FUNCTIONALIZED EXENDIN-4 DERIVATIVES

• US 20170216406A1
• Filed: 04/12/2017
• Published: 08/03/2017
• Est. Priority Date: 12/21/2012
• Status: Active Grant

• Current Assignee: Sanofi
• Original Assignee: Sanofi
• Inventors: Lorenz, Katrin, Lorenz, Martin, Haack, Torsten, Wagner, Michael, Henkel, Bernd, Stengelin, Siegfried, Evers, Andreas
• Granted Patent: US 10,253,079 B2
• Time in Patent Office: Days
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• 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: A61K 38/2264 Obesity-gene products, e.g. leptin
• CPC Class Codes: A61K 38/26 Glucagons
• CPC Class Codes: A61K 38/28 Insulins
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 25/30 for treating abuse or dependence
• CPC Class Codes: A61P 3/00 Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• CPC Class Codes: A61P 3/04 Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 3/06 Antihyperlipidemics
• CPC Class Codes: A61P 3/08 for glucose homeostasis pancreatic hormones A61P5/48
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 39/02 Antidotes
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/10 : for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: A61P 9/12 : Antihypertensives
• CPC Class Codes: C07K 14/605 : Glucagons
• CPC Class Codes: Y02A 50/30 : Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

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.

Claims

1-31. -31. (canceled)

32. A method of treating or preventing of diseases or disorders caused by, associated with and/or accompanied by disturbances in carbohydrate and/or lipid metabolism, in a patient in need thereof, comprising administering to said patient a therapeutically effective amount of a peptidic compound having formula (I):

R¹-Z-R²  

 

(I),

or a salt or solvate thereof, or a pharmaceutical composition comprising a compound of formula (I) or salt or solvate thereof as an active agent together with at least one pharmaceutically acceptable carrier,

wherein Z is a peptide moiety having the formula (II);

33. The method according to claim 32, wherein said method comprises delaying or preventing disease progression in type 2 diabetes, treating metabolic syndrome, treating obesity or preventing overweight, decreasing food intake, increasing energy expenditure, reducing body weight, delaying the progression from impaired glucose tolerance (IGT) to type 2 diabetes;

delaying the progression from type 2 diabetes to insulin-requiring diabetes;

regulating appetite;

inducing satiety;

preventing weight regain after successful weight loss;

treating a disease or state related to overweight or obesity;

treating bulimia;

treating binge eating;

treating atherosclerosis, hypertension, IGT, dyslipidemia, coronary heart disease, hepatic steatosis, treatment of beta-blocker poisoning, inhibition of the motility of the gastro-intestinal tract, investigations of the gastro-intestinal tract using techniques such as X-ray, CT- and NMR-scanning.

39. The method according to claim 32, wherein said pharmaceutical composition is administered parenterally.

40. The method according to claim 39, wherein said parenteral administration is selected from subcutaneous, intramuscular, intravenous, intradermal and transdermal administration.

41. The method according to claim 32, wherein said pharmaceutical composition is administered in a single dose injectable form.

42. The method according to claim 41, wherein said single dose injectable form is in the form of a pen.

43. The method according to claim 32, wherein said compound, salt or solvate thereof of formula (I) or said pharmaceutical composition is administered in combination with at least one additional therapeutically active agent.

44. The method according to claim 43, wherein said at least one additional therapeutically active agent is administered simultaneously, separately or sequentially with respect to the administration of the compound, salt or solvate thereof of formula (I) or the pharmaceutical composition.

45. The method according to claim 43, wherein said pharmaceutical composition comprises the at least one additional therapeutically active agent.

46. The method according to claim 43, wherein said at least one additional therapeutically active agent is selected from insulin and insulin derivatives, GLP-1, GLP-1 analogues and GLP-1 receptor agonists, and a gastrointestinal peptide.

