Optically pure benzyl-4-chlorophenyl C-glucoside derivatives

A benzyl and trimethylsilyl technology, applied in the field of optically pure C-glycoside derivatives of benzyl-4-chlorophenyl, can solve the problem of increasing research and development risks, reducing drug efficacy and quality control difficulties, toxic and side effects And other issues

Active Publication Date: 2015-07-08
JILIN HUISHENG BIOPHARMACEUTICAL CO LTD +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Considering that many chiral mixture drugs in the prior art have potential problems such as easy to produce unknown toxic and side effects, reduced drug efficacy and difficulty in quality control, it will greatly increase the risk of research and development, and optically pure stereoisomers have more advantages than chiral mixtures. The advantages of safer, lower probability of toxic side effects, better stability and easier quality control, and optically pure stereoisomers also have potential improvements in pharmacodynamics, pharmacokinetics and toxicology Therefore, the development of a single stereoisomer with high selectivity, fast onset, high efficiency, safety, and good stability for SGLT-2 is of great significance for subsequent drug development and quality control in drug production after marketing

Method used

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  • Optically pure benzyl-4-chlorophenyl C-glucoside derivatives

Examples

Experimental program
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Effect test

experiment example 1

[0069] Experimental Example 1 The in vitro activity test of the compound of the present invention

[0070] Test product: the compound of formula (II), formula (III), formula (IV) and formula (V) of the present invention, its chemical name and preparation method are shown in the preparation examples of each compound.

[0071] Control drug 1: compound 4 in patent WO2013 / 000275A1, self-made (refer to patent WO2013 / 000275A1 for the preparation method), and its structural formula is as follows:

[0072] Compound 4 is the compound of formula (I).

[0073] The meanings represented by the abbreviations of the following experiments are as follows:

[0074] NMG N-methylglucosamine (N-methyl-glucosamine)

[0075] KRH Krebs-Ringer-Henseleit

[0076] Experimental method: The human SGLT-2 and SGLT-1 sequences were transfected into Chinese hamster ovary cells for stable expression, and by inhibiting the cells to [ 14 C]-labeled-R-methyl-D-glucopyranoside (AMG) sodium-dependent absorpt...

experiment example 2

[0085] Experimental Example 2 Pharmacokinetics experiment in rats of compounds of the present invention

[0086] Test animals: 6-8 week old male SD rats (purchased from Beijing Weitong Lihua Experimental Animal Technology Co., Ltd.), 3 rats / compound, body weight 200-240g.

Embodiment 1

[0088] Control drug 1: compound 4 in patent WO2013 / 000275A1, self-made (refer to patent WO2013 / 000275A1 for the preparation method), and its structural formula is as follows:

[0089] Compound 4 is the compound of formula (I).

[0090] Control drug 2: compound 22 in patent WO2013 / 000275A1, self-made (refer to patent WO2013 / 000275A1 for the preparation method), and its structural formula is as follows:

[0091] Compound 22.

[0092] Solvent: 0.5% MC (methylcellulose) solution + 0.1% SDS (sodium dodecyl sulfate).

[0093] experimental method:

[0094] See Table 2 for the administration method of intragastric administration (PO)

[0095] Rat PK (pharmacokinetics) administration method of table 2 compound

[0096]

[0097] Blood collection: 0.17 hours, 0.5 hours, 1 hour, 2 hours, 4 hours, 6 hours, 8 hours, 24 hours, 30 hours, 48 ​​hours, 54 hours, 72 hours, take about 200 μL whole blood at each time point, at low temperature High-speed centrifuge (5415R, Eppendorf) wa...

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Abstract

The invention belongs to the technical filed of medicines, and concretely relates to optically pure benzyl-4-chlorophenyl C-glucoside derivatives represented by formula (II) and formula (III), a method for preparing the above compounds and intermediates thereof, a medicinal preparation and a medicinal composition containing the compounds, and an application of the optically pure benzyl-4-chlorophenyl C-glucoside derivatives in the preparation of medicines for treating and/or preventing insulin-dependent diabetes, non-insulin dependent diabetes, insulin resistance diseases or obesity, various diabetes and relevant diseases as a sodium-glucose cotransporter (SGLT) inhibitor.

Description

technical field [0001] The invention belongs to the technical field of medicine, in particular to optically pure benzyl-4-chlorophenyl C-glycoside derivatives or pharmaceutically acceptable salts thereof, methods for preparing these compounds and their intermediates, and medicines containing these compounds Preparations and pharmaceutical compositions, and C-glycoside derivatives of optically pure benzyl-4-chlorophenyl of the present invention or pharmaceutically acceptable salts thereof are used as sodium-glucose cotransporter (SGLT) inhibitors in the preparation of therapeutic And / or application in drugs for preventing various diabetes (including insulin-dependent diabetes and non-insulin-dependent diabetes) or various diabetes-related diseases (including insulin resistance disease and obesity). Background technique [0002] Approximately 100 million people worldwide suffer from type 2 diabetes, characterized by hyperglycemia due to excess hepatic glucose production and pe...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D309/10C07C43/247C07C41/16A61K31/351A61P3/10A61P5/50A61P3/04
CPCY02P20/55
Inventor 吴永谦
Owner JILIN HUISHENG BIOPHARMACEUTICAL CO LTD
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