, D Asn or D Ser; P 12 But, Agb, Agp, Dab, Dab(iPr), Dap, Dap(iPr), Lys, Lys(iPr), Narg, Ndab, Nlys, Norn, Orn, Orn(iPr), Arg, NMeLys; alloThr, Cit, Hgn, Hse, Leu((3R)OH), Asn, Gln, Ser, Thr; Ala, Ala(cPr), Ala(tetrahydropyran-4-yl), Abu, alloIle, Cha, Cyg, Dea, Ile, Leu, Nle, tBuGly, tBuAla, Val, NMeAla, NMeVal, Nva; Phe, His, Phe(3OH), Phe(4F), Trp(6Cl), Trp, Tyr, 4Thz, Phe(4-(4-hydroxyphenoxy)), Phe(4NH2), Tyr(Me), Ntyr or Nphe; P 13 is Agb, Agp, Dab, Dab(iPr), Dap, Dap(iPr), Lys, Lys(iPr), Narg, Ndab, Nlys, Norn, Orn, Orn(iPr), Arg, NMeLys; alloThr, Cit, Hgn, Hse, Leu((3R)OH), Asn, Gln, Ser, Thr; Ala, Ala(cPr), Ala(tetrahydropyran-4-yl), Abu, alloIle, Cha, Cyg, Dea, Ile, Leu, Nle, tBuGly, tBuAla, Val, NMeAla, NMeVal, Nva; P 14 is Agb, Agp, Dab, Dab(iPr), Dap, Dap(iPr), Lys, Lys(iPr), Narg, Ndab, Nlys, Norn, Orn, Orn(iPr), Arg, NMeLys; D Dab, D Dab(iPr), D Dap, D Dap(iPr), D Lys, D Lys(iPr), D Orn, D Orn(iPr), D Arg; alloThr, Cit, Hgn, Hse, Leu((3R)OH), Asn, Gln, Ser, Thr; Ala, Ala(cPr), Ala(tetrahydropyran-4-yl), Abu, alloIle, Cha, Cyg, Dea, Ile, Leu, Nle, tBuGly, tBuAla, Val, NMeAla, NMeVal, Nva; Phe, His, Phe(3OH), Phe(4F), Trp(6Cl), Trp, Tyr, 4Thz, Phe(4(4hydroxyphenoxy)), Phe(4NH2), Tyr(Me), Ntyr or Nphe; P 15 But, Pra, Abu(4N3); Dab, Dap; Cys, Hcy, NMeCys, Pen; Asp, Glu or HgI; P 16 are Phe, His, Phe(3OH), Phe(4F), Trp(6Cl), Trp, Tyr, 4Thz, Phe(4(4hydroxyphenoxy)), Phe(4NH2), Tyr(Me), Ntyr, and Nphe; A compound which is Ala, Ala(cPr), Ala(tetrahydropyran-4-yl), Abu, alloIle, Cha, Cyg, Dea, Ile, Leu, Nle, tBuGly, tBuAla, Val, NMeAla, NMeVal or Nva, If present, P 4 Cys, Hcy, NMeCys or Pen in 15 Cys, Hcy, NMeCys or Pen in the formula (I) is optionally 4 and P 15 or forms a disulfide bridge between If present, P 4 Dab or Dap in and, if present, P 15 Asp, Glu or HgI in 4 and P 15 or forming a lactam bridge between If present, P 4 Asp, Glu or HgI and, if present, P 15 Dab or Dap in the formula (I) is optionally P4 and P 15 or forming a lactam bridge between If present, P 4 Pra in and, if present, P 15 Abu(4N3) in the formula (I) is optionally 4 and P 15 or forming a 1,2,3-triazole bridge between If present, P 4 Abu(4N3) in and, if present, P 15 Pra in the formula (I) is optionally P 4 and P 15 Forms a 1,2,3-triazole bridge between However, at position P 6 , P 8 , P 9 and P 11 ~P 14 At least five of the seven amino acid residues in D Dab, D Dab(iPr), D Dap, D Dap(iPr), D Lys, D Lys(iPr), D Orn, D Orn(iPr) or D or a tautomer, rotamer, salt, hydrate or solvate thereof, wherein the basic amino acid residue is selected from the group consisting of: Arg.

[0016] A more preferred embodiment of the further embodiment of the first aspect comprises P 1 is Abu, tBuGly, or Val; P 1 wherein the amino group is optionally substituted by a guanidino group (Gua) or a tetramethylguanidino (TMG) group; P 2 But Hyp; Pro; Pro((4S)F), Pro((4R)F), Pro(4,4F2), Pro((4R)OMe) or Pro(3,4 dehydro); P 3 is Cpg or Ile; P 4 But, Dab, Dap; Cys, Pen; Asp or Glu; P 5 are Phe, His, Phe(3OH), Phe(4F), Trp(6Cl), Trp, Tyr, 4Thz, Phe(4(4hydroxyphenoxy)), Phe(4NH2), Tyr(Me), Ntyr, and Nphe; Ala, Ala(cPr), Ala(tetrahydropyran-4-yl), Abu, alloIle, Cha, Cyg, Dea, Gly, Ile, Leu, Nle, tBuGly, tBuAla, Val, NMeAla, NMeVal, Nva; alloThr, Cit, Hgn, Hse, Leu((3R)OH), Asn, Gln, Ser, Thr, Asp, Glu, or Hgl; P 6 is alloThr, Cit, Hgn, Hse, Leu((3R)OH), Asn, Gln, Ser, Thr, Asp, Glu, Hgl; Agb, Agp, Dab, Dab(iPr), Dap, Dap(iPr), Lys, Lys(iPr), Narg, Ndab, Nlys, Norn, Orn, Orn(iPr), Arg, NMeLys; Ala, Ala(cPr), Ala(tetrahydropyran-4-yl), Abu, alloIle, Cha, Cyg, Dea, Gly, Ile, Leu, Nle, tBuGly, tBuAla, Val, NMeAla, NMeVal or Nva; P 7 is alloThr, Cit, Hgn, Hse, Leu((3R)OH), Asn, Gln, Ser, Thr, Asp, Glu, Hgl; Ala, Ala(cPr), Ala(tetrahydropyran-4-yl), Abu, alloIle, Cha, Cyg, Dea, Ile, Leu, Nle, tBuGly, tBuAla, Val, NMeAla, NMeVal or Nva; P 8 Wherein, is Arg; P 9 But, Agb, Agp, Dab, Dab(iPr), Dap, Dap(iPr), Lys, Lys(iPr), Narg, Ndab, Nlys, Norn, Orn, Orn(iPr), Arg, NMeLys; D Dab, D Dab(iPr), D Dap, D Dap(iPr), D Lys, D Lys(iPr), D Orn, D Orn(iPr), D Arg; alloThr, Cit, Hgn, Hse, Leu((3R)OH), Asn, Gln, Ser, Thr; Ala, Ala(cPr), Ala(tetrahydropyran-4-yl), Abu, alloIle, Cha, Cyg, Dea, Ile, Leu, Nle, tBuGly, tBuAla, Val, NMeAla, NMeVal or Nva; P 10 is Asn, Ser or Thr; P 11 but, D Dab, D Dab(iPr), D Dap, D Dap(iPr), D Lys, D Lys(iPr), D Orn, D Orn(iPr), D Arg; D Cit, D Asn or D Ser; P 12is Agb, Agp, Dab, Dab(iPr), Dap, Dap(iPr), Lys, Lys(iPr), Narg, Ndab, Nlys, Norn, Orn, Orn(iPr), Arg, NMeLys; alloThr, Cit, Hgn, Hse, Leu((3R)OH), Asn, Gln, Ser, Thr; Ala, Ala(cPr), Ala(tetrahydropyran-4-yl), Abu, alloIle, Cha, Cyg, Dea, Ile, Leu, Nle, tBuGly, tBuAla, Val, NMeAla, NMeVal, Nva; Phe, His, Phe(3OH), Phe(4F), Trp(6Cl), Trp, Tyr, 4Thz, Phe(4(4-hydroxyphenoxy)), Phe(4NH2), Tyr(Me), Ntyr or Nphe; P 13 is Agb, Agp, Dab, Dab(iPr), Dap, Dap(iPr), Lys, Lys(iPr), Narg, Ndab, Nlys, Norn, Orn, Orn(iPr), Arg, NMeLys; alloThr, Cit, Hgn, Hse, Leu((3R)OH), Asn, Gln, Ser, Thr; Ala, Ala(cPr), Ala(tetrahydropyran-4-yl), Abu, alloIle, Cha, Cyg, Dea, Ile, Leu, Nle, tBuGly, tBuAla, Val, NMeAla, NMeVal or Nva; P 14 is Agb, Agp, Dab, Dab(iPr), Dap, Dap(iPr), Lys, Lys(iPr), Narg, Ndab, Nlys, Norn, Orn, Orn(iPr), Arg, NMeLys; D Dab, D Dab(iPr), D Dap, D Dap(iPr), D Lys, D Lys(iPr), D Orn, D Orn(iPr), D Arg; alloThr, Cit, Hgn, Hse, Leu((3R)OH), Asn, Gln, Ser, Thr; Ala, Ala(cPr), Ala(tetrahydropyran-4-yl), Abu, alloIle, Cha, Cyg, Dea, Gly, Ile, Leu, Nle, tBuGly, tBuAla, Val, NMeAla, NMeVal, Nva; Phe, His, Phe(3OH), Phe(4F), Trp(6Cl), Trp, Tyr, 4Thz, Phe(4(4hydroxyphenoxy)), Phe(4NH2), Tyr(Me), Ntyr or Nphe; P 15 But, Dab, Dap; Cys, Pen; Asp or Glu; P 16 are Phe, His, Phe(3OH), Phe(4F), Trp(6Cl), Trp, Tyr, 4Thz, Phe(4(4hydroxyphenoxy)), Phe(4NH2), Tyr(Me), Ntyr, and Nphe; 1. A compound which is Ala, Ala(cPr), Ala(tetrahydropyran-4-yl), Abu, alloIle, Cha, Cyg, Dea, Gly, Ile, Leu, Nle, tBuGly, tBuAla, Val, NMeAla, NMeVal or Nva, If present, P 4 Cys or Pen in 15 Cys or Pen in the formula (I) is optionally P 4 and P 15 or forms a disulfide bridge between If present, P 4 Dab or Dap in and, if present, P 15 Asp or Glu in the formula (I) is optionally 4 and P 15 or forming a lactam bridge between If present, P 4 Asp or Glu in 15 Dab or Dap in the formula (I) is optionally P4 and P 15 forming a lactam bridge between However, at position P 6 , P 8 , P 9 and P 11 ~P 14 At least five of the seven amino acid residues in D Dab, D Dab(iPr), D Dap, D Dap(iPr), D Lys, D Lys(iPr), D Orn, D Orn(iPr) or D or a tautomer, rotamer, salt, hydrate or solvate thereof, wherein the basic amino acid residue is selected from the group consisting of: Arg.

[0017] Another more preferred embodiment of the further embodiment of the first aspect comprises P 1 is Abu, tBuGly, or Val; P 1 wherein the amino group is optionally substituted by a guanidino group (Gua) or a tetramethylguanidino (TMG) group; P 2 But Hyp; Pro; Pro((4S)F), Pro((4R)F), Pro(4,4F2), Pro((4R)OMe) or Pro(3,4 dehydro); P 3 But, Ile; P 4 But, Dab, Dap; Cys, Pen; Asp or Glu; P 5are Phe, His, Phe(3OH), Phe(4F), Trp(6Cl), Trp, Tyr, 4Thz, Phe(4(4hydroxyphenoxy)), Phe(4NH2), Tyr(Me), Ntyr, and Nphe; Ala, Ala(cPr), Ala(tetrahydropyran-4-yl), Abu, alloIle, Cha, Cyg, Dea, Gly, Ile, Leu, Nle, tBuGly, tBuAla, Val, NMeAla, NMeVal, Nva; alloThr, Cit, Hgn, Hse, Leu((3R)OH), Asn, Gln, Ser, Thr, Asp, Glu, or Hgl; P 6 is alloThr, Cit, Hgn, Hse, Leu((3R)OH), Asn, Gln, Ser, Thr, Asp, Glu, Hgl; Agb, Agp, Dab, Dab(iPr), Dap, Dap(iPr), Lys, Lys(iPr), Narg, Ndab, Nlys, Norn, Orn, Orn(iPr), Arg, NMeLys; Ala, Ala(cPr), Ala(tetrahydropyran-4-yl), Abu, alloIle, Cha, Cyg, Dea, Gly, Ile, Leu, Nle, tBuGly, tBuAla, Val, NMeAla, NMeVal or Nva; P 7 is alloThr, Cit, Hgn, Hse, Leu((3R)OH), Asn, Gln, Ser, Thr, Asp, Glu, Hgl; Ala, Ala(cPr), Ala(tetrahydropyran-4-yl), Abu, alloIle, Cha, Cyg, Dea, Ile, Leu, Nle, tBuGly, tBuAla, Val, NMeAla, NMeVal or Nva; P 8 Wherein, is Arg; P 9 But, Agb, Agp, Dab, Dab(iPr), Dap, Dap(iPr), Lys, Lys(iPr), Narg, Ndab, Nlys, Norn, Orn, Orn(iPr), Arg, NMeLys; DDab, D Dab(iPr), D Dap, D Dap(iPr), D Lys, D Lys(iPr), D Orn, D Orn(iPr), D Arg; alloThr, Cit, Hgn, Hse, Leu((3R)OH), Asn, Gln, Ser, Thr; Ala, Ala(cPr), Ala(tetrahydropyran-4-yl), Abu, alloIle, Cha, Cyg, Dea, Ile, Leu, Nle, tBuGly, tBuAla, Val, NMeAla, NMeVal or Nva; P 10 is Asn, Ser or Thr; P 11 but, D Dab, D Dab(iPr), D Dap, D Dap(iPr), D Lys, D Lys(iPr), D Orn, D Orn(iPr), D Arg; D Cit, D Asn or D Ser; P 12 But, Agb, Agp, Dab, Dab(iPr), Dap, Dap(iPr), Lys, Lys(iPr), Narg, Ndab, Nlys, Norn, Orn, Orn(iPr), Arg, NMeLys; alloThr, Cit, Hgn, Hse, Leu((3R)OH), Asn, Gln, Ser, Thr; Ala, Ala(cPr), Ala(tetrahydropyran-4-yl), Abu, alloIle, Cha, Cyg, Dea, Ile, Leu, Nle, tBuGly, tBuAla, Val, NMeAla, NMeVal, Nva; Phe, His, Phe(3OH), Phe(4F), Trp(6Cl), Trp, Tyr, 4Thz, Phe(4(4hydroxyphenoxy)), Phe(4NH2), Tyr(Me), Ntyr or Nphe; P 13 But, Agb, Agp, Dab, Dab(iPr), Dap, Dap(iPr), Lys, Lys(iPr), Narg, Ndab, Nlys, Norn, Orn, Orn(iPr), Arg, NMeLys; alloThr, Cit, Hgn, Hse, Leu((3R)OH), Asn, Gln, Ser, Thr; Ala, Ala(cPr), Ala(tetrahydropyran-4-yl), Abu, alloIle, Cha, Cyg, Dea, Ile, Leu, Nle, tBuGly, tBuAla, Val, NMeAla, NMeVal or Nva; P 14 But, Agb, Agp, Dab, Dab(iPr), Dap, Dap(iPr), Lys, Lys(iPr), Narg, Ndab, Nlys, Norn, Orn, Orn(iPr), Arg, NMeLys; D Dab, D Dab(iPr), D Dap, D Dap(iPr), D Lys, D Lys(iPr), D Orn, D Orn(iPr), D Arg; alloThr, Cit, Hgn, Hse, Leu((3R)OH), Asn, Gln, Ser, Thr; Ala, Ala(cPr), Ala(tetrahydropyran-4-yl), Abu, alloIle, Cha, Cyg, Dea, Gly, Ile, Leu, Nle, tBuGly, tBuAla, Val, NMeAla, NMeVal, Nva; Phe, His, Phe(3OH), Phe(4F), Trp(6Cl), Trp, Tyr, 4Thz, Phe(4(4hydroxyphenoxy)), Phe(4NH2), Tyr(Me), Ntyr or Nphe; P 15 But, Dab, Dap; Cys, Pen; Asp or Glu; P 16 are Phe, His, Phe(3OH), Phe(4F), Trp(6Cl), Trp, Tyr, 4Thz, Phe(4(4hydroxyphenoxy)), Phe(4NH2), Tyr(Me), Ntyr, and Nphe; 1. A compound which is Ala, Ala(cPr), Ala(tetrahydropyran-4-yl), Abu, alloIle, Cha, Cyg, Dea, Gly, Ile, Leu, Nle, tBuGly, tBuAla, Val, NMeAla, NMeVal or Nva, If present, P 4 Cys or Pen in 15 Cys or Pen in the formula (I) is optionally P 4 and P 15 or forms a disulfide bridge between If present, P 4 Dab or Dap in and, if present, P 15 Asp or Glu in the formula (I) is optionally 4 and P 15 or forming a lactam bridge between If present, P 4 Asp or Glu in 15 Dab or Dap in the formula (I) is optionally P 4 and P 15 forming a lactam bridge between However, at position P 6 , P 8 , P 9 and P 11 ~P 14 At least five of the seven amino acid residues in D Dab,D Dab(iPr), D Dap, D Dap(iPr), D Lys, D Lys(iPr), D Orn, D Orn(iPr) or D or a tautomer, rotamer, salt, hydrate or solvate thereof, wherein the basic amino acid residue is selected from the group consisting of: Arg.

[0018] Particular embodiments of the first aspect include P 1 is Val, Abu, tBuGly, Gua-Val or Gua-Abu; P 2 is Hyp, Pro, Pro((4S)F), Pro((4R)F), Pro(4,4F2), Pro((4R)OMe) or Pro(3,4 dehydro); P 3 is Cpg or Ile; P 4 is Cys, Pen, Dab or Glu; P 5 is Tyr, Ala or Ser; P 6 is Ser, Thr, Ile, Glu, Asn, Cit, Hse or Dab; P 7 is Asn, Ala, Ile, Ser, Asp or Glu; P 8 Wherein, is Arg; P 9 But, Dab, D Dab, Dab(iPr), Agb, Cit, Asn, Ser or Ala; P 10 is Thr, Ser or Asn; P 11 but, D Dab, D Dab(iPr), D Lys, D Arg or D Cit; P 12is Lys, Ala, Ile, Ser, Asn, Cit, Dab, Orn, Val or Tyr; P 13 is Dab, Dab(iPr), Orn, Arg, Ala, Ser, Thr or Cit; P 14 But, Dab, D Dab, Dab(iPr), Lys, Orn, Agb, Ile, Tyr, Ser, Asn, Thr or Cit; P 15 is Cys, Pen, Dab or Glu; P 16 is Tyr, Trp, Cha or Nle, If present, P 4 Cys or Pen in 15 Cys or Pen in the formula (I) is optionally P 4 and P 15 or If present, P 4 Glu in and, if present, P 15 Dab in optionally P 4 and P 15 or forming a lactam bridge between If present, P 4 Dab in and, if present, P 15 Glu in the formula (I) is optionally selected from the group consisting of P 4 and P 15 forming a lactam bridge between However, at position P 6 , P 8 , P 9 and P 11 ~P 14 At least five of the seven amino acid residues in D Dab, D Dab(iPr), D Lys or Dor a tautomer, rotamer, salt, hydrate or solvate thereof, wherein the basic amino acid residue is selected from the group consisting of: Arg.

[0019] Another particular embodiment of the first aspect comprises P 1 is Val, Abu, tBuGly, Gua-Val or Gua-Abu; P 2 is Hyp, Pro, Pro((4S)F), Pro((4R)F), Pro(4,4F2), Pro((4R)OMe) or Pro(3,4 dehydro); P 3 But, Ile; P 4 is Cys, Pen, Dab or Glu; P 5 is Tyr, Ala or Ser; P 6 is Ser, Thr, Ile, Glu, Asn, or Dab; P 7 is Asn, Ala, Ile, Ser, Asp or Glu; P 8 Wherein, is Arg; P 9 But, Dab, D Dab, Dab(iPr), Agb, Cit, Asn, Ser or Ala; P 10 is Thr, Ser or Asn; P 11 but, D Dab, D Dab(iPr), D Lys, D Arg or D Cit; P 12 is Lys, Ala, Ile, Ser, Asn, Cit or Tyr; P 13 is Dab, Dab(iPr), Orn, Arg, Ala, Ser, Thr or Cit; P 14 But, Dab, DDab, Dab(iPr), Lys, Orn, Agb, Ile, Tyr, Ser, Asn or Cit; P 15 is Cys, Pen, Dab or Glu; P 16 is Tyr, Trp, Cha or Nle, If present, P 4 Cys or Pen in 15 Cys or Pen in the formula (I) is optionally P 4 and P 15 or If present, P 4 Glu in and, if present, P 15 Dab in optionally P 4 and P 15 or forming a lactam bridge between If present, P 4 Dab in and, if present, P 15 Glu in the formula (I) is optionally selected from the group consisting of P 4 and P 15 forming a lactam bridge between However, at position P 6 , P 8 , P 9 and P 11 ~P 14 At least five of the seven amino acid residues in D Dab, D Dab(iPr), D Lys or D or a tautomer, rotamer, salt, hydrate or solvate thereof, wherein the basic amino acid residue is selected from the group consisting of: Arg.

