# US 10,370,412 B2 · Beta-hairpin peptidomimetics

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- Number: US 10,370,412 B2
- Document ID: US10370412B2
- Status: Granted
- Kind: B2
- Application number: 15/816,955
- Filed: 2017-11-17
- Published: 2018-03-15
- Granted: 2019-08-06
- Earliest claimed: 2013-03-30
- Assignees: Polyphor AG
- Applicants: Polyphor AG
- Inventors: Daniel Obrecht; Anatol Luther; Francesca Bernardini; Peter Zbinden
- Web page: https://patentgrep.com/patent/US10370412B2

## CPC

- C07K 7/64: Cyclic peptides containing only normal peptide links
- A61P 1/00: Drugs for disorders of the alimentary tract or the digestive system
- A61P 1/04: for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
- A61P 1/12: Antidiarrhoeals
- A61P 1/18: for pancreatic disorders, e.g. pancreatic enzymes
- A61P 9/00: Drugs for disorders of the cardiovascular system
- A61P 11/00: Drugs for disorders of the respiratory system
- A61P 11/06: Antiasthmatics
- A61P 13/02: of urine or of the urinary tract, e.g. urine acidifiers
- A61P 13/08: of the prostate
- A61P 15/08: for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
- A61P 17/00: Drugs for dermatological disorders
- A61P 17/02: for treating wounds, ulcers, burns, scars, keloids, or the like
- A61P 19/00: Drugs for skeletal disorders
- A61P 25/00: Drugs for disorders of the nervous system
- A61P 27/02: Ophthalmic agents
- A61P 27/16: Otologicals
- A61P 31/00: Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P 31/02: Local antiseptics
- A61P 31/04: Antibacterial agents
- A61P 35/00: Antineoplastic agents
- A61K 38/00: Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00)
- Y02A 50/30: Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- Y02A: TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE

## Abstract

Beta-hairpin peptidomimetics of the general formula (I), cyclo[P1—P2—P3—P4—P5—P6—P7—P8—P9—P10—P11—P12-T1-T2], and pharmaceutically acceptable salts thereof, with P1 to P12, T1 and T2 being elements as defined in the description and the claims, have broad spectrum Gram-negative antimicrobial activity to e.g. inhibit the growth or to kill microorganisms such as Klebsiella pneumoniae and/or Acinetobacter baumannii and/or Escherichia coli. They can be used as medicaments to treat or prevent infections or as disinfectants for foodstuffs, cosmetics, medicaments or other nutrient-containing materials. These peptidomimetics can be manufactured by a process which is based on a mixed solid- and solution phase synthetic strategy.

## Claims

### Claim 1

A method for the treatment of infections caused by gram-negative bacteria or for the treatment or prevention of the onset of diseases related to such infections, comprising:
administering a compound to a subject in need thereof,
wherein said infections relate to respiratory diseases or skin or soft tissue diseases or gastrointestinal diseases or eye diseases or ear diseases or CNS diseases or bone diseases or cardiovascular diseases or genitourinary diseases, or nosocomial infections, or catheter-related and non-catheter-related infections, or urinary tract infections, or bloodstream infections; and
wherein said compound is a compound of the general formula (I),
cyclo[P1—P2—P3—P4—P5—P6—P7—P8—P9—P10—P11—P12-T1-T2] (I)
wherein the single elements T or P are connected in either direction from the carbonyl (C═O) point of attachment to the nitrogen (N) of the next element and wherein
T1 is DPro;
T2 is Pro; or Pro((3S)OH);
P1 is Leu; Ile; Val; Nva; or Trp;
P2 is His; Trp; or Tyr;
P3 is Leu; Cha; tBuGly; Trp; Tyr; or Tyr(Me);
P4 is Dab;
P5 is Orn; or Lys;
P6 is Dab; DDab; or Pip;
P7 is Dab;
P8 is Trp;
P9 is Hse; or Dab
P10 is tBuGly; Ile; Val; Nva; Cha; Chg; or Trp;
P11 is Ala; Val; Alb; Ser; Asn; or Tyr; and
P12 is Val; Ser; or alloThr;
or a pharmaceutically acceptable salt thereof.

### Claim 2

A method for disinfecting or preserving foodstuffs, cosmetics, medicaments or other nutrient-containing materials against gram-negative bacteria, comprising the step:
adding a compound to foodstuffs, cosmetics, medicaments or other nutrient-containing materials, thereby disinfecting or preserving said foodstuffs, cosmetics, medicaments or other nutrient-containing materials,
wherein said compound is a compound of the general formula (I),
cyclo[P1—P2—P3—P4—P5—P6—P7—P8—P9—P10—P11—P12-T1-T2] (I)
wherein the single elements T or P are connected in either direction from the carbonyl (C═O) point of attachment to the nitrogen (N) of the next element and wherein
T1 is DPro;
T2 is Pro; or Pro((3S)OH);
P1 is Leu; Ile; Val; Nva; or Trp;
P2 is His; Trp; or Tyr;
P3 is Leu; Cha; tBuGly; Trp; Tyr; or Tyr(Me);
P4 is Dab;
P5 is Orn; or Lys;
P6 is Dab; DDab; or Pip;
P7 is Dab;
P8 is Trp;
P9 is Hse; or Dab
P10 is tBuGly; Ile; Val; Nva; Cha; Chg; or Trp;
P11 is Ala; Val; Alb; Ser; Asn; or Tyr; and
P12 is Val; Ser; or alloThr;
or a pharmaceutically acceptable salt thereof.

### Claim 3

A method for the manufacture of a medicament to treat infections caused by gram-negative bacteria or to treat or prevent the onset of diseases related to such infections, comprising the step:
formulating a compound with one or more physiologically acceptable carriers, diluents, excipients, or auxiliaries,
wherein said infections relate to respiratory diseases or skin or soft tissue diseases or gastrointestinal diseases or eye diseases or ear diseases or CNS diseases or bone diseases or cardiovascular diseases or genitourinary diseases, or nosocomial infections, or catheter-related and non-catheter-related infections, or urinary tract infections, or bloodstream infections;
wherein said compound is a compound of the general formula (I),
cyclo[P1—P2—P3—P4—P5—P6—P7—P8—P9—P10—P11—P12-T1-T2] (I)
wherein the single elements T or P are connected in either direction from the carbonyl (C═O) point of attachment to the nitrogen (N) of the next element and wherein
T1 is DPro;
T2 is Pro; or Pro((3S)OH);
P1 is Leu; Ile; Val; Nva; or Trp;
P2 is His; Trp; or Tyr;
P3 is Leu; Cha; tBuGly; Trp; Tyr; or Tyr(Me);
P4 is Dab;
P5 is Orn; or Lys;
P6 is Dab; DDab; or Pip;
P7 is Dab;
P8 is Trp;
P9 is Hse; or Dab
P10 is tBuGly; Ile; Val; Nva; Cha; Chg; or Trp;
P11 is Ala; Val; Alb; Ser; Asn; or Tyr; and
P12 is Val; Ser; or alloThr;
or a pharmaceutically acceptable salt thereof.

### Claim 4

A method for the manufacture of a disinfectant or preservative against gram-negative bacteria for foodstuffs, cosmetics, medicaments and other nutrient-containing materials, comprising the step:
formulating a compound with one or more physiologically acceptable carriers, diluents, excipients, or auxiliaries,
wherein said compound is a compound of the general formula (I),
cyclo[P1—P2—P3—P4—P5—P6—P7—P8—P9—P10—P11—P12-T1-T2] (I)
wherein the single elements T or P are connected in either direction from the carbonyl (C═O) point of attachment to the nitrogen (N) of the next element and wherein
T1 is DPro;
T2 is Pro; or Pro((3S)OH);
P1 is Leu; Ile; Val; Nva; or Trp;
P2 is His; Trp; or Tyr;
P3 is Leu; Cha; tBuGly; Trp; Tyr; or Tyr(Me);
P4 is Dab;
P5 is Orn; or Lys;
P6 is Dab; DDab; or Pip;
P7 is Dab;
P8 is Trp;
P9 is Hse; or Dab
P10 is tBuGly; Ile; Val; Nva; Cha; Chg; or Trp;
P11 is Ala; Val; Alb; Ser; Asn; or Tyr; and
P12 is Val; Ser; or alloThr;
or a pharmaceutically acceptable salt thereof.

