Novel exendin agonist compounds

Abstract

Novel exendin agonist compounds are provided. These compounds are useful in treating diabetes and conditions which would be benefited by lowering plasma glucose or delaying and/or slowing gastric emptying.

1 - 73 . (canceled) 
     
     
         74 . A peptide comprising the amino acid sequence of any one of SEQ ID NOs. 5-93 and 95-110. 
     
     
         75 . The peptide of  claim 74 , wherein the amino acid sequence is any one of SEQ ID NOs. 11-93. 
     
     
         76 . A pharmaceutical composition comprising the peptide of  claim 74  and a pharmaceutically acceptable carrier. 
     
     
         77 . A method for treating diabetes in a patient in need thereof comprising administering to the patient a therapeutically effective amount of the peptide of  claim 74 . 
     
     
         78 . The peptide of  claim 74 , wherein the amino acid sequence is SEQ ID NO. 92 or 93. 
     
     
         79 . A pharmaceutical composition comprising the peptide of  claim 78  and a pharmaceutically acceptable carrier. 
     
     
         80 . A method for treating diabetes in a patient in need thereof comprising administering to the patient a therapeutically effective amount of the peptide of  claim 78 . 
     
     
         81 . A peptide comprising the amino acid sequence of the formula:
   Xaa 1  Gly Xaa 3  Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Xaa 14  Glu Glu Glu Ala Val Arg Leu Phe Ile Glu Xaa 25  Leu Lys Asn Gly Gly Pro Ser Ser Gly Ala Pro Pro Pro Ser-Z 2      wherein: Xaa 1  is Ala or His; Xaa 3  is Glu or Ala; Xaa 14  is Met or Leu; Xaa 25  Phe or Trp;   and Z 2  is —OH or —NH 2 .   
     
     
         82 . The peptide of  claim 81 , wherein Xaa 1  is Ala; Xaa 3  is Glu; Xaa 14  is Met; and Xaa 25  is Trp (SEQ ID NO: 92). 
     
     
         83 . The peptide of  claim 81 , wherein Xaa 1  is Ala; Xaa 3  is Ala; Xaa 14  is Leu; and Xaa 25  is Phe (SEQ ID NO: 93). 
     
     
         84 . The peptide of  claim 81 , wherein Xaa 1  is His; Xaa 3  is Glu; Xaa 14  is Leu; and Xaa 25  is Trp. 
     
     
         85 . The peptide of  claim 81 , wherein: Xaa 1  is Ala; and
 (i) Xaa 3  is Glu; Xaa 14  is Met; and Xaa 25  is Phe;   (ii) Xaa 3  is Glu; Xaa 14  is Leu; and Xaa 25  is Trp;   (iii) Xaa 3  is Glu; Xaa 14  is Leu; and Xaa 25  is Phe;   (iv) Xaa 3  is Ala; Xaa 14  is Met; and Xaa 25  is Trp;   (v) Xaa 3  is Ala; Xaa 14  is Met; and Xaa 25  is Phe; or   (vi) Xaa 3  is Ala; Xaa 14  is Leu; and Xaa 25  is Trp.   
     
     
         86 . The peptide of  claim 81 , wherein Xaa 1  is His; and
 (i) Xaa 3  is Glu; Xaa 14  is Met; and Xaa 25  is Trp;   (ii) Xaa 3  is Glu; Xaa 14  is Met; and Xaa 25  is Phe;   (iii) Xaa 3  is Glu; Xaa 14  is Leu; and Xaa 25  is Phe;   (iv) Xaa 3  is Ala; Xaa 14  is Met; and Xaa 25  is Trp;   (v) Xaa 3  is Ala; Xaa 14  is Met; and Xaa 25  is Phe;   (vi) Xaa 3  is Ala; Xaa 14  is Leu; and Xaa 25  is Trp; or   (vii) Xaa 3  is Ala; Xaa 14  is Leu; and Xaa 25  is Phe.   
     
     
         87 . A pharmaceutical composition comprising the peptide of  claim 81  and a pharmaceutically acceptable carrier. 
     
     
         88 . A method for treating diabetes in a patient in need thereof comprising administering to the patient a therapeutically effective amount of the peptide of  claim 81 . 
     
     
         89 . A peptide comprising the amino acid sequence having the formula:
   Xaa 1  Gly Glu Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Xaa 14  Glu Glu Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser Ser Gly Ala Pro Pro Pro Ser-Z 2      wherein: Xaa 1  is Ala or His; Xaa 14  is Met or Leu; and Z 2  is —OH or —NH 2 .   
     
     
         90 . The peptide of  claim 89 , wherein Xaa 1  is Ala; and Xaa 14  is Met (SEQ ID NO: 92). 
     
     
         91 . The peptide of  claim 89 , wherein Xaa 1  is His; and Xaa 14  is Leu. 
     
     
         92 . A pharmaceutical composition comprising the peptide of  claim 89  and a pharmaceutically acceptable carrier. 
     
     
         93 . A method for treating diabetes in a patient in need thereof comprising administering to the patient a therapeutically effective amount of the peptide of  claim 89 .