[0020] A particularly preferred embodiment of the first aspect comprises P 1 is Val, Abu, tBuGly or Gua-Val; P 2is Hyp, Pro, Pro((4S)F), Pro((4R)F), Pro(4,4F2), Pro((4R)OMe) or Pro(3,4 dehydro); P 3 is Cpg or Ile; P 4 is Pen, Dab or Glu; P 5 But Tyr; P 6 is Cit, Hse, Ser, Thr, Asn or Dab; P 7 is Asn, Ile, or Ser; P 8 Wherein, is Arg; P 9 is Dab, Dab(iPr) or Agb; P 10 is Thr, Ser or Asn; P 11 but, D Dab, D Dab(iPr), D Lys or D Arg; P 12 is Dab, Orn, Lys, Ser, Cit or Tyr; P 13 is Dab, Dab(iPr), Orn, Arg, Ser or Thr; P 14 But, Dab, D Dab, Dab(iPr), Lys, Orn, Agb, Ser or Thr; P 15 is Cys, Dab or Glu; P 16 is Tyr, Trp, Cha or Nle, If present, P 4 Pen in and, if present, P 15 Cys in the formula (I) is optionally selected from the group consisting of P 4 and P 15 or If present, P 4Glu in and, if present, P 15 Dab in optionally P 4 and P 15 or forming a lactam bridge between If present, P 4 Dab in and, if present, P 15 Glu in the formula (I) is optionally selected from the group consisting of P 4 and P 15 forming a lactam bridge between However, at position P 6 , P 8 , P 9 and P 11 ~P 14 At least five of the seven amino acid residues in D Dab, D Dab(iPr), D Lys or D or a tautomer, rotamer, salt, hydrate or solvate thereof, wherein the basic amino acid residue is selected from the group consisting of: Arg.

[0021] Another particularly preferred embodiment of the first aspect comprises P 1 is Val, Abu, tBuGly or Gua-Val; P 2 is Hyp, Pro, Pro((4S)F), Pro((4R)F), Pro(4,4F2), Pro((4R)OMe) or Pro(3,4 dehydro); P 3 But, Ile; P 4 is Pen, Dab or Glu; P 5 But Tyr; P 6 is Ser, Thr, Asn or Dab; P 7 is Asn, Ile, or Ser; P 8 Wherein, is Arg; P 9is Dab, Dab(iPr) or Agb; P 10 is Thr, Ser or Asn; P 11 but, D Dab, D Dab(iPr), D Lys or D Arg; P 12 is Lys, Ser, Cit or Tyr; P 13 is Dab, Dab(iPr), Orn, Arg, Ser or Thr; P 14 But, Dab, D Dab, Dab(iPr), Lys, Orn, Agb or Ser; P 15 is Cys, Dab or Glu; P 16 is Tyr, Trp, Cha or Nle, If present, P 4 Pen in and, if present, P 15 Cys in the formula (I) is optionally selected from the group consisting of P 4 and P 15 or If present, P 4 Glu in and, if present, P 15 Dab in optionally P 4 and P 15 or forming a lactam bridge between If present, P 4 Dab in and, if present, P 15 Glu in the formula (I) is optionally selected from the group consisting of P 4 and P 15 forming a lactam bridge between However, at position P 6 , P 8 , P 9 and P 11 ~P 14At least five of the seven amino acid residues in D Dab, D Dab(iPr), D Lys or D or a tautomer, rotamer, salt, hydrate or solvate thereof, wherein the basic amino acid residue is selected from the group consisting of: Arg.

[0022] A further particularly preferred embodiment of the first aspect comprises P 1 But, Val; P 2 is Hyp or Pro; P 3 But, Ile; P 4 is Pen, Dab or Glu; P 5 is Tyr, Ala or Ser; P 6 is Ser, Thr, Glu, Asn or Dab; P 7 is Asn, Ala, Asp or Glu; P 8 Wherein, is Arg; P 9 But, Dab, D Dab, Cit, Asn or Ser; P 10 is Thr or Asn; P 11 but, D Dab or D Cit; P 12 is Lys, Ile, Ser or Asn; P 13 is Dab, Orn, Ser or Thr; P 14 But, Dab, D Dab, Ser, Asn or Cit; P 15 is Cys, Dab or Glu; P 16is Tyr or Trp, If present, P 4 Pen in and, if present, P 15 Cys in the formula (I) is optionally selected from the group consisting of P 4 and P 15 or If present, P 4 Glu in and, if present, P 15 Dab in optionally P 4 and P 15 or forming a lactam bridge between If present, P 4 Dab in and, if present, P 15 Glu in the formula (I) is optionally selected from the group consisting of P 4 and P 15 forming a lactam bridge between However, at position P 6 , P 8 , P 9 and P 11 ~P 14 At least five of the seven amino acid residues in D Dab or a tautomer, rotamer, salt, hydrate or solvate thereof.

[0023] A further particularly preferred embodiment of the first aspect comprises Val-Hyp-Ile-Pen-Tyr-Ser-Asn-Arg-Dab-Thr- D Dab-Lys-Dab-Dab-Cys-Tyr; (= Example 1); Abu-Hyp-Ile-Pen-Tyr-Ser-Asn-Arg-Dab-Thr- D Dab-Lys-Dab-Dab-Cys-Tyr; (= Example 2); tBuGly-Hyp-Ile-Pen-Tyr-Ser-Asn-Arg-Dab-Thr- D Dab-Lys-Dab-Dab-Cys-Tyr; (= Example 3); Val-Pro-Ile-Pen-Tyr-Ser-Asn-Arg-Dab-Thr- D Dab-Lys-Dab-Dab-Cys-Tyr;(= Example 4); Val-Pro-Ile-Pen-Tyr-Thr-Asn-Arg-Dab-Thr- D Dab-Lys-Dab-Dab-Cys-Tyr;(= Example 5); Val-Pro((4R)OMe)-Ile-Pen-Tyr-Thr-Asn-Arg-Dab-Thr- D Dab-Lys-Dab-Dab-Cys-Tyr;(= Example 6); Val-Pro((4S)F)-Ile-Pen-Tyr-Thr-Asn-Arg-Dab-Thr- D Dab-Lys-Dab-Dab-Cys-Tyr;(= Example 7); Val-Pro((4R)F)-Ile-Pen-Tyr-Thr-Asn-Arg-Dab-Thr- D Dab-Lys-Dab-Dab-Cys-Tyr;(= Example 8); Val-Pro(4,4F2)-Ile-Pen-Tyr-Thr-Asn-Arg-Dab-Thr- D Dab-Lys-Dab-Dab-Cys-Tyr;(= Example 9); Val-Pro(3,4 dehydro)-Ile-Pen-Tyr-Thr-Asn-Arg-Dab-Thr- D Dab-Lys-Dab-Dab-Cys-Tyr;(= Example 10); Val-Hyp-Ile-Cys-Tyr-Ser-Asn-Arg-Dab-Thr- D Dab-Lys-Dab-Dab-Cys-Tyr;(= Example 11); Val-Hyp-Ile-Cys-Tyr-Ser-Asn-Arg-Dab-Thr- D Dab-Lys-Dab-Dab-Pen-Tyr;(= Example 12); Val-Hyp-Ile-Pen-Ala-Ser-Asn-Arg-Dab-Thr- DDab-Lys-Dab-Dab-Cys-Tyr; (=Example 13); Val-Hyp-Ile-Pen-Ser-Ser-Asn-Arg-Dab-Thr- D Dab-Lys-Dab-Dab-Cys-Tyr; (=Example 14); Val-Hyp-Ile-Pen-Tyr-Thr-Asn-Arg-Dab-Thr- D Dab-Lys-Dab-Dab-Cys-Tyr; (=Example 15); Val-Hyp-Ile-Pen-Tyr-Ile-Asn-Arg-Dab-Thr- D Dab-Lys-Arg-Dab-Cys-Tyr; (=Example 16); Val-Hyp-Ile-Pen-Tyr-Glu-Asn-Arg-Dab-Thr- D Dab-Lys-Dab-Dab-Cys-Tyr; (=Example 17); Val-Hyp-Ile-Pen-Tyr-Asn-Asn-Arg-Dab-Thr- D Dab-Lys-Dab-Dab-Cys-Tyr; (=Example 18); Val-Hyp-Ile-Pen-Tyr-Thr-Asn-Arg-Dab-Asn- D Dab-Lys-Dab-Dab-Cys-Tyr; (=Example 19); Val-Hyp-Ile-Pen-Tyr-Ser-Ala-Arg-Dab-Thr- D Dab-Lys-Dab-Dab-Cys-Tyr; (=Example 20); Val-Hyp-Ile-Pen-Tyr-Ser-Ile-Arg-Dab-Thr- D Dab-Lys-Dab-Dab-Cys-Tyr; (=Example 21); Val-Hyp-Ile-Pen-Tyr-Ser-Glu-Arg-Dab-Thr- D Dab-Lys-Dab-Dab-Cys-Tyr; (=Example 22); Val-Hyp-Ile-Pen-Tyr-Ser-Asp-Arg-Dab-Thr- DDab-Lys-Dab-Dab-Cys-Tyr; (=Example 23); Val-Hyp-Ile-Pen-Tyr-Ser-Ser-Arg-Dab-Thr- D Dab-Lys-Dab-Dab-Cys-Tyr; (=Example 24); Val-Hyp-Ile-Pen-Tyr-Ser-Asn-Arg-Ala-Thr- D Dab-Lys-Dab-Dab-Cys-Tyr; (=Example 25); Val-Hyp-Ile-Pen-Tyr-Ser-Asn-Arg- D Dab-Thr- D Dab-Lys-Dab-Dab-Cys-Tyr; (=Example 26); Val-Hyp-Ile-Pen-Tyr-Ser-Asn-Arg-Cit-Thr- D Dab-Lys-Dab-Dab-Cys-Tyr; (=Example 27); Val-Hyp-Ile-Pen-Tyr-Ser-Asn-Arg-Asn-Thr- D Dab-Lys-Dab-Dab-Cys-Tyr; (=Example 28); Val-Hyp-Ile-Pen-Tyr-Ser-Asn-Arg-Ser-Thr- D Dab-Lys-Dab-Dab-Cys-Tyr; (=Example 29); Val-Hyp-Ile-Pen-Tyr-Ser-Asn-Arg-Agb-Thr- D Dab-Lys-Dab-Dab-Cys-Tyr; (=Example 30); Val-Hyp-Ile-Pen-Tyr-Ser-Asn-Arg-Dab-Asn- D Dab-Lys-Dab-Dab-Cys-Tyr; (=Example 31); Val-Hyp-Ile-Pen-Tyr-Dab-Asn-Arg-Dab-Ser- D Dab-Lys-Dab-Ser-Cys-Tyr; (=Example 32); Val-Hyp-Ile-Pen-Tyr-Ser-Asn-Arg-Dab-Ser- DDab-Lys-Dab-Dab-Cys-Tyr; (=Example 33); Val-Hyp-Ile-Pen-Tyr-Ser-Asn-Arg-Dab-Thr- D Lys-Lys-Dab-Dab-Cys-Tyr; (=Example 35); Val-Hyp-Ile-Pen-Tyr-Ser-Asn-Arg-Dab-Thr- D Arg-Lys-Dab-Dab-Cys-Tyr; (=Example 36); Val-Hyp-Ile-Pen-Tyr-Ser-Asn-Arg-Dab-Thr- D Cit-Lys-Dab-Dab-Cys-Tyr; (=Example 37); Val-Hyp-Ile-Pen-Tyr-Ser-Asn-Arg-Dab-Thr- D Dab(iPr)-Lys-Dab-Dab-Cys-Tyr; (=Example 38); Val-Hyp-Ile-Pen-Tyr-Ser-Asn-Arg-Dab-Thr- D Dab-Ala-Dab-Dab-Cys-Tyr; (=Example 39); Val-Hyp-Ile-Pen-Tyr-Ser-Asn-Arg-Dab-Thr- D Dab-Cit-Dab-Dab-Cys-Tyr; (=Example 40); Val-Hyp-Ile-Pen-Tyr-Ser-Asn-Arg-Dab-Thr- D Dab-Tyr-Dab-Dab-Cys-Tyr; (=Example 41); Val-Hyp-Ile-Pen-Tyr-Ser-Asn-Arg-Dab-Thr- D Dab-Ile-Dab-Dab-Cys-Tyr; (=Example 42); Val-Hyp-Ile-Pen-Tyr-Ser-Asn-Arg-Dab-Thr- D Dab-Asn-Dab-Dab-Cys-Tyr; (=Example 43); Val-Hyp-Ile-Pen-Tyr-Ser-Asn-Arg-Dab-Thr- DDab-Ser-Dab-Dab-Cys-Tyr; (=Example 44); Val-Hyp-Ile-Pen-Tyr-Dab-Asn-Arg-Dab-Thr- D Dab-Lys-Ser-Dab-Cys-Tyr; (=Example 45); Val-Hyp-Ile-Pen-Tyr-Ser-Asn-Arg-Dab-Thr- D Dab-Lys-Ala-Dab-Cys-Tyr; (=Example 46); Val-Hyp-Ile-Pen-Tyr-Ser-Asn-Arg-Dab-Thr- D Dab-Lys-Ser-Dab-Cys-Tyr; (=Example 47); Val-Hyp-Ile-Pen-Tyr-Dab-Asn-Arg-Dab-Thr- D Dab-Lys-Ser-Ser-Cys-Tyr; (=Example 48); Val-Hyp-Ile-Pen-Tyr-Dab-Asn-Arg-Dab-Thr- D Dab-Lys-Thr-Cit-Cys-Tyr; (=Example 49); Val-Hyp-Ile-Pen-Tyr-Dab-Asn-Arg-Dab-Thr- D Dab-Lys-Thr-Ile-Cys-Tyr; (=Example 50); Val-Hyp-Ile-Pen-Tyr-Dab-Asn-Arg-Dab-Thr- D Dab-Lys-Thr-Asn-Cys-Tyr; (=Example 51); Val-Hyp-Ile-Pen-Tyr-Dab-Asn-Arg-Dab-Thr- D Dab-Lys-Thr-Ser-Cys-Tyr; (=Example 52); Val-Hyp-Ile-Pen-Tyr-Ser-Asn-Arg-Dab-Thr- D Dab-Lys-Cit-Dab-Cys-Tyr; (=Example 53); Val-Hyp-Ile-Pen-Tyr-Ser-Asn-Arg-Dab-Thr- DDab-Lys-Arg-Dab-Cys-Tyr; (=Example 54); Val-Hyp-Ile-Pen-Tyr-Ser-Asn-Arg-Dab-Thr- D Dab-Lys-Orn-Ser-Cys-Tyr; (=Example 55); Val-Hyp-Ile-Pen-Tyr-Dab-Asn-Arg-Dab-Thr- D Dab-Lys-Dab-Ser-Cys-Tyr; (=Example 56); Val-Hyp-Ile-Pen-Tyr-Ser-Asn-Arg-Dab-Thr- D Dab-Lys-Dab-Ser-Cys-Tyr; (=Example 57); Val-Hyp-Ile-Pen-Tyr-Ser-Asn-Arg-Dab-Thr- D Dab-Lys-Dab- D Dab-Cys-Tyr; (=Example 58); Val-Hyp-Ile-Pen-Tyr-Ser-Asn-Arg-Dab-Thr- D Dab-Lys-Dab-Cit-Cys-Tyr; (=Example 59); Val-Hyp-Ile-Pen-Tyr-Ser-Asn-Arg-Dab-Thr- D Dab-Lys-Dab-Tyr-Cys-Tyr; (=Example 60); Val-Hyp-Ile-Pen-Tyr-Ser-Asn-Arg-Dab-Thr- D Dab-Lys-Dab-Asn-Cys-Tyr; (=Example 61); Val-Hyp-Ile-Pen-Tyr-Ser-Asn-Arg-Dab-Thr- D Dab-Lys-Dab-Lys-Cys-Tyr; (=Example 62); Val-Hyp-Ile-Pen-Tyr-Ser-Asn-Arg-Dab-Thr- D Dab-Lys-Dab-Dab(iPr)-Cys-Tyr; (=Example 63); Val-Hyp-Ile-Pen-Tyr-Ser-Asn-Arg-Dab-Thr-D Dab-Lys-Dab-Orn-Cys-Tyr; (=Example 64); Val-Hyp-Ile-Pen-Tyr-Ser-Asn-Arg-Dab-Thr- D Dab-Lys-Dab-Dab-Cys-Cha; (=Example 65); Val-Hyp-Ile-Pen-Tyr-Ser-Asn-Arg-Dab-Thr- D Dab-Lys-Dab-Dab-Cys-Trp; (=Example 66); Val-Hyp-Ile-Pen-Tyr-Ser-Asn-Arg-Dab-Thr- D Dab-Lys-Dab-Dab-Cys-Nle; (=Example 67); Gua-Val-Hyp-Ile-Pen-Tyr-Thr-Asn-Arg-Dab-Thr- D Dab-Lys-Dab-Dab-Cys-Tyr; (=Example 68); Gua-Val-Hyp-Ile-Pen-Tyr-Dab-Asn-Arg-Dab-Thr- D Dab-Lys-Ser-Dab-Cys-Tyr; (=Example 69); Gua-Val-Hyp-Ile-Pen-Tyr-Ser-Asn-Arg-Dab(iPr)-Thr- D Dab-Lys-Dab(iPr)-Dab-Cys-Tyr; (=Example 70); Gua-Val-Hyp-Ile-Pen-Tyr-Ser-Asn-Arg-Dab-Thr- D Dab(iPr)-Lys-Dab-Dab-Cys-Tyr; (=Example 71); Gua-Val-Hyp-Ile-Pen-Tyr-Dab-Asn-Arg-Dab-Thr- D Dab-Lys-Thr-Tyr-Cys-Tyr; (=Example 72); Gua-Val-Hyp-Ile-Pen-Tyr-Dab-Asn-Arg-Dab-Thr- D Dab-Lys-Thr-Ile-Cys-Tyr; (=Example 73); Gua-Val-Hyp-Ile-Pen-Tyr-Dab-Asn-Arg-Dab-Thr- D Dab-Lys-Thr-Ser-Cys-Tyr;(= Example 74); Gua-Val-Hyp-Ile-Pen-Tyr-Ser-Asn-Arg-Dab-Thr- D Dab-Lys-Dab-Agb-Cys-Tyr;(= Example 75); Gua-Abu-Hyp-Ile-Pen-Tyr-Ser-Asn-Arg-Dab-Thr- D Dab-Lys-Dab-Dab-Cys-Tyr;(= Example 76); Gua-Val-Hyp-Ile-Pen-Tyr-Ser-Asn-Arg-Dab-Thr- D Dab-Lys-Orn-Ser-Cys-Tyr;(= Example 77); Val-Hyp-Ile-Dab-Tyr-Ser-Asn-Arg-Dab-Thr- D Dab-Lys-Dab-Dab-Glu-Tyr;(= Example 78); Val-Hyp-Ile-Glu-Tyr-Ser-Asn-Arg-Dab-Thr- D Dab-Lys-Dab-Dab-Dab-Tyr;(= Example 79); Gua-Val-Hyp-Ile-Pen-Tyr-Thr-Asn-Arg-Dab-Ser- D Dab-Lys-Dab-Dab-Cys-Tyr;(= Example 80); Gua-Val-Hyp-Ile-Pen-Tyr-Thr-Asn-Arg-Dab-Thr- D Dab-Ser-Dab-Dab-Cys-Tyr;(= Example 81); Gua-Val-Hyp-Ile-Pen-Tyr-Thr-Asn-Arg-Dab-Ser- D Dab-Ser-Dab-Dab-Cys-Tyr;(= Example 82); Gua-Val-Hyp-Ile-Dab-Tyr-Ser-Asn-Arg-Dab-Thr- DDab-Lys-Dab-Dab-Glu-Tyr; (=Example 83); Gua-Val-Hyp-Ile-Dab-Tyr-Ser-Asn-Arg-Dab-Ser- D Dab-Lys-Dab-Dab-Glu-Tyr; (=Example 84); Gua-Val-Hyp-Ile-Dab-Tyr-Thr-Asn-Arg-Dab-Thr- D Dab-Lys-Dab-Dab-Glu-Tyr; (=Example 85); Gua-Val-Hyp-Ile-Dab-Tyr-Thr-Asn-Arg-Dab-Ser- D Dab-Lys-Dab-Dab-Glu-Tyr; (=Example 86); Gua-Val-Hyp-Ile-Glu-Tyr-Ser-Asn-Arg-Dab-Thr- D Dab-Lys-Dab-Dab-Dab-Tyr; (=Example 87); Gua-Val-Hyp-Ile-Glu-Tyr-Thr-Asn-Arg-Dab-Thr- D Dab-Lys-Dab-Dab-Dab-Tyr; (=Example 88); Gua-Val-Hyp-Ile-Glu-Tyr-Thr-Asn-Arg-Dab-Ser- D Dab-Lys-Dab-Dab-Dab-Tyr; (=Example 89); Gua-Val-Hyp-Ile-Pen-Tyr-Ser-Asn-Arg-Dab-Thr- D Dab-Thr-Dab-Dab-Cys-Tyr; (=Example 90); Gua-Val-Hyp-Ile-Pen-Tyr-Thr-Asn-Arg-Cit-Thr- D Dab-Lys-Dab-Dab-Cys-Y; (=Example 91); Gua-Val-Hyp-Ile-Pen-Tyr-Thr-Asn-Arg-Dab(iPr)-Thr- D Dab-Lys-Dab-Dab-Cys-Tyr; (=Example 92); Gua-Val-Hyp-Ile-Pen-Tyr-Thr-Asn-Arg-Dab(iPr)-Thr- D Dab-Ser-Dab-Dab-Cys-Tyr;(= Example 93); Gua-Val-Hyp-Ile-Pen-Tyr-Ser-Asn-Arg-Dab-Asn- D Dab-Lys-Dab-Dab-Cys-Tyr;(= Example 94); Gua-Val-Hyp-Ile-Pen-Tyr-Thr-Asn-Arg-Dab-Thr- D Dab(iPr)-Lys-Dab-Dab-Cys-Tyr;(= Example 95); Gua-Val-Hyp-Ile-Pen-Tyr-Thr-Asn-Arg-Dab-Thr- D Dab(iPr)-Ser-Dab-Dab-Cys-Tyr;(= Example 96); Gua-Val-Hyp-Ile-Pen-Tyr-Thr-Asn-Arg-Dab-Thr- D Dab-Cit-Dab-Dab-Cys-Tyr;(= Example 97); Gua-Val-Hyp-Ile-Pen-Tyr-Thr-Asn-Arg-Dab-Thr- D Dab-Lys-Dab-Cit-Cys-Tyr;(= Example 98); Gua-Val-Hyp-Ile-Pen-Tyr-Ser-Asn-Arg-Dab-Thr- D Dab-Ser-Dab-Dab-Cys-Tyr;(= Example 99); Gua-Val-Hyp-Ile-Pen-Tyr-Thr-Asn-Arg-Dab-Thr- D Dab-Ser-Dab-Orn-Cys-Tyr;(= Example 100); Gua-Val-Hyp-Ile-Pen-Tyr-Dab-Asn-Arg-Dab-Thr- D Dab-Lys-Thr-Dab-Cys-Tyr;(= Example 101); Gua-Val-Hyp-Ile-Pen-Tyr-Dab-Asn-Arg-Dab-Thr- DDab-Ser-T-Dab-Cys-Tyr; (=Example 102); Gua-Val-Hyp-Ile-Pen-Tyr-Thr-Asn-Arg- D Dab-Thr- D Dab-Ser-Dab-Dab-Cys-Tyr; (=Example 103); Gua-Val-Hyp-Ile-Pen-Tyr-Ser-Asn-Arg- D Dab-Thr- D Dab-Ser-Dab-Dab-Cys-Tyr; (=Example 104); Gua-Val-Hyp-Ile-Pen-Tyr-Thr-Asn-Arg-Dab-Thr- D Dab-Asn-Dab-Dab-Cys-Tyr; (=Example 105); Gua-Val-Hyp-Ile-Pen-Tyr-Ser-Asn-Arg-Dab-Thr- D Dab-Cit-Dab-Dab-Cys-Tyr; (=Example 106); Gua-Val-Hyp-Ile-Pen-Tyr-Ser-Asn-Arg-Dab-Thr- D Dab-Asn-Dab-Dab-Cys-Tyr; (=Example 107); Gua-Val-Hyp-Ile-Pen-Tyr-Thr-Asn-Arg-Dab-Thr- D Dab-Lys-Dab-S-Cys-Tyr; (=Example 108); Gua-Val-Pro(3,4 dehydro)-Ile-Pen-Tyr-Thr-Asn-Arg-Dab-Thr- D Dab-Lys-Dab-Dab-Cys-Tyr; (=Example 109); Gua-Val-Pro(3,4 dehydro)-Ile-Pen-Tyr-Ser-Asn-Arg-Dab-Thr- D Dab-Lys-Dab-Dab-Cys-Tyr; (=Example 110); Gua-Val-Pro(3,4 dehydro)-Ile-Pen-Tyr-Thr-Asn-Arg-Dab-Thr- DDab-Ser-Dab-Dab-Cys-Tyr; (=Example 111); Gua-Val-Hyp-Ile-Dab-Tyr-Thr-Asn-Arg-Dab-Thr- D Dab-Ser-Dab-Dab-Glu-Tyr; (=Example 112); Gua-Val-Hyp-Ile-Dab-Tyr-Thr-Asn-Arg-Dab-Thr- D Dab-Thr-Dab-Dab-Glu-Tyr; (=Example 113); Gua-Val-Hyp-Ile-Dab-Tyr-Thr-Asn-Arg-Dab-Thr- D Dab-Cit-Dab-Dab-Glu-Tyr; (=Example 114); Gua-Val-Hyp-Ile-Pen-Tyr-Cit-Asn-Arg-Dab-Thr- D Dab-Lys-Dab-Dab-Cys-Tyr; (=Example 115); Gua-Val-Hyp-Ile-Dab-Tyr-Cit-Asn-Arg-Dab-Thr- D Dab-Lys-Dab-Dab-Glu-Tyr; (=Example 116); Gua-Val-Hyp-Ile-Pen-Tyr-Hse-Asn-Arg-Dab-Thr- D Dab-Lys-Dab-Dab-Cys-Tyr; (=Example 117); Gua-Val-Hyp-Ile-Dab-Tyr-Hse-Asn-Arg-Dab-Thr- D Dab-Lys-Dab-Dab-Glu-Tyr; (=Example 118); Gua-Val-Hyp-Ile-Dab-Tyr-Thr-Asn-Arg-Dab-Thr- D Dab-Orn-Dab-Dab-Glu-Tyr; (=Example 119); Gua-Val-Hyp-Ile-Pen-Tyr-Dab-Asn-Arg-Dab-Thr- D Dab-Dab-Thr-Dab-Cys-Tyr; (=Example 120); Gua-Val-Hyp-Ile-Pen-Tyr-Dab-Asn-Arg-Dab-Thr- D Dab-Orn-Thr-Dab-Cys-Tyr;(= Example 121); Gua-Val-Hyp-Ile-Pen-Tyr-Cit-Asn-Arg-Dab-Thr- D Dab-Ser-Dab-Dab-Cys-Tyr;(= Example 122); Gua-Val-Hyp-Ile-Pen-Tyr-Thr-Asn-Arg-Dab-Thr- D Dab-Dab-Dab-Dab-Cys-Tyr;(= Example 123); Gua-Val-Hyp-Ile-Pen-Tyr-Thr-Asn-Arg-Dab-Thr- D Dab-Orn-Dab-Dab-Cys-Tyr;(= Example 124); Gua-Val-Hyp-Ile-Pen-Tyr-Ser-Asn-Arg-Dab-Thr- D Dab-Dab-Dab-Dab-Cys-Tyr;(= Example 125); Gua-Val-Hyp-Ile-Pen-Tyr-Ser-Asn-Arg-Dab-Thr- D Dab-Orn-Dab-Dab-Cys-Tyr;(= Example 126); Gua-Val-Hyp-Ile-Pen-Tyr-Thr-Asn-Arg-Dab-Thr- D Dab-Dab-Dab-Ser-Cys-Tyr;(= Example 127); Gua-Val-Hyp-Ile-Pen-Tyr-Thr-Asn-Arg-Dab-Thr- D Dab-Orn-Dab-Ser-Cys-Tyr;(= Example 128); Gua-Val-Hyp-Ile-Pen-Tyr-Dab-Asn-Arg-Dab-Thr- D Dab-Dab-Thr-Ser-Cys-Tyr;(= Example 129); Gua-Val-Hyp-Ile-Pen-Tyr-Dab-Asn-Arg-Dab-Thr- DDab-Orn-Thr-Ser-Cys-Tyr; (= Example 130); Gua-Val-Hyp-I-Pen-Tyr-Thr-Asn-Arg-Dab-Thr- D Dab-Lys-Dab-Thr-Cys-Tyr; (= Example 131); Gua-Val-Hyp-Ile-Pen-Tyr-Thr-Asn-Arg-Dab-Thr- D Dab-Dab-Dab-Thr-Cys-Tyr; (= Example 132); Gua-Val-Hyp-Ile-Pen-Tyr-Thr-Asn-Arg-Dab-Thr- D Dab-Orn-Dab-Thr-Cys-Tyr; (= Example 133); Gua-Val-Hyp-Cpg-Pen-Tyr-Thr-Asn-Arg-Dab-Thr- D Dab-Ser-Dab-Dab-Cys-Tyr; (= Example 134); Gua-Val-Hyp-Ile-Dab-Tyr-Thr-Asn-Arg-Dab-Thr- D Dab-Dab-Dab-Dab-Glu-Tyr; (= Example 135); Gua-Val-Hyp-Ile-Dab-Tyr-Thr-Asn-Arg-Dab-Thr- D Dab-Val-Dab-Dab-Glu-Tyr; (= Example 136) A compound selected from the group consisting of: If present, P 4 Cys or Pen in the formula (I) and, if present, P 15 Cys or Pen in the formula (I) is optionally P 4 and P 15 or If present, P 4 Glu in and, if present, P 15 Dab in optionally P 4 and P 15 or forming a lactam bridge between If present, P 4Dab in and, if present, P 15 Glu in the formula (I) is optionally selected from the group consisting of P 4 and P 15 or a tautomer, rotamer, salt, hydrate or solvate thereof, which forms a lactam bridge between