### Claim 5

A method of treating an infection caused by gram-negative bacteria or a disease or disorder associated with an infection caused by gram-negative bacteria, comprising:
administering to a subject in need thereof a pharmaceutically acceptable amount of a compound or pharmaceutical composition,
wherein said compound is a compound of the general formula (I),
cyclo[P1—P2—P3—P4—P5—P6—P7—P8—P9—P10—P11—P12-T1-T2] (I)
wherein the single elements T or P are connected in either direction from the carbonyl (C═O) point of attachment to the nitrogen (N) of the next element and wherein
T1 is DPro;
T2 is Pro; or Pro((3S)OH);
P1 is Leu; Ile; Val; Nva; or Trp;
P2 is His; Trp; or Tyr;
P3 is Leu; Cha; tBuGly; Trp; Tyr; or Tyr(Me);
P4 is Dab;
P5 is Orn; or Lys;
P6 is Dab; DDab; or Pip;
P7 is Dab;
P8 is Trp;
P9 is Hse; or Dab
P10 is tBuGly; Ile; Val; Nva; Cha; Chg; or Trp;
P11 is Ala; Val; Alb; Ser; Asn; or Tyr; and
P12 is Val; Ser; or alloThr;
or a pharmaceutically acceptable salt thereof; and
wherein said composition contains said compound of the general formula (I) or a mixture of compounds of general formula (I) and at least one pharmaceutically inert carrier.

### Claim 6 (depends on 5)

The method of claim 5, wherein said infections are selected from the group consisting of nosocomial infections, catheter-related and non-catheter-related infections, urinary tract infections, and bloodstream infections.

### Claim 7 (depends on 5)

The method of claim 5, wherein said diseases or disorders are selected from the group consisting of ventilator-associated pneumonia (VAP), hospital-acquired pneumonia (HAP), healthcare-associated pneumonia (HCAP), cystic fibrosis, emphysema, asthma, pneumonia, epidemic diarrhea, necrotizing enterocolitis, typhlitis, gastroenteritis, pancreatitis, keratitis, endophthalmitis, otitis, brain abscess, meningitis, encephalitis, osteochondritis, pericarditis, epididymitis, prostatitis, urethritis, surgical wounds, traumatic wounds and burns.

### Claim 8

A method for the treatment of infections caused by gram-negative bacteria or for the treatment or prevention of the onset of diseases related to such infections, comprising:
administering a composition to a subject in need thereof,
wherein said infections are related to respiratory diseases or skin or soft tissue diseases or gastrointestinal diseases or eye diseases or ear diseases or CNS diseases or bone diseases or cardiovascular diseases or genitourinary diseases, or nosocomial infections, or catheter-related and non-catheter-related infections, or urinary tract infections, or bloodstream infections,
wherein said composition contains a compound of the general formula (I) or a mixture of compounds of general formula (I) and at least one pharmaceutically inert carrier,
wherein general formula (I) is
cyclo[P1—P2—P3—P4—P5—P6—P7—P8—P9—P10—P11—P12-T1-T2] (I)
wherein the single elements T or P are connected in either direction from the carbonyl (C═O) point of attachment to the nitrogen (N) of the next element and wherein
T1 is DPro;
T2 is Pro; or Pro((3S)OH);
P1 is Leu; Ile; Val; Nva; or Trp;
P2 is His; Trp; or Tyr;
P3 is Leu; Cha; tBuGly; Trp; Tyr; or Tyr(Me);
P4 is Dab;
P5 is Orn; or Lys;
P6 is Dab; DDab; or Pip;
P7 is Dab;
P8 is Trp;
P9 is Hse; or Dab
P10 is tBuGly; Ile; Val; Nva; Cha; Chg; or Trp;
P11 is Ala; Val; Alb; Ser; Asn; or Tyr; and
P12 is Val; Ser; or alloThr;
or a pharmaceutically acceptable salt thereof.

### Claim 9

A method for disinfecting or preserving foodstuffs, cosmetics, medicaments or other nutrient-containing materials against gram-negative bacteria, comprising the step:
adding a composition to foodstuffs, cosmetics, medicaments or other nutrient-containing materials, thereby disinfecting or preserving said foodstuffs, cosmetics, medicaments or other nutrient-containing materials,
wherein said composition contains a compound of the general formula (I) or a mixture of compounds of general formula (I) and at least one pharmaceutically inert carrier,
wherein general formula (I) is
cyclo[P1—P2—P3—P4—P5—P6—P7—P8—P9—P10—P11—P12-T1-T2] (I)
wherein the single elements T or P are connected in either direction from the carbonyl (C═O) point of attachment to the nitrogen (N) of the next element and wherein
T1 is DPro;
T2 is Pro; or Pro((3S)OH);
P1 is Leu; Ile; Val; Nva; or Trp;
P2 is His; Trp; or Tyr;
P3 is Leu; Cha; tBuGly; Trp; Tyr; or Tyr(Me);
P4 is Dab;
P5 is Orn; or Lys;
P6 is Dab; DDab; or Pip;
P7 is Dab;
P8 is Trp;
P9 is Hse; or Dab
P10 is tBuGly; Ile; Val; Nva; Cha; Chg; or Trp;
P11 is Ala; Val; Alb; Ser; Asn; or Tyr; and
P12 is Val; Ser; or alloThr;
or a pharmaceutically acceptable salt thereof.

### Claim 10 (depends on 1)

The method according to claim 1, wherein the compound is selected from
cyclo(-Trp-His-Tyr-Dab-Orn-DDab-Dab-Trp-Hse-tBuGly-Ala-Ser-DPro-Pro-);
cyclo(-Trp-His-Tyr-Dab-Orn-DDab-Dab-Trp-Dab-tBuGly-Ala-Ser-DPro-Pro-);
cyclo(-Trp-His-Cha-Dab-Orn-DDab-Dab-Trp-Dab-Nva-Ala-Ser-DPro-Pro-);
cyclo(-Trp-His-Cha-Dab-Orn-DDab-Dab-Trp-Dab-tBuGly-Val-Ser-DPro-Pro-);
cyclo(-Leu-His-Tyr-Dab-Orn-DDab-Dab-Trp-Dab-tBuGly-Ala-Ser-DPro-Pro-);
cyclo(-Leu-His-Cha-Dab-Orn-Pip-Dab-Trp-Dab-tBuGly-Alb-Ser-DPro-Pro-);
cyclo(-Val-His-Tyr-Dab-Orn-DDab-Dab-Trp-Dab-tBuGly-Ala-Ser-DPro-Pro-);
cyclo(-Nva-His-Tyr-Dab-Orn-DDab-Dab-Trp-Dab-tBuGly-Ala-Ser-DPro-Pro-);
cyclo(-Trp-His-Cha-Dab-Orn-DDab-Dab-Trp-Dab-Chg-Alb-Ser-DPro-Pro-);
cyclo(-Trp-Trp-Cha-Dab-Lys-DDab-Dab-Trp-Dab-Chg-Ala-Ser-DPro-Pro-);
cyclo(-Trp-Trp-Cha-Dab-Lys-DDab-Dab-Trp-Dab-tBuGly-Ala-Ser-DPro-Pro-);
cyclo(-Trp-Trp-tBuGly-Dab-Orn-DDab-Dab-Trp-Dab-Cha-Ala-Ser-DPro-Pro-);
cyclo(-Trp-Trp-Leu-Dab-Orn-DDab-Dab-Trp-Dab-Val-Ala-Val-DPro-Pro-);
cyclo(-Trp-His-Cha-Dab-Orn-Pip-Dab-Trp-Dab-tBuGly-Ser-Ser-DPro-Pro((3S)OH)—);
cyclo(-Trp-Trp-Cha-Dab-Orn-DDab-Dab-Trp-Dab-tBuGly-Ser-Ser-DPro-Pro((3S)OH)—);
cyclo(-Trp-His-Tyr(Me)-Dab-Orn-DDab-Dab-Trp-Hse-tBuGly-Ala-Ser-DPro-Pro-);
cyclo(-Leu-His-Cha-Dab-Orn-DDab-Dab-Trp-Dab-tBuGly-Ala-alloThr-DPro-Pro-);
cyclo(-Trp-His-Tyr-Dab-Orn-Dab-Dab-Trp-Dab-tBuGly-Ala-Ser-DPro-Pro-);
cyclo(-Trp-His-Cha-Dab-Orn-Dab-Dab-Trp-Dab-tBuGly-Ala-Ser-DPro-Pro-);
cyclo(-Ile-His-Tyr-Dab-Orn-DDab-Dab-Trp-Dab-tBuGly-Ala-Ser-DPro-Pro-);
cyclo(-Ile-His-Tyr-Dab-Orn-DDab-Dab-Trp-Dab-Ile-Ala-Ser-DPro-Pro-);
cyclo(-Leu-His-Tyr-Dab-Orn-Dab-Dab-Trp-Dab-Chg-Ala-Ser-DPro-Pro-);
cyclo(-Leu-His-Tyr-Dab-Orn-DDab-Dab-Trp-Dab-Chg-Ala-Ser-DPro-Pro-);
cyclo(-Leu-His-Trp-Dab-Orn-DDab-Dab-Trp-Dab-tBuGly-Ala-Ser-DPro-Pro-);
cyclo(-Leu-His-Tyr-Dab-Lys-DDab-Dab-Trp-Dab-tBuGly-Ala-Ser-DPro-Pro-);
cyclo(-Leu-Trp-Tyr-Dab-Orn-DDab-Dab-Trp-Dab-Cha-Ala-Ser-DPro-Pro-);
cyclo(-Leu-Trp-Trp-Dab-Orn-DDab-Dab-Trp-Dab-tBuGly-Ala-Ser-DPro-Pro-);
cyclo(-Leu-Trp-Tyr-Dab-Orn-DDab-Dab-Trp-Dab-tBuGly-Ala-Ser-DPro-Pro-);
cyclo(-Leu-His-Tyr-Dab-Orn-DDab-Dab-Trp-Dab-Trp-Ala-Ser-DPro-Pro-);
cyclo(-Leu-His-Tyr-Dab-Orn-DDab-Dab-Trp-Dab-tBuGly-Ser-Ser-DPro-Pro-);
cyclo(-Leu-Trp-Tyr-Dab-Lys-DDab-Dab-Trp-Dab-Cha-Ser-Ser-DPro-Pro-);
cyclo(-Leu-Trp-Tyr-Dab-Orn-DDab-Dab-Trp-Dab-Cha-Ser-Ser-DPro-Pro-);
cyclo(-Leu-Tyr-Tyr-Dab-Orn-DDab-Dab-Trp-Dab-tBuGly-Asn-Ser-DPro-Pro-);
cyclo(-Leu-Trp-tBuGly-Dab-Orn-DDab-Dab-Trp-Dab-Chg-Ala-Ser-DPro-Pro-);
cyclo(-Ile-Trp-tBuGly-Dab-Lys-DDab-Dab-Trp-Dab-Cha-Ala-Ser-DPro-Pro);
cyclo(-Leu-Trp-tBuGly-Dab-Orn-DDab-Dab-Trp-Dab-Chg-Ser-Ser-DPro-Pro-);
cyclo(-Leu-Trp-Cha-Dab-Orn-DDab-Dab-Trp-Dab-tBuGly-Ser-Ser-DPro-Pro-);
cyclo(-Leu-Tyr-Tyr-Dab-Orn-DDab-Dab-Trp-Dab-tBuGly-Tyr-Ser-DPro-Pro-);
or a pharmaceutically acceptable salt thereof.