47. The method according to claim 32, wherein, in said peptidic compound of formula (I) or salt or solvate thereof,

wherein X14 is an amino acid residue with a functionalized —

NH₂ side chain group selected from functionalized Lys, Orn, Dab and Dap, wherein at least one H atom of the —

NH₂ side chain group is replaced by —

C(O)—

R⁵, which is selected from the group consisting of (S)-4-Carboxy-4-hexadecanoylamino-butyryl-, (S)-4-Carboxy-4-octadecanoylamino-butyryl-, 4-Hexadecanoylamino-butyryl-, 4-{3-[(R)-2,5,7,8-tetramethyl-2-((4R,8R)-4,8,12-trimethyl-tridecyl)-chroman-6-yloxycarbonyl]-propionylamino}-butyryl-, 4-octadecanoylamino-butyryl-, 4-((Z)-octadec-9-enoylamino)-butyryl-, 6-[(4,4-Diphenyl-cyclohexyloxy)-hydroxy-phosphoryloxy]-hexanoyl-, Hexadecanoyl-, (S)-4-Carboxy-4-(15-carboxy-pentadecanoylamino)-butyryl-, (S)-4-Carboxy-4-{3-[3-((2S,3R,4S,5R)-5-carboxy-2,3,4,5-tetrahydroxy-pentanoylamino)-propionylamino]-propionylamino}-butyryl, (S)-4-Carboxy-4-{3-[(R)-2,5,7,8-tetramethyl-2-((4R,8R)-4,8,12-trimethyl-tridecyl)-chroman-6-yloxycarbonyl]-propionylamino}-butyryl-, (S)-4-Carboxy-4-((9Z,12Z)-octadeca-9,12-dienoylamino)-butyryl-, (S)-4-Carboxy-4-[6-((2S,3R,4S,5R)-5-carboxy-2,3,4,5-tetrahydroxy-pentanoylamino)-hexanoylamino]-butyryl-, (S)-4-Carboxy-4-((2S,3R,4S,5R)-5-carboxy-2,3,4,5-tetrahydroxy-pentanoylamino)-butyryl-, (S)-4-Carboxy-4-tetradecanoylamino-butyryl-, (S)-4-(11-Benzyloxycarbonyl-undecanoylamino)-4-carboxy-butyryl-, (S)-4-Carboxy-4-[11-((2S,3R,4R,5R)-2,3,4,5,6-pentahydroxy-hexylcarbamoyl)-undecanoylamino]-butyryl-, (S)-4-Carboxy-4-((Z)-octadec-9-enoylamino)-butyryl-, (S)-4-Carboxy-4-(4-dodecyloxy-benzoylamino)-butyryl-, (S)-4-Carboxy-4-henicosanoylamino-butyryl-, (S)-4-Carboxy-4-docosanoylamino-butyryl-, (S)-4-Carboxy-4-((Z)-nonadec-10-enoylamino)-butyryl-, (S)-4-Carboxy-4-(4-decyloxy-benzoylamino)-butyryl-, (S)-4-Carboxy-4-[(4′