[0024] Another further particularly preferred embodiment of the first aspect comprises Val-Hyp-Ile-Pen-Tyr-Ser-Asn-Arg-Dab-Thr- D Dab-Lys-Dab-Dab-Cys-Tyr; (= Example 1); Abu-Hyp-Ile-Pen-Tyr-Ser-Asn-Arg-Dab-Thr- D Dab-Lys-Dab-Dab-Cys-Tyr; (= Example 2); tBuGly-Hyp-Ile-Pen-Tyr-Ser-Asn-Arg-Dab-Thr- D Dab-Lys-Dab-Dab-Cys-Tyr; (= Example 3); Val-Pro-Ile-Pen-Tyr-Ser-Asn-Arg-Dab-Thr- D Dab-Lys-Dab-Dab-Cys-Tyr; (= Example 4); Val-Pro-Ile-Pen-Tyr-Thr-Asn-Arg-Dab-Thr- D Dab-Lys-Dab-Dab-Cys-Tyr; (= Example 5); Val-Pro((4R)OMe)-Ile-Pen-Tyr-Thr-Asn-Arg-Dab-Thr- D Dab-Lys-Dab-Dab-Cys-Tyr; (= Example 6); Val-Pro((4S)F)-Ile-Pen-Tyr-Thr-Asn-Arg-Dab-Thr- D Dab-Lys-Dab-Dab-Cys-Tyr; (= Example 7); Val-Pro((4R)F)-Ile-Pen-Tyr-Thr-Asn-Arg-Dab-Thr- D Dab-Lys-Dab-Dab-Cys-Tyr; (= Example 8); Val-Pro(4,4F2)-Ile-Pen-Tyr-Thr-Asn-Arg-Dab-Thr- D Dab-Lys-Dab-Dab-Cys-Tyr;(= Example 9); Val-Pro(3,4 dehydro)-Ile-Pen-Tyr-Thr-Asn-Arg-Dab-Thr- D Dab-Lys-Dab-Dab-Cys-Tyr;(= Example 10); Val-Hyp-Ile-Cys-Tyr-Ser-Asn-Arg-Dab-Thr- D Dab-Lys-Dab-Dab-Cys-Tyr;(= Example 11); Val-Hyp-Ile-Cys-Tyr-Ser-Asn-Arg-Dab-Thr- D Dab-Lys-Dab-Dab-Pen-Tyr;(= Example 12); Val-Hyp-Ile-Pen-Ala-Ser-Asn-Arg-Dab-Thr- D Dab-Lys-Dab-Dab-Cys-Tyr;(= Example 13); Val-Hyp-Ile-Pen-Ser-Ser-Asn-Arg-Dab-Thr- D Dab-Lys-Dab-Dab-Cys-Tyr;(= Example 14); Val-Hyp-Ile-Pen-Tyr-Thr-Asn-Arg-Dab-Thr- D Dab-Lys-Dab-Dab-Cys-Tyr;(= Example 15); Val-Hyp-Ile-Pen-Tyr-Ile-Asn-Arg-Dab-Thr- D Dab-Lys-Arg-Dab-Cys-Tyr;(= Example 16); Val-Hyp-Ile-Pen-Tyr-Glu-Asn-Arg-Dab-Thr- D Dab-Lys-Dab-Dab-Cys-Tyr;(= Example 17); Val-Hyp-Ile-Pen-Tyr-Asn-Asn-Arg-Dab-Thr- DDab-Lys-Dab-Dab-Cys-Tyr; (=Example 18); Val-Hyp-Ile-Pen-Tyr-Thr-Asn-Arg-Dab-Asn- D Dab-Lys-Dab-Dab-Cys-Tyr; (=Example 19); Val-Hyp-Ile-Pen-Tyr-Ser-Ala-Arg-Dab-Thr- D Dab-Lys-Dab-Dab-Cys-Tyr; (=Example 20); Val-Hyp-Ile-Pen-Tyr-Ser-Ile-Arg-Dab-Thr- D Dab-Lys-Dab-Dab-Cys-Tyr; (=Example 21); Val-Hyp-Ile-Pen-Tyr-Ser-Glu-Arg-Dab-Thr- D Dab-Lys-Dab-Dab-Cys-Tyr; (=Example 22); Val-Hyp-Ile-Pen-Tyr-Ser-Asp-Arg-Dab-Thr- D Dab-Lys-Dab-Dab-Cys-Tyr; (=Example 23); Val-Hyp-Ile-Pen-Tyr-Ser-Ser-Arg-Dab-Thr- D Dab-Lys-Dab-Dab-Cys-Tyr; (=Example 24); Val-Hyp-Ile-Pen-Tyr-Ser-Asn-Arg-Ala-Thr- D Dab-Lys-Dab-Dab-Cys-Tyr; (=Example 25); Val-Hyp-Ile-Pen-Tyr-Ser-Asn-Arg- D Dab-Thr- D Dab-Lys-Dab-Dab-Cys-Tyr; (=Example 26); Val-Hyp-Ile-Pen-Tyr-Ser-Asn-Arg-Cit-Thr- D Dab-Lys-Dab-Dab-Cys-Tyr; (=Example 27); Val-Hyp-Ile-Pen-Tyr-Ser-Asn-Arg-Asn-Thr- DDab-Lys-Dab-Dab-Cys-Tyr; (=Example 28); Val-Hyp-Ile-Pen-Tyr-Ser-Asn-Arg-Ser-Thr- D Dab-Lys-Dab-Dab-Cys-Tyr; (=Example 29); Val-Hyp-Ile-Pen-Tyr-Ser-Asn-Arg-Agb-Thr- D Dab-Lys-Dab-Dab-Cys-Tyr; (=Example 30); Val-Hyp-Ile-Pen-Tyr-Ser-Asn-Arg-Dab-Asn- D Dab-Lys-Dab-Dab-Cys-Tyr; (=Example 31); Val-Hyp-Ile-Pen-Tyr-Dab-Asn-Arg-Dab-Ser- D Dab-Lys-Dab-Ser-Cys-Tyr; (=Example 32); Val-Hyp-Ile-Pen-Tyr-Ser-Asn-Arg-Dab-Ser- D Dab-Lys-Dab-Dab-Cys-Tyr; (=Example 33); Val-Hyp-Ile-Pen-Tyr-Ser-Asn-Arg-Dab-Thr- D Lys-Lys-Dab-Dab-Cys-Tyr; (=Example 35); Val-Hyp-Ile-Pen-Tyr-Ser-Asn-Arg-Dab-Thr- D Arg-Lys-Dab-Dab-Cys-Tyr; (=Example 36); Val-Hyp-Ile-Pen-Tyr-Ser-Asn-Arg-Dab-Thr- D Cit-Lys-Dab-Dab-Cys-Tyr; (=Example 37); Val-Hyp-Ile-Pen-Tyr-Ser-Asn-Arg-Dab-Thr- D Dab(iPr)-Lys-Dab-Dab-Cys-Tyr; (=Example 38); Val-Hyp-Ile-Pen-Tyr-Ser-Asn-Arg-Dab-Thr- DDab-Ala-Dab-Dab-Cys-Tyr; (=Example 39); Val-Hyp-Ile-Pen-Tyr-Ser-Asn-Arg-Dab-Thr- D Dab-Cit-Dab-Dab-Cys-Tyr; (=Example 40); Val-Hyp-Ile-Pen-Tyr-Ser-Asn-Arg-Dab-Thr- D Dab-Tyr-Dab-Dab-Cys-Tyr; (=Example 41); Val-Hyp-Ile-Pen-Tyr-Ser-Asn-Arg-Dab-Thr- D Dab-Ile-Dab-Dab-Cys-Tyr; (=Example 42); Val-Hyp-Ile-Pen-Tyr-Ser-Asn-Arg-Dab-Thr- D Dab-Asn-Dab-Dab-Cys-Tyr; (=Example 43); Val-Hyp-Ile-Pen-Tyr-Ser-Asn-Arg-Dab-Thr- D Dab-Ser-Dab-Dab-Cys-Tyr; (=Example 44); Val-Hyp-Ile-Pen-Tyr-Dab-Asn-Arg-Dab-Thr- D Dab-Lys-Ser-Dab-Cys-Tyr; (=Example 45); Val-Hyp-Ile-Pen-Tyr-Ser-Asn-Arg-Dab-Thr- D Dab-Lys-Ala-Dab-Cys-Tyr; (=Example 46); Val-Hyp-Ile-Pen-Tyr-Ser-Asn-Arg-Dab-Thr- D Dab-Lys-Ser-Dab-Cys-Tyr; (=Example 47); Val-Hyp-Ile-Pen-Tyr-Dab-Asn-Arg-Dab-Thr- D Dab-Lys-Ser-Ser-Cys-Tyr; (=Example 48); Val-Hyp-Ile-Pen-Tyr-Dab-Asn-Arg-Dab-Thr- DDab-Lys-Thr-Cit-Cys-Tyr; (=Example 49); Val-Hyp-Ile-Pen-Tyr-Dab-Asn-Arg-Dab-Thr- D Dab-Lys-Thr-Ile-Cys-Tyr; (=Example 50); Val-Hyp-Ile-Pen-Tyr-Dab-Asn-Arg-Dab-Thr- D Dab-Lys-Thr-Asn-Cys-Tyr; (=Example 51); Val-Hyp-Ile-Pen-Tyr-Dab-Asn-Arg-Dab-Thr- D Dab-Lys-Thr-Ser-Cys-Tyr; (=Example 52); Val-Hyp-Ile-Pen-Tyr-Ser-Asn-Arg-Dab-Thr- D Dab-Lys-Cit-Dab-Cys-Tyr; (=Example 53); Val-Hyp-Ile-Pen-Tyr-Ser-Asn-Arg-Dab-Thr- D Dab-Lys-Arg-Dab-Cys-Tyr; (=Example 54); Val-Hyp-Ile-Pen-Tyr-Ser-Asn-Arg-Dab-Thr- D Dab-Lys-Orn-Ser-Cys-Tyr; (=Example 55); Val-Hyp-Ile-Pen-Tyr-Dab-Asn-Arg-Dab-Thr- D Dab-Lys-Dab-Ser-Cys-Tyr; (=Example 56); Val-Hyp-Ile-Pen-Tyr-Ser-Asn-Arg-Dab-Thr- D Dab-Lys-Dab-Ser-Cys-Tyr; (=Example 57); Val-Hyp-Ile-Pen-Tyr-Ser-Asn-Arg-Dab-Thr- D Dab-Lys-Dab- D Dab-Cys-Tyr; (=Example 58); Val-Hyp-Ile-Pen-Tyr-Ser-Asn-Arg-Dab-Thr- DDab-Lys-Dab-Cit-Cys-Tyr; (=Example 59); Val-Hyp-Ile-Pen-Tyr-Ser-Asn-Arg-Dab-Thr- D Dab-Lys-Dab-Tyr-Cys-Tyr; (=Example 60); Val-Hyp-Ile-Pen-Tyr-Ser-Asn-Arg-Dab-Thr- D Dab-Lys-Dab-Asn-Cys-Tyr; (=Example 61); Val-Hyp-Ile-Pen-Tyr-Ser-Asn-Arg-Dab-Thr- D Dab-Lys-Dab-Lys-Cys-Tyr; (=Example 62); Val-Hyp-Ile-Pen-Tyr-Ser-Asn-Arg-Dab-Thr- D Dab-Lys-Dab-Dab(iPr)-Cys-Tyr; (=Example 63); Val-Hyp-Ile-Pen-Tyr-Ser-Asn-Arg-Dab-Thr- D Dab-Lys-Dab-Orn-Cys-Tyr; (=Example 64); Val-Hyp-Ile-Pen-Tyr-Ser-Asn-Arg-Dab-Thr- D Dab-Lys-Dab-Dab-Cys-Cha; (=Example 65); Val-Hyp-Ile-Pen-Tyr-Ser-Asn-Arg-Dab-Thr- D Dab-Lys-Dab-Dab-Cys-Trp; (=Example 66); Val-Hyp-Ile-Pen-Tyr-Ser-Asn-Arg-Dab-Thr- D Dab-Lys-Dab-Dab-Cys-Nle; (=Example 67); Gua-Val-Hyp-Ile-Pen-Tyr-Thr-Asn-Arg-Dab-Thr- D Dab-Lys-Dab-Dab-Cys-Tyr; (=Example 68); Gua-Val-Hyp-Ile-Pen-Tyr-Dab-Asn-Arg-Dab-Thr- DDab-Lys-Ser-Dab-Cys-Tyr; (=Example 69); Gua-Val-Hyp-Ile-Pen-Tyr-Ser-Asn-Arg-Dab(iPr)-Thr- D Dab-Lys-Dab(iPr)-Dab-Cys-Tyr; (=Example 70); Gua-Val-Hyp-Ile-Pen-Tyr-Ser-Asn-Arg-Dab-Thr- D Dab(iPr)-Lys-Dab-Dab-Cys-Tyr; (=Example 71); Gua-Val-Hyp-Ile-Pen-Tyr-Dab-Asn-Arg-Dab-Thr- D Dab-Lys-Thr-Tyr-Cys-Tyr; (=Example 72); Gua-Val-Hyp-Ile-Pen-Tyr-Dab-Asn-Arg-Dab-Thr- D Dab-Lys-Thr-Ile-Cys-Tyr; (=Example 73); Gua-Val-Hyp-Ile-Pen-Tyr-Dab-Asn-Arg-Dab-Thr- D Dab-Lys-Thr-Ser-Cys-Tyr; (=Example 74); Gua-Val-Hyp-Ile-Pen-Tyr-Ser-Asn-Arg-Dab-Thr- D Dab-Lys-Dab-Agb-Cys-Tyr; (=Example 75); Gua-Abu-Hyp-Ile-Pen-Tyr-Ser-Asn-Arg-Dab-Thr- D Dab-Lys-Dab-Dab-Cys-Tyr; (=Example 76); Gua-Val-Hyp-Ile-Pen-Tyr-Ser-Asn-Arg-Dab-Thr- D Dab-Lys-Orn-Ser-Cys-Tyr; (=Example 77); Val-Hyp-Ile-Dab-Tyr-Ser-Asn-Arg-Dab-Thr- D Dab-Lys-Dab-Dab-Glu-Tyr; (=Example 78); Val-Hyp-Ile-Glu-Tyr-Ser-Asn-Arg-Dab-Thr- D Dab-Lys-Dab-Dab-Dab-Tyr; (= Example 79) A compound selected from the group consisting of: If present, P 4 Cys or Pen in 15 Cys or Pen in the formula (I) is optionally P 4 and P 15 or If present, P 4 Glu in and, if present, P 15 Dab in optionally P 4 and P 15 or forming a lactam bridge between If present, P 4 Dab in and, if present, P 15 Glu in the formula (I) is optionally selected from the group consisting of P 4 and P 15 or a tautomer, rotamer, salt, hydrate or solvate thereof, which forms a lactam bridge between

