# US 4,396,606 A · Novel polypeptide analgesics

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 4,396,606 A
- Document ID: US4396606A
- Status: Granted
- Kind: A
- Application number: 06/091,615
- Filed: 1979-11-05
- Granted: 1983-08-02
- Earliest claimed: 1979-11-05
- Assignees: Addiction Research Foundation
- Inventors: Avram Goldstein
- Web page: https://patentgrep.com/patent/US4396606A

## CPC

- C07K 14/665: derived from pro-opiomelanocortin, pro-enkephalin or pro-dynorphin
- A61P 25/04: Centrally acting analgesics, e.g. opioids
- C07K 16/26: against hormones {; against hormone releasing or inhibiting factors}
- G01N 33/68: involving proteins, peptides or amino acids {(involving lipoproteins G01N33/92)}
- G01N 33/9486: {Analgesics, e.g. opiates, aspirine}
- 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)
- 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
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)
- 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)

## Abstract

Novel opioid compounds are provided having a phenolic hydroxyl and a pentet of alternating basic hydrophilic and hydrophobic groups derived from basic amino acids and hydrophobic amino acids. Desirably, the pentet, usually sextet, is separated from the phenolic ring by at least about 3 atoms in a chain, preferably at least about 15 atoms in a chain and not more than about 30 atoms in a chain (for rings one will take the average of the shortest and longest distances). Particularly, a polypeptide is provided having tyrosyl at the amine end, desirably as the first amino acid of leu- or met-enkephalin and a sextet of alternating basic hydrophilic and hydrophobic amino acids spaced from the enkephalin by at least about one amino acid. Desirably, the polypeptide is at least 1,200 molecular weight and under about 2,500 molecular weight.

## Claims

### Claim 1

Dynorphin substantially free of products from the pituitary gland.

### Claim 2

A compound of the formula
H-tyr-gly-gly-phe-leu-arg-arg-ile-arg-pro-lys-leu-lys-W.sup.3,
where W.sup.3 is hydroxyl or amino.

### Claim 3

A compound of the formula
H-tyr-gly-gly-phe-leu-arg-ile-arg-pro-lys-leu-lys-W.sup.3,
where W.sup.3 is hydroxyl or amino.

### Claim 4

A compound of the formula
H-tyr-gly-gly-phe-leu-gly-arg-arg-ile-arg-pro-lys-leu-lys-W.sup.3,
where W.sup.3 is hydroxyl or amino.

### Claim 5

A compound of the formula
Tyr-gly-gly-phe-leu-(arg or lys).sub.r4 -(arg or lys)-ile-arg-(pro or HOpro)-(arg or lys)-leu-(arg or lys)-W.sup.2
wherein:
r.sup.4 is 0 or one; and
W.sup.2 is hydroxyl or amino.

### Claim 6 (depends on 1, 2, 3, 4)

A method for inducing analgesia in a mammalian host which comprises administering to said host in an amount sufficient to induce analgesia a compound according to any of claims 2, 3, 4 or 1.