Novel derivatives of gamma-endorphins, intermediates therefor, and compositions and methods employing said derivatives

• US 4,127,518 A
• Filed: 06/16/1977
• Issued: 11/28/1978
• Est. Priority Date: 06/16/1977
• Status: Expired due to Term

• Current Assignee: Veterans Administration The United States of America As Represented By
• Original Assignee: Abba J. Kastin, David H. Coy
• Inventors: Coy, David H., Kastin, Abba J.
• Primary Examiner(s): Phillips, Delbert R.
• Application Number:
  US05/807,120
• Time in Patent Office: 530 Days
• Field of Search: 260/112.5 R, 260/112.5 E, 260/8, 424/177
• US Class Current: 525/54.11
• CPC Class Codes: 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
• CPC Class Codes: C07K 14/6755 with at least 1 amino acid in D-form
• CPC Class Codes: Y10S 930/28 Bound to a nonpeptide drug, nonpeptide label, nonpeptide carrier, or a nonpeptide resin

Abstract

Novel γ-endorphins represented by the formula 1

H-Tyr-X-Gly-Phe-Met-Thr-Ser-Glu-Lys-Ser-Gln-Thr-Pro-Leu-Val-Thr-Leu-Y

wherein: X is a chiral residue of a D-amino acid selected from the group consisting of D-alanine, D-leucine, D-isoleucine, D-valine, D-phenylalanine, D-tyrosine, D-tryptophan, D-serine, D-threonine, D-methionine, D-glutamic acid, D-glutamine, D-proline D-aspartic acid, D-asparagine, D-lysine, D-arginine and D-histidine; and Y is selected from the group consisting of hydroxy, amino, loweralkylamino, diloweralkylamino and lower alkoxy; and the pharmaceutically acceptable salts thereof; intermediates useful in making the novel compounds; and pharmaceutical compositions and methods employing the novel compounds.

Claims

1. A heptadecapeptide represented by the formula

View Dependent Claims (2, 3, 4, 5, 6, 13, 14, 15, 16, 17, 18, 19)

2. The novel heptadecapeptides of claim 1 wherein Y is hydroxy.

3. The novel heptadecapeptides of claim 1 wherein Y is amino.

4. A novel heptadecapeptides of claim 1 wherein Y is loweralkylamino

5. The heptadecapeptides of claim 1 wherein Y is diloweralkylamino.

6. The novel heptadecapeptides of claim 1 wherein Y is lower alkoxy.

13. A pharmaceutical composition suitable for oral, parenteral, nasal, rectal or vaginal or sublingual administration comprising a therapeutically effective amount of a compound of claim 1 and a pharmaceutically acceptable carrier or diluent.

14. A pharmaceutical composition in accordance with claim 13 adapted for oral administration..

15. A pharmaceutical composition in accordance with claim 13 adapted for parenteral administration.

16. A pharmaceutical composition in accordance with claim 13 adapted for nasal administration.

17. A pharmaceutical composition in accordance with claim 13 adapted for rectal administration.

18. A pharmaceutical composition in accordance with claim 13 adapted for vaginal administration.

19. A pharmaceutical composition in accordance with claim 13 adapted for sublingual administration.

7. A hexadecapeptide having the following amino acid sequence:

space="preserve" listing-type="equation">H-Tyr-D-Ala-Gly-Phe-Met-Thr-Ser-Glu-Lys-Ser-Gln-Thr-Pro-Leu-Val-Thr-Leu-y

wherein Y is selected from the group consisting of hyroxy, amino, loweralkylamino, lowerdialkylamino and lower alkoxy; and

the pharmaceutically acceptable salts thereof.

8. The heptadecapeptide of claim 7 wherein Y is loweralkylamino.

9. The heptadecapeptide of claim 7 wherein Y is diloweralkylamino

10. The heptadecapeptide of claim 7 wherein Y is lowe alkoxy.

11. D-Ala² -β

-lipotropin fragment 61-77 or a pharmaceutically acceptable salt thereof.

12. D-Ala² -β

-lipotropin fragment 61-77 amide or a pharmaceutically acceptable salt thereof.

20. Novel heptadecapeptides of the formula