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|Title:||Exendin agonist compounds|
|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.|
|Inventor(s):||Beeley; Nigel Robert Arnold (San Diego, CA), Prickett; Kathryn S. (Foster City, CA)|
|Assignee:||Amylin Pharmaceuticals, Inc. (San Diego, CA)|
|Filing Date:||Dec 02, 2010|
|Claims:||1. A compound comprising the amino acid sequence of Formula (II): TABLE-US-00007 Xaa.sub.1 Xaa.sub.2 Xaa.sub.3 Gly Thr Xaa.sub.4 Xaa.sub.5 Xaa.sub.6 Xaa.sub.7 Xaa.sub.8 Ser Lys Gln Xaa.sub.9 Glu Glu Glu Ala Val Arg Leu Xaa.sub.10 Xaa.sub.11 Xaa.sub.12 Xaa.sub.13 Leu X.sub.1 Gly Gly Xaa.sub.14 Ser Ser Gly Ala Xaa.sub.15 Xaa.sub.16 Xaa.sub.17 Xaa.sub.18-Z; |
wherein: Xaa.sub.1 4-imidazopropionyl; Xaa.sub.2 is Ser, Gly, Ala or Thr; Xaa.sub.3 is Asp or Glu; Xaa.sub.4 is Phe, Tyr or naphthylalanine; Xaa.sub.5 is Thr or Ser; Xaa.sub.6 is Ser or Thr; Xaa.sub.7 is Asp or Glu; Xaa.sub.8 is Leu, Ile, Val, pentylglycine or Met; Xaa.sub.9 is Leu, Ile, pentylglycine, Val or Met; Xaa.sub.10 is Phe, Tyr or naphthylalanine; Xaa.sub.11 is Ile, Val, Leu, pentylglycine, tert-butylglycine or Met; Xaa.sub.12 is Glu or Asp; Xaa.sub.13 is Trp, Phe, Tyr, or naphthylalanine; X.sub.1 is Lys Asn, Asn Lys, Lys-NH.sup.e-R Asn, or Asn Lys-NH.sup.e-R where R is Lys, Arg, C.sub.1-C.sub.10 straight chain or branched alkanoyl or cycloalkyanoyl; Xaa.sub.14, Xaa.sub.15, Xaa.sub.16 and Xaa.sub.17 are independently Pro, homoproline, 3Hyp, 4Hyp, thioproline, N-alkylglycine, N-alkylpentylglycine or N-alkylalanine; Xaa.sub.18 is Ser, Thr or Tyr; and Z is --OH or --NH.sub.2; with the proviso that the compound does not have the formula of SEQ ID. NO:1 or 2.
2. The compound of claim 1, wherein: Xaa.sub.2 is Gly; Xaa.sub.3 is Glu; Xaa.sub.4 is Phe; Xaa.sub.5 is Thr; Xaa.sub.6 is Ser; Xaa.sub.7 is Asp; Xaa.sub.8 is Leu; Xaa.sub.9 is Leu or Met; Xaa.sub.10 is Phe; Xaa.sub.11 is Ile; Xaa.sub.12 is Glu; Xaa.sub.13 is Trp or Phe; X.sub.1 is Lys Asn; Xaa.sub.14, Xaa.sub.15, Xaa.sub.16 and Xaa.sub.17 are independently Pro; Xaa.sub.18 is Ser; and Z is --NH.sub.2.
3. The compound of claim 2, wherein Xaa.sub.9 is Met and Xaa.sub.13 is Trp.
4. The compound of claim 2, wherein Xaa.sub.9 is Len.
5. The compound of claim 4, wherein Xaa.sub.9 is Len and Xaa.sub.13 is Phe.
6. A pharmaceutical composition comprising a therapeutically effective amount of the compound of claim 1 and a pharmaceutically acceptable carrier.
7. A pharmaceutical composition comprising a therapeutically effective amount of the compound of claim 2 and a pharmaceutically acceptable carrier.
8. A pharmaceutical composition comprising a therapeutically effective amount of the compound of claim 3 and a pharmaceutically acceptable carrier.
9. A pharmaceutical composition comprising a therapeutically effective amount of the compound of claim 4 and a pharmaceutically acceptable carrier.
10. A pharmaceutical composition comprising a therapeutically effective amount of the compound of claim 5 and a pharmaceutically acceptable carrier.
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