### Claim 11 (depends on 2)

The method according to claim 2, wherein the compound is selected from
cyclo(-Trp-His-Tyr-Dab-Orn-DDab-Dab-Trp-Hse-tBuGly-Ala-Ser-DPro-Pro);
cyclo(-Trp-His-Tyr-Dab-Orn-DDab-Dab-Trp-Dab-tBuGly-Ala-Ser-DPro-Pro-);
cyclo(-Trp-His-Cha-Dab-Orn-DDab-Dab-Trp-Dab-Nva-Ala-Ser-DPro-Pro-);
cyclo(-Trp-His-Cha-Dab-Orn-DDab-Dab-Trp-Dab-tBuGly-Val-Ser-DPro-Pro-);
cyclo(-Leu-His-Tyr-Dab-Orn-DDab-Dab-Trp-Dab-tBuGly-Ala-Ser-DPro-Pro-);
cyclo(-Leu-His-Cha-Dab-Orn-Pip-Dab-Trp-Dab-tBuGly-Alb-Ser-DPro-Pro-);
cyclo(-Val-His-Tyr-Dab-Orn-DDab-Dab-Trp-Dab-tBuGly-Ala-Ser-DPro-Pro-);
cyclo(-Nva-His-Tyr-Dab-Orn-DDab-Dab-Trp-Dab-tBuGly-Ala-Ser-DPro-Pro-);
cyclo(-Trp-His-Cha-Dab-Orn-DDab-Dab-Trp-Dab-Chg-Alb-Ser-DPro-Pro-);
cyclo(-Trp-Trp-Cha-Dab-Lys-DDab-Dab-Trp-Dab-Chg-Ala-Ser-DPro-Pro-);
cyclo(-Trp-Trp-Cha-Dab-Lys-DDab-Dab-Trp-Dab-tBuGly-Ala-Ser-DPro-Pro-);
cyclo(-Trp-Trp-tBuGly-Dab-Orn-DDab-Dab-Trp-Dab-Cha-Ala-Ser-DPro-Pro-);
cyclo(-Trp-Trp-Leu-Dab-Orn-DDab-Dab-Trp-Dab-Val-Ala-Val-DPro-Pro-);
cyclo(-Trp-His-Cha-Dab-Orn-Pip-Dab-Trp-Dab-tBuGly-Ser-Ser-DPro-Pro((3S)OH)—);
cyclo(-Trp-Trp-Cha-Dab-Orn-DDab-Dab-Trp-Dab-tBuGly-Ser-Ser-DPro-Pro((3S)OH)—);
cyclo(-Trp-His-Tyr(Me)-Dab-Orn-DDab-Dab-Trp-Hse-tBuGly-Ala-Ser-DPro-Pro-);
cyclo(-Leu-His-Cha-Dab-Orn-DDab-Dab-Trp-Dab-tBuGly-Ala-alloThr-DPro-Pro-);
cyclo(-Trp-His-Tyr-Dab-Orn-Dab-Dab-Trp-Dab-tBuGly-Ala-Ser-DPro-Pro-);
cyclo(-Trp-His-Cha-Dab-Orn-Dab-Dab-Trp-Dab-tBuGly-Ala-Ser-DPro-Pro-);
cyclo(-Ile-His-Tyr-Dab-Orn-DDab-Dab-Trp-Dab-tBuGly-Ala-Ser-DPro-Pro-);
cyclo(-Ile-His-Tyr-Dab-Orn-DDab-Dab-Trp-Dab-Ile-Ala-Ser-DPro-Pro-);
cyclo(-Leu-His-Tyr-Dab-Orn-Dab-Dab-Trp-Dab-Chg-Ala-Ser-DPro-Pro-);
cyclo(-Leu-His-Tyr-Dab-Orn-DDab-Dab-Trp-Dab-Chg-Ala-Ser-DPro-Pro-);
cyclo(-Leu-His-Trp-Dab-Orn-DDab-Dab-Trp-Dab-tBuGly-Ala-Ser-DPro-Pro-);
cyclo(-Leu-His-Tyr-Dab-Lys-DDab-Dab-Trp-Dab-tBuGly-Ala-Ser-DPro-Pro-);
cyclo(-Leu-Trp-Tyr-Dab-Orn-DDab-Dab-Trp-Dab-Cha-Ala-Ser-DPro-Pro-);
cyclo(-Leu-Trp-Trp-Dab-Orn-DDab-Dab-Trp-Dab-tBuGly-Ala-Ser-DPro-Pro-);
cyclo(-Leu-Trp-Tyr-Dab-Orn-DDab-Dab-Trp-Dab-tBuGly-Ala-Ser-DPro-Pro-);
cyclo(-Leu-His-Tyr-Dab-Orn-DDab-Dab-Trp-Dab-Trp-Ala-Ser-DPro-Pro-);
cyclo(-Leu-His-Tyr-Dab-Orn-DDab-Dab-Trp-Dab-tBuGly-Ser-Ser-DPro-Pro-);
cyclo(-Leu-Trp-Tyr-Dab-Lys-DDab-Dab-Trp-Dab-Cha-Ser-Ser-DPro-Pro-);
cyclo(-Leu-Trp-Tyr-Dab-Orn-DDab-Dab-Trp-Dab-Cha-Ser-Ser-DPro-Pro-);
cyclo(-Leu-Tyr-Tyr-Dab-Orn-DDab-Dab-Trp-Dab-tBuGly-Asn-Ser-DPro-Pro-);
cyclo(-Leu-Trp-tBuGly-Dab-Orn-DDab-Dab-Trp-Dab-Chg-Ala-Ser-DPro-Pro-);
cyclo(-Ile-Trp-tBuGly-Dab-Lys-DDab-Dab-Trp-Dab-Cha-Ala-Ser-DPro-Pro-);
cyclo(-Leu-Trp-tBuGly-Dab-Orn-DDab-Dab-Trp-Dab-Chg-Ser-Ser-DPro-Pro-);
cyclo(-Leu-Trp-Cha-Dab-Orn-DDab-Dab-Trp-Dab-tBuGly-Ser-Ser-DPro-Pro-);
cyclo(-Leu-Tyr-Tyr-Dab-Orn-DDab-Dab-Trp-Dab-tBuGly-Tyr-Ser-DPro-Pro-);
or a pharmaceutically acceptable salt thereof.