[0025] Further embodiments of the first aspect include compounds identical to compounds of formula (I) except that one or more atoms are replaced by atoms having an atomic mass number or mass different from the atomic mass number or mass normally found in nature, e.g. 2 H(D), 3 H, 11 C. 14 C. 127 Such isotopically substituted analogs and pharmaceutical salts and formulations thereof are believed to be useful therapeutic and / or diagnostic agents, for example, but not limited to, where administration regimes can be optimized by fine tuning in vivo half-life.

[0026] In a second aspect, the present invention relates to an enantiomer of a compound of formula (I) according to the first aspect.

[0027] Below is a list of abbreviations which, according to commonly accepted convention, are used for the abbreviations of amino acids or derivatives thereof mentioned herein or whose residues are suitable for the purposes of the present invention.

[0028] Although amino acids or derivatives thereof have been specifically identified, it should be noted that those skilled in the art will appreciate that functional analogs having similar biological activity can be obtained from derivatives having similar structural and physicochemical properties to these amino acids or derivatives thereof, and therefore these also form part of the spirit of the present invention. Ala A L-Alanine Arg R L-Arginine D Arg D-Arginine Asn N L-Asparagine Asp D L-Aspartic acid Cys C L-Cysteine Gln Q L-Glutamine Glu E L-Glutamic Acid Gly Glycine His H L-histidine Ile I L-Isoleucine Leu L L-Leucine Lys K L-Lysine D Lys D-Lysine Met M L-Methionine Phe F L-Phenylalanine Pro P L-Proline Ser S L-Serine Thr T L-Threonine Trp W L-tryptophan Tyr Y L-Tyrosine Val V L-Valine 2OHVal (S)-2-hydroxy-3-methylbutanoic acid Ala(cPr) (S)-2-amino-3-cyclopropylpropanoic acid Ala(tetrahydropyran-4-yl) (S)-2-amino-3-(tetrahydro-2H-pyran-4-yl)propanoic acid Abu (S)-2-aminobutanoic acid Gua-Abu (S)-2-Guanidinobutanoic acid alloIle L-Alloisoleucine betaGly 3-aminopropanoic acid Cha (S)-2-amino-3-cyclohexylpropanoic acid Cpa (S)-2-amino-3-cyclopentylpropanoic acid Cpg (S)-2-amino-2-cyclopentylacetic acid Cyg (S)-2-amino-2-cyclopropylacetic acid Dea (S)-2-amino-3-ethylpentanoic acid Hle (S)-2-amino-5-methylhexanoic acid Nle (S)-2-aminohexanoic acid OctGly (S)-2-aminodecanoic acid Sar N-Methylglycine tBuGly (S)-2-amino-3,3-dimethylbutanoic acid tBuAla (S)-2-amino-4,4-dimethylpentanoic acid NMeAla N-Methyl-L-alanine NMeVal N-methyl-L-valine Gua-Val N-Amidino-L-Valine TMG-Val (S)-2-(N,N,N',N'-tetramethylguanidino)-propanoic acid Nva (S)-2-aminopentanoic acid Pro((4R)F) (2S,4R)-4-fluoropyrrolidine-2-carboxylic acid Pro((4S)F) (2S,4S)-4-fluoropyrrolidine-2-carboxylic acid Pro(4,4F2) (S)-4,4-difluoropyrrolidine-2-carboxylic acid Pro((4R)OMe) (2S,4R)-4-Methoxypyrrolidine-2-carboxylic acid Pro(3,4 dehydro) (S)-2,5-dihydro-1H-pyrrole-2-carboxylic acid Phe(3OH) (S)-2-amino-3-(3-hydroxyphenyl)propanoic acid Phe(4F) (S)-2-amino-3-(4-fluorophenyl)propanoic acid Phe(4OCF3) (S)-2-amino-3-(4-(trifluoromethoxy)phenyl)propanoic acid Trp(6Cl) (S)-2-amino-3-(6-chloro-1H-indol-3-yl)propanoic acid Tyr(3Cl) (S)-2-amino-3-(3-chloro-4-hydroxyphenyl)propanoic acid Tyr(3F) (S)-2-amino-3-(3-fluoro-4-hydroxyphenyl)propanoic acid Tyr(phenyl) (S)-2-amino-3-(4-phenoxyphenyl)propanoic acid 4Thz (R)-Thiazolidine-4-carboxylic acid Phe(4(4-hydroxyphenoxy)) (S)-2-amino-3-(4-(4-hydroxyphenoxy)phenyl)propanoic acid Phe(4NH2) (S)-2-amino-3-(4-aminophenyl)propanoic acid Tyr(Me) (S)-2-amino-3-(4-methoxyphenyl)propanoic acid Ntyr N-(4-hydroxybenzyl)glycine Nphe N-(benzyl)glycine Agb (S)-2-amino-4-guanidinobutanoic acid Agp (S)-2-amino-3-guanidinopropanoic acid Dab (S)-2,4-diaminobutanoic acid D Dab (R)-2,4-diaminobutanoic acid Dab(iPr) (S)-2-amino-4-(isopropylamino)butanoic acid Dap (S)-2,3-diaminopropanoic acid Dap(iPr) (S)-2-amino-3-(isopropylamino)propanoic acid Har N6-Carbamimidoyl-L-lysine Lys(iPr) N6-isopropyl-L-lysine Narg N-(3-guanidinopropyl)glycine Ndab N-(2-aminoethyl)glycine Nlys N-(4-aminobutyl)glycine Norn N-(3-aminopropyl)glycine Orn (S)-2,5-diaminopentanoic acid Orn(iPr) (S)-2-amino-5-(isopropylamino)pentanoic acid Pro((4R)guanidine (2S,4R)-4-guanidinopyrrolidine-2-carboxylic acid Pro((4R)NH2) (2S,4R)-4-aminopyrrolidine-2-carboxylic acid Pro((4S)NH2) (2S,4S)-4-aminopyrrolidine-2-carboxylic acid NMeLys Nα-methyl-L-lysine alloThr L-AlloThreonine Cit (S)-2-amino-5-ureidopentanoic acid D Cit (R)-2-amino-5-ureidopentanoic acid Hgn (S)-2,6-diamino-6-oxohexanoic acid Hse L-Homoserine Hyp (2S,4R)-4-Hydroxypyrrolidine-2-carboxylic acid Leu((3R)OH) (2S,3R)-2-amino-3-hydroxy-4-methylpentanoic acid Hgl (S)-2-aminohexanedioic acid Pra L-Propargylglycine Abu(4N3) (S)-2-amino-4-azidobutanoic acid Hcy L-Homocysteine NMeCys N-methyl-L-cysteine Pen (R)-2-amino-3-mercapto-3-methylbutanoic acid.

[0029] Abbreviations for D isomers, e.g. D Lys corresponds to the epimer at position 2 of the corresponding amino acid listed above.

[0030] In the above list, the abbreviation "Gua-" followed by the abbreviation of the amino acid or amino acid residue corresponds to an N-amidinylated amino acid or amino acid residue in which the N-terminal amino group is replaced by a guanidino (Gua) group, e.g., Gua-Glu N-amidino-L-glutamic acid, (S)-2-guanidino-pentanedioic acid, etc.

[0031] In the above list, the abbreviation "TMG-" followed by the abbreviation of the amino acid or amino acid residue corresponds to an amino acid or amino acid residue in which the N-terminal amino group has been replaced by N,N,N',N'-tetramethylguanidino (TMG), such as TMG-Trp (S)-2-(N,N,N',N'-tetramethylguanidino)-3-(1H-indol-3-yl)propanoic acid.

[0032] In a third aspect, the present invention relates to a pharmaceutical composition comprising a compound or a mixture of compounds according to the first aspect and at least one pharma- ceutically inert carrier.

[0033] In one embodiment of the third aspect, the pharmaceutical composition is in a form suitable for oral, topical, transdermal, injectable, buccal, transmucosal, rectal, pulmonary or inhalation administration. In a further embodiment of the third aspect, the pharmaceutical composition is in the form of a tablet, dragee, capsule, solution, liquid, gel, plaster, cream, ointment, syrup, slurry, suspension, spray, nebulizer, aerosol or suppository.

[0034] In a fourth aspect, the present invention relates to a compound of formula (I) according to the first aspect or a pharma- ceutically acceptable salt thereof.

[0035] In a fifth aspect, the present invention relates to a compound of formula (I) or a pharma- ceutically acceptable salt thereof according to the first aspect, for use as a medicament.

[0036] In a sixth aspect, the present invention relates to a compound according to the first aspect for use as a medicament active substance having antibiotic activity.

[0037] In a seventh aspect, the present invention relates to the use of a compound according to the first aspect for the manufacture of a medicament for the treatment or prevention of an infection or a disease associated with such an infection; in particular an infection associated with a respiratory disease, or a skin or soft tissue disease, or a gastrointestinal disease, or an eye disease, or an ear disease, or a CNS disease, or a bone disease, or a cardiovascular disease, or a genitourinary disease, or a hospital-acquired infection, or a catheter-associated and non-catheter-associated infection, or a urinary tract infection, or a bloodstream infection; or sepsis induced by an infection.

[0038] In an eighth aspect, the present invention relates to the use of a compound according to the first aspect as a disinfectant or preservative for food, cosmetic, pharmaceutical and / or other nutrient-containing materials.

[0039] In a ninth embodiment, the invention relates to the use of a compound according to the first aspect as a medicament active substance having antibiotic activity.

[0040] In a tenth aspect, the invention relates to the use of a compound according to the first aspect or a composition according to the third aspect for treating or preventing an infection or a disease associated with such an infection; in particular an infection associated with a respiratory disease, or a skin or soft tissue disease, or a gastrointestinal disease, or an eye disease, or an ear disease, or a CNS disease, or a bone disease, or a cardiovascular disease, or a genitourinary disease, or a hospital-acquired infection, or a catheter-associated and non-catheter-associated infection, or a urinary tract infection, or a bloodstream infection; or sepsis induced by an infection.

[0041] In an eleventh aspect, the present invention relates to the use of a compound according to the first aspect or a composition according to the third aspect as a disinfectant or preservative for food, cosmetic, pharmaceutical and / or other nutrient-containing materials.

[0042] In a twelfth aspect, the present invention relates to a method for treating an infection, particularly an infection or an infection-related disease or disorder such as hospital-acquired infections, catheter-associated and non-catheter-associated infections, urinary tract infections, bloodstream infections, in particular a disease or disorder such as ventilator-associated pneumonia (VAP), ventilator-associated bacterial pneumonia (VABP), hospital-acquired pneumonia (HAP), hospital-acquired bacterial pneumonia (HABP), healthcare-associated pneumonia (HCAP), cystic fibrosis, emphysema, asthma, pneumonia, infectious diarrhea, necrotizing enterocolitis, appendicitis, gastroenteritis, pancreatitis, keratitis, endophthalmitis, otitis, brain abscess, meningitis, encephalitis, osteochondritis, pericarditis, epididymitis, prostatitis, urethritis, sepsis; surgical wounds, traumatic wounds, burns, the method comprising administering to a subject in need thereof a pharma- ceutically acceptable or therapeutically effective amount of a compound or mixture of compounds according to the first aspect or a therapeutically effective amount of a pharmaceutical composition according to the third aspect.

[0043] In a thirteenth aspect, the present invention provides a process for preparing a compound according to the first aspect, comprising the steps of: (a) Attaching an appropriately functionalized solid support to a position P 16 with a suitably N-protected derivative of an amino acid in (b) removing the N-protecting groups from the product thus obtained; (c) The product thus obtained is substituted with a compound having a position P 15 with a suitably N-protected derivative of an amino acid in (d) At position P in the desired final product 14 ~P 4 carrying out steps substantially corresponding to steps (b) and (c) using a suitably N-protected derivative of an amino acid in (e) optionally, selectively deprotecting one or several protected functional groups present in the molecule and chemically transforming the reactive groups thus liberated; (f) At position P in the desired final product 3 ~P 2 carrying out steps substantially corresponding to steps (b) and (c) using a suitably N-protected derivative of the amino acid in (g) At position P in the desired final product 1 further carrying out steps substantially corresponding to (b) and (c) using a suitably N-protected derivative of an amino acid in (a) or optionally a suitably protected derivative of a hydroxy acid in (b), where any functional groups that may be present in said N-protected amino acid derivative or hydroxy acid derivative are likewise suitably protected, and optionally, following the coupling, selectively deprotecting one or several protected functional groups present in the molecule and chemically transforming the reactive groups thus liberated; (h) optionally, selectively deprotecting one or several protected functional groups present in the molecule and chemically transforming the reactive groups thus liberated; (i) optionally, at a position P 1 and removing the N-protecting group in (j) cleaving the product thus obtained from the solid support; (k) optionally, selectively deprotecting one or several protected functional groups present in the molecule and chemically transforming the reactive groups thus liberated; (l) removing any protecting groups present on the functional groups of any of the constituents of the chain of residues and, optionally, any protecting groups that may additionally be present in the molecule; (m) optionally carrying out additional chemical transformations of one or more reactive groups present in the molecule; (n) optionally removing any protecting groups present on the functional groups of any of the constituents of the chain of residues and, optionally, any protecting groups that may additionally be present in the molecule; (o) optionally converting the product thus obtained into a pharma- ceutically acceptable salt; or Optionally, converting the pharma- ceutically acceptable or unacceptable salt thus obtained into the corresponding free compound of formula (I); or Optionally, converting the pharma- ceutically acceptable or unacceptable salt thus obtained into a different pharma-ceutically acceptable salt. The present invention relates to a process comprising:

[0044] Enantiomers of the compounds defined herein above also form part of the present invention. Such enantiomers can be prepared by modifications of the above process, utilizing the enantiomer of any chiral starting material.

[0045] The process of the invention can advantageously be carried out as a parallel array synthesis to obtain a library of β-hairpin peptidomimetics of the invention. Such parallel synthesis allows obtaining a large array of compounds as described above (usually 12-576, typically 96) in moderate to high yields and defined purities while minimizing the formation of dimer and polymer by-products.

[0046] The functionalized solid supports are preferably polystyrene cross-linked with 1-5% divinylbenzene; polystyrene coated with a polyethylene glycol spacer (Tentagel); TM); and polyacrylamide resins (see also D. Obrecht, J.-M. Villalgordo, "Solid-Supported Combinatorial and Parallel Synthesis of Small-Molecular-Weight Compound Libraries", Tetrahedron Organic Chemistry Series, Vol. 17, Pergamon, Elsevier Science, 1998).

[0047] The solid support is functionalized with a linker, a bifunctional spacer molecule that contains at one end an anchor group for attachment to the solid support and at the other end a selectively cleavable functional group used for subsequent chemical transformations and cleavage procedures. For the purposes of this invention, two types of linkers are used.

[0048] Type 1 linkers are designed to release amide groups under acidic conditions (H. Rink, Tetrahedron Lett. 1987, 28, 3783-3790). This type of linker forms an amide of the carboxyl group of an amino acid; examples of resins functionalized with such linker structures include 4-[(((2,4-dimethoxyphenyl)Fmoc-aminomethyl)phenoxyacetamido)amino-methyl]PS resin, 4-[(((2,4-dimethoxyphenyl)Fmoc-aminomethyl)phenoxyacetamido)-aminomethyl]-4-methyl-benzydrylamine PS resin (Rink amide MBHA PS resin) and 4-[(((2,4-dimethoxy-phenyl)Fmoc-aminomethyl)phenoxyacetamido)aminomethyl]benzhydrylamine PS resin (Rink amide BHA PS resin) and Fmoc-amino-xanthen-3-yloxy PS resin, Sieber linker resin). Preferably, the support is derived from polystyrene cross-linked, most preferably with 1-5% divinylbenzene, and functionalized with a 4-(((2,4-dimethoxyphenyl)Fmoc-aminomethyl)phenoxyacetamide) linker.

[0049] Type 2 linkers are designed to ultimately release a carboxyl group under acidic conditions. This type of linker forms an acid-labile ester with the carboxyl group of the amino acid, usually the acid-labile benzyl, benzhydryl, and trityl esters; examples of this type of linker structure include 2-methoxy-4-hydroxymethylphenoxy (Sasrin TM Linkers), 4-(2,4-dimethoxyphenyl-hydroxy-methyl)-phenoxy (Rink linker), 4-(4-hydroxymethyl-3-methoxyphenoxy)butyric acid (HMPB linker), trityl and 2-chlorotrityl. Preferably, the support is derived from polystyrene, most preferably crosslinked with 1-5% divinylbenzene, and functionalized with a 2-chlorotrityl linker.

[0050] When carried out as a parallel array synthesis, the process of the invention can advantageously be carried out as described herein below, although it will be clear to one skilled in the art how these procedures must be modified if it is desired to synthesize a single compound of the invention.

[0051] A number of reaction vessels equal to the total number of compounds to be synthesized in the parallel method (usually 12-576, typically 96) are charged with 10-1000 mg, preferably 40 mg, of an appropriately functionalized solid support, preferably 1-5% cross-linked polystyrene.

[0052] The solvent used must be capable of swelling the resin, and includes, but is not limited to, dichloromethane (DCM), dimethylformamide (DMF), N-methylpyrrolidone (NMP), dioxane, toluene, tetrahydrofuran (THF), ethanol (EtOH), trifluoroethanol (TFE), isopropyl alcohol, etc. Solvent mixtures containing at least one polar solvent as a component (e.g., 20% TFE / DCM, 35% THF / NMP) are advantageous for ensuring high reactivity and solvation of the peptide chains bound to the resin (GB Fields, CG Fields, J. Am. Chem. Soc. 1991, 113, 4202-4207).

