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US 2014/0213513 A1Published application
Exendin-4 Derivatives as dual GLP1/GIP or trigonal GLP1/GIP/Glucagon Agonists
AssigneeSanofi
InventorsTorsten Haack, Michael Wagner, Bernd Henkel, Siegfried Stengelin, Andreas Evers, Martin Lorenz, Katrin Lorenz
Life of this patent
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Abstract
The present invention relates to exendin-4 derivatives and their medical use, for example in the treatment of disorders of the metabolic syndrome, including diabetes and obesity, as well as reduction of excess food intake.
Claims33
A peptidic compound having the formula (I):
- R1—Z—R2 (I)
- wherein Z is a peptide moiety having the formula (II)
- (II)
- Tyr-Aib-X3-Gly-Thr-Phe-Thr-Ser-Asp-Leu-Ser-X12-Gln-X14-X15-X16-X17-X18-X19-X20
- X21-Phe-Ile-Glu-Trp-Leu-Lys-X28-X29-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser-X40
- X3 represents an amino acid residue selected from Gln, Glu and His,
- X12 represents an amino acid residue selected from Ile and Lys,
- X14 represents an amino acid residue having a side chain with an —NH2 group, wherein the —NH2 side chain group is functionalized by —C(O)—R5, wherein R5 may be a moiety comprising up to 50 or up to 100 carbon atoms and optionally heteroatoms selected from halogen, N, O, S and/or P,
- X15 represents an amino acid residue selected from Asp and Glu,
- X16 represents an amino acid residue selected from Ser, Lys, Glu and Gln,
- X17 represents an amino acid residue selected from Arg, Lys, Glu, Ile, Gln, Leu, Aib, Tyr and Ala,
- X18 represents an amino acid residue selected from Ala, Arg, Aib, Leu, Lys and Tyr,
- X19 represents an amino acid residue selected from Ala, Gln, Val and Aib,
- X20 represents an amino acid residue selected from Gln, Aib, Phe, Arg, Leu, Lys and His,
- X21 represents an amino acid residue selected from Asp, Glu, Tyr, and Leu,
- X28 represents an amino acid residue selected from Asn, Ala, Aib, Arg and Lys,
- X29 represents an amino acid residue selected from Gly, Thr, Aib, D-Ala and Ala,
- X40 is either absent or represents Lys,
- R1 represents NH2,
- R2 represents the C-terminal group of the peptidic compound and is selected from OH and NH2,
- or a salt or solvate thereof.
18 more elements
A pharmaceutical composition comprising a peptidic compound having the formula (I):
- R1—Z—R2 (I)
- wherein Z is a peptide moiety having the formula (II)
- (II)
- Tyr-Aib-X3-Gly-Thr-Phe-Thr-Ser-Asp-Leu-Ser-X12-Gln-X14-X15-X16-X17-X18-X19-X20
- X21-Phe-Ile-Glu-Trp-Leu-Lys-X28-X29-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser-X40
- X3 represents an amino acid residue selected from Gln, Glu and His,
- X12 represents an amino acid residue selected from Ile and Lys,
- X14 represents an amino acid residue having a side chain with an —NH2 group, wherein the —NH2 side chain group is functionalized by —C(O)—R5, wherein R5 may be a moiety comprising up to 50 or up to 100 carbon atoms and optionally heteroatoms selected from halogen, N, O S and/or P,
- X15 represents an amino acid residue selected from Asp and Glu,
- X16 represents an amino acid residue selected from Ser, Lys, Glu and Gln,
- X17 represents an amino acid residue selected from Arg, Lys, Glu, Ile, Gln, Leu, Aib, Tyr and Ala
- X18 represents an amino acid residue selected from Ala, Arg, Aib, Leu, Lys and Tyr,
- X19 represents an amino acid residue selected from Ala, Gln, Val and Aib,
- X20 represents an amino acid residue selected from Gln, Aib, Phe, Arg, Leu, Lys and His,
- X21 represents an amino acid residue selected from Asp, Glu, Tyr, and Leu,
- X28 represents an amino acid residue selected from Asn, Ala, Aib, Arg and Lys,
- X29 represents an amino acid residue selected from Gly, Thr, Aib, D-Ala and Ala,
- X40 is either absent or represents Lys,
- R1 represents NH2,
- R2 represents the C-terminal group of the peptidic compound and is selected from OH and NH2,
- or a salt or solvate thereof.
18 more elements
A method for the treatment or prevention of a disease or condition, the method comprising administering to a subject in need thereof a peptidic compound having the formula (I):
- R1—Z—R2 (I)
- wherein Z is a peptide moiety having the formula (II)
- (II)
- Tyr-Aib-X3-Gly-Thr-Phe-Thr-Ser-Asp-Leu-Ser-X12-Gln-X14-X15-X16-X17-X18-X19-X20
- X21-Phe-Ile-Glu-Trp-Leu-Lys-X28-X29-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser-X40
- X3 represents an amino acid residue selected from Gln, Glu and His,
- X12 represents an amino acid residue selected from Ile and Lys,
- X14 represents an amino acid residue having a side chain with an —NH2 group, wherein the —NH2 side chain group is functionalized by —C(O)—R5, wherein R5 may be a moiety comprising up to 50 or up to 100 carbon atoms and optionally heteroatoms selected from halogen, N, O, S and/or P,
- X15 represents an amino acid residue selected from Asp and Glu,
- X16 represents an amino acid residue selected from Ser, Lys, Glu and Gln,
- X17 represents an amino acid residue selected from Arg, Lys, Glu, Ile, Gln, Leu, Aib, Tyr and Ala,
- X18 represents an amino acid residue selected from Ala, Arg, Aib, Leu, Lys and Tyr,
- X19 represents an amino acid residue selected from Ala, Gln, Val and Aib,
- X20 represents an amino acid residue selected from Gln, Aib, Phe, Arg, Leu, Lys and His,
- X21 represents an amino acid residue selected from Asp, Glu, Tyr, and Leu,
- X28 represents an amino acid residue selected from Asn, Ala, Aib, Arg and Lys,
- X29 represents an amino acid residue selected from Gly, Thr, Aib, D-Ala and Ala,
- X40 is either absent or represents Lys,
- R1 represents NH2,
- R2 represents the C-terminal group of the peptidic compound and is selected from OH and NH2,
- or a salt or solvate thereof.
18 more elements
Dependencies are inferred from the claim text.