### Claim 12 (depends on 3)

The method according to claim 3, wherein the compound is selected from
cyclo(-Trp-His-Tyr-Dab-Orn-DDab-Dab-Trp-Hse-tBuGly-Ala-Ser-DPro-Pro-);
cyclo(-Trp-His-Tyr-Dab-Orn-DDab-Dab-Trp-Dab-tBuGly-Ala-Ser-DPro-Pro-);
cyclo(-Trp-His-Cha-Dab-Orn-DDab-Dab-Trp-Dab-Nva-Ala-Ser-DPro-Pro-);
cyclo(-Trp-His-Cha-Dab-Orn-DDab-Dab-Trp-Dab-tBuGly-Val-Ser-DPro-Pro-);
cyclo(-Leu-His-Tyr-Dab-Orn-DDab-Dab-Trp-Dab-tBuGly-Ala-Ser-DPro-Pro-);
cyclo(-Leu-His-Cha-Dab-Orn-Pip-Dab-Trp-Dab-tBuGly-Alb-Ser-DPro-Pro-);
cyclo(-Val-His-Tyr-Dab-Orn-DDab-Dab-Trp-Dab-tBuGly-Ala-Ser-DPro-Pro-);
cyclo(-Nva-His-Tyr-Dab-Orn-DDab-Dab-Trp-Dab-tBuGly-Ala-Ser-DPro-Pro-);
cyclo(-Trp-His-Cha-Dab-Orn-DDab-Dab-Trp-Dab-Chg-Alb-Ser-DPro-Pro-);
cyclo(-Trp-Trp-Cha-Dab-Lys-DDab-Dab-Trp-Dab-Chg-Ala-Ser-DPro-Pro-);
cyclo(-Trp-Trp-Cha-Dab-Lys-DDab-Dab-Trp-Dab-tBuGly-Ala-Ser-DPro-Pro-);
cyclo(-Trp-Trp-tBuGly-Dab-Orn-DDab-Dab-Trp-Dab-Cha-Ala-Ser-DPro-Pro-);
cyclo(-Trp-Trp-Leu-Dab-Orn-DDab-Dab-Trp-Dab-Val-Ala-Val-DPro-Pro-);
cyclo(-Trp-His-Cha-Dab-Orn-Pip-Dab-Trp-Dab-tBuGly-Ser-Ser-DPro-Pro((3S)OH)—);
cyclo(-Trp-Trp-Cha-Dab-Orn-DDab-Dab-Trp-Dab-tBuGly-Ser-Ser-DPro-Pro((3S)OH)—);
cyclo(-Trp-His-Tyr(Me)-Dab-Orn-DDab-Dab-Trp-Hse-tBuGly-Ala-Ser-DPro-Pro-);
cyclo(-Leu-His-Cha-Dab-Orn-DDab-Dab-Trp-Dab-tBuGly-Ala-alloThr-DPro-Pro-);
cyclo(-Trp-His-Tyr-Dab-Orn-Dab-Dab-Trp-Dab-tBuGly-Ala-Ser-DPro-Pro-);
cyclo(-Trp-His-Cha-Dab-Orn-Dab-Dab-Trp-Dab-tBuGly-Ala-Ser-DPro-Pro-);
cyclo(-Ile-His-Tyr-Dab-Orn-DDab-Dab-Trp-Dab-tBuGly-Ala-Ser-DPro-Pro-);
cyclo(-Ile-His-Tyr-Dab-Orn-DDab-Dab-Trp-Dab-Ile-Ala-Ser-DPro-Pro-);
cyclo(-Leu-His-Tyr-Dab-Orn-Dab-Dab-Trp-Dab-Chg-Ala-Ser-DPro-Pro-);
cyclo(-Leu-His-Tyr-Dab-Orn-DDab-Dab-Trp-Dab-Chg-Ala-Ser-DPro-Pro-);
cyclo(-Leu-His-Trp-Dab-Orn-DDab-Dab-Trp-Dab-tBuGly-Ala-Ser-DPro-Pro-);
cyclo(-Leu-His-Tyr-Dab-Lys-DDab-Dab-Trp-Dab-tBuGly-Ala-Ser-DPro-Pro-);
cyclo(-Leu-Trp-Tyr-Dab-Orn-DDab-Dab-Trp-Dab-Cha-Ala-Ser-DPro-Pro-);
cyclo(-Leu-Trp-Trp-Dab-Orn-DDab-Dab-Trp-Dab-tBuGly-Ala-Ser-DPro-Pro-);
cyclo(-Leu-Trp-Tyr-Dab-Orn-DDab-Dab-Trp-Dab-tBuGly-Ala-Ser-DPro-Pro-);
cyclo(-Leu-His-Tyr-Dab-Orn-DDab-Dab-Trp-Dab-Trp-Ala-Ser-DPro-Pro-);
cyclo(-Leu-His-Tyr-Dab-Orn-DDab-Dab-Trp-Dab-tBuGly-Ser-Ser-DPro-Pro-);
cyclo(-Leu-Trp-Tyr-Dab-Lys-DDab-Dab-Trp-Dab-Cha-Ser-Ser-DPro-Pro-);
cyclo(-Leu-Trp-Tyr-Dab-Orn-DDab-Dab-Trp-Dab-Cha-Ser-Ser-DPro-Pro-);
cyclo(-Leu-Tyr-Tyr-Dab-Orn-DDab-Dab-Trp-Dab-tBuGly-Asn-Ser-DPro-Pro-);
cyclo(-Leu-Trp-tBuGly-Dab-Orn-DDab-Dab-Trp-Dab-Chg-Ala-Ser-DPro-Pro-);
cyclo(-Ile-Trp-tBuGly-Dab-Lys-DDab-Dab-Trp-Dab-Cha-Ala-Ser-DPro-Pro-);
cyclo(-Leu-Trp-tBuGly-Dab-Orn-DDab-Dab-Trp-Dab-Chg-Ser-Ser-DPro-Pro-);
cyclo(-Leu-Trp-Cha-Dab-Orn-DDab-Dab-Trp-Dab-tBuGly-Ser-Ser-DPro-Pro-);
cyclo(-Leu-Tyr-Tyr-Dab-Orn-DDab-Dab-Trp-Dab-tBuGly-Tyr-Ser-DPro-Pro-);
or a pharmaceutically acceptable salt thereof.