[0053] The synthesis of protected peptide fragments has been greatly advanced by the development of various linkers that release the C-terminal carboxylic acid group under mildly acidic conditions that do not affect the acid-labile groups protecting the side chain functionalities. TMThe linker, Mergler et al., Tetrahedron Lett. 1988, 29 4005-4008), is cleavable with dilute trifluoroacetic acid (0.5-1% TFA in DCM) and is stable under the Fmoc deprotection conditions used during peptide synthesis, making additional Boc / tBu-based protecting groups compatible with this scheme. Other linkers suitable for the process of the invention include the extremely acid-labile 4-(2,4-dimethoxyphenyl-hydroxymethyl)-phenoxy linker (Rink linker, H. Rink, Tetrahedron Lett. 1987, 28, 3787-3790), which requires 10% acetic acid in DCM or 0.2% trifluoroacetic acid in DCM for removal of the peptide; the linker derived from 4-(4-hydroxymethyl-3-methoxyphenoxy)butyric acid (HMPB-linker, Floersheimer & Riniker, 1991, Peptides 1990: Proceedings of the Twenty-First European Peptide Symposium, 131), which is also cleaved with 1% TFA / DCM to give a peptide fragment containing all the acid-labile side chain protecting groups; and the 2-chlorotrityl chloride linker (Barlos et al., 1992), which allows the peptide to be cleaved using a mixture of glacial acetic acid / trifluoroethanol / DCM (1:2:7) for 30 minutes. al., Tetrahedron Lett. 1989, 30, 3943-3946).

[0054] Examples of amino acids and suitable protecting groups for each residue are given below: - Amino groups (e.g. those present in the side chain of lysine) Cbz benzyloxycarbonyl Boc tert.-Butyloxycarbonyl Fmoc 9-Fluorenylmethoxycarbonyl Alloc allyloxycarbonyl Teoc Trimethylsilylethoxycarbonyl Tcc Trichloroethoxycarbonyl Nps o-Nitrophenylsulfonyl Trt Triphenylmethyl or Trityl ivDe 1-(4,4-dimethyl-2,6-dioxocyclohex-1-ylidene)-3-methylbutyl; - for carboxyl groups (e.g. those present in the side chains of aspartic and glutamic acids as well) (converted into esters using alcohol components) tBu tert.-Butyl Bn Benzyl Me Methyl Ph Phenyl Pac Phenacyl All Allyl Tse Trimethylsilylethyl Tce Trichloroethyl Dmab 4-N-(1-[dimethyl-2,6-dioxocyclohexylidene]-3-methylbutyl)-aminobenzyl; 2-PhiPr 2-Phenyl-isopropyl; - Guanidino groups (e.g., those found in the side chain of arginine) Pmc 2,2,5,7,8-Pentamethylchroman-6-sulfonyl Ts Tosyl (i.e. p-toluenesulfonyl) Cbz benzyloxycarbonyl Pbf pentamethyldihydrobenzofuran-5-sulfonyl; - and hydroxy groups (e.g., those present in the side chains of threonine and serine) tBu tert.-Butyl Bn Benzyl Trt Trityl Alloc Allyloxycarbonyl.

[0055] As building blocks for constructing the peptidomimetics of the invention, preferably 9-fluorenylmethoxycarbonyl-(Fmoc) protected amino acid derivatives are used. For deprotection, i.e. cleavage of the Fmoc group, 20% piperidine in DMF or 2% DBU / 2% piperidine in DMF can be used.

[0056] The amount of reactant, i.e., amino acid derivative, is usually 1-20 equivalents (eq), based on the milliequivalents (meq / g) supported per gram of functionalized solid support (typically 0.1-2.85 meq / g polystyrene resin) initially weighed into the reaction tube. If necessary, additional equivalents of reactant can be used to complete the reaction within a reasonable time. Preferred workstations (but are not limited to these) are the Combi-chem station from Labsource, the Symphony X from Protein Technologies and the Syro synthesizer from MultiSynTech, the latter further comprising a transfer unit and a storage box during the process of cleaving the fully protected linear peptide from the solid support. Any synthesis apparatus can provide a controlled environment, for example the reaction can be carried out at a temperature different from room temperature and under an inert gas atmosphere, if necessary.

[0057] The formation of the amide bond requires activation of the α-carboxyl group to carry out the acylation step. When this activation is carried out with conventional carbodiimides such as dicyclohexylcarbodiimide (DCC, Sheehan & Hess, J. Am. Chem. Soc. 1955, 77, 1067-1068) or diisopropylcarbodiimide (DIC, Sarantakis et al Biochem. Biophys. Res. Commun. 1976, 73, 336-342), the resulting dicyclohexylurea or diisopropylurea are insoluble and soluble, respectively, in commonly used solvents. In a variation of the carbodiimide method, 1-hydroxybenzotriazole (HOBt, Koenig & Geiger, Chem. Ber. 1970, 103, 788-798) or HOAt (ref) or ethyl cyano(hydroxyimino)acetate (Oxyma (R. Subiros-Funosas, et al, Chem. Eur. J. 2009, 15, 9394-9403)) is included as an additive in the coupling mixture. HOBt, HOAt and Oxyma act as catalysts to prevent dehydration, suppress racemization of activated amino acids and improve poorly performing coupling reactions.As direct coupling reagents, benzotriazol-1-yl-oxy-tris-(dimethyl-amino)-phosphonium hexafluorophosphate (BOP, Castro et al., Tetrahedron Lett. 1975, 14, 1219-1222; Synthesis 1976, 751-752) or benzotriazol-1-yl-oxy-tris-pyrrolidino-phosphonium hexafluorophosphate (Py-BOP, Coste et al., Tetrahedron Lett. 1990, 31, 205-208) or 2-(1H-benzotriazol-1-yl-)1,1,3,3-tetramethyluronium tetrafluoroborate (TBTU) or hexafluorophosphate (HBTU, Knorr et al., Tetrahedron Lett. 1995, 31, 205-208) were used. Certain phosphonium reagents such as aryl esters (HBOt esters) have been used; these phosphonium reagents are also suitable for the in situ formation of HOBt esters with protected amino acid derivatives.Coupling reagents include diphenoxyphosphoryl azide (DPPA) or O-(7-aza-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate (TATU) or O-(7-aza-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate (HATU) / 7-aza-1-hydroxybenzotriazole (HOAt, Carpino et al., Tetrahedron Lett. 1994, 35, 2279-2281) or -(6-chloro-1H-benzotriazol-1-yl)-N,N,N',N'-1,1,3,3-tetramethyluronium tetrafluoroborate (TCTU) or hexafluorophosphate (HCTU, Marder, Shivo and Albericio: HCTU and TCTU: New Coupling Reagents: Development and Industrial Applications, Poster Presentation, Gordon Conference February 2002), as well as 1,1,3,3-bis(tetramethylene)chlorouronium hexafluorophosphate (PyClU) (J. Coste, E. Frerot, P. Jouin, B. Castro, Tetrahedron Lett. 1991, 32, 1967) or pentafluorophenyl diphenylphosphinate (S. Chen, J. Xu, Tetrahedron Lett. 1991, 32, 6711), especially for coupling of N-methylated amino acids, can be used. More recently, new Oxyma-based coupling reagents have been introduced, such as ([(1-(cyano-2-ethoxy-2-oxoethylideneaminooxy)dimethylaminomorpholino)]uronium hexafluorophosphate (COMU, A. El-Faham, et al. Chem. Eur. J 2009, 15, 9404-9416)).

[0058] Since it is essential that the coupling reaction is nearly quantitative, experimental evidence of reaction completion is desirable. The ninhydrin test (Kaiser et al., Anal. Biochemistry 1970, 34, 595) and the 2,4,6-trinitrobenzenesulfonic acid (TNBS) test (Hancook WSet al, Anal. Biochem 1976, 71, 260) qualitatively indicate the presence of primary amines when the peptide or a peptide preparation bound to the resin shows a positive color response, and can be easily and quickly performed after each coupling step. The chloranil test (Vojkovsky T., Pept. Res. 1995, 68, 236) can be used to detect secondary amines, e.g., proline derivatives. The chemistry of Fmoc allows spectrophotometric detection of the Fmoc chromophore liberated by base (Meienhofer et al., Int. J. Peptide Protein Res. 1979, 13, 35-42).

[0059] Within each reaction vessel, the resin-bound intermediate is washed free of excess retained reagents, solvents and by-products by repeated exposure to pure solvent.

[0060] The washing procedure is repeated up to about 30 times (preferably about 5 times) while monitoring the efficiency of removal of reagents, solvents and by-products by methods such as TLC, GC, LC-MS or examination of the washings.

[0061] In the well, the procedure described above, i.e., reaction of the resin-bound compound with reagents followed by removal of excess reagents, by-products and solvents, is repeated for each successive transformation until the fully protected, resin-bound linear peptide of interest is obtained.

[0062] Before the fully protected linear peptide is cleaved from the solid support, it is possible to selectively deprotect one or several protected functional groups present in the molecule, if necessary, and to appropriately substitute the reactive groups thus liberated. For this purpose, the functional group of interest must first be protected with a protecting group that can be selectively removed without affecting the remaining protecting groups present. An example of such an amino protecting group is Alloc (allyloxycarbonyl), which can be selectively removed, for example, with Pd° and dimethylbarbituric acid (DMBA) in DCM / DMSO, without affecting the remaining protecting groups present in the molecule, such as Fmoc. The reactive groups thus liberated can then be treated with suitable agents for functionalization or for further cyclization of the peptide on the solid support using the well-established lactam bridge. This bridge is formed, for example, by linking the amino-bearing side chains of 2,4-diaminobutyric acid (Dab), ornithine and lysine, respectively, with the carboxyl-bearing side chains of glutamic acid and aspartic acid residues located on opposite sides of the structure, by forming an amide bond. Preferred protecting groups for the side chains are allyloxycarbonyl (alloc) for the side chain amino groups and allyl ester (allyl) for the side chain carboxyl groups of aspartic acid and glutamic acid. For example, the formation of lactam bridges on solid supports can be carried out by selectively removing alloc and allyl protecting groups from the amino and carboxyl groups of the side chains of the amino acid residues to be linked by applying 0.2 eq tetrakis(triphenylphosphine)palladium(0) (10 mM) in dry DCM and 10 eq dimethylbarbituric acid in DMSO after assembling the linear peptide on the resin. After repeating the above procedure, lactam bridges are formed on solid supports by adding 4 eq DIPEA in NMP followed by 2 eq PyBOP in DMF or by using 2 eq Oxyma and 4 eq DIC in DCM.

[0063] Finally, after completing the synthesis on the support, including elongation and modification, e.g., N-terminal functionalization or cyclization, cleavage of the peptide derivative and complete deprotection can be carried out simultaneously using 95% TFA, 2.5% HO, 2.5% TIS or 82.5% TFA, 5% anisole, 5% thioanisole, 5% HO and 2.5% TIS or other combinations of scavengers to achieve cleavage of the protected peptide and removal of the protecting groups. The deprotection reaction time is generally 30 minutes to 12 hours, preferably about 2.5 hours. The deprotected linear or cyclic peptide can be precipitated and washed using cold EtO or isopropyl ether (IPE).

[0064] Some of the compounds of the invention according to general formula (I) require additional synthetic steps. These transformations can be applied either to the fully protected or partially deprotected linear or cyclic peptides, either bound to the solid support or already free, or to the final deprotected molecules.

[0065] In addition to the lactam bridges described above, various methods for forming interstrand linkages are known, including those described in JPTam et al., Synthesis 1979, 955-957; JM Stewart et al., Solid Phase Peptide Synthesis, 2d Ed., Pierce Chemical Company, Rockford, IL, 1984; AKA Ahmed et al., J. Biol. Chem. 1975, 250, 8477-8482; and MWPennington et al., Peptides, pages 164-166, Giralt and Andreu, Eds., ESCOM Leiden, The Netherlands, 1990; CE Schafmeister et al., J. Am. Chem. Soc. 2000, 122, 5891.

[0066] The most widely known linkages are disulfide bridges formed by, for example, cysteine, homocysteine ​​or penicillamine (Pen) located at opposing positions in the structure.

[0067] Recently, a further class of interstrand linkages based on 1,4-disubstituted 1,2,3-triazole-containing alkanediyl groups has been introduced (copper(I)-catalyzed alkyne-azide cycloaddition (CuAAC) "click" reaction). This linkage is obtained by 1,3-dipolar cycloaddition between an ω-yne group in the side chain of an amino acid residue, such as L-propargylglycine, and an ω-azido group in the side chain of an amino acid residue, such as (S)-2-amino-4-azidobutanoic acid, both of which are located at opposite positions in the structure. This cycloaddition is advantageously carried out in the presence of copper(I). For example, the formation of such triazole-containing bridges is carried out by stirring the purified, fully deprotected linear peptide in a buffer containing copper(II) sulfate pentahydrate (CuSO4·5H2O) and L(+)-ascorbic acid, which are used for the in situ generation of copper(I).

[0068] Depending on its purity, the final product obtained according to the above procedure can be used directly in biological assays or needs to be further purified, for example by preparative HPLC.

[0069] If necessary, it is then possible to convert the thus obtained fully deprotected product into a pharma- ceutically acceptable salt or to convert the thus obtained pharma-ceutically acceptable or unacceptable salt into the corresponding free compound or into a different pharma-ceutically acceptable salt, all of which can be carried out by methods known to those skilled in the art.

[0070] In general, the building blocks of the peptide derivatives of the present invention can be synthesized according to literature methods known to those skilled in the art or are commercially available. All other corresponding amino acids are depicted as either unprotected or Boc- or Fmoc-protected, racemic, (D)- or (L)-isomers. It will be understood that the unprotected amino acid building blocks can be easily converted to the corresponding Fmoc-protected amino acid building blocks required for the present invention by standard manipulations of protecting groups. Reviews describing general methods for the synthesis of α-amino acids include: R. Duthaler, Tetrahedron (Report) 1994, 349, 1540-1650; RM Williams, "Synthesis of optically active α-amino acids", Tetrahedron Organic Chemistry Series, Vol. 7, JE Baldwin, PD Magnus (Eds.), Pergamon Press., Oxford 1989. A particularly useful method for synthesizing optically active α-amino acids related to the present invention is kinetic optical resolution using hydrolases (MA Verhovskaya, IAYamskov, Russian Chem. Rev. 1991, 60, 1163-1179; RM Williams, "Synthesis of optically active α-amino acids", Tetrahedron Organic Chemistry Series, Vol. 7, JE Baldwin, PD Magnus (Eds.), Pergamon Press., Oxford 1989, Chapter 7, p. 257-279). Kinetic optical resolution using hydrolases includes hydrolysis of amides and nitriles with aminopeptidases or nitrilases, cleavage of N-acyl groups with acylases, and hydrolysis of esters with lipases or proteases.It is well documented that the use of certain enzymes leads specifically to the pure (L)-enantiomer, whereas the use of other enzymes leads to the corresponding (D)-enantiomer (e.g. R. Duthaler, Tetrahedron Report 1994, 349, 1540-1650; R. M. Williams, "Synthesis of optically active α-amino acids", Tetrahedron Organic Chemistry Series, Vol. 7, J. E. Baldwin, P. D. Magnus (Eds.), Pergamon Press., Oxford 1989).

[0071] The peptidomimetics of the present invention can be used in a wide range of applications aimed at inhibiting the growth or killing of microorganisms to obtain a desired therapeutic effect in humans and other mammals with pathologies similar to those of humans, in particular they can be used to inhibit the growth or kill of Gram-negative bacteria, particularly Enterobacteriaceae bacteria, more specifically Klebsiella pneumoniae and / or Escherichia coli.

[0072] They can be used, for example, as disinfectants or as preservatives for materials such as foods, cosmetics, pharmaceuticals and other nutrient-containing materials.

[0073] The peptidomimetics of the invention may also be used to treat or prevent diseases associated with microbial infections in plants and animals.

[0074] When used as disinfectants or antiseptics, the peptidomimetics can be added to the desired material alone, as a mixture of several peptidomimetics, or in combination with other antimicrobial agents.

[0075] The peptidomimetics of the invention can be used to treat or prevent infections or diseases associated with such infections, particularly hospital-acquired infections due to gram-negative bacteria, associated with diseases such as ventilator-associated pneumonia (VAP), hospital-acquired pneumonia (HAP), healthcare-associated pneumonia (HCAP); catheter-associated and non-catheter-associated infections such as urinary tract infections (UTI) or bloodstream infections (BSI); infections associated with respiratory diseases such as cystic fibrosis, emphysema, asthma or pneumonia; infections associated with skin or soft tissue diseases such as surgical wounds, traumatic wounds or burns; infections associated with digestive diseases such as infectious diarrhea, necrotizing enterocolitis, appendicitis, gastroenteritis or pancreatitis; infections associated with eye diseases such as keratitis and endophthalmitis; infections associated with ear diseases such as otitis; infections associated with CNS diseases such as brain abscess and meningitis or encephalitis; infections associated with bone diseases such as osteochondritis and osteomyelitis; infections associated with cardiovascular diseases such as endocarditis and pericarditis; or infections associated with urogenital diseases such as epididymitis, prostatitis and urethritis. They can be administered alone, as a mixture of several peptidomimetics, in combination with other antimicrobial or antibiotic agents, in combination with anti-cancer or anti-viral (e.g., anti-HIV) agents or in combination with other pharma- ceutical active agents. The peptidomimetics can be administered on their own or as a pharmaceutical composition.

[0076] The peptidomimetics of the present invention can be administered per se or can be applied together with carriers, diluents or excipients known to those skilled in the art as appropriate formulations.

[0077] The pharmaceutical composition containing the peptidomimetic of the present invention can be manufactured by using conventional mixing, dissolving, granulating, tablet coating, levigating, emulsifying, encapsulating, encapsulating or lyophilizing processes.The pharmaceutical composition can be formulated in a conventional manner using one or more physiologically acceptable carriers, diluents, excipients or adjuvants that facilitate the processing of the active peptidomimetic into a pharmaceutical preparation that can be used.The appropriate formulation depends on the selected method of administration.

[0078] When used for topical administration, the peptidomimetics of the invention can be formulated into solutions, gels, ointments, creams, suspensions, and the like, as are well known in the art.

[0079] Systemic formulations include those designed to be administered by injection, e.g., subcutaneous, intravenous, intramuscular, intrathecal or intraperitoneal injection, and those designed for transdermal, transmucosal, oral or pulmonary administration.

[0080] For injection, the peptidomimetics of the invention can be formulated in a suitable solution, preferably a physiologically compatible buffer solution such as Hinks' solution, Ringer's solution or buffered saline. The solution may contain formulating agents such as suspending, stabilizing and / or dispersing agents. Alternatively, the peptidomimetics of the invention can be in powder form for combination with a suitable vehicle, e.g., sterile pyrogen-free water, before use.

[0081] For transmucosal administration, penetrants appropriate to the barrier to be permeated are used in the formulation as is known in the art.

[0082] For oral administration, the active peptidomimetics of the present invention can be easily formulated by combining them with pharma- ceutically acceptable carriers known in the art. Using such carriers, the peptidomimetics of the present invention can be formulated into tablets, pills, dragees, capsules, liquids, gels, syrups, slurries, suspensions, etc., for oral ingestion by the patient to be treated. Suitable excipients for oral formulations, such as powders, capsules, and tablets, include: sugars, e.g., lactose, sucrose, mannitol, and sorbitol; cellulose preparations, such as corn starch, wheat starch, rice starch, potato starch, gelatin, tragacanth, methylcellulose, hydroxypropylmethylcellulose, sodium carboxymethylcellulose, and / or polyvinylpyrrolidone (PVP); granulating agents; and binding agents. If necessary, disintegrants, such as cross-linked polyvinylpyrrolidone, agar, or alginic acid or a salt thereof, such as sodium alginate, can also be added. If desired, solid dosage forms may be sugar coated or enteric coated using standard techniques.

[0083] For oral liquid preparations such as suspensions, elixirs and solutions, suitable carriers, excipients or diluents include water, glycols, oils, alcohols, etc. In addition, flavoring agents, preservatives, coloring agents, etc. can also be added.

[0084] For buccal administration, the compositions may take the form of conventionally formulated tablets or lozenges.

[0085] When administered by inhalation, the peptidomimetics of the present invention are conveniently delivered in the form of an aerosol spray from a pressurized fill or nebulizer using a suitable propellant, such as dichlorodifluoromethane, trichlorofluoromethane, carbon dioxide or other suitable gas. In the case of a pressurized aerosol, the dosage unit can be determined by providing a valve to deliver a metered amount. Capsules and cartridges, for example made of gelatin, for use in an inhaler or insufflator can be formulated to contain a powder mix of the peptidomimetics of the present invention and a suitable powder base, such as lactose or starch.

[0086] The compounds may also be formulated in rectal and vaginal compositions such as suppositories with a suitable suppository base such as cocoa butter or other glycerides.

[0087] In addition to the above-mentioned formulations, the peptidomimetics of the present invention can also be formulated as depot preparations.This type of long-acting formulation can be administered by implantation (e.g., subcutaneously or intramuscularly) or intramuscular injection.To prepare this type of depot preparation, the peptidomimetics of the present invention can be formulated with suitable polymeric or hydrophobic materials (e.g., as an emulsion in acceptable oil), or with ion exchange resins, or as sparingly soluble salts.

[0088] In addition, other drug delivery systems such as liposomes and emulsions known in the art can be used. Certain organic solvents such as dimethylsulfoxide can also be used. Furthermore, the peptidomimetics of the present invention can be delivered using sustained-release systems such as semipermeable matrices of solid hydrophobic polymers containing the therapeutic agent (e.g., for coated stents). A variety of sustained-release materials have been established and are known to those skilled in the art. Sustained-release capsules can release the compounds for weeks up to over 100 days, depending on their chemical nature. Depending on the chemical nature and biological stability of the therapeutic agent, additional strategies can be employed to stabilize proteins.

