# US 7,408,024 B2 · Somatostatin antagonists

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- Number: US 7,408,024 B2
- Document ID: US7408024B2
- Status: Granted
- Kind: B2
- Application number: 11/894,231
- Filed: 2007-08-20
- Published: 2008-01-24
- Granted: 2008-08-05
- Earliest claimed: 2001-03-08
- Assignees: The Administrators of the Tulane Educational Fund
- Inventors: David H. Coy; William A. Murphy; Walajapet G. Rajeswaran
- Web page: https://patentgrep.com/patent/US7408024B2

## CPC

- A61K 38/31: Somatostatins
- A61K 38/08: Peptides having 5 to 11 amino acids {(A61K38/043 - A61K38/046 take precedence)}
- A61P 1/04: for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
- A61P 3/00: Drugs for disorders of the metabolism (of the blood or the extracellular fluid A61P7/00)
- A61P 3/10: for hyperglycaemia, e.g. antidiabetics
- A61P 5/00: Drugs for disorders of the endocrine system
- A61P 5/02: of the hypothalamic hormones, e.g. TRH, GnRH, CRH, GRH, somatostatin
- A61P 5/04: for decreasing, blocking or antagonising the activity of the hypothalamic hormones
- A61P 5/06: of the anterior pituitary hormones, e.g. TSH, ACTH, FSH, LH, PRL, GH
- A61P 5/50: for increasing or potentiating the activity of insulin
- A61P 7/00: Drugs for disorders of the blood or the extracellular fluid
- A61P 9/00: Drugs for disorders of the cardiovascular system
- A61P 17/02: for treating wounds, ulcers, burns, scars, keloids, or the like
- A61P 35/00: Antineoplastic agents
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07K 14/655: Somatostatins
- 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)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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)

## Abstract

The present invention is directed to a somatostatin antagonist according to formula (I): A1-cyclo {D-Cys-A2-D-Trp-A3-A4-Cys}-A5Y1, wherein A1 is an optionally substituted aromatic a-amino acid; A2 is an optionally substituted aromatic α-amino acid; A3 is Dab, Dap, Lys or Om; A4 is β-Hydroxyvaline, Ser, Hser, or Thr; A5 is an optionally substituted D- or L-aromatic amino acid; and Y1 is OH, NH2 or NHR1′ where RI is (C1-6)alkyl; wherein each said optionally substituted aromatic amino acid is optionally substituted with one or more substituents each independently selected from the group consisting of halogen, NO2, OH, CN, (C1-6) alkyl, (C2-6) alkenyl, (C2-6) alkynyl, (C1-6)alkoxy, Bzl, O-Bzl, and NR9R10′ wherein R9 ad R10 each is independently H, O, or (C1-6) alkyl; and wherein the amine nitrogen of each of amide peptide bond and the amino group of A1 of formula (I) is optionally substituted with a methyl group, provided that there is at least one said methyl group; or a pharmaceutically acceptable salt thereof, and is directed to uses thereof.

## Claims

### Claim 1

A somatostatin antagonist compound of the structure NMeCpa-c(D-Cys-3-Pal-D-Trp-Lys-Thr-Cys)-2-Nal-NH2 or a pharmaceutically acceptable salt thereof.

### Claim 2 (depends on 1)

A method of binding one or more somatostatin subtype receptors -1, -2, -3, -4 and -5, which comprises the step of contacting the compound of claim 1 or a pharmaceutically acceptable salt thereof with one or more of said somatostatin subtype receptors thereby said binding occurs.

### Claim 3 (depends on 1)

A method of eliciting an antagonist effect from an isolated cell, wherein said cell comprises one or more somatostatin receptors, said method comprising contacting said cell with an effective amount of the compound of claim 1 or a pharmaceutically acceptable salt thereby said antagonist effect occurs.

### Claim 4 (depends on 1)

A method of eliciting a somatostatin antagonist effect in a human or animal subject, which comprises the step of administering to said subject an effective amount the compound of claim 1 or a pharmaceutically acceptable salt thereof to said subject in need thereof thereby said antagonist effect occurs.

### Claim 5 (depends on 1)

A method of promoting the release of growth hormone in a human or animal subject in need thereof, which comprises administering to said subject an effective amount of the compound of claim 1 or a pharmaceutically acceptable salt thereof thereby said promoting the release of growth hormone occurs.

### Claim 6 (depends on 1)

A method of promoting the release of insulin in a human or animal subject in need thereof, which comprises administering to said subject an effective amount of the compound of claim 1 or a pharmaceutically acceptable salt thereof thereby said promoting the release of growth hormone occurs.

### Claim 7 (depends on 1)

A method of enhancing wound healing in a human or animal subject in need thereof, which comprises administering to said subject an effective amount of the compound of claim 1 or a pharmaceutically acceptable salt thereof thereby said wound healing is enhanced.

### Claim 8 (depends on 1)

A method of promoting angiogenesis in a human or animal subject in need thereof, which comprises administering to said subject an effective amount of the compound of claim 1 or a pharmaceutically acceptable salt thereof thereby said promoting angiogenesis occurs.

### Claim 9 (depends on 1)

A method of treating a disease or condition in a human or other animal subject in need thereof, which comprises the step of administering an effective amount of a compound of claim 1 or a pharmaceutically acceptable salt thereof to said subject, wherein said disease or condition is selected from the group consisting of short stature, cachexia, wasting, type 2 diabetes, and poor ciculation thereby said disease is treated.