### Claim 13 (depends on 4)

The method according to claim 4, wherein the compound is selected from
cyclo(-Trp-His-Tyr-Dab-Orn-DDab-Dab-Trp-Hse-tBuGly-Ala-Ser-DPro-Pro-);
cyclo(-Trp-His-Tyr-Dab-Orn-DDab-Dab-Trp-Dab-tBuGly-Ala-Ser-DPro-Pro-);
cyclo(-Trp-His-Cha-Dab-Orn-DDab-Dab-Trp-Dab-Nva-Ala-Ser-DPro-Pro-);
cyclo(-Trp-His-Cha-Dab-Orn-DDab-Dab-Trp-Dab-tBuGly-Val-Ser-DPro-Pro-);
cyclo(-Leu-His-Tyr-Dab-Orn-DDab-Dab-Trp-Dab-tBuGly-Ala-Ser-DPro-Pro-);
cyclo(-Leu-His-Cha-Dab-Orn-Pip-Dab-Trp-Dab-tBuGly-Alb-Ser-DPro-Pro-);
cyclo(-Val-His-Tyr-Dab-Orn-DDab-Dab-Trp-Dab-tBuGly-Ala-Ser-DPro-Pro-);
cyclo(-Nva-His-Tyr-Dab-Orn-DDab-Dab-Trp-Dab-tBuGly-Ala-Ser-DPro-Pro-);
cyclo(-Trp-His-Cha-Dab-Orn-DDab-Dab-Trp-Dab-Chg-Alb-Ser-DPro-Pro-);
cyclo(-Trp-Trp-Cha-Dab-Lys-DDab-Dab-Trp-Dab-Chg-Ala-Ser-DPro-Pro-);
cyclo(-Trp-Trp-Cha-Dab-Lys-DDab-Dab-Trp-Dab-tBuGly-Ala-Ser-DPro-Pro-);
cyclo(-Trp-Trp-tBuGly-Dab-Orn-DDab-Dab-Trp-Dab-Cha-Ala-Ser-DPro-Pro-);
cyclo(-Trp-Trp-Leu-Dab-Orn-DDab-Dab-Trp-Dab-Val-Ala-Val-DPro-Pro-);
cyclo(-Trp-His-Cha-Dab-Orn-Pip-Dab-Trp-Dab-tBuGly-Ser-Ser-DPro-Pro((3S)OH)—);
cyclo(-Trp-Trp-Cha-Dab-Orn-DDab-Dab-Trp-Dab-tBuGly-Ser-Ser-DPro-Pro((3S)OH)—);
cyclo(-Trp-His-Tyr(Me)-Dab-Orn-DDab-Dab-Trp-Hse-tBuGly-Ala-Ser-DPro-Pro-);
cyclo(-Leu-His-Cha-Dab-Orn-DDab-Dab-Trp-Dab-tBuGly-Ala-alloThr-DPro-Pro-);
cyclo(-Trp-His-Tyr-Dab-Orn-Dab-Dab-Trp-Dab-tBuGly-Ala-Ser-DPro-Pro-);
cyclo(-Trp-His-Cha-Dab-Orn-Dab-Dab-Trp-Dab-tBuGly-Ala-Ser-DPro-Pro-);
cyclo(-Ile-His-Tyr-Dab-Orn-DDab-Dab-Trp-Dab-tBuGly-Ala-Ser-DPro-Pro-);
cyclo(-Ile-His-Tyr-Dab-Orn-DDab-Dab-Trp-Dab-Ile-Ala-Ser-DPro-Pro-);
cyclo(-Leu-His-Tyr-Dab-Orn-Dab-Dab-Trp-Dab-Chg-Ala-Ser-DPro-Pro-);
cyclo(-Leu-His-Tyr-Dab-Orn-DDab-Dab-Trp-Dab-Chg-Ala-Ser-DPro-Pro-);
cyclo(-Leu-His-Trp-Dab-Orn-DDab-Dab-Trp-Dab-tBuGly-Ala-Ser-DPro-Pro-);
cyclo(-Leu-His-Tyr-Dab-Lys-DDab-Dab-Trp-Dab-tBuGly-Ala-Ser-DPro-Pro-);
cyclo(-Leu-Trp-Tyr-Dab-Orn-DDab-Dab-Trp-Dab-Cha-Ala-Ser-DPro-Pro-);
cyclo(-Leu-Trp-Trp-Dab-Orn-DDab-Dab-Trp-Dab-tBuGly-Ala-Ser-DPro-Pro-);
cyclo(-Leu-Trp-Tyr-Dab-Orn-DDab-Dab-Trp-Dab-tBuGly-Ala-Ser-DPro-Pro-);
cyclo(-Leu-His-Tyr-Dab-Orn-DDab-Dab-Trp-Dab-Trp-Ala-Ser-DPro-Pro-);
cyclo(-Leu-His-Tyr-Dab-Orn-DDab-Dab-Trp-Dab-tBuGly-Ser-Ser-DPro-Pro-);
cyclo(-Leu-Trp-Tyr-Dab-Lys-DDab-Dab-Trp-Dab-Cha-Ser-Ser-DPro-Pro-);
cyclo(-Leu-Trp-Tyr-Dab-Orn-DDab-Dab-Trp-Dab-Cha-Ser-Ser-DPro-Pro-);
cyclo(-Leu-Tyr-Tyr-Dab-Orn-DDab-Dab-Trp-Dab-tBuGly-Asn-Ser-DPro-Pro-);
cyclo(-Leu-Trp-tBuGly-Dab-Orn-DDab-Dab-Trp-Dab-Chg-Ala-Ser-DPro-Pro-);
cyclo(-Ile-Trp-tBuGly-Dab-Lys-DDab-Dab-Trp-Dab-Cha-Ala-Ser-DPro-Pro-);
cyclo(-Leu-Trp-tBuGly-Dab-Orn-DDab-Dab-Trp-Dab-Chg-Ser-Ser-DPro-Pro-);
cyclo(-Leu-Trp-Cha-Dab-Orn-DDab-Dab-Trp-Dab-tBuGly-Ser-Ser-DPro-Pro-);
cyclo(-Leu-Tyr-Tyr-Dab-Orn-DDab-Dab-Trp-Dab-tBuGly-Tyr-Ser-DPro-Pro-);
or a pharmaceutically acceptable salt thereof.

### Claim 14 (depends on 5)

The method according to claim 5, wherein the compound is selected from
cyclo(-Trp-His-Tyr-Dab-Orn-DDab-Dab-Trp-Hse-tBuGly-Ala-Ser-DPro-Pro-);
cyclo(-Trp-His-Tyr-Dab-Orn-DDab-Dab-Trp-Dab-tBuGly-Ala-Ser-DPro-Pro-);
cyclo(-Trp-His-Cha-Dab-Orn-DDab-Dab-Trp-Dab-Nva-Ala-Ser-DPro-Pro-);
cyclo(-Trp-His-Cha-Dab-Orn-DDab-Dab-Trp-Dab-tBuGly-Val-Ser-DPro-Pro-);
cyclo(-Leu-His-Tyr-Dab-Orn-DDab-Dab-Trp-Dab-tBuGly-Ala-Ser-DPro-Pro-);
cyclo(-Leu-His-Cha-Dab-Orn-Pip-Dab-Trp-Dab-tBuGly-Alb-Ser-DPro-Pro-);
cyclo(-Val-His-Tyr-Dab-Orn-DDab-Dab-Trp-Dab-tBuGly-Ala-Ser-DPro-Pro-);
cyclo(-Nva-His-Tyr-Dab-Orn-DDab-Dab-Trp-Dab-tBuGly-Ala-Ser-DPro-Pro-);
cyclo(-Trp-His-Cha-Dab-Orn-DDab-Dab-Trp-Dab-Chg-Alb-Ser-DPro-Pro-);
cyclo(-Trp-Trp-Cha-Dab-Lys-DDab-Dab-Trp-Dab-Chg-Ala-Ser-DPro-Pro-);
cyclo(-Trp-Trp-Cha-Dab-Lys-DDab-Dab-Trp-Dab-tBuGly-Ala-Ser-DPro-Pro-);
cyclo(-Trp-Trp-tBuGly-Dab-Orn-DDab-Dab-Trp-Dab-Cha-Ala-Ser-DPro-Pro-);
cyclo(-Trp-Trp-Leu-Dab-Orn-DDab-Dab-Trp-Dab-Val-Ala-Val-DPro-Pro-);
cyclo(-Trp-His-Cha-Dab-Orn-Pip-Dab-Trp-Dab-tBuGly-Ser-Ser-DPro-Pro((3S)OH)—);
cyclo(-Trp-Trp-Cha-Dab-Orn-DDab-Dab-Trp-Dab-tBuGly-Ser-Ser-DPro-Pro((3S)OH)—);
cyclo(-Trp-His-Tyr(Me)-Dab-Orn-DDab-Dab-Trp-Hse-tBuGly-Ala-Ser-DPro-Pro-);
cyclo(-Leu-His-Cha-Dab-Orn-DDab-Dab-Trp-Dab-tBuGly-Ala-alloThr-DPro-Pro-);
cyclo(-Trp-His-Tyr-Dab-Orn-Dab-Dab-Trp-Dab-tBuGly-Ala-Ser-DPro-Pro-);
cyclo(-Trp-His-Cha-Dab-Orn-Dab-Dab-Trp-Dab-tBuGly-Ala-Ser-DPro-Pro-);
cyclo(-Ile-His-Tyr-Dab-Orn-DDab-Dab-Trp-Dab-tBuGly-Ala-Ser-DPro-Pro-);
cyclo(-Ile-His-Tyr-Dab-Orn-DDab-Dab-Trp-Dab-Ile-Ala-Ser-DPro-Pro);
cyclo(-Leu-His-Tyr-Dab-Orn-Dab-Dab-Trp-Dab-Chg-Ala-Ser-DPro-Pro-);
cyclo(-Leu-His-Tyr-Dab-Orn-DDab-Dab-Trp-Dab-Chg-Ala-Ser-DPro-Pro-);
cyclo(-Leu-His-Trp-Dab-Orn-DDab-Dab-Trp-Dab-tBuGly-Ala-Ser-DPro-Pro-);
cyclo(-Leu-His-Tyr-Dab-Lys-DDab-Dab-Trp-Dab-tBuGly-Ala-Ser-DPro-Pro-);
cyclo(-Leu-Trp-Tyr-Dab-Orn-DDab-Dab-Trp-Dab-Cha-Ala-Ser-DPro-Pro-);
cyclo(-Leu-Trp-Trp-Dab-Orn-DDab-Dab-Trp-Dab-tBuGly-Ala-Ser-DPro-Pro-);
cyclo(-Leu-Trp-Tyr-Dab-Orn-DDab-Dab-Trp-Dab-tBuGly-Ala-Ser-DPro-Pro-);
cyclo(-Leu-His-Tyr-Dab-Orn-DDab-Dab-Trp-Dab-Trp-Ala-Ser-DPro-Pro-);
cyclo(-Leu-His-Tyr-Dab-Orn-DDab-Dab-Trp-Dab-tBuGly-Ser-Ser-DPro-Pro-);
cyclo(-Leu-Trp-Tyr-Dab-Lys-DDab-Dab-Trp-Dab-Cha-Ser-Ser-DPro-Pro-);
cyclo(-Leu-Trp-Tyr-Dab-Orn-DDab-Dab-Trp-Dab-Cha-Ser-Ser-DPro-Pro-);
cyclo(-Leu-Tyr-Tyr-Dab-Orn-DDab-Dab-Trp-Dab-tBuGly-Asn-Ser-DPro-Pro-);
cyclo(-Leu-Trp-tBuGly-Dab-Orn-DDab-Dab-Trp-Dab-Chg-Ala-Ser-DPro-Pro-);
cyclo(-Ile-Trp-tBuGly-Dab-Lys-DDab-Dab-Trp-Dab-Cha-Ala-Ser-DPro-Pro-);
cyclo(-Leu-Trp-tBuGly-Dab-Orn-DDab-Dab-Trp-Dab-Chg-Ser-Ser-DPro-Pro-);
cyclo(-Leu-Trp-Cha-Dab-Orn-DDab-Dab-Trp-Dab-tBuGly-Ser-Ser-DPro-Pro-);
cyclo(-Leu-Tyr-Tyr-Dab-Orn-DDab-Dab-Trp-Dab-tBuGly-Tyr-Ser-DPro-Pro-);
or a pharmaceutically acceptable salt thereof.

