GLUCAGON-LIKE PEPTIDE-1 ANALOGUES AND USES THEREOF

• US 20130053304A1
• Filed: 04/29/2011
• Published: 02/28/2013
• Est. Priority Date: 04/27/2010
• Status: Active Grant

• Current Assignee: Betta Pharmaceuticals Co., Ltd., Halliburton Energy Services Incorporated (Halliburton Company)
• Original Assignee: Betta Pharmaceuticals Co., Ltd.
• Inventors: Wang, Yinxiang, Tan, Fenlai, Ma, Cunbo, Hu, Yunyan, Cao, Hong, Long, Wei, Hu, Shaojing, Zhao, Xiangdong, Wang, Yanping, Shen, Xiaoyan, Ding, Lieming
• Granted Patent: US 8,951,959 B2
• Time in Patent Office: Days
• US Class Current: 514/1.9
• 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: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• 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 7/02 Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
• CPC Class Codes: A61P 7/12 Antidiuretics, e.g. drugs for diabetes insipidus ADH A61P5/10
• 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

Abstract

Provided is a glucagon-like peptide-1 (GLP-1) analogue shown as the following formula, wherein X is selected from glycine and glycinamide. The GLP-1 analogue has a non-proteogenic amino acid residue in position 8 relative to the sequence GLP-1, and is acylated with a moiety comprising two acidic groups to the lysine residue in position 26. The GLP-1 analogue is resistant to dipeptidyl peptidase IV so as to have an extended half-life in vivo. Also provided is a use of the GLP-1 analogue in conquering blood sugar.

Claims

1. A compound of Formula I,

2. A pharmaceutical composition comprising a therapeutically effective amount of at least one compound of claim 1 and at least one pharmaceutically acceptable excipient.

3. Use of the pharmaceutical composition of claim 2 for preparation of a medicament.

4. The use of the pharmaceutical composition of claim 3 for preparation of a medicament for the treatment or prevention of type II diabetes, impaired glucose tolerance, type I diabetes, obesity, hypertension, syndrome X, dyslipidemia, cognitive disorders, atherosclerosis, myocardial infarction, coronary heart disease, cardiovascular disease, stroke, inflammatory bowel syndrome and/or dyspepsia or stomach ulcers.

5. The use of the pharmaceutical composition of claim 3 for preparation of a medicament for delaying or preventing deterioration of type II diabetes.

6. The use of the pharmaceutical composition of claim 3 for preparation of a medicament for decreasing food intake, decreasing β

-cell apoptosis, increasing β

-cell function, increasing β

-cell mass and/or for restoring β

-cell sensitivity to glucose.

7. Use of a compound of claim 1 for preparation of a medicament for the treatment or prevention of type II diabetes, impaired glucose tolerance, type I diabetes, obesity, hypertension, syndrome X, dyslipidemia, cognitive disorders, atherosclerosis, myocardial infarction, coronary heart disease, cardiovascular disease, stroke, inflammatory bowel syndrome, dyspepsia and/or gastric ulcers.

8. Use of a compound of claim 1 for preparation of a medicament for delaying or preventing deterioration of type II diabetes.

9. Use of a compound of claim 1 for preparation of a medicament for decreasing food intake, decreasing β

-cell apoptosis, increasing β

-cell function, increasing β

-cell mass and/or for restoring glucose sensitivity to the β

-cells.

10. A method of modulating the blood glucose level in a subject comprising administering to the subject a compound of claim 1.

11. A method for treating, preventing, or delaying a disease, disorder, or condition in a subject thereof, comprising administering to the subject in need thereof a therapeutically effective amount of a compound of claim 1, wherein the disease, disorder, or condition is type II diabetes, impaired glucose tolerance, type I diabetes, obesity, hypertension, syndrome X, dyslipidemia, cognitive disorders, atherosclerosis, myocardial infarction, coronary heart disease, cardiovascular disease, stroke, inflammatory bowel syndrome and/or dyspepsia or stomach ulcers.

12. A method for treating, preventing, or delaying a disease, disorder, or condition in a subject thereof, comprising administering to the subject in need thereof a therapeutically effective amount of a compound of claim 1, wherein the disease, disorder, or condition is deterioration of type II diabetes.

13. A method for decreasing food intake, decreasing β

-cell apoptosis, increasing β

-cell function, increasing β

-cell mass and/or for restoring glucose sensitivity to the β

-cells in a subject, comprising administering to the subject in need thereof a therapeutically effective amount of a compound of claim 1.