-octyloxy-biphenyl-4-carbonyl)-amino]-butyryl-, (S)-4-Carboxy-4-(12-phenyl-dodecanoylamino)-butyryl-, (S)-4-Carboxy-4-icosanoylamino-butyryl-, (S)-4-Carboxy-4-((S)-4-carboxy-4-hexadecanoylamino-butyrylamino)-butyryl-, (S)-4-Carboxy-4-((S)-4-carboxy-4-octadecanoylamino-butyrylamino)-butyryl-, 3-(3-Octadecanoylamino-propionylamino)-propionyl-, 3-(3-Hexadecanoylamino-propionylamino)-propionyl-, 3-Hexadecanoylamino-propionyl-, (S)-4-Carboxy-4-[(R)-4-((3R,5S,7R,8R,9R,10S,12S,13R,14R,17R)-3,7,12-trihydroxy-8,10,13-trimethyl-hexadecahydro-cyclopenta[a]phenanthren-17-yl)-pentanoylamino]-butyryl-, (S)-4-Carboxy-4-[(R)-4-((3R,5R,8R,9S,10S,13R,14S,17R)-3-hydroxy-10,13-dimethyl-hexadecahydro-cyclopenta[a]phenanthren-17-yl)-pentanoylamino]-butyryl-, (S)-4-Carboxy-4-((9S,10R)-9,10,16-trihydroxy-hexadecanoylamino)-butyryl-, tetradecanoyl-, 11-Carboxy-undecanoyl-, 11-Benzyloxycarbonyl-undecanoyl-, (S)-4-Carboxy-4-((S)-4-carboxy-4-tetradecanoylamino-butyrylamino)-butyryl-, 6-[Hydroxy-(naphthalen-2-yloxy)-phosphoryloxy]-hexanoyl-, 6-[Hydroxy-(5-phenyl-pentyloxy)-phosphoryloxy]-hexanoyl-, 4-(Naphthalene-2-sulfonylamino)-4-oxo-butyryl-, 4-(Biphenyl-4-sulfonylamino)-4-oxo-butyryl-, (S)-4-Carboxy-4-{(S)-4-carboxy-4-[2-(2-{2-[2-(2-{2-[(S)-4-carboxy-4-(17-carboxy-heptadecanoylamino)-butyrylamino]-ethoxy}- ethoxy)-acetylamino]-ethoxy}-ethoxy)-acetylamino]-butyrylamino}-butyryl-, (S)-4-Carboxy-4-[2-(2-{2-[2-(2-{2-[(S)-4-carboxy-4-(17-carboxy-heptadecanoylamino)-butyrylamino]-ethoxy}-ethoxy)-acetylamino]-ethoxy}-ethoxy)-acetylamino]-butyryl-, (S)-4-Carboxy-2-{(S)-4-carboxy-2-[2-(2-{2-[2-(2-{2-[(S)-4-carboxy-4-(17-carboxy-heptadecanoylamino)-butyrylamino]-ethoxy}-ethoxy)-acetylamino]-ethoxy}-ethoxy)-acetylamino]- butyrylamino}-butyryl-, (S)-4-Carboxy-2-[2-(2-{2-[2-(2-{2-[(S)-4-carboxy-4-(17-carboxy-heptadecanoylamino)-butyrylamino]-ethoxy}-ethoxy)-acetylamino]-ethoxy}- ethoxy)-acetylamino]-butyryl-, (S)-4-Carboxy-4-{(S)-4-carboxy-4-[2-(2-{2-[(S)-4-carboxy-4-(17-carboxy-heptadecanoylamino)-butyrylamino]-ethoxy}-ethoxy)-acetylamino]-butyrylamino}- butyryl-, (S)-4-Carboxy-4-[2-(2-{2-[(S)-4-carboxy-4-(17-carboxy-heptadecanoylamino)-butyrylamino]-ethoxy}-ethoxy)-acetylamino]-butyryl-, (S)-4-Carboxy-2-{(S)-4-carboxy-2-[2-(2-{2-[(S)-4-carboxy-4-(17-carboxy-heptadecanoylamino)-butyrylamino]-ethoxy}-ethoxy)-acetylamino]-butyrylamino}-butyryl-, (S)-4-Carboxy-2-[2-(2-{2-[(S)-4-carboxy-4-(17-carboxy-heptadecanoylamino)-butyrylamino]-ethoxy}-ethoxy)-acetylamino]-butyryl-, 2-(2-{2-[2-(2-{2-[(S)-4-Carboxy-4-(17-carboxy-heptadecanoylamino)-butyrylamino]-ethoxy}-ethoxy)-acetylamino]-ethoxy}-ethoxy)-acetyl-, 2-(2-{2-[(S)-4-Carboxy-4-(17-carboxy-heptadecanoylamino)-butyrylamino]-ethoxy}-ethoxy)-acetyl-, (S)-4-Carboxy-4-((S)-4-carboxy-4-{(S)-4-carboxy-4-[(S)-4-carboxy-4-(19-carboxy-nonadecanoylamino)-butyrylamino]-butyrylamino}-butyrylamino)-butyryl-, 2-(2-{2-[2-(2-{2-[(S)-4-Carboxy-4-(16-1H-tetrazol-5-yl-hexadecanoylamino)-butyrylamino]-ethoxy}-ethoxy)-acetylamino]-ethoxy}-ethoxy)-acetyl-, 2-(2-{2-[2-(2-{2-[(S)-4-Carboxy-4-(16-carboxy-hexadecanoylamino)-butyrylamino]-ethoxy}-ethoxy)-acetylamino]-ethoxy}-ethoxy)-acetyl-, (S)-4-Carboxy-4-{(S)-4-carboxy-4-[(S)-4-carboxy-4-(17-carboxy-heptadecanoylamino)-butyrylamino]-butyrylamino}-butyryl-, (S)-4-Carboxy-4-((S)-4-carboxy-4-{2-[2-(2-{2-[2-(2-{(S)-4-carboxy-4-[10-(4-carboxy-phenoxy)-decanoylamino]-butyrylamino}-ethoxy)-ethoxy]-acetylamino}-ethoxy)- ethoxy]-acetylamino}-butyryl-, (S)-4-Carboxy-4-{(S)-4-carboxy-4-[2-(2-{2-[2-(2-{2-[(S)-4-carboxy-4-(7-carboxy-heptanoylamino)-butyrylamino]-ethoxy}-ethoxy)- acetylamino]-ethoxy}-ethoxy)-acetylamino]-butyrylamino}-butyryl-, (S)-4-Carboxy-4-{(S)-4-carboxy-4-[2-(2-{2-[2-(2-{2-[(S)-4-carboxy-4-(11-carboxy-undecanoylamino)-butyrylamino]-ethoxy}-ethoxy)-acetylamino]-ethoxy}-ethoxy)-acetylamino]-butyrylamino}-butyryl-, (S)-4-Carboxy-4-{(S)-4-carboxy-4-[2-(2-{2-[2-(2-{2-[(S)-4-carboxy-4-(13-carboxy-tridecanoylamino)-butyrylamino]-ethoxy}-ethoxy)-acetylamino]-ethoxy}-ethoxy)- acetylamino]-butyrylamino}-butyryl-, (S)-4-Carboxy-4-{(S)-4-carboxy-4-[2-(2-{2-[2-(2-{2-[(S)-4-carboxy-4-(15-carboxy-pentadecanoylamino)-butyrylamino]-ethoxy}-ethoxy)-acetylamino]-ethoxy}-ethoxy)-acetylamino]-butyrylamino}-butyryl-, and (S)-4-Carboxy-4-{(S)-4-carboxy-4-[2-(2-{2-[2-(2-{2-[(S)-4-carboxy-4-(19-carboxy-nonadecanoylamino)-butyrylamino]-ethoxy}-ethoxy)-acetylamino]- ethoxy}-ethoxy)-acetylamino]-butyrylamino}-butyryl-.