### Claim 15 (depends on 6)

The method according to claim 6, wherein the compound is selected from
cyclo(-Trp-His-Tyr-Dab-Orn-DDab-Dab-Trp-Hse-tBuGly-Ala-Ser-DPro-Pro-);
cyclo(-Trp-His-Tyr-Dab-Orn-DDab-Dab-Trp-Dab-tBuGly-Ala-Ser-DPro-Pro-);
cyclo(-Trp-His-Cha-Dab-Orn-DDab-Dab-Trp-Dab-Nva-Ala-Ser-DPro-Pro-);
cyclo(-Trp-His-Cha-Dab-Orn-DDab-Dab-Trp-Dab-tBuGly-Val-Ser-DPro-Pro-);
cyclo(-Leu-His-Tyr-Dab-Orn-DDab-Dab-Trp-Dab-tBuGly-Ala-Ser-DPro-Pro-);
cyclo(-Leu-His-Cha-Dab-Orn-Pip-Dab-Trp-Dab-tBuGly-Alb-Ser-DPro-Pro-);
cyclo(-Val-His-Tyr-Dab-Orn-DDab-Dab-Trp-Dab-tBuGly-Ala-Ser-DPro-Pro-);
cyclo(-Nva-His-Tyr-Dab-Orn-DDab-Dab-Trp-Dab-tBuGly-Ala-Ser-DPro-Pro-);
cyclo(-Trp-His-Cha-Dab-Orn-DDab-Dab-Trp-Dab-Chg-Alb-Ser-DPro-Pro-);
cyclo(-Trp-Trp-Cha-Dab-Lys-DDab-Dab-Trp-Dab-Chg-Ala-Ser-DPro-Pro-);
cyclo(-Trp-Trp-Cha-Dab-Lys-DDab-Dab-Trp-Dab-tBuGly-Ala-Ser-DPro-Pro-);
cyclo(-Trp-Trp-tBuGly-Dab-Orn-DDab-Dab-Trp-Dab-Cha-Ala-Ser-DPro-Pro-);
cyclo(-Trp-Trp-Leu-Dab-Orn-DDab-Dab-Trp-Dab-Val-Ala-Val-DPro-Pro-);
cyclo(-Trp-His-Cha-Dab-Orn-Pip-Dab-Trp-Dab-tBuGly-Ser-Ser-DPro-Pro((3S)OH)—);
cyclo(-Trp-Trp-Cha-Dab-Orn-DDab-Dab-Trp-Dab-tBuGly-Ser-Ser-DPro-Pro((3S)OH)—);
cyclo(-Trp-His-Tyr(Me)-Dab-Orn-DDab-Dab-Trp-Hse-tBuGly-Ala-Ser-DPro-Pro-);
cyclo(-Leu-His-Cha-Dab-Orn-DDab-Dab-Trp-Dab-tBuGly-Ala-alloThr-DPro-Pro-);
cyclo(-Trp-His-Tyr-Dab-Orn-Dab-Dab-Trp-Dab-tBuGly-Ala-Ser-DPro-Pro-);
cyclo(-Trp-His-Cha-Dab-Orn-Dab-Dab-Trp-Dab-tBuGly-Ala-Ser-DPro-Pro-);
cyclo(-Ile-His-Tyr-Dab-Orn-DDab-Dab-Trp-Dab-tBuGly-Ala-Ser-DPro-Pro-);
cyclo(-Ile-His-Tyr-Dab-Orn-DDab-Dab-Trp-Dab-Ile-Ala-Ser-DPro-Pro-);
cyclo(-Leu-His-Tyr-Dab-Orn-Dab-Dab-Trp-Dab-Chg-Ala-Ser-DPro-Pro-);
cyclo(-Leu-His-Tyr-Dab-Orn-DDab-Dab-Trp-Dab-Chg-Ala-Ser-DPro-Pro-);
cyclo(-Leu-His-Trp-Dab-Orn-DDab-Dab-Trp-Dab-tBuGly-Ala-Ser-DPro-Pro-);
cyclo(-Leu-His-Tyr-Dab-Lys-DDab-Dab-Trp-Dab-tBuGly-Ala-Ser-DPro-Pro-);
cyclo(-Leu-Trp-Tyr-Dab-Orn-DDab-Dab-Trp-Dab-Cha-Ala-Ser-DPro-Pro-);
cyclo(-Leu-Trp-Trp-Dab-Orn-DDab-Dab-Trp-Dab-tBuGly-Ala-Ser-DPro-Pro-);
cyclo(-Leu-Trp-Tyr-Dab-Orn-DDab-Dab-Trp-Dab-tBuGly-Ala-Ser-DPro-Pro-);
cyclo(-Leu-His-Tyr-Dab-Orn-DDab-Dab-Trp-Dab-Trp-Ala-Ser-DPro-Pro-);
cyclo(-Leu-His-Tyr-Dab-Orn-pDab-Dab-Trp-Dab-tBuGly-Ser-Ser-DPro-Pro-);
cyclo(-Leu-Trp-Tyr-Dab-Lys-DDab-Dab-Trp-Dab-Cha-Ser-Ser-DPro-Pro-);
cyclo(-Leu-Trp-Tyr-Dab-Orn-DDab-Dab-Trp-Dab-Cha-Ser-Ser-DPro-Pro-);
cyclo(-Leu-Tyr-Tyr-Dab-Orn-DDab-Dab-Trp-Dab-tBuGly-Asn-Ser-DPro-Pro-);
cyclo(-Leu-Trp-tBuGly-Dab-Orn-DDab-Dab-Trp-Dab-Chg-Ala-Ser-DPro-Pro-);
cyclo(-Ile-Trp-tBuGly-Dab-Lys-DDab-Dab-Trp-Dab-Cha-Ala-Ser-DPro-Pro-);
cyclo(-Leu-Trp-tBuGly-Dab-Orn-DDab-Dab-Trp-Dab-Chg-Ser-Ser-DPro-Pro-);
cyclo(-Leu-Trp-Cha-Dab-Orn-DDab-Dab-Trp-Dab-tBuGly-Ser-Ser-DPro-Pro-);
cyclo(-Leu-Tyr-Tyr-Dab-Orn-DDab-Dab-Trp-Dab-tBuGly-Tyr-Ser-DPro-Pro-);
or a pharmaceutically acceptable salt thereof.

