NOVEL EXENDIN AGONIST COMPOUNDS

• US 20110071076A1
• Filed: 12/02/2010
• Published: 03/24/2011
• Est. Priority Date: 08/08/1997
• Status: Active Grant

• Current Assignee: Amylin Pharmaceuticals Incorporated (Bristol-Myers Squibb Company)
• Original Assignee: Amylin Pharmaceuticals Incorporated (Bristol-Myers Squibb Company)
• Inventors: Prickett, Kathryn Susan, BEELEY, Nigel Robert Arnold
• Granted Patent: US 8,263,550 B2
• Time in Patent Office: Days
• US Class Current: 514/6.9
• 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: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: C07K 14/57563 Vasoactive intestinal peptide [VIP]; Related peptides

Abstract

Novel exendin agonist compounds are provided. These compounds are useful in treating Type I and II diabetes and conditions which would benefit by lower plasma glucose and delaying and/or slowing gastric emptying.

Claims

1. A compound comprising the amino acid sequence of Formula (II) (SEQ ID NO:

36);

2. The compound of claim 1, wherein Xaa₁ is 4-imidazopropionyl.

3. The compound of claim 2, wherein:

Xaa₂ is Gly;

Xaa₃ is Glu;

Xaa₄ is Phe;

Xaa₅ is Thr;

Xaa₆ is Ser;

Xaa₇ is Asp;

Xaa₈ is Leu;

Xaa₉ is Leu or Met;

Xaa₁₀ is Phe;

Xaa₁₁ is Ile;

Xaa₁₂ is Glu;

Xaa₁₃ is Trp or Phe;

X₁ is Lys Asn;

Xaa₁₄, Xaa₁₅, Xaa₁₆ and Xaa₁₇ are independently Pro;

Xaa₁₈ is Ser; and

Z is —

NH₂.

4. The compound of claim 3, wherein Xaa₉ is Met and Xaa₁₃ is Trp.

5. The compound of claim 3, wherein Xaa₉ is Leu.

6. The compound of claim 5, wherein Xaa₉ is Leu and Xaa₁₃ is Phe.

7. The compound of claim 1, comprising the amino acid sequence of SEQ ID NO:

36, 37, 38, or 39.

8. A pharmaceutical composition comprising a therapeutically effective amount of the compound of claim 1 and a pharmaceutically acceptable carrier.

9. A pharmaceutical composition comprising a therapeutically effective amount of the compound of claim 2 and a pharmaceutically acceptable carrier.

10. A pharmaceutical composition comprising a therapeutically effective amount of the compound of claim 3 and a pharmaceutically acceptable carrier.

11. A pharmaceutical composition comprising a therapeutically effective amount of the compound of claim 4 and a pharmaceutically acceptable carrier.

12. A pharmaceutical composition comprising a therapeutically effective amount of the compound of claim 5 and a pharmaceutically acceptable carrier.

13. A pharmaceutical composition comprising a therapeutically effective amount of the compound of claim 6 and a pharmaceutically acceptable carrier.

14. A pharmaceutical composition comprising a therapeutically effective amount of the compound of claim 7 and a pharmaceutically acceptable carrier.

15. A method of treating diabetes in a human in need thereof comprising administering a therapeutically effective amount of the compound of claim 1 to the human to treat diabetes.

16. A method of treating diabetes in a human in need thereof comprising administering a therapeutically effective amount of the compound of claim 2 to the human to treat diabetes.

17. A method of treating diabetes in a human in need thereof comprising administering a therapeutically effective amount of the compound of claim 3 to the human to treat diabetes.

18. A method of treating diabetes in a human in need thereof comprising administering a therapeutically effective amount of the compound of claim 4 to the human to treat diabetes.

19. A method of treating diabetes in a human in need thereof comprising administering a therapeutically effective amount of the compound of claim 5 to the human to treat diabetes.

20. A method of treating diabetes in a human in need thereof comprising administering a therapeutically effective amount of the compound of claim 6 to the human to treat diabetes.