[0089] The peptidomimetics of the invention may contain charged residues and therefore may be included in any of the formulations described above either as such or as a pharma- ceutically acceptable salt, which tend to be more soluble in aqueous and other protic solvents than the corresponding free forms.

[0090] The peptidomimetics of the present invention or compositions thereof will generally be used in an amount effective to achieve its intended purpose, it being understood that the amount used will depend on the particular application.

[0091] For example, when used as a disinfectant or preservative, an antimicrobially effective amount of the peptidomimetic of the present invention or a composition thereof is applied or added to the material to be disinfected or preserved. By antimicrobially effective amount is meant an amount of the peptidomimetic of the present invention or a composition thereof that inhibits the growth of or is lethal to the targeted microbial population. Although the antimicrobially effective amount will depend on the specific application, when used as a disinfectant or preservative, the peptidomimetic of the present invention or a composition thereof is usually added or applied in a relatively small amount to the material to be disinfected or preserved. Typically, the peptidomimetic of the present invention comprises less than about 5% by weight, preferably less than 1% by weight, more preferably less than 0.1% by weight of the disinfectant solution or the material to be preserved. Those skilled in the art will be able to determine the antimicrobially effective amount of a specific peptidomimetic of the present invention for use in a specific application without undue experimentation, for example, using the results of the in vitro assays shown in the Examples.

[0092] When used to treat or prevent a microbial infection or a disease associated with such an infection, the peptidomimetic of the invention or a composition thereof is administered or applied in a therapeutically effective amount. By therapeutically effective amount is meant an amount effective for ameliorating the symptoms of, or ameliorating, treating or preventing, a microbial infection or a disease associated therewith. Determination of a therapeutically effective amount is well within the capabilities of those skilled in the art, especially in light of the detailed disclosure provided herein.

[0093] As with disinfectants and antiseptics, therapeutically effective doses for topical administration to treat or prevent bacterial and / or viral infections can be determined, for example, using the results of the in vitro assays shown in the Examples. Treatment can be applied while the infection is discernible or even when it is not. One of ordinary skill in the art will be able to determine therapeutically effective amounts for treating a localized infection without undue experimentation.

[0094] For systemic administration, the therapeutically effective dose can be estimated initially from in vitro assays. For example, the peptidomimetic can be administered at IC 50 Doses can be formulated in animal models to achieve a circulating concentration range that includes the test compound (i.e., the concentration of the test compound that is lethal to 50% of the cells in culture). Such information can be used to more accurately determine useful doses in humans.

[0095] Initial dosages can also be determined from in vivo data, e.g., animal models, using techniques well known in the art. Those skilled in the art can readily optimize human dosing based on the animal data.

[0096] For anti-infective applications, dosages can be adjusted individually to provide plasma concentrations of the peptidomimetics of the invention sufficient to maintain therapeutic efficacy, and therapeutically effective serum concentrations may be achieved by administering multiple doses daily.

[0097] In cases of local administration or selective uptake, the effective local concentration of the peptidomimetics of the invention may not be related to plasma concentration. One of ordinary skill in the art will be able to determine a therapeutically effective local dosage without undue experimentation.

[0098] The amount of peptidomimetic administered will, of course, be dependent on the subject being treated, on the subject's weight, the severity of the affliction, the manner of administration and the judgment of the prescribing physician.

[0099] Antimicrobial therapy can be repeated intermittently when infection is detectable or even when infection is undetectable. This therapy can be provided alone or in combination with other drugs, such as anti-HIV or anti-cancer or other antimicrobial agents.

[0100] Typically, a therapeutically effective amount of the peptidomimetics described herein will provide a therapeutic effect without substantial toxicity.

[0101] Toxicity of the peptidomimetics of the invention can be assessed by standard pharmaceutical procedures in cell cultures or experimental animals, e.g., LD 50 (the dose at which 50% of the population is lethal) or LD 100 The therapeutic index can be determined by determining the dose at which 100% of the population is lethal. The dose ratio between the toxic dose and the therapeutic dose is the therapeutic index. Compounds with high therapeutic indexes are preferred. Data obtained from these cell culture assays and animal studies can be used to formulate a range of dosages that are non-toxic for use in humans. The dosage of the peptide mimetic of the present invention is preferably within a range whose circulating concentration includes an effective dose that produces little or no toxicity. The dosage can vary within this range depending on the dosage form employed and the route of administration utilized. The exact formulation, route of administration and dosage can be selected by the individual physician in view of the patient's condition (see, for example, Fingl et al. 1975, In: The Pharmacological Basis of Therapeutics, Ch. 1, p. 1).

[0102] The following examples illustrate the present invention and should not be construed as in any way limiting its scope.

[0103] Abbreviation: Ac Acetyl; BSA bovine serum albumin; Boc tert-butyloxycarbonyl; DCHA dicyclohexylamine; DCM dichloromethane; DEAD Diethyl azodicarboxylate; DIC diisopropylcarbodiimide; DIPEA diisopropylethylamine; DMF Dimethylformamide; DMEM Dulbecco's modified Eagle's medium; DODT 3,6-dioxa-1,8-octanedithiol; FCS fetal calf serum; Fmoc fluorenylmethyloxycarbonyl; HATU O-(7-aza-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; HBSS Hanks Balanced Salt Solution; HBTU O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; HCTU O-(6-chlorobenzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; Hepes 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid; HFIP Hexafluoroisopropanol HOAt 1-hydroxy-7-azabenzotriazole; IMDM Iscove's modified Dulbecco's medium; IPE isopropyl ether; iPrOH Isopropanol NMP N-methyl-2-pyrrolidone; NMM N-methylmorpholine; Oxyma ethyl cyanohydroxyiminoacetate; PyBop® (benzotriazol-1-yloxy)tripyrrolidinophosphonium hexafluorophosphate; TIS Triisopropylsilane; TPP triphenylphosphine; RPMI Roswell Park Memorial Institute medium; rt room temperature. EXAMPLES

[0104] 1. Peptide Synthesis 1.1 General synthetic procedure General methods for synthesizing the peptidomimetics of the invention are illustrated below, which are intended to illustrate the main concepts and in no way limit or restrict the invention. Those skilled in the art can easily modify these procedures.

[0105] Step A. Attachment of the first protected amino acid residue to the resin In a dry flask, 2-chlorotrityl chloride resin (polystyrene, 1% cross-linked; typical loading: 1.1-1.4 mmol / g) was swollen in anhydrous DCM for 30 min (7-10 mL DCM per g resin). A solution of 0.8 eq Fmoc-protected amino acid and 6 eq DIPEA in anhydrous DCM / DMF (4 / 1) was added (7 mL-10 mL per g resin). After shaking for 2-4 h at rt, the resin was filtered and washed successively with DCM, DMF, DCM, DMF and DCM. The resin was treated three times with a mixture of DCM / MeOH / DIPEA (17:2:1 or 15:2:3) (7-10 mL per g resin), 3×30 min. The resin was filtered through a pre-weighed sintered glass funnel and washed successively with DCM, DMF, DCM, MeOH, DCM, MeOH, DCM (2x) and Et2O (2x). The resin was dried under high vacuum overnight. The final mass of the resin was determined before quality control.

[0106] Resin loadings were typically in the range of 0.6-0.7 mmol / g.

[0107] The following pre-loaded resins were prepared: Fmoc-Nle-2-chlorotrityl resin, Fmoc-Cha-chlorotrityl resin, Fmoc-Tyr(tBu)-2-chlorotrityl resin, Fmoc-Trp(Boc)-2-chlorotrityl resin.

[0108] Step B. Synthesis of fully protected peptide fragments The synthesis was carried out on a Syro peptide synthesizer (MultiSynTech GmbH) using 24–576 reaction vessels. Depending on the scale used (0.005–0.25 mmol), the above dried resin was charged into the size-corresponding reactor.

[0109] A program was set up and run to carry out the following reaction cycle: Step Reagent Time 1 DCM, wash and swell 1x 3 min 2 NMP, wash and swell 2 x 30 min 3 20% piperidine / DMF 1x 5 min and 1x 15 min 4 NMP, wash 5 x 1 min 5 7.2 eq Fmoc amino acids in NMP + 6.8 eq HATU in NMP + 21.6 eq NMM in NMP 1 × 15 min 6 7.2 eq Fmoc amino acids in NMP + 6.8 eq HATU in NMP + 21.6 eq NMM in NMP 1 × 15 min 7 NMP, wash 5 x 1 min 8 12 eq acetic anhydride in NMP + 12 eq NMM in NMP 1 x 5 min 9 20% piperidine in DMF 2 x 2 min 10 NMP, wash 5 x 1 min 11 DCM, washing (at the end of synthesis) 3 x 1 min Steps 5-10 constitute one standard SPPS cycle, which is repeated for the addition of each amino acid residue.

[0110] In Examples 78 and 79, amino acids with side chain protection by Allyl / Alloc were used as P 4 and P 15 Standard Fmoc / tBu amino acid building blocks were used, except for the above.

[0111] Step C. Cleavage / Deprotection After assembly of the protected peptide, the resin was suspended in the cleavage / deprotection cocktail TFA / anisole / thioanisole / water / TIS 82.5 / 5 / 5 / 5 / 2.5 (v / v / v / v / v) (20 mL / mmol resin) for 1 min. After filtration, this cleavage / deprotection step was repeated twice. The filtrates were combined and shaken at room temperature for 3 h. The linear peptide was precipitated in cold Et2O / pentane (1 / 1 v / v) and washed three times with the same solvent mixture. The solid was air-dried.

[0112] Procedure D. Purification Procedure (Preparative Reversed-Phase LC-MS) Compounds were purified by reversed-phase chromatography using two Waters BEH XBridge C8 OBD columns, 30×150 mm, 5 μm (catalog no. 186003083) columns in series. Mobile phase used: A: 0.1% TFA in water / acetonitrile (98 / 2 v / v) B: 0.1% TFA in acetonitrile

[0113] The gradient slope of the preparative run was adjusted for each run based on the analytical LC-MS analysis of the crude product. As an example, a typical run was performed at a flow rate of 35 mL / min with the following gradient:

[0114] [Table 1]

[0115] The retention time of the target compound in this exemplary purification was 10.4 minutes.

[0116] Detection: MS (ESI positive 60V profile mode) and UV @ 220nm and 254nm

[0117] The collected fractions were evaporated on a Genevac HT4 evaporator or a Büchi system.

[0118] 1.2 Analysis method Analytical HPLC retention time (RT, in min) was measured using a HPLC system: Thermo Scientific Ultimate 3000RS, MS: Thermo Scientific MSQ plus, Ascentis Express C8 column, 100×3 mm, 2.7 μm, run at 55° C. with the following solvents A (HO+0.1% TFA) and B (CHCN+0.085% TFA) and gradients:

[0119] [Table 2]

[0120] Detection: MS (ESI positive 60V profile mode) and UV @ 220nm and 254nm

[0121] 1.3 Synthesis of peptide sequences Examples 1 to 67: The protected peptides were synthesized from the C-terminus to the N-terminus. The starting amino acid-modified resins used in the synthesis (obtained according to procedure A) were P 16 The protected linear peptide immobilized on the resin (resin-P 16 -P 15 -P 14 -P 13 -P 12 -P 11 -P 10 -P 9 -P 8 -P 7 -P 6 -P 5 -P 4 -P 3 -P 2 -P 1 ) was synthesized according to procedure B. Cleavage / deprotection of the modified peptide was carried out according to procedure C. The globally deprotected linear peptide was dissolved in 1 M ammonium acetate buffer at pH 6 containing 5% (v / v) DMSO (140 mL / mmol). The peptide solution was stirred for 48 h in an open flask. The crude product was purified according to procedure D. The analytical data for each example are summarized in Table 1.

[0122] Examples 68 to 77, 80 to 82, 90 to 111, 115, 117, 120 to 134: The protected peptides were synthesized from the C-terminus to the N-terminus. The starting amino acid-modified resins used in the synthesis (obtained according to procedure A) were P 16 The protected linear peptide immobilized on the resin (resin-P 16 -P 15 -P 14 -P 13 -P 12 -P 11 -P 10 -P 9 -P 8 -P 7 -P 6 -P 5 -P 4 -P 3 -P 2 -P 1 ) was synthesized according to procedure B. The resin was swollen in DMF and N,N'-bis-Boc-guanylpyrazole (10 eq) in DMSO / DMF (1 / 1 v / v) was added to the resin. The reaction was shaken overnight and the resin was washed extensively with DMF and DCM. Cleavage / deprotection of the modified peptide was carried out as described in procedure C. The globally deprotected linear peptide was dissolved in 1 M ammonium acetate buffer at pH 6 containing 5% (v / v) DMSO (140 mL / mmol). The peptide solution was stirred in an open flask for 48 h. The crude product was purified according to procedure D. The analytical data for each example are summarized in Table 1.

[0123] Examples 78-79: The protected peptide was synthesized from the C-terminus to the N-terminus. The amino acid-modified resin used in the synthesis (obtained according to procedure A) was P 16 According to procedure B, the protected peptide was converted to an N-terminal Fmoc-protected P 4 (Resin-P 16 -P 15 -P 14 -P 13 -P 12 -P 11 -P 10 -P9 -P 8 -P 7 -P 6 -P 5 -P 4 After assembly, the resin was allowed to swell in DCM for at least 15 min. 4 and P 15 To selectively remove the alloc and allyl protecting groups from the amino and carboxyl groups of P, respectively, 0.2 eq of tetrakis(triphenylphosphine)palladium(0) (10 mM) and 10 eq of DMBA in anhydrous DCM were added. The reaction mixture was shaken for 5 min at rt, after which the resin was filtered and washed with NMP, iPrOH, IPE and DCM. The procedure was repeated with the addition of fresh solutions of reagents. The resin was subsequently washed with NMP, iPrOH, IPE and DCM, after which the resin was swollen in DCM. 2 eq of Oxyma dissolved in anhydrous DCM was added to the resin, followed by the addition of 4 eq of DIC in anhydrous DCM. After 1 h, 2 eq of DIC in anhydrous DCM was added. The reaction mixture was stirred overnight, after which the resin was filtered and washed extensively with DCM and NMP. The peptide elongation was continued according to procedure A (P 3 From P 1 ). Cleavage / deprotection of the modified peptides was carried out as described in procedure C and purification was carried out according to procedure D. The analytical data for each example are summarized in Table 1.

[0124] Examples 83 to 89, 112 to 114, 116, 118 to 119, and 135 to 136: The protected peptide was synthesized from the C-terminus to the N-terminus. The amino acid-modified resin used in the synthesis (obtained according to procedure A) was P 16 According to procedure B, the protected peptide was converted to an N-terminal Fmoc-protected P 4 (Resin-P 16 -P 15 -P 14 -P 13 -P 12 -P 11 -P 10 -P 9 -P 8 -P 7 -P 6 -P5 -P 4 After assembly, the resin was allowed to swell in DCM for at least 15 min. 4 and P 15 To selectively remove the alloc and allyl protecting groups from the amino and carboxyl groups of P, respectively, 0.2 eq of tetrakis(triphenylphosphine)palladium(0) (10 mM) and 10 eq of DMBA in anhydrous DCM were added. The reaction mixture was shaken for 5 min at rt, after which the resin was filtered and washed with NMP, iPrOH, IPE and DCM. The procedure was repeated with the addition of fresh solutions of reagents. The resin was subsequently washed with NMP, iPrOH, IPE and DCM, after which the resin was swollen in DCM. 2 eq of Oxyma dissolved in anhydrous DCM was added to the resin, followed by the addition of 4 eq of DIC in anhydrous DCM. After 1 h, 2 eq of DIC in anhydrous DCM was added. The reaction mixture was stirred overnight, after which the resin was filtered and washed extensively with DCM and NMP. The peptide elongation was continued according to procedure A (P 3 From P 1 ). The resin was swelled in DMF and N,N'-bis-Boc-guanylpyrazole (10 eq) in DMSO / DMF (1 / 1 v / v) was added to the resin. The reaction was shaken overnight and the resin was washed extensively with DMF and DCM. Cleavage / deprotection of the modified peptide was carried out as described in procedure C and purification was carried out according to procedure D. The analytical data for each example are summarized in Table 1.

[0125] [Table 3]

[0126] [Table 4]

[0127] [Table 5]

[0128] [Table 6]

[0129] [Table 7]

[0130] [Table 8]

[0131] 2. Biological methods 2.1. Preparation of peptides Lyophilized peptides were weighed out on a microbalance (Mettler MT5) and dissolved in sterile water to a final concentration of 1 mg / mL. Stock solutions were kept protected from light at +4°C.

[0132] 2.2. Antimicrobial activity of peptides The selective antimicrobial activity of peptides was determined using 96-well plates (Greiner, polystyrene) according to the standard CLSI broth microdilution method (Clinical and Laboratory Standards Institute. Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically; Approved Standard-Ninth Edition. CLSI document M07-A9 (ISBN 1-56238-783-9 [Print]; ISBN 1-56238-784-7 [Electronic]) Clinical and Laboratory Standards Institute, 950 West Valley Road, Suite 2500, Wayne, Pennsylvania 19087, USA, 2012) with some modifications.

[0133] Microbial colonies were diluted in saline (0.85%, NaCl) and adjusted to a 0.5 McFarland standard turbidity using a McFarland turbidimeter (bioMerieux SA, Marcy-l'Etoile, France). The bacterial suspension was then diluted with Mueller-Hinton II (MHII, cation-adjusted) broth to obtain approximately 5 × 10 5 The count was expressed as colony forming units (CFU / mL).

[0134] The microbial inoculum was diluted in Mueller-Hinton II (MH, cation-adjusted) broth and compared to a 0.5 McFarland turbidity standard to obtain a turbidity of approximately 10 6 The concentrations were expressed as colony forming units (CFU) / mL. An aliquot of the inoculum (90 μl) was added to 10 μl of peptide in water + P-80 (polysorbate 80, final concentration 0.002%), diluted 2-fold to 10x the final concentration. The following microorganisms were used to determine the antibiotic selectivity of the peptides: Escherichia coli ATCC 25922, Escherichia coli MCR-1 Af 45, and Klebsiella pneumoniae SSI3010. The antimicrobial activity of the peptides was expressed as the minimum inhibitory concentration (MIC) (in μg / mL) at which no visible growth was observed after 18–20 h of incubation at 35°C.

[0135] 2.3.Hemolysis The hemolytic activity of peptides against human red blood cells (hRBCs) was tested. Fresh hRBCs were washed three times with phosphate buffered saline (PBS) and centrifuged at 3000×g for 5 min. Compounds (200 μg / mL) were incubated with 20% hRBCs (v / v) for 1 h at 37° C. with shaking at 300 rpm. Values ​​for 0% and 100% cell lysis, respectively, were determined by incubating hRBCs in the presence of PBS and 2.5% Triton X-100 in H2O, respectively. Samples were centrifuged, the supernatants were diluted 8-fold with PBS buffer, and the optical density (OD) was measured at 540 nm. The 100% lysis value (OD 540 H2O) is OD 540It was about 0.5 to 1.0.

[0136] The hemolysis rate was calculated as follows: (OD 540 Peptide / OD 540 H2O) x 100%.

[0137] The results of the experiments described in 2.2-2.3 are shown in Table 2 below.