### Claim 16 (depends on 7)

The method according to claim 7, wherein the compound is selected from
cyclo(-Trp-His-Tyr-Dab-Orn-DDab-Dab-Trp-Hse-tBuGly-Ala-Ser-DPro-Pro-);
cyclo(-Trp-His-Tyr-Dab-Orn-DDab-Dab-Trp-Dab-tBuGly-Ala-Ser-DPro-Pro-);
cyclo(-Trp-His-Cha-Dab-Orn-DDab-Dab-Trp-Dab-Nva-Ala-Ser-DPro-Pro-);
cyclo(-Trp-His-Cha-Dab-Orn-DDab-Dab-Trp-Dab-tBuGly-Val-Ser-DPro-Pro-);
cyclo(-Leu-His-Tyr-Dab-Orn-DDab-Dab-Trp-Dab-tBuGly-Ala-Ser-DPro-Pro-);
cyclo(-Leu-His-Cha-Dab-Orn-Pip-Dab-Trp-Dab-tBuGly-Alb-Ser-DPro-Pro-);
cyclo(-Val-His-Tyr-Dab-Orn-DDab-Dab-Trp-Dab-tBuGly-Ala-Ser-DPro-Pro-);
cyclo(-Nva-His-Tyr-Dab-Orn-DDab-Dab-Trp-Dab-tBuGly-Ala-Ser-DPro-Pro-);
cyclo(-Trp-His-Cha-Dab-Orn-DDab-Dab-Trp-Dab-Chg-Alb-Ser-DPro-Pro-);
cyclo(-Trp-Trp-Cha-Dab-Lys-DDab-Dab-Trp-Dab-Chg-Ala-Ser-DPro-Pro-);
cyclo(-Trp-Trp-Cha-Dab-Lys-DDab-Dab-Trp-Dab-tBuGly-Ala-Ser-DPro-Pro-);
cyclo(-Trp-Trp-tBuGly-Dab-Orn-DDab-Dab-Trp-Dab-Cha-Ala-Ser-DPro-Pro-);
cyclo(-Trp-Trp-Leu-Dab-Orn-DDab-Dab-Trp-Dab-Val-Ala-Val-DPro-Pro-);
cyclo(-Trp-His-Cha-Dab-Orn-Pip-Dab-Trp-Dab-tBuGly-Ser-Ser-DPro-Pro((3S)OH)—);
cyclo(-Trp-Trp-Cha-Dab-Orn-DDab-Dab-Trp-Dab-tBuGly-Ser-Ser-DPro-Pro((3S)OH)—);
cyclo(-Trp-His-Tyr(Me)-Dab-Orn-DDab-Dab-Trp-Hse-tBuGly-Ala-Ser-DPro-Pro-);
cyclo(-Leu-His-Cha-Dab-Orn-DDab-Dab-Trp-Dab-tBuGly-Ala-alloThr-DPro-Pro-);
cyclo(-Trp-His-Tyr-Dab-Orn-Dab-Dab-Trp-Dab-tBuGly-Ala-Ser-DPro-Pro-);
cyclo(-Trp-His-Cha-Dab-Orn-Dab-Dab-Trp-Dab-tBuGly-Ala-Ser-DPro-Pro-);
cyclo(-Ile-His-Tyr-Dab-Orn-DDab-Dab-Trp-Dab-tBuGly-Ala-Ser-DPro-Pro-);
cyclo(-Ile-His-Tyr-Dab-Orn-DDab-Dab-Trp-Dab-Ile-Ala-Ser-DPro-Pro-);
cyclo(-Leu-His-Tyr-Dab-Orn-Dab-Dab-Trp-Dab-Chg-Ala-Ser-DPro-Pro-);
cyclo(-Leu-His-Tyr-Dab-Orn-DDab-Dab-Trp-Dab-Chg-Ala-Ser-DPro-Pro-);
cyclo(-Leu-His-Trp-Dab-Orn-DDab-Dab-Trp-Dab-tBuGly-Ala-Ser-DPro-Pro-);
cyclo(-Leu-His-Tyr-Dab-Lys-DDab-Dab-Trp-Dab-tBuGly-Ala-Ser-DPro-Pro-);
cyclo(-Leu-Trp-Tyr-Dab-Orn-DDab-Dab-Trp-Dab-Cha-Ala-Ser-DPro-Pro-);
cyclo(-Leu-Trp-Trp-Dab-Orn-DDab-Dab-Trp-Dab-tBuGly-Ala-Ser-DPro-Pro-);
cyclo(-Leu-Trp-Tyr-Dab-Orn-DDab-Dab-Trp-Dab-tBuGly-Ala-Ser-DPro-Pro-);
cyclo(-Leu-His-Tyr-Dab-Orn-DDab-Dab-Trp-Dab-Trp-Ala-Ser-DPro-Pro-);
cyclo(-Leu-His-Tyr-Dab-Orn-DDab-Dab-Trp-Dab-tBuGly-Ser-Ser-DPro-Pro-);
cyclo(-Leu-Trp-Tyr-Dab-Lys-DDab-Dab-Trp-Dab-Cha-Ser-Ser-DPro-Pro-);
cyclo(-Leu-Trp-Tyr-Dab-Orn-DDab-Dab-Trp-Dab-Cha-Ser-Ser-DPro-Pro-);
cyclo(-Leu-Tyr-Tyr-Dab-Orn-DDab-Dab-Trp-Dab-tBuGly-Asn-Ser-DPro-Pro-);
cyclo(-Leu-Trp-tBuGly-Dab-Orn-DDab-Dab-Trp-Dab-Chg-Ala-Ser-DPro-Pro-);
cyclo(-Ile-Trp-tBuGly-Dab-Lys-DDab-Dab-Trp-Dab-Cha-Ala-Ser-DPro-Pro-);
cyclo(-Leu-Trp-tBuGly-Dab-Orn-DDab-Dab-Trp-Dab-Chg-Ser-Ser-DPro-Pro-);
cyclo(-Leu-Trp-Cha-Dab-Orn-DDab-Dab-Trp-Dab-tBuGly-Ser-Ser-DPro-Pro-);
cyclo(-Leu-Tyr-Tyr-Dab-Orn-DDab-Dab-Trp-Dab-tBuGly-Tyr-Ser-DPro-Pro-);
or a pharmaceutically acceptable salt thereof.

### Claim 17 (depends on 8)

The method according to claim 8, wherein the compound is selected from
cyclo(-Trp-His-Tyr-Dab-Orn-DDab-Dab-Trp-Hse-tBuGly-Ala-Ser-DPro-Pro-);
cyclo(-Trp-His-Tyr-Dab-Orn-DDab-Dab-Trp-Dab-tBuGly-Ala-Ser-DPro-Pro-);
cyclo(-Trp-His-Cha-Dab-Orn-DDab-Dab-Trp-Dab-Nva-Ala-Ser-DPro-Pro-);
cyclo(-Trp-His-Cha-Dab-Orn-DDab-Dab-Trp-Dab-tBuGly-Val-Ser-DPro-Pro-);
cyclo(-Leu-His-Tyr-Dab-Orn-DDab-Dab-Trp-Dab-tBuGly-Ala-Ser-DPro-Pro-);
cyclo(-Leu-His-Cha-Dab-Orn-Pip-Dab-Trp-Dab-tBuGly-Alb-Ser-DPro-Pro-);
cyclo(-Val-His-Tyr-Dab-Orn-DDab-Dab-Trp-Dab-tBuGly-Ala-Ser-DPro-Pro-);
cyclo(-Nva-His-Tyr-Dab-Orn-DDab-Dab-Trp-Dab-tBuGly-Ala-Ser-DPro-Pro-);
cyclo(-Trp-His-Cha-Dab-Orn-DDab-Dab-Trp-Dab-Chg-Alb-Ser-DPro-Pro-);
cyclo(-Trp-Trp-Cha-Dab-Lys-DDab-Dab-Trp-Dab-Chg-Ala-Ser-DPro-Pro-);
cyclo(-Trp-Trp-Cha-Dab-Lys-DDab-Dab-Trp-Dab-tBuGly-Ala-Ser-DPro-Pro-);
cyclo(-Trp-Trp-tBuGly-Dab-Orn-DDab-Dab-Trp-Dab-Cha-Ala-Ser-DPro-Pro-);
cyclo(-Trp-Trp-Leu-Dab-Orn-DDab-Dab-Trp-Dab-Val-Ala-Val-DPro-Pro-);
cyclo(-Trp-His-Cha-Dab-Orn-Pip-Dab-Trp-Dab-tBuGly-Ser-Ser-DPro-Pro((3S)OH)—);
cyclo(-Trp-Trp-Cha-Dab-Orn-DDab-Dab-Trp-Dab-tBuGly-Ser-Ser-DPro-Pro((3S)OH)—);
cyclo(-Trp-His-Tyr(Me)-Dab-Orn-DDab-Dab-Trp-Hse-tBuGly-Ala-Ser-DPro-Pro-);
cyclo(-Leu-His-Cha-Dab-Orn-DDab-Dab-Trp-Dab-tBuGly-Ala-alloThr-DPro-Pro-);
cyclo(-Trp-His-Tyr-Dab-Orn-Dab-Dab-Trp-Dab-tBuGly-Ala-Ser-DPro-Pro-);
cyclo(-Trp-His-Cha-Dab-Orn-Dab-Dab-Trp-Dab-tBuGly-Ala-Ser-DPro-Pro-);
cyclo(-Ile-His-Tyr-Dab-Orn-DDab-Dab-Trp-Dab-tBuGly-Ala-Ser-DPro-Pro-);
cyclo(-Ile-His-Tyr-Dab-Orn-DDab-Dab-Trp-Dab-Ile-Ala-Ser-DPro-Pro-);
cyclo(-Leu-His-Tyr-Dab-Orn-Dab-Dab-Trp-Dab-Chg-Ala-Ser-DPro-Pro-);
cyclo(-Leu-His-Tyr-Dab-Orn-DDab-Dab-Trp-Dab-Chg-Ala-Ser-DPro-Pro-);
cyclo(-Leu-His-Trp-Dab-Orn-DDab-Dab-Trp-Dab-tBuGly-Ala-Ser-DPro-Pro-);
cyclo(-Leu-His-Tyr-Dab-Lys-DDab-Dab-Trp-Dab-tBuGly-Ala-Ser-DPro-Pro-);
cyclo(-Leu-Trp-Tyr-Dab-Orn-DDab-Dab-Trp-Dab-Cha-Ala-Ser-DPro-Pro-);
cyclo(-Leu-Trp-Trp-Dab-Orn-DDab-Dab-Trp-Dab-tBuGly-Ala-Ser-DPro-Pro-);
cyclo(-Leu-Trp-Tyr-Dab-Orn-DDab-Dab-Trp-Dab-tBuGly-Ala-Ser-DPro-Pro-);
cyclo(-Leu-His-Tyr-Dab-Orn-DDab-Dab-Trp-Dab-Trp-Ala-Ser-DPro-Pro-);
cyclo(-Leu-His-Tyr-Dab-Orn-DDab-Dab-Trp-Dab-tBuGly-Ser-Ser-DPro-Pro-);
cyclo(-Leu-Trp-Tyr-Dab-Lys-DDab-Dab-Trp-Dab-Cha-Ser-Ser-DPro-Pro-);
cyclo(-Leu-Trp-Tyr-Dab-Orn-DDab-Dab-Trp-Dab-Cha-Ser-Ser-DPro-Pro-);
cyclo(-Leu-Tyr-Tyr-Dab-Orn-DDab-Dab-Trp-Dab-tBuGly-Asn-Ser-DPro-Pro-);
cyclo(-Leu-Trp-tBuGly-Dab-Orn-DDab-Dab-Trp-Dab-Chg-Ala-Ser-DPro-Pro-);
cyclo(-Ile-Trp-tBuGly-Dab-Lys-DDab-Dab-Trp-Dab-Cha-Ala-Ser-DPro-Pro-);
cyclo(-Leu-Trp-tBuGly-Dab-Orn-DDab-Dab-Trp-Dab-Chg-Ser-Ser-DPro-Pro);
cyclo(-Leu-Trp-Cha-Dab-Orn-DDab-Dab-Trp-Dab-tBuGly-Ser-Ser-DPro-Pro-);
cyclo(-Leu-Tyr-Tyr-Dab-Orn-DDab-Dab-Trp-Dab-tBuGly-Tyr-Ser-DPro-Pro-);
or a pharmaceutically acceptable salt thereof.