48. The method according to claim 32, wherein, in said peptidic compound of formula (I) or salt or solvate thereof,

wherein the —

NH₂ side chain group is functionalized by one of the groups selected from the group consisting of (S)-4-Carboxy-4-hexadecanoylamino-butyryl-, (S)-4-Carboxy-4-octadecanoylamino-butyryl-, 4-octadecanoylamino-butyryl-, Hexadecanoyl-, (S)-4-Carboxy-4-henicosanoylamino-butyryl-, (S)-4-Carboxy-4-((S)-4-carboxy-4-octadecanoylamino-butyrylamino)-butyryl-, and 3-(3-Octadecanoylamino-propionylamino)-propionyl-.

49. The method according to claim 32, wherein, in said peptidic compound of formula (I) or salt or solvate thereof,

wherein X14 is Lys functionalized by one of the groups selected from the group consisting of (S)-4-carboxy-4-hexadecanoylamino-butyryl (γ

E-x53), (S)-4-carboxy-4-octadecanoylamino-butyryl (γ

E-x70), (S)-4-Carboxy-4-((S)-4-carboxy-4-octadecanoylamino-butyrylamino)-butyryl (γ

E-γ

E-x70), 4-octadecanoylamino-butyryl (GABA-x70), (S)-4-Carboxy-4-henicosanoylamino-butyryl (γ

E-x76), and 3-(3-Octadecanoylamino-propionylamino)-propionyl (β

-Ala-β

-Ala-x70).

50. The method according to claim 32, wherein, in said peptidic compound of formula (I) or salt or solvate thereof, wherein R² is —

NH₂.

