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Methoxyphenyl thiophene amide structure-containing double-target inhibitors and use thereof

An acid chloride and substituent technology, applied in the field of SGLT2/SGLT1 dual-target inhibitors, can solve the problem of weak SGLT1 inhibition

Inactive Publication Date: 2017-05-10
FOSHAN SAIWEISI MEDICINE SCI & TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] These marketed inhibitors are all selective SGLT2 inhibitors with weak inhibitory effect on SGLT1

Method used

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  • Methoxyphenyl thiophene amide structure-containing double-target inhibitors and use thereof
  • Methoxyphenyl thiophene amide structure-containing double-target inhibitors and use thereof
  • Methoxyphenyl thiophene amide structure-containing double-target inhibitors and use thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0021] The synthesis of embodiment 1 compound I-1

[0022]

[0023] A. Synthesis of Compound V-1

[0024] 4.68g (20mmol) of compound II-1 was dissolved in 10mL of dry dichloromethane, stirred at room temperature, slowly added dropwise 3.81g (30mmol) of freshly distilled oxalyl chloride, and then 2 drops of DMF, and then the reaction mixture was heated at room temperature Stir overnight. The reaction mixture was evaporated to dryness on a rotary evaporator, then dried on a vacuum oil pump for 5 minutes, then dissolved in 10 mL of dichloromethane, stirred under ice-water bath cooling, and then slowly added dropwise 3.10 g (20 mmol) IV-1 and 6.07 g ( 60mmol) triethylamine, after the dropwise addition, the reaction mixture was stirred at room temperature overnight, and TLC was checked for completion of the reaction. After the reaction is complete, pour the reaction mixture into 100mL ice water, stir, and use 50mL×3 CH 2 Cl 2 After extraction, the extract phases were combine...

Embodiment 2-4

[0028] Referring to the operation steps of Example 1, the compounds listed in the following table were synthesized.

[0029]

Embodiment 5

[0030] Inhibition of the compound of Example 5 on human SGLT2 and human SGLT1 in vitro

[0031] Preparation of human SGLT2 expression vector

[0032] The full-length cDNA clone expressing human SGLT2 (purchased from GenScript Company) (with Hind III and Not I sites placed at both ends of the cDNA) was subcloned into the pEAK15 expression vector (Theracos, USA) between the Hind III and Not I sites between. Clones containing the target gene were identified by restriction endonuclease digestion.

[0033] Preparation of human SGLT2 stable transfection cell line

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Abstract

The invention relates to the field of medicines related to type 2 diabetes, and particularly relates to methoxyphenyl thiophene amide structure-containing SGLT2 / SGLT1 (sodium-glucose linked transporter 2 / sodium-glucose linked transporter 1) double-target inhibitors, as well as a preparation method and application thereof to preparation of a medicament for type 2 diabetes. A structural formula is shown in the description, wherein X is selected from a halogen substituent.

Description

technical field [0001] The invention relates to the pharmaceutical field for the treatment of type 2 diabetes. Specifically, the present invention relates to a class of SGLT2 / SGLT1 dual-target inhibitors containing a methoxyphenylthiophene amide structure that has a therapeutic effect on type 2 diabetes, its preparation method, and its use in medicine. Background technique [0002] Diabetes is a metabolic disease characterized by high blood sugar. Hyperglycemia is caused by defective insulin secretion or impaired biological action, or both. The long-term high blood sugar in diabetes leads to chronic damage and dysfunction of various tissues, especially the eyes, kidneys, heart, blood vessels, and nerves. There is currently no cure for diabetes, but the progression of diabetes can be properly controlled through a variety of treatments. It mainly includes several aspects: education of diabetic patients, self-monitoring of blood sugar, diet therapy, exercise therapy and drug...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D333/38A61K31/381A61P3/10
CPCC07D333/38
Inventor 蔡子洋
Owner FOSHAN SAIWEISI MEDICINE SCI & TECH