### Claim 18 (depends on 9)

The method according to claim 9, wherein the compound is selected from
cyclo(-Trp-His-Tyr-Dab-Orn-DDab-Dab-Trp-Hse-tBuGly-Ala-Ser-DPro-Pro-);
cyclo(-Trp-His-Tyr-Dab-Orn-DDab-Dab-Trp-Dab-tBuGly-Ala-Ser-DPro-Pro-);
cyclo(-Trp-His-Cha-Dab-Orn-DDab-Dab-Trp-Dab-Nva-Ala-Ser-DPro-Pro-);
cyclo(-Trp-His-Cha-Dab-Orn-DDab-Dab-Trp-Dab-tBuGly-Val-Ser-DPro-Pro-);
cyclo(-Leu-His-Tyr-Dab-Orn-DDab-Dab-Trp-Dab-tBuGly-Ala-Ser-DPro-Pro-);
cyclo(-Leu-His-Cha-Dab-Orn-Pip-Dab-Trp-Dab-tBuGly-Alb-Ser-DPro-Pro-);
cyclo(-Val-His-Tyr-Dab-Orn-DDab-Dab-Trp-Dab-tBuGly-Ala-Ser-DPro-Pro-);
cyclo(-Nva-His-Tyr-Dab-Orn-DDab-Dab-Trp-Dab-tBuGly-Ala-Ser-DPro-Pro-);
cyclo(-Trp-His-Cha-Dab-Orn-DDab-Dab-Trp-Dab-Chg-Alb-Ser-DPro-Pro-);
cyclo(-Trp-Trp-Cha-Dab-Lys-DDab-Dab-Trp-Dab-Chg-Ala-Ser-DPro-Pro-);
cyclo(-Trp-Trp-Cha-Dab-Lys-DDab-Dab-Trp-Dab-tBuGly-Ala-Ser-DPro-Pro-);
cyclo(-Trp-Trp-tBuGly-Dab-Orn-DDab-Dab-Trp-Dab-Cha-Ala-Ser-DPro-Pro-);
cyclo(-Trp-Trp-Leu-Dab-Orn-DDab-Dab-Trp-Dab-Val-Ala-Val-DPro-Pro-);
cyclo(-Trp-His-Cha-Dab-Orn-Pip-Dab-Trp-Dab-tBuGly-Ser-Ser-DPro-Pro((3S)OH)—);
cyclo(-Trp-Trp-Cha-Dab-Orn-DDab-Dab-Trp-Dab-tBuGly-Ser-Ser-DPro-Pro((3S)OH)—);
cyclo(-Trp-His-Tyr(Me)-Dab-Orn-DDab-Dab-Trp-Hse-tBuGly-Ala-Ser-DPro-Pro-);
cyclo(-Leu-His-Cha-Dab-Orn-DDab-Dab-Trp-Dab-tBuGly-Ala-alloThr-DPro-Pro-);
cyclo(-Trp-His-Tyr-Dab-Orn-Dab-Dab-Trp-Dab-tBuGly-Ala-Ser-DPro-Pro-);
cyclo(-Trp-His-Cha-Dab-Orn-Dab-Dab-Trp-Dab-tBuGly-Ala-Ser-DPro-Pro-);
cyclo(-Ile-His-Tyr-Dab-Orn-DDab-Dab-Trp-Dab-tBuGly-Ala-Ser-DPro-Pro-);
cyclo(-Ile-His-Tyr-Dab-Orn-DDab-Dab-Trp-Dab-Ile-Ala-Ser-DPro-Pro-);
cyclo(-Leu-His-Tyr-Dab-Orn-Dab-Dab-Trp-Dab-Chg-Ala-Ser-DPro-Pro-);
cyclo(-Leu-His-Tyr-Dab-Orn-DDab-Dab-Trp-Dab-Chg-Ala-Ser-DPro-Pro-);
cyclo(-Leu-His-Trp-Dab-Orn-DDab-Dab-Trp-Dab-tBuGly-Ala-Ser-DPro-Pro-);
cyclo(-Leu-His-Tyr-Dab-Lys-DDab-Dab-Trp-Dab-tBuGly-Ala-Ser-DPro-Pro-);
cyclo(-Leu-Trp-Tyr-Dab-Orn-DDab-Dab-Trp-Dab-Cha-Ala-Ser-DPro-Pro-);
cyclo(-Leu-Trp-Trp-Dab-Orn-DDab-Dab-Trp-Dab-tBuGly-Ala-Ser-DPro-Pro-);
cyclo(-Leu-Trp-Tyr-Dab-Orn-DDab-Dab-Trp-Dab-tBuGly-Ala-Ser-DPro-Pro-);
cyclo(-Leu-His-Tyr-Dab-Orn-DDab-Dab-Trp-Dab-Trp-Ala-Ser-DPro-Pro-);
cyclo(-Leu-His-Tyr-Dab-Orn-DDab-Dab-Trp-Dab-tBuGly-Ser-Ser-DPro-Pro-);
cyclo(-Leu-Trp-Tyr-Dab-Lys-DDab-Dab-Trp-Dab-Cha-Ser-Ser-DPro-Pro-);
cyclo(-Leu-Trp-Tyr-Dab-Orn-DDab-Dab-Trp-Dab-Cha-Ser-Ser-DPro-Pro-);
cyclo(-Leu-Tyr-Tyr-Dab-Orn-DDab-Dab-Trp-Dab-tBuGly-Asn-Ser-DPro-Pro-);
cyclo(-Leu-Trp-tBuGly-Dab-Orn-DDab-Dab-Trp-Dab-Chg-Ala-Ser-DPro-Pro-);
cyclo(-Ile-Trp-tBuGly-Dab-Lys-DDab-Dab-Trp-Dab-Cha-Ala-Ser-DPro-Pro-);
cyclo(-Leu-Trp-tBuGly-Dab-Orn-DDab-Dab-Trp-Dab-Chg-Ser-Ser-DPro-Pro-);
cyclo(-Leu-Trp-Cha-Dab-Orn-DDab-Dab-Trp-Dab-tBuGly-Ser-Ser-DPro-Pro-);
cyclo(-Leu-Tyr-Tyr-Dab-Orn-DDab-Dab-Trp-Dab-tBuGly-Tyr-Ser-DPro-Pro-);
or a pharmaceutically acceptable salt thereof.