51. The method according to claim 32, wherein, in said peptidic compound of formula (I) or salt or solvate thereof,

X3 is Glu,

X12 is Ile,

X14 is Lys, wherein the —

NH₂ side chain group is functionalized by one of the groups selected from the group consisting of (S)-4-Carboxy-4-hexadecanoylamino-butyryl-, (S)-4-Carboxy-4-octadecanoylamino-butyryl-, (S)-4-Carboxy-4-((S)-4-carboxy-4-octadecanoylamino-butyrylamino)-butyryl-, 3-(3-Octadecanoylamino-propionylamino)-propionyl-4-octadecanoylamino-butyryl-, and (S)-4-Carboxy-4-henicosanoylamino-butyryl-,

X15 is an amino acid residue selected from Glu and Asp,

X16 is an amino acid residue selected from Ser and Lys,

X17 is Arg,

X18 is Ala,

X19 is Ala,

X20 is an amino acid residue selected from Gln and Aib,

X21 is an amino acid residue selected from Asp and Glu,

X28 is an amino acid residue selected from Asn and Ala,

X29 is an amino acid residue selected from Gly and Thr, and

X40 is absent.

52. The method according to claim 32, wherein, in said peptidic compound of formula (I) or salt or solvate thereof,

X14 is Lys, wherein the —

NH₂ side chain group is functionalized by one of the groups selected from the group consisting of (S)-4-Carboxy-4-octadecanoylamino-butyryl-, 4-octadecanoylamino-butyryl-, (S)-4-Carboxy-4-henicosanoylamino-butyryl-, (S)-4-Carboxy-4-((S)-4-carboxy-4-octadecanoylamino-butyrylamino)-butyryl-, and 3-(3-Octadecanoylamino-propionylamino)-propionyl-.

53. The method according to claim 32, wherein, in said peptidic compound of formula (I) or salt or solvate thereof,

X14 is Lys, wherein the —

NH₂ side chain group is functionalized by one of the groups selected from the group consisting of (S)-4-Carboxy-4-hexadecanoylamino-butyryl-, and (S)-4-Carboxy-4-octadecanoylamino-butyryl-.

54. The method according to claim 32, wherein, in said peptidic compound of formula (I) or salt or solvate thereof,

X3 is Glu,

X12 is Ile,

X14 is Lys, wherein the —

NH₂ side chain group is functionalized by one of the groups selected from the group consisting of (S)-4-Carboxy-4-hexadecanoylamino-butyryl- and (S)-4-Carboxy-4-octadecanoylamino-butyryl-,

X15 is an amino acid residue selected from Glu and Asp,

X16 is an amino acid residue selected from Ser and Lys,

X17 is Arg,

X18 is Ala,

X19 is Ala,

X20 is an amino acid residue selected from Gln and Aib,

X21 is an amino acid residue selected from Asp and Glu,

X28 is an amino acid residue selected from Asn and Ala,

X29 is an amino acid residue selected from Gly and Thr, and

X40 is absent.

55. The method according to claim 32, wherein, in said peptidic compound of formula (I) or salt or solvate thereof, X19 is Ala.

56. The method according to claim 32, wherein, in said peptidic compound of formula (I) or salt or solvate thereof, X28 is Ala and X29 is Gly.

57. The method according to claim 32, wherein, in said peptidic compound of formula (I) or salt or solvate thereof, X28 is Asn and X29 is Thr.

58. The method according to claim 32, wherein, in said peptidic compound of formula (I) or salt or solvate thereof,

X3 is Glu,

X12 is Ile,

X14 is Lys, wherein the —

NH₂ side chain group is functionalized by one of the groups selected from the group consisting of (S)-4-Carboxy-4-hexadecanoylamino-butyryl- (γ

E-x53), (S)-4-Carboxy-4-octadecanoylamino-butyryl- (γ

E-x70), (S)-4-Carboxy-4-((S)-4-carboxy-4-octadecanoylamino-butyrylamino)-butyryl- (γ

E-γ

E-x70), 3-(3-Octadecanoylamino-propionylamino)-propionyl- (β

A-β

A-x70), 4-octadecanoylamino-butyryl- (GABA-x70), and (S)-4-Carboxy-4-henicosanoylamino-butyryl- (γ

E-x76),

X15 is an amino acid residue selected from Asp and Glu,

X16 is an amino acid residue selected from Ser and Lys,

X17 is Arg,

X18 is Ala,

X19 is Ala,

X20 is an amino acid residue selected from Gln and Aib,

X21 is an amino acid residue selected from Asp and Glu,

X28 is an amino acid residue selected from Asn and Ala,

X29 is an amino acid residue selected from Gly and Thr, and

X40 is absent.

