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Modified exenatide and its use

A technology of exenatide and modifier, applied in the field of therapeutic peptides, can solve the problems of short duration of hypoglycemia, poor clinical use effect, low binding force, etc., and achieve long duration of hypoglycemia, GLP-1 receptor High agonist activity and good stability

Active Publication Date: 2021-08-31
BRIGHTGENE BIO MEDICAL TECH (SUZHOU) CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0010] The technical problem to be solved by the present invention is to overcome the shortcomings of the currently disclosed exenatide modified GLP-1 receptor binding ability and short duration of hypoglycemia, resulting in poor clinical effect or frequent injections

Method used

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  • Modified exenatide and its use
  • Modified exenatide and its use
  • Modified exenatide and its use

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0116] Example 1 Preparation of Compound 1

[0117] Preparation of BP103n01

[0118] Add 1.0g of compound BP103n00 (1.0eq), 10ml of dichloromethane, 10ml of tert-butanol, 0.40g of DIC (1.0eq), 0.39g of DMAP (1.0eq) into a 50mL three-neck flask, stir overnight at room temperature, and monitor the completion of the reaction by TLC. Diluted with ether, washed three times with water, washed with saturated brine, dried over anhydrous sodium sulfate, and column chromatographed to obtain 0.4 g of foamy powder BP103n01.

[0119] Preparation of BP103n02

[0120] Add 0.95 g of N-hydroxysuccinimide (HOSU), 2.0 g of compound 19 and 15 ml of dichloromethane into a 100 mL three-neck flask, add 1.58 g of EDC·HCl, react at room temperature for 2 h, monitor the completion of the reaction by TLC, and use dichloromethane After dilution, it was washed twice with 50 mmol / L potassium dihydrogen phosphate aqueous solution at pH=6.0, washed with saturated brine, dried over anhydrous sodium sulfat...

Embodiment 2

[0138] Example 2 Preparation of Compound 2

[0139] Compound 2 was prepared by the method of reference example 1:

[0140]

[0141] Finally, 31.2 mg of pure target peptide was obtained.

[0142] MS (ESI + ,m / e): 4667.52[M+H] +

Embodiment 3

[0143] Example 3 Preparation of Compound 3

[0144] Compound 3 was prepared by the method of reference example 1:

[0145]

[0146] Finally, 32.3 mg of pure target peptide was obtained.

[0147] MS (ESI + ,m / e): 5263.78[M+H] +

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Abstract

The invention discloses a modified exenatide in which exenatide is connected to an aliphatic chain with a carboxyl group through a hydrophilic linking arm, and its use in the preparation of a drug as a GLP‑1 receptor agonist Use; Use in the preparation of medicines for preventing and / or treating diseases and / or symptoms associated with GLP-1 receptor activity; Use in the preparation of medicines for diseases and / or symptoms related to glucose metabolism ; Use in the preparation of a medicament for diabetes; Use in the preparation of a medicament for fatty liver; Use in the preparation of a medicament for weight loss.

Description

technical field [0001] The invention relates to the field of therapeutic peptides, in particular to exenatide modifications, preparation methods, pharmaceutical compositions containing them, and the use of the modifications and compositions in treating diseases related to glucose metabolism. Background technique [0002] Exenatide (also known as Exenatide or Exendin-4, trade name Byetta) is a polypeptide composed of 39 amino acids with a molecular weight of 4186.6 and a molecular formula of C 184 h 282 N 50 o 60 S, [0003] The amino acid sequence is: His-Gly-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Leu-Ser-Lys-Gln-Met-Glu-Glu [0004] -Glu-Ala-Val-Arg-Leu-Phe-Ile-Glu-Trp-Leu-Lys-Asn-Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser-NH 2 ; manufactured and marketed by Amylin Pharmaceuticals and Eli Lilly and Company. Exenatide was approved for marketing by the FDA in April 2005. It is a subcutaneous injection preparation that can promote glucose-dependent insulin secretion, restore first...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07K14/575A61K38/22A61P3/10A61P1/16A61P3/04
CPCC07K14/575A61K38/00C07K14/605C07K14/46A61P3/10A61P3/04A61K9/0019A61K38/2278A61K38/26A61K47/14
Inventor 袁建栋黄仰青宋云松袁芳
Owner BRIGHTGENE BIO MEDICAL TECH (SUZHOU) CO LTD