[0138] [Table 9]

[0139] [Table 10]

[0140] [Table 11]

[0141] [Table 12]

Claims

1. General formula (I) P １ -P ２ -P ３ -P ４ -P ５ -P ６ -P ７ -P ８ -P ９ -P １０ -P １１ -P １２ -P １３ -P １４ -P １５ -P １６ (I) (wherein P １ is Abu, tBuGly or Val; P １ wherein the amino group is unsubstituted or substituted by a guanidino group (Gua) or by a tetramethylguanidino (TMG) group; P ２ ,Hyp; Pro, Pro((4S)F), Pro((4R)F), Pro(4,4F ２ ), Pro((4R)OMe) or Pro(3,4 dehydro); P ３ is Cpg or Ile; P ４ is Dab, Dap, Cys, Pen, Asp or Glu; . ５ は、; (. ______、!yr (uェニル)、!!0、\9r、. (4): Ala, Ala(cPr), Abu, Met, Val, NMeAla, NMeVal, Nva; alloThr, Hse, Ser or Thr; 7 ６ は、alloThr、Cit、Hgn、Hse、Leu((3R)OH)、Asn、Gln、Ser、Thr、Asp、Glu、Hgl; Agb, Agp, Dab, Dab(iPr), Dap, Dap(iPr), Har, Lys, Lys(iPr), Orn, Orn(iPr), Arg, NMeLys; Ala(cPr), Abu, alloIle, Dea, Hle, Ile, Leu, Nle, OctGly, tBuGly, tBuAla, Val, NMeVal or Nva; P ７ は、alloThr、Hse、Leu((3R)OH)、Asn、Gln、Ser、Thr、Asp、Glu、Hgl; Ala, Ala(cPr), Abu, alloIle, Dea, Hle, Ile, Leu, Nle, OctGly, tBuGly, tBuAla, Val, NMeAla, NMeVal or Nva; P ８ is Lys, Orn or Arg; P ９ Agb, Agp, Dab, Dab (iPr), Dap, Dap (iPr), Har, Lys, Lys (iPr), Narg, Ndab, Nlys, Norn, Orn, Orn (iPr), Arg, Nmelys; Ｄ Dab, Ｄ Dab(iｰr) Ｄ Yes, Ｄ Dap(irr) Ｄ Lys, Ｄ Lys(iｰr) Ｄ Orrn, Ｄ Orn(iｰr) Ｄ Ar; Cit, Hgn, Hse, Hyp, Asn, Gln, Ser, Thr; Ｄ Cit, Ｄ Asn, Ｄ Gln, Ｄ Ser or Ｄ Thr; Ala or Pro; P １０ is Hyp, Asn, Gln, Ser or Thr; P １１ は、 Ｄ Dab, Ｄ Dab(iｰr) Ｄ Yes, Ｄ Dap(irr) Ｄ Lys, Ｄ Lys(iｰr) Ｄ Orrn, Ｄ Orn(iｰr) Ｄ Ar; Ｄ Cit, Ｄ Asn, Ｄ Gln, Ｄ Ser or Ｄ Thr; P １２ are Agb, Agp, Dab, Dab(iPr), Dap, Dap(iPr), Har, Lys, Lys(iPr), Narg, Ndab, Nlys, Norn, Orn, Orn(iPr), Pro((4R)guanidine), Pro((4R)NH ２ ), Pro((4S)NH ２ ), Arg, NMeLys; alloThr, Cit, Hgn, Hse, Hyp, Leu((3R)OH), Asn, Gln, Ser, Thr; Ala, Ala(cPr), Ala(tetrahydropyran-4-yl), Abu, alloIle, betaGly, Cha, Cpa, Cpg, Cyq, Dea, Gly, Hle, Ile, Leu, Met, Nle, OctGly, Sar, tBuGly, tBuAla, Val, Pro, NMeAla, NMeVal, Nva; Phe, His, Phe(3OH), Phe(4F), Phe(4OCF3), Trp(6Cl), Tyr(3Cl), Tyr(3F), Trp, Tyr, Phe(4NH2), Tyr(Me), Ntyr or Nphe; P １３ Agb, Agp, Dab, Dab (iPr), Dap, Dap (iPr), Har, Lys, Lys (iPr), Narg, Ndab, Nlys, Norn, Orn, Orn (iPr), Arg, Nmelys; alloThr, Cit, Hgn, Hse, Leu((3R)OH), Ser, Thr; Ala, Ala(cPr), Abu, Met, Val, NMeAla, NMeVal or Nva; P １４ Agb, Agp, Dab, Dab (iPr), Dap, Dap (iPr), Har, Lys, Lys (iPr), Narg, Ndab, Nlys, Norn, Orn, Orn (iPr), Arg, Nmelys; Ｄ Dab, Ｄ Dab(iｰr) Ｄ Yes, Ｄ Dap(irr) Ｄ Lys, Ｄ Lys(iｰr) Ｄ Orrn, Ｄ Orn(iｰr) Ｄ Ar; alloThr, Cit, Hgn, Hse, Leu((3R)OH), Asn, Gln, Ser, Thr; Abu, alloIle, Dea, Hle, Ile, Leu, Met, Nle, OctGly, tBuGly, tBuAla, Val, NMeAla, NMeVal, Nva; Phe, Phe(3OH), Phe(4F), Phe(4OCF3), Trp(6Cl), Tyr(3Cl), Tyr(3F), Trp, Tyr, Phe(4NH2), Tyr(Me), Ntyr or Nphe; P １５ , Dab, Dap; Cys, Pen; Asp or Glu; P １６ are Phe, Phe(3OH), Phe(4F), Phe(4OCF3), Trp(6Cl), Tyr(3Cl), Tyr(3F), Trp, Tyr, 4Thz, Phe(4(4hydroxyphenoxy)), Phe(4NH2), Tyr(Me), Ntyr, Nphe; Ala (cPr), Abu, alloIle, Cha, Cpa, Cpg, Cyg, Dea, Hle, He, Leu, Nle, OctGly, tBuGly, tBuAla, Val, NMeAla, NMeVal or Nva) or a tautomer, rotamer, enantiomer, salt, hydrate or solvate thereof, However, position P ６ , P ８ , P ９ and P １１ ~P １４ At least five of the seven amino acid residues in Ｄ Dab, Ｄ Dab (iPr), Ｄ Dap, Ｄ Dap(iPr), Ｄ Lys, Ｄ Lys(iPr), Ｄ Orn, Ｄ Orn (iPr) or Ｄ is a basic amino acid residue selected from Arg, A peptidomimetic compound, or a tautomer, rotamer, enantiomer, salt, hydrate or solvate thereof.

2. When Cys or Pen is present in P 4 and when Cys or Pen is present in P 15 , a disulfide bridge is formed between P 4 and P 15 ; or If Dab or Dap is present at P 4 and Asp or Glu is present at P 15 , a lactam bridge is formed between P 4 and P 15 ; or When Asp or Glu is present at P 4 and Dab or Dap is present at P 15 , a lactam bridge is formed between P 4 and P 15 .

2. A compound, tautomer, rotamer, enantiomer, salt, hydrate or solvate of claim 1.

3. P １ is Abu, tBuGly or Val; P １ wherein the amino group is unsubstituted or substituted by a guanidino group (Gua) or by a tetramethylguanidino (TMG) group; P ２ ,Hyp; Pro, Pro((4S)F), Pro((4R)F), Pro(4,4F ２ ), Pro((4R)OMe) or Pro(3,4 dehydro); P ３ is Cpg or Ile; P ４ , Dab, Dap; Cys, Pen; Asp or Glu; . ５ は、; 3,late,lashlashlashlashlashexflow r、P(!!!y)r(\e); Ala, Met, NMeAla; Hse, Ser or Thr; P ６ は、alloThr、Cit、Hse、Leu((3R)OH)、Asn、Gln、Ser、Thr、Asp、Glu、Hgl; Agb, Agp, Dab, Dap, Har, Lys, Orn, Arg; Abu, alloIle, Dea, Hle, Ile, Leu, Nle, tBuGly, tBuAla, Val, NMeVal or Nva; P ７ は、alloThr、Hse、Asn、Gln、Ser、Thr、Asp、Glu、Hgl; Ala, Abu, alloIle, Dea, Hle, Ile, Leu, Nle, tBuGly, tBuAla, Val, NMeAla, NMeVal or Nva; P ８ is Arg; P ９ Agb, Agp, Dab, Dab (iPr), Dap, Dap (iPr), Har, Lys, Lys (iPr), Narg, Ndab, Nlys, Norn, Orn, Orn (iPr), Arg, Nmelys; Ｄ Dab, Ｄ Dab(iｰr) Ｄ Yes, Ｄ Dap(irr) Ｄ Lys, Ｄ Lys(iｰr) Ｄ Orrn, Ｄ Orn(iｰr) Ｄ Ar; Cit, Hgn, Hse, Hyp, Asn, Gln, Ser, Thr; Ala, Ala(cPr), Ala(tetrahydropyran-4-yl), Abu, or Pro; P １０ is Asn, Ser or Thr; P １１ は、 Ｄ Dab, Ｄ Dab(iｰr) Ｄ Yes, Ｄ Dap(irr) Ｄ Lys, Ｄ Lys(iｰr) Ｄ Orrn, Ｄ Orn(iｰr) Ｄ Ar; Ｄ Cit, Ｄ Asn, Ｄ Gln, Ｄ Ser or Ｄ Thr; P １２ は、Agb、Agp、Dab、Dap、Har、Lys、Orn、Arg; alloThr, Cit, Hgn, Hse, Leu ((3R)OH), Asn, Gln, Ser, Thr; Ala, Abu, alloIle, Dea, Hle, He, Leu, Met, Nle, OctGly, tBuGly, tBuAla, Val, Nva; Phe, Phe(3OH), Phe(4F), Phe(4OCF), Tyr(3Cl), Tyr(3F), Trp, Tyr, Phe(4NH) or Tyr(Me); P １３ は、Agb、Agp、Da、Da(iPr)、Da、Da(iPr)、Har、Lys、Lys(iPr); alloThr, Cit, Hse, Leu ((3R)OH), Ser, Thr; Ala or Met; P １４ は、Agb、Agp、Da、Da(iPr)、Da、Da(iPr)、Har、Lys、Lys(iPr); Ｄ Dab, Ｄ Dab(iｰr) Ｄ Yes, Ｄ Dap(irr) Ｄ Lys, Ｄ Lys(iｰr) Ｄ Orrn, Ｄ Orn(iｰr) Ｄ Ar; alloThr, Cit, Hgn, Hse, Leu ((3R)OH), Asn, Gln, Ser, Thr; Abu, alloIle, Dea, Hle, He, Leu, Met, Nle, tBuGly, tBuAla, Val, Nva; Phe, Phe (3OH), Phe (4F), Phe (4OCF3), Tyr (3Cl), Tyr (3F), Tyr, Phe (4NH2) or Tyr (Me); P １５ , Dab, Dap; Cys, Pen; Asp or Glu; . １６ は、; 、!(!!!()、)、 (4)、(())、 (*)、? Ala(cPr), Abu, alloIle, Cha, Cpa, Cpg, Cyg, Dea, Hle, Ile, Leu, Nle, OctGly, tBuGly, tBuAla or Nva, 10. A compound according to claim 1, or a tautomer, rotamer, enantiomer, salt, hydrate or solvate thereof, However, position P ６ , P ８ , P ９ and P １１ ~P １４ At least five of the seven amino acid residues in Ｄ Dab, Ｄ Dab (iPr), Ｄ Dap, Ｄ Dap(iPr), Ｄ Lys, Ｄ Lys(iPr), Ｄ Orn, Ｄ Orn (iPr) or Ｄ is a basic amino acid residue selected from Arg, 2. A compound according to claim 1, or a tautomer, rotamer, enantiomer, salt, hydrate or solvate thereof.

4. When Cys or Pen is present in P 4 and when Cys or Pen is present in P 15 , a disulfide bridge is formed between P 4 and P 15 ; or If Dab or Dap is present at P 4 and Asp or Glu is present at P 15 , a lactam bridge is formed between P 4 and P 15 ; or When Asp or Glu is present at P 4 and Dab or Dap is present at P 15 , a lactam bridge is formed between P 4 and P 15 .

4. A compound, tautomer, rotamer, enantiomer, salt, hydrate or solvate according to claim 3.

5. P 9 is Agb, Agp, Dab, Dab(iPr), Dap, Dap(iPr), Har, Lys, Lys(iPr), Narg, Ndab, Nlys, Norn, Orn, Orn(iPr), Arg, NMeLys; D Dab, D Dab (iPr), D Dap, D Dap (iPr), D Lys, D Lys (iPr), D Orn, D Orn (iPr), D Arg; Cit, Hgn, Hse, Asn, Gln, Ser, Thr; Ala, Ala(cPr), Ala(tetrahydropyran-4-yl) or Abu; 4. A compound according to claim 3, or a tautomer, rotamer, enantiomer, salt, hydrate or solvate thereof.

6. P 1 is Abu, tBuGly or Val; the amino group of P 1 is unsubstituted or substituted by a guanidino group (Gua); P 2 is Hyp; Pro, Pro((4S)F), Pro((4R)F), Pro(4,4F 2 ), Pro((4R)OMe) or Pro(3,4 dehydro); P 3 is Cpg or Ile; P 4 is Dab; Cys, Pen; or Glu; P5 is Phe, Trp, Tyr; Ala; or Ser; P 6 is alloThr, Cit, Hse, Asn, Ser, Thr, Glu; Dab, Dap, Lys, Orn, Arg; or He; P 7 is Hse, Asn, Gln, Ser, Thr, Asp, Glu; Ala or He; P 8 is Arg; P 9 is Agb, Dab, Dab(iPr), Lys, Orn, Arg; D Dab, D Lys, D Orn, D Arg; Cit, Hyp, Asn, Ser, Thr; Ala or Pro; P 10 is Asn, Ser or Thr; P 11 is D Dab, D Dab (iPr), D Dap, D Dap (iPr), D Lys, D Lys (iPr), D Orn, D Orn (iPr), D Arg; or D Cit; P 12 is Agb, Agp, Dab, Dap, Har, Lys, Orn, Arg; alloThr, Cit, Hgn, Hse, Leu ((3R)OH), Asn, Gln, Ser, Thr; Ala, Abu, alloIle, Dea, Hle, He, Leu, Met, Nle, OctGly, tBuGly, tBuAla, Val, Nva; Phe, Phe(3OH), Trp, Tyr, Phe(4NH2) or Tyr(Me); P 13 is Dab, Dab(iPr), Lys, Orn, Arg; alloThr, Cit, Hse, Ser or Thr; P 14 is Agb, Dab, Dab (iPr), Dap, Lys, Orn, Arg; D Dab, D Lys, D Arg; alloThr, Cit, Hse, Asn, Gln, Ser, Thr; Ile; or Tyr; P 15 is Dab; Cys, Pen; or Glu; P 16 is Phe, Trp, Tyr, Phe (4NH2), Tyr (Me); Cha or Nle) 10. A compound according to claim 1, or a tautomer, rotamer, enantiomer, salt, hydrate or solvate thereof, with the proviso that at least five of the seven amino acid residues at positions P6, P8, P9 and P11 to P14 are basic amino acid residues selected from Agb, Agp, Dab, Dab(iPr), Dap, Dap(iPr), Har, Lys, Lys(iPr), Orn, Orn(iPr), Arg, D Dab, D Dab(iPr), D Dap, D Dap(iPr), D Lys, D Lys(iPr), D Orn, D Orn(iPr) or D Arg, 2. A compound according to claim 1, or a tautomer, rotamer, enantiomer, salt, hydrate or solvate thereof.

7. When Cys or Pen is present in P 4 and when Cys or Pen is present in P 15 , a disulfide bridge is formed between P 4 and P 15 ; or If a Dab is present at P 4 and a Glu is present at P 15 , a lactam bridge is formed between P 4 and P 15 ; or When Glu is present at P 4 and Dab is present at P 15 , a lactam bridge is formed between P 4 and P 15 .

7. A compound, tautomer, rotamer, enantiomer, salt, hydrate or solvate according to claim 6.

8. P 9 is Agb, Dab, Dab(iPr), Lys, Orn, Arg; D Dab, D Lys, D Orn, D Arg; Cit, Asn, Ser, Thr; or Ala, 7. A compound according to claim 6, or a tautomer, rotamer, enantiomer, salt, hydrate or solvate thereof.

9. P １ is Val, Abu, tBuGly, Gua-Val or Gua-Abu; P ２ are Hyp, Pro, Pro((4S)F), Pro((4R)F), Pro(4,4F ２ ), Pro((4R)OMe) or Pro(3,4 dehydro); P ３ is Cpg or Ile; P ４ is Cys, Pen, Dab or Glu; P ５ is Tyr, Ala or Ser; P ６ is Ser, Thr, Ile, Glu, Asn, Cit, Hse or Dab; P ７ is Asn, Ala, Ile, Ser, Asp or Glu; P ８ is Arg; P ９ Dab, Ｄ Dab, Dab(iPr), Agb, Cit, Asn, Ser or Ala; P １０ is Thr, Ser or Asn; P １１ teeth, Ｄ Dab, Ｄ Dab (iPr), Ｄ Lys, Ｄ Arg or Ｄ Cit; P １２ is Lys, Ala, Ile, Ser, Asn, Cit, Dab, Orn, Val or Tyr; P １３ is Dab, Dab(iPr), Orn, Arg, Ala, Ser, Thr or Cit; P １４ Dab, Ｄ Dab, Dab(iPr), Lys, Orn, Agb, Ile, Tyr, Ser, Asn, Thr or Cit; P １５ is Cys, Pen, Dab or Glu; P １６ is Tyr, Trp, Cha or Nle; 10. A compound according to claim 1, or a tautomer, rotamer, enantiomer, salt, hydrate or solvate thereof, However, position P ６ , P ８ , P ９ and P １１ ~P １４ At least five of the seven amino acid residues in Ｄ Dab, Ｄ Dab (iPr), Ｄ Lys or Ｄ is a basic amino acid residue selected from Arg, 2. A compound according to claim 1, or a tautomer, rotamer, enantiomer, salt, hydrate or solvate thereof.

10. When Cys or Pen is present in P 4 and when Cys or Pen is present in P 15 , a disulfide bridge is formed between P 4 and P 15 , or If Glu is present at P 4 and Dab is present at P 15 , a lactam bridge is formed between P 4 and P 15 , or When Dab is present at P 4 and Glu is present at P 15 , a lactam bridge is formed between P 4 and P 15 .

10. A compound, tautomer, rotamer, enantiomer, salt, hydrate or solvate according to claim 9.

11. P １ is Val, Abu, tBuGly or Gua-Val; P ２ are Hyp, Pro, Pro((4S)F), Pro((4R)F), Pro(4,4F ２ ), Pro((4R)OMe) or Pro(3,4 dehydro); P ３ is Cpg or Ile; P ４ is Pen, Dab or Glu; P ５ is Tyr; P ６ is Cit, Hse, Ser, Thr, Asn or Dab; P ７ is Asn, He or Ser; P ８ is Arg; P ９ is Dab, Dab(iPr) or Agb; P １０ is Thr, Ser or Asn; P １１ teeth, Ｄ Dab, Ｄ Dab (iPr), Ｄ Lys or Ｄ Arg; P １２ is Dab, Orn, Lys, Ser, Cit or Tyr; P １３ is Dab, Dab(iPr), Orn, Arg, Ser or Thr; P １４ Dab, Ｄ Dab, Dab(iPr), Lys, Orn, Agb, Ser or Thr; P １５ is Cys, Dab or Glu; P １６ is Tyr, Trp, Cha or Nle; 10. A compound according to claim 1, or a tautomer, rotamer, enantiomer, salt, hydrate or solvate thereof, However, position P ６ , P ８ , P ９ and P １１ ~P １４ At least five of the seven amino acid residues in Ｄ Dab, Ｄ Dab (iPr), Ｄ Lys or Ｄ is a basic amino acid residue selected from Arg, 2. A compound according to claim 1, or a tautomer, rotamer, enantiomer, salt, hydrate or solvate thereof.

12. When Pen is present at P 4 and Cys is present at P 15 , a disulfide bridge is formed between P 4 and P 15 , or If Glu is present at P 4 and Dab is present at P 15 , a lactam bridge is formed between P 4 and P 15 , or When Dab is present at P 4 and Glu is present at P 15 , a lactam bridge is formed between P 4 and P 15 .

12. A compound, tautomer, rotamer, enantiomer, salt, hydrate or solvate of claim 11.

13. P １ is Val; P ２ is Hyp or Pro; P ３ is Ile; P ４ is Pen, Dab or Glu; P ５ is Tyr, Ala or Ser; P ６ is Ser, Thr, Glu, Asn or Dab; P ７ is Asn, Ala, Asp or Glu; P ８ is Arg; P ９ Dab, Ｄ Dab, Cit, Asn or Ser; P １０ is Thr or Asn; P １１ teeth, Ｄ Dab or Ｄ Cit; P １２ is Lys, Ile, Ser or Asn; P １３ is Dab, Orn, Ser or Thr; P １４ Dab, Ｄ Dab, Ser, Asn, or Cit; P １５ is Cys, Dab or Glu; P １６ is Tyr or Trp; 10. A compound according to claim 1, or a tautomer, rotamer, enantiomer, salt, hydrate or solvate thereof, However, position P ６ , P ８ , P ９ and P １１ ~P １４ At least five of the seven amino acid residues in Ｄ is a basic amino acid residue selected from Dab; 2. A compound according to claim 1, or a tautomer, rotamer, enantiomer, salt, hydrate or solvate thereof.

14. When Pen is present at P 4 and Cys is present at P 15 , a disulfide bridge is formed between P 4 and P 15 , or If Glu is present at P 4 and Dab is present at P 15 , a lactam bridge is formed between P 4 and P 15 , or When Dab is present at P 4 and Glu is present at P 15 , a lactam bridge is formed between P 4 and P 15 .

