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Generated: August 16, 2017

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Title:Exendin agonist compounds
Abstract: The present invention relates to novel exendin agonist compounds useful in treatment of Type I and II diabetes, and useful in lowering plasma glucose levels, reducing body weight, and delaying and/or slowing gastric emptying.
Inventor(s): Beeley; Nigel Robert Arnold (Solana Beach, CA), Prickett; Kathryn Susan (San Diego, CA)
Assignee: Amylin Pharmaceuticals, Inc. (San Diego, CA)
Filing Date:Nov 13, 1998
Application Number:09/554,533
Claims:1. An isolated peptide compound according to SEQ ID NO:4 and having the formula: His Xaa.sub.2 Xaa.sub.3 Gly Thr Phe Thr Xaa.sub.8 Asp Xaa.sub.10 Ser Lys Gln Xaa.sub.14 Glu Glu Glu Ala Val Arg Leu Xaa.sub.22 Xaa.sub.23 Glu Xaa.sub.25 Leu Lys Xaa.sub.28 Gly Gly Pro Ser Ser Gly Ala Pro Pro Pro-Z Wherein Xaa.sub.2 is Ser, Gly or Thr, Xaa.sub.3 is Asp or Glu Xaa.sub.8 is Ala, Ser, or Thr, Xaa.sub.10 is Leu, Ile, Val, pentylglycine or Met, Xaa.sub.14 is Ala, Leu, Ile, pentylglycine, Val, Xaa.sub.22 is Phe, Tyr or naphthylalanine, Xaa.sub.23 is Ile, Val, Leu, pentylglycine, tert-butylglycine or Met, Xaa.sub.25 is Ala, Trp, Phe, Tyr or naphthylalanine, Xaa.sub.28 is Ala or Asn, and Z is --OH or NH.sub.2; or a pharmaceutically acceptable salt thereof.

2. The isolated peptide compound or salt thereof of claim 1, wherein Xaa.sub.2 is Ser.

3. The isolated peptide compound or salt thereof of claim 1, wherein Xaa.sub.2 is Gly.

4. The isolated peptide compound or salt thereof of claim 1, wherein Xaa.sub.3 is Asp.

5. The isolated peptide compound or salt thereof of claim 1, wherein Xaa.sub.14 is Leu.

6. The isolated peptide compound or salt thereof of claim 1, wherein Xaa.sub.25 is Phe.

7. The isolated peptide compound or salt thereof of claim 1, wherein Xaa.sub.28 is Ala.

8. The isolated peptide compound or salt thereof of claim 1, wherein Z is NH.sub.2.

9. An isolated peptide compound according to SEQ ID NO:4 and having the formula: His Xaa.sub.2 Xaa.sub.3 Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Met Glu Glu Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser Ser Gly Ala Pro Pro Pro-Z Wherein Xaa.sub.2 is Ala or Thr, Xaa.sub.3 is Glu or Asp; and Z is --OH or NH.sub.2, wherein said peptide compound is an exendin agonist; or a pharmaceutically acceptable salt thereof.

10. The isolated peptide compound or salt thereof of claim 9, wherein Xaa.sub.2 is Ser.

11. The isolated peptide compound or salt thereof of claim 9, wherein Xaa.sub.3 is Asp.

12. The isolated peptide compound or salt thereof of claim 9, wherein Z is NH.sub.2.

13. A method for the treatment of diabetes mellitus comprising the administration, to a subject in need thereof, of a therapeutically effective amount of a compound or salt thereof according to claim 1.

14. The method of claim 13 further comprising the administration of a therapeutically effective amount of an insulin.

15. A method for the treatment of diabetes mellitus comprising the administration, to a subject in need thereof, of a therapeutically effective amount of a compound or a salt thereof according to claim 9.

16. The method of claim 15 further comprising the administration of a therapeutically effective amount of an insulin.
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