59. The method according to claim 32, wherein, in said peptidic compound of formula (I) or salt or solvate thereof,

X3 is Glu,

X12 is Ile,

X14 is Lys, wherein the —

NH₂ side chain group is functionalized by (S)-4-Carboxy-4-hexadecanoylamino-butyryl- (γ

E-x53),

X15 is an amino acid residue selected from Asp and Glu,

X16 is an amino acid residue selected from Ser and Lys,

X17 is Arg,

X18 is Ala,

X19 is Ala,

X20 is an amino acid residue selected from Gln and Aib,

X21 is an amino acid residue selected from Asp and Glu,

X28 is an amino acid residue selected from Asn and Ala,

X29 is an amino acid residue selected from Gly and Thr, and

X40 is absent.

60. The method according to claim 32, wherein, in said peptidic compound of formula (I) or salt or solvate thereof,

X3 is Glu,

X12 is Ile,

X14 is Lys, wherein the —

NH₂ side chain group is functionalized by one of the groups selected from the group consisting of (S)-4-Carboxy-4-octadecanoylamino-butyryl- (γ

E-x70), (S)-4-Carboxy-4-((S)-4-carboxy-4-octadecanoylamino-butyrylamino)-butyryl- (γ

E-γ

E-x70), 3-(3-Octadecanoylamino-propionylamino)-propionyl- (β

A-β

A-x70), 4-octadecanoylamino-butyryl- (GABA-x70), and (S)-4-Carboxy-4-henicosanoylamino-butyryl- (γ

E-x76),

X15 is Glu,

X16 is an amino acid residue selected from Ser and Lys,

X17 is Arg,

X18 is Ala,

X19 is Ala,

X20 is an amino acid residue selected from Gln and Aib,

X21 is Glu,

X28 is an amino acid residue selected from Asn and Ala,

X29 is an amino acid residue selected from Gly and Thr, and

X40 is absent.

61. The method according to claim 32, wherein said peptidic compound of formula (I) is any one of SEQ ID NOs:

9-12, 14-27, 31, 33-36 and 39, or a salt, or solvate thereof.

62. The method according to claim 32, wherein said peptidic compound of formula (I) is any one of SEQ ID NOs:

9, 10, 12, 14-27, 31, and 33-36, or a salt, or solvate thereof.

63. The method according to claim 32, wherein said peptidic compound of formula (I) is any one of SEQ ID NOs:

9-12, and 39, or a salt, or solvate thereof.

64. The method according to claim 32, wherein said peptidic compound of formula (I) is any one of SEQ ID NOs:

9, 10 and 12, or a salt, or solvate thereof.

65. The method according to claim 32, wherein said peptidic compound of formula (I) is any one of SEQ ID NOs:

14-21, or a salt, or solvate thereof.

66. The method according to claim 32, wherein said peptidic compound of formula (I) is any one of SEQ ID NOs:

22-27, 31, and 33-36, or a salt, or solvate thereof.

67. A method of treating or preventing of diseases or disorders caused by, associated with and/or accompanied by disturbances in carbohydrate and/or lipid metabolism, in a patient in need thereof, comprising administering to said patient a therapeutically effective amount of a peptidic compound of the amino acid sequence of

SEQ ID NO:

9 or a salt or solvate thereof,

SEQ ID NO;

12 or a salt or solvate thereof,

SEQ ID NO;

14 or a salt or solvate thereof,

SEQ ID NO;

16 or a salt or solvate thereof,

SEQ ID NO;

17 or a salt or solvate thereof,

SEQ ID NO;

18 or a salt or solvate thereof,

SEQ ID NO;

20 or a salt or solvate thereof, or

SEQ ID NO;

21 or a salt or solvate thereof.