14. A compound, tautomer, rotamer, enantiomer, salt, hydrate or solvate of claim 13. **Claim 15**: Val-Hyp-Ile-Pen-Tyr-Ser-Asn-Arg-Dab-Thr- Ｄ Dab-Lys-Dab-Dab-Cys-Tyr; Abu-Hyp-Ile-Pen-Tyr-Ser-Asn-Arg-Dab-Thr- Ｄ Dab-Lys-Dab-Dab-Cys-Tyr; tBuGly-Hyp-Ile-Pen-Tyr-Ser-Asn-Arg-Dab-Thr- Ｄ Dab-Lys-Dab-Dab-Cys-Tyr; Val-Pro-Ile-Pen-Tyr-Se-Ssn-Brg-Ob-Tr- Ｄ Dab-Lys-Dab-Dab-Cys-Tyr; The Ｄ Dab-Lys-Dab-Dab-Cys-Tyr; Val-Pro((4R)OMe)-Ile-Pen-Tyr-Thr-Asn-Arg-Dab-Thr- Ｄ Dab-Lys-Dab-Dab-Cys-Tyr; Val-Pro((4S)F)-Ile-Pen-Tyr-Thr-Asn-Arg-Dab-Thr- Ｄ Dab-Lys-Dab-Dab-Cys-Tyr; Val-Pro((4R)F)-Ile-Pen-Tyr-Thr-Asn-Arg-Dab-Thr- Ｄ Dab-Lys-Dab-Dab-Cys-Tyr; Val-Pro(4,4F ２ )-Ile-Pen-Tyr-Thr-Asn-Arg-Dab-Thr- Ｄ Dab-Lys-Dab-Dab-Cys-Tyr; The Ｄ Dab-Lys-Dab-Dab-Cys-Tyr; The Ｄ Dab-Lys-Dab-Dab-Cys-Tyr; The Ｄ Dab-Lys-Dab-Dab-P-Tyr; ______________________________________ 3) _________________________________________________ Ｄ . Val-Hyp-Il-Pen-Se-Se-Se-Se-Ps Ｄ Dab-Lys-Dab-Dab-Cys-Tyr; Val-Hyp-Ile-Pen-Tyr-Thr-Asn-Arg-Dab-Thr- Ｄ Dab-Lys-Dab-Dab-Cys-Tyr; _________________________________ ____________________________________________ Ｄ . Val-Hyp-Ile-Pen-Tyr-G5-Asn-Arg-Dab-Thr- Ｄ Dab-Lys-Dab-Dab-Cys-Tyr; The Ｄ Dab-Lys-Dab-Dab-Cys-Tyr; The Ｄ Dab-Lys-Dab-Dab-Cys-Tyr; _________________________________ 3) _____________________________ Ｄ . _________________________________ 3) _______________________________________________ Ｄ . Val-Hyp-Ile-Pen-Tyr-S-Glu-Bs-Pr Ｄ Dab-Lys-Dab-Dab-Cys-Tyr; Val-Hyp-Ile-Pen-Tyr-Se-Bs-Brg-Bab-Tr- Ｄ Dab-Lys-Dab-Dab-Cys-Tyr; The Ｄ Dab-Lys-Dab-Dab-Cys-Tyr; _________________________________ 3) _______________________________ Ｄ . Val-Hyp-Ile-P--Tyr-Ser-Asn-Arg- Ｄ Dab-Thr- Ｄ Dab-Lys-Dab-Dab-Cys-Tyr; Val-Hyp-Ile-Pen-Tyr-Se-Cit-Thr- Ｄ Dab-Lys-Dab-Dab-Cys-Tyr; Val-Hyp-Il%-Pen-Tyr-Se-Bsn�hr- Ｄ Dab-Lys-Dab-Dab-Cys-Tyr; Val-Hyp-Ile-Pen-Tyr-S�+- Ｄ Dab-Lys-Dab-Dab-Cys-Tyr; The Ｄ Dab-Lys-Dab-Dab-Cys-Tyr; Val-Hyp-Il-Pen-Tyr-Se-Bsn-Bs-Bab-Bs- Ｄ Dab-Lys-Dab-Dab-Cys-Tyr; Val-Hyp-Ile-Pen-Tyr-Dab-Bsn-Bs-Dab-S-BE-BE Ｄ Dab-Lys-Dab-S�9; Val-Hyp-Ile-Pen-Tyr-S Ｄ Dab-Lys-Dab-Dab-Cys-Tyr; The Ｄ Lys-Lys-Dab-Dab-Cys-Tyr; Val-Hyp-Ile-Pen-Tyr-Se-Bsn-Bs-Dab-Thr- Ｄ Arg-Lys-Dab�ys-Tyr; The Ｄ Cit-Lys-Dab�ys-Dyr; Val-Hyp-Ile-Pen-Tyr-Se-Bsn-Bs-Dab-Thr- Ｄ Dab(iPr)-Lys-Dab�ys-Er; Val-Hyp-Ile-Pen-Tyr-Se-Bsn-Bs-Dab-Thr- Ｄ Dab-Ala-Dab-Dab-Cys-Tyr; The Ｄ Dab-C~-Dab-Dab-Cys-Tyr; The Ｄ Dab-Tyr-Dab-Tyr; The Ｄ Dab-Ile-Dab-Dab-Cys-Tyr; Val-Hyp-Ile-Pen-Tyr-Se-Bsn-Bs-Dab-Thr- Ｄ Dab-Asn-Dab-Dab-Cys-Tyr; The Ｄ Dab-Ser-Dab-Dab-Cys-Tyr; The Ｄ Dab-Lys-Se-Ob-E; _________________________________ 3) _________________________________________________ Ｄ . The Ｄ Dab-Lys-Se-Ob-E; The Ｄ Dab-Lys-Ser-Ser-Cys-Tyr; Val-Hyp-Ile-Pen-Tyr-Dab-Asn-Arg-Dab-Thr- Ｄ Dab-Lys-Thr-Cit-Cys-Tyr; Val-Hyp-Ile-Pen-Tyr-Dab-Asn-Arg-Dab-Thr- Ｄ Dab-Lys-Thr-Ile-Cys-Tyr; Val-Hyp-Ile-Pen-Tyr-Dab-Asn-Arg-Dab-Thr- Ｄ Dab-Lys-Thr-Asn-Cys-Tyr; The Ｄ Dab-Lys-Thr-Ser-Cys-Tyr; The Ｄ Dab-Lys-Cit-Dab-Cys-Tyr; Val-Hyp-Ile-Pen-Tyr-Se-Bsn-Bs-Dab-Thr- Ｄ Dab-Lys-Bs-Dab-Cys-Tyr; Val-Hyp-Ile-Pen-Tyr-Se-Bsn-Bs-Dab-Thr- Ｄ Dab-Lys-Orn-Ser-Cys-Tyr; The Ｄ Dab-Lys-Dab-S�9; The Ｄ Dab-Lys-Dab-S�9; The Ｄ Dab-Lys-Dab- Ｄ Dab-Cys-Tyr; The Ｄ Dab-Lys-Dab-CitCys-Tyr; The Ｄ Dab-Lys-Dab-Tyr-Cys-Tyr; Val-Hyp-Ile-Pen-Tyr-Se-Bsn-Bs-Dab-Thr- Ｄ Dab-Lys-Dab-Asn-Cys-Tyr; The Ｄ Dab-Lys-Dab-Lys-Cys-Tyr; Val-Hyp-Ile-Pen-Tyr-Se-Bsn-Bs-Dab-Thr- Ｄ Dab-Lys-Dab-Dab(iPr)-Cys-Er; Val-Hyp-Ile-Pen-Tyr-Se-Bsn-Bs-Dab-Thr- Ｄ Dab-Lys-Dab-Orn-Cys-Tyr; _________________________________ 3) _________________________________________________ Ｄ . Val-Hyp-Ile-Pen-Tyr-Se-Bsn-Bs-Dab-Thr- Ｄ Dab-Lys-Dab-Dab-Cys-Trp; _________________________________ 3) _________________________________________________ Ｄ . ______________________________________________ ______________________________________ Ｄ . ______________________________________________ ____________________________________________________ Ｄ . Gu-Va-Hy-I-Phu-Phu-Phu-Thu-Shu-A-A-Ar-Dab()Phu)-Thu- Ｄ Dab-Lys-Dab(iPr)-Dab-Cys-Kyr; - Ｄ Dab(iPr)-Lys-Dab�ys-Er; ______________________________________________ ____________________________________________________ Ｄ .. . . . . . . . . . . . .) . ______________________________________________ ____________________________________________________ Ｄ ! y s ) ) y ¨ 4 . ______________________________________________ ____________________________________________________ Ｄ _________________________________________________________ ______________________________________________ _____________________________________________________ Ｄ ___________________________ ___________________________________________ _____________________________________________________ Ｄ . ______________________________________________ _____________________________________________________ Ｄ ____________________________________ The Ｄ Dab-Lys-Dab-Flu-Ky; The Ｄ Dab-Lys-Dab-Dab-Dab-Tyr; ______________________________________________ ____________________________________________________________________ Ｄ . Gua-Val-Hyp-Ile-Pen-Tyr-Thr-Asn-Arg-Dab-Thr- Ｄ Dab-Ser-Dab-Dab-Cys-Tyr; ______________________________________________ ____________________________________________________________________ Ｄ twentieth  aax‐expresent e′ n--f   ′                                                                                              lan a exalan a exalan a extressed - Ｄ Dab-Lys-Dab-Flu-Ky; - Ｄ Dab-Lys-Dab-Flu-Ky; - Ｄ Dab-Lys-Dab-Daa-Glu-Tyr; - Ｄ Dab-Lys-Dab-Flu-Ky; - Ｄ Dab-Lys-Dab-Dab-Dab-Tyr; - Ｄ Dab-Lys-Dab-Dab-Dab-Tyr; - Ｄ Dab-Lys-Dab-Dab-Dab-Tyr; Gua-Val-Hyp-Ile-Pen-Tyr-Ser-Asn-Arg-Dab-Thr- Ｄ Dab-Thr-Dab-Dab-Cys-Tyr; ______________________________________________ pi Ｄ _________________________ Gua-Val-Hyp-Ile-Pen-Tyr-Thr-Asn-Arg-Dab(iPr)-Thr- Ｄ Dab-Lys-Dab-Dab-Cys-Tyr; Gua-Val-Hyp-Ile-Pen-Tyr-Thr-Asn-Arg-Dab(iPr)-Thr- Ｄ Dab-Ser-Dab-Dab-Cys-Tyr; ______________________________________________ _______________________________________ Ｄ . Gua-Val-Hyp-Ile-Pen-Tyr-Thr-Asn-Arg-Dab-Thr- Ｄ Dab(iPr)-Lys-Dab-Dab-Cys-Tyr; Gua-Val-Hyp-Ile-Pen-Tyr-Thr-Asn-Arg-Dab-Thr- Ｄ Dab(iPr)-Ser-Dab-Dab-Cys-Tyr; - Ｄ t0.834597374 ______________________________________________ ______________________________________ Ｄ ________________|______ ______________________________________________ _____________________________________________________ Ｄ twentieth  aax‐expresent e′ n--f   ′                                                                                              lan a exalan a exalan a extressed ______________________________________________ ______________________________________ Ｄ __________________________________________________________________ ______________________________________________ ____________________________________________________ Ｄ  avaaency n, s s s‐expanion‐fa                                                            alate a        chlement of       la differential ready ______________________________________________ ____________________________________________________ Ｄ .. . . . . . . . . . . .. .. .. .. .. . Gua-Val-Hyp-Ile-Pen-Tyr-Thr-Asn-Arg- Ｄ Dab-Thr- Ｄ Dab-Ser-Dab-Dab-Cys-Tyr; ______________________________________________. Ｄ �������� Ｄ twentieth  aax‐expresent e′ n--f   ′                                                                                              lan a exalan a exalan a extressed Gua-Val-Hyp-Ile-Pen-Tyr-Thr-Asn-Arg-Dab-Thr- Ｄ Dab-Asn-Dab-Dab-Cys-Tyr; ______________________________________________ _____________________________________________________ Ｄ .. . . . . . .. . ______________________________________________ _____________________________________________________ Ｄ . ______________________________________________ ______________________________________ Ｄ aaxa8fixifiMants a s a Gua-Val-Pro(3,4デヒドロ)-Ile-PPen-Tyr-Thr-Asn-Arg-Dar-Thr- Ｄ Dab-Lys-Dab-Dab-Cys-Tyr; Gua-Val-Pro(3,4デヒドロ)--le-PPen-Tyr-Ser-Asn-Arg-Daa-Thr- Ｄ Dab-Lys-Dab-Dab-Cys-Tyr; Gua-Val-Pro(3,4デヒドロ)-Ile-PPen-Tyr-Thr-Asn-Arg-Dar-Thr- Ｄ Dab-Ser-Dab-Dab-Cys-Tyr; - Ｄ Dab-S-Dab-Dab--u-Tyr; - Ｄ Dab-Thr-Dab-Dab-Glu-Tyr; - Ｄ Dab-Cit-Dab-Dab-Glu-Tyr; ______________________________________________ _________________________________ Ｄ . ________________________________________________ _________________________________ Ｄ . ______________________________________________ ______________________________________________________________ Ｄ . ________________________________________________ ______________________________________________________________ Ｄ . - Ｄ Dab-Orn-Dab-Dab-Glu-Tyr; Gua-Val-Hyp-Ile-Pen-Tyr-Dab-Asn-Arg-Dab-Thr- Ｄ Dab-Dab-Thr-Dab-Cys-Tyr; Gua-Val-Hyp-Ile-Pen-Tyr-Dab-Asn-Arg-Dab-Thr- Ｄ Dab-Orn-Thr-Dab-Cys-Tyr; ______________________________________________ _________________________________ Ｄ __________________________________________________________ Gua-Val-Hyp-Ile-Pen-Tyr-Thr-Asn-Arg-Dab-Thr- Ｄ Dab-Dab-Dab-Dab-Cys-Tyr; Gua-Val-Hyp-Ile-Pen-Tyr-Thr-Asn-Arg-Dab-Thr- Ｄ Dab-Orn-Dab-Dab-Cys-Tyr; ______________________________________________ _____________________________________________________ Ｄ . ______________________________________________ _____________________________________________________ Ｄ _________________________________ Gua-Val-Hyp-Ile-Pen-Tyr-Thr-Asn-Arg-Dab-Thr- Ｄ Dab-Dab-Dab-Ser-Cys-Tyr; ______________________________________________ ______________________________________ Ｄ _________________________________________ Gua-Val-Hyp-Ile-Pen-Tyr-Dab-Asn-Arg-Dab-Thr- Ｄ Dab-Dab-Thr-Ser-Cys-Tyr; ______________________________________________ ____________________________________________________ Ｄ ________________________________________ Gua-Val-Hyp-I-Pen-Tyr-Thr-Asn-Arg-Dab-Thr- Ｄ Dab-Lys-Dab-Thr-Cys-Tyr; Gua-Val-Hyp-Ile-Pen-Tyr-Thr-Asn-Arg-Dab-Thr- Ｄ Dab-Dab-Dab-Thr-Cys-Tyr; Gua-Val-Hyp-Ile-Pen-Tyr-Thr-Asn-Arg-Dab-Thr- Ｄ Dab-Orn-Dab-Thr-Cys-Tyr; Gua-Val-Hyp-Cpg-Pen-Tyr-Thr-Asn-Arg-Dab-Thr- Ｄ Dab-Ser-Dab-Dab-Cys-Tyr; - Ｄ Dab-Dab-Dab-Dab-Glu-Tyr; - Ｄ Dab-Val-Dab-Dab-Glu-Tyr; selected from the group consisting of 2. A compound according to claim 1, or a tautomer, rotamer, enantiomer, salt, hydrate or solvate thereof.

16. When Cys or Pen is present in P 4 and when Cys or Pen is present in P 15 , a disulfide bridge is formed between P 4 and P 15 , or If Glu is present at P 4 and Dab is present at P 15 , a lactam bridge is formed between P 4 and P 15 , or When Dab is present at P 4 and Glu is present at P 15 , a lactam bridge is formed between P 4 and P 15 .

16. A compound, tautomer, rotamer, enantiomer, salt, hydrate or solvate of claim 15.

17. The compound of claim 1, which is Gua-Val-Hyp-Ile-Pen-Tyr-Dab-Asn-Arg-Dab-Thr-D Dab-Lys-Ser-Dab-Cys-Tyr, or a tautomer, rotamer, enantiomer, salt, hydrate or solvate thereof, wherein Pen at P4 and Cys at P15 form a disulfide bridge between P4 and P15.

18. The compound of claim 1, which is Gua-Val-Hyp-Ile-Pen-Tyr-Thr-Asn-Arg-Dab-Thr-D Dab-Ser-Dab-Dab-Cys-Tyr, or a tautomer, rotamer, enantiomer, salt, hydrate or solvate thereof, wherein Pen at P4 and Cys at P15 form a disulfide bridge between P4 and P15.

19. The compound of claim 1, which is Gua-Val-Hyp-Ile-Dab-Tyr-Thr-Asn-Arg-Dab-Ser-D Dab-Lys-Dab-Dab-Glu-Tyr, or a tautomer, rotamer, enantiomer, salt, hydrate or solvate thereof, wherein the Dab at P 4 and the Glu at P 15 form a lactam bridge between P 4 and P 15. The compound of claim 1, or a tautomer, rotamer, enantiomer, salt, hydrate or solvate thereof.

20. The compound of claim 1, which is Gua-Val-Hyp-Ile-Pen-Tyr-Thr-Asn-Arg-Dab-Thr-D Dab-Dab-Dab-Dab-Cys-Tyr, or a tautomer, rotamer, enantiomer, salt, hydrate or solvate thereof, wherein Pen at P4 and Cys at P15 form a disulfide bridge between P4 and P15.

21. The compound of claim 1, which is Gua-Val-Hyp-Ile-Pen-Tyr-Thr-Asn-Arg-Dab-Thr-D Dab-Dab-Dab-Ser-Cys-Tyr, or a tautomer, rotamer, enantiomer, salt, hydrate or solvate thereof, wherein Pen at P4 and Cys at P15 form a disulfide bridge between P4 and P15.

22. A composition comprising a compound or a mixture of compounds according to any one of claims 1 to 21, or a pharmaceutically acceptable salt thereof.

23. 23. The composition of claim 22 in a form suitable for oral, topical, transdermal, injectable, buccal, transmucosal, rectal, pulmonary or inhalation administration.

24. The composition of claim 22 in the form of a tablet, dragee, capsule, solution, liquid, gel, plaster, cream, ointment, syrup, slurry, suspension, spray, nebulizer, aerosol or suppository.

25. The composition of claim 22 for treating or preventing a bacterial infection or a disease associated with such an infection.

26. The composition of claim 25, wherein the bacterial infection is associated with a respiratory disease, or a skin or soft tissue disease, or a gastrointestinal disease, or an eye disease, or an ear disease, or a CNS disease, or a bone disease, or a cardiovascular disease, or a genitourinary disease, or a hospital-acquired infection, or a catheter-associated and non-catheter-associated infection, or a urinary tract infection, or a bloodstream infection, or infection-induced sepsis.

27. The composition described in claim 25, wherein the bacterial infection or disease associated with the infection is caused by a gram-negative bacterium.

28. The composition of claim 25, wherein the bacterial infection or disease associated with the infection is caused by Enterobacteriaceae bacteria.

29. The composition of claim 25, wherein the bacterial infection or disease associated with the infection is caused by Klebsiella pneumoniae and / or Escherichia coli.

30. The composition of claim 25, wherein the disease is selected from ventilator-associated pneumonia (VAP), ventilator-associated bacterial pneumonia (VABP), hospital-acquired pneumonia (HAP), hospital-acquired bacterial pneumonia (HABP), healthcare-associated pneumonia (HCAP), cystic fibrosis, emphysema, asthma, pneumonia, infectious diarrhea, necrotizing enterocolitis, appendicitis, gastroenteritis, pancreatitis, keratitis, endophthalmitis, otitis, brain abscess, meningitis, encephalitis, osteochondritis, pericarditis, epididymitis, prostatitis, urethritis, and sepsis.

31. 23. The composition of claim 22 for use as a disinfectant or preservative for food, cosmetics, pharmaceuticals and / or other nutrient-containing materials. (a) Attaching an appropriately functionalized solid support to a site P in the desired final product. １６ with a suitably N-protected derivative of an amino acid in (b) removing the N-protecting group from the product so obtained; (c) The product thus obtained is converted to a compound at position P １５ with a suitably N-protected derivative of an amino acid in (d) Position P in the desired final product １４ ~P ４ carrying out steps substantially corresponding to steps (b) and (c) using a suitably N-protected derivative of an amino acid in (e) selectively deprotecting one or several protected functional groups present in the molecule and chemically transforming the reactive groups thus liberated; (f) Position P in the desired final product ３ ~P ２ carrying out steps substantially corresponding to steps (b) and (c) using appropriately N-protected derivatives of the amino acids in (g) Position P in the desired final product １ further carrying out steps substantially corresponding to steps (b) and (c) using a suitably N-protected derivative of an amino acid or a suitably protected derivative of a hydroxy acid in the formula (I), wherein any functional groups that may be present in said N-protected amino acid derivative or hydroxy acid derivative are likewise suitably protected; and, after coupling, selectively deprotecting one or several protected functional groups present in the molecule and chemically converting the reactive groups thus liberated; (h) selectively deprotecting one or several protected functional groups present in the molecule and chemically transforming the reactive groups thus liberated; (i) Position P １ removing the N-protecting group in (j) cleaving the product so obtained from the solid support; (k) selectively deprotecting one or several protected functional groups present in the molecule and chemically transforming the reactive groups thus liberated; (l) removing any protecting groups present on the functional groups of any constituent of the chain of residues, and additionally any protecting groups that may be present in the molecule; (m) carrying out additional chemical transformations of one or more reactive groups present in the molecule; (n) removing, if necessary, any protecting groups present on the functional groups of any constituent of the chain of residues and, in addition, any protecting groups that may be present in the molecule; (o) converting the product so obtained into a pharmaceutically acceptable salt; or converting the pharmaceutically acceptable or unacceptable salts thus obtained into the corresponding free compounds of formula (I); or converting the pharmaceutically acceptable or unacceptable salt thus obtained into a different pharmaceutically acceptable salt; 22. A process for preparing a compound according to any one of claims 1 to 21, comprising:

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