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Synthesis method for compound and application thereof in field of medicines used for improving insulin resistance

A synthesis method and compound technology, applied in the field of improving insulin resistance drugs, in the field of compound synthesis, can solve the problems of low synthesis yield and complicated purification

Active Publication Date: 2020-03-31
SHENZHEN LINGLAN BIO PHARMA TECH CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] In view of this, the present invention provides a compound synthesis method and its application in the field of drugs for improving insulin resistance, which are used to solve the technical defects of low synthesis yield and complicated purification of SN159 in the prior art

Method used

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  • Synthesis method for compound and application thereof in field of medicines used for improving insulin resistance
  • Synthesis method for compound and application thereof in field of medicines used for improving insulin resistance
  • Synthesis method for compound and application thereof in field of medicines used for improving insulin resistance

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0036] This example is one of the specific examples of synthesizing SN158.

[0037] 1.1 Step i—preparation of intermediate product 1 (5-bromo-2,4-hydroxybenzaldehyde)

[0038] 2,4-Dihydroxybenzaldehyde (10 g, 72.4 mmol) was dissolved in acetic acid, and the reaction was placed in an ice bath. Under stirring condition, liquid bromine (3.78ml, 72.4mmol) was slowly added dropwise, and the reaction temperature was slowly raised to room temperature. After reacting for 3 hours, the reaction solution was poured into 100 mL of cold water, filtered, washed with 100 mL of cold water, dried, and recrystallized with 1:1 acetonitrile / toluene to obtain 13.09 g of intermediate product 1 crystals (yield: 83%).

[0039] Structural characterization of intermediate product 1:

[0040] Melting point: 165-168°C.

[0041] 1.2 Step ii—Preparation of intermediate product 2 (5-bromo-2-hydroxyl-4-(methoxymethyl)benzaldehyde)

[0042] Intermediate 1 (10.9 g, 50 mmol) and potassium carbonate (20.8 g,...

Embodiment 2

[0069] This example is another specific example of synthesizing SN158.

[0070] 2.1 Step i—preparation of intermediate product 1 (5-bromo-2,4-hydroxybenzaldehyde)

[0071] 2,4-Dihydroxybenzaldehyde (10 g, 72.4 mmol) was dissolved in acetic acid, and the reaction was placed in an ice bath. Under stirring condition, liquid bromine (3.78ml, 72.4mmol) was slowly added dropwise, and the reaction temperature was slowly raised to room temperature. After reacting for 3 hours, the reaction solution was poured into 100 mL of cold water, filtered, washed with 100 mL of cold water, dried, and recrystallized with 1:1 acetonitrile / toluene to obtain 13.09 g of intermediate product 1 crystals (yield: 83%).

[0072] Structural characterization of intermediate product 1:

[0073] Melting point: 165-168°C.

[0074] 2.2 Step ii—Preparation of intermediate product 2 (5-bromo-2-hydroxyl-4-(methoxymethyl)benzaldehyde)

[0075] Intermediate 1 (10.9 g, 50 mmol) and potassium carbonate (20.8 g, 150...

Embodiment 3

[0115] This example is a specific example for verifying that the prepared SN159 improves insulin resistance.

[0116] C2C12 myoblasts were differentiated into myotubes over 4 days in DMEM medium with 2% horse serum. They were then cultured in DMEM containing 2% BSA and 10% FBS for 16 hours, and controlled for normal or insulin-resistant conditions by adding or not adding 0.75 mM palmitate.

[0117] After being stimulated by insulin for 1 hour, the myotubes were incubated with 50 μM 2-NBDG (purchased from Invitrogen) for 15 minutes, and washed 3 times with PBS to remove free 2-NBDG. In the Infinite M1000 microplate reader (TECKAN, Switzerland) to measure the fluorescence intensity of 2-NBDG entering the cell, the excitation wavelength is 485nm, and the emission wavelength is 535nm.

[0118] For the experimental results obtained, please refer to figure 1 and figure 2 ,in, figure 1 is the effect of compound SN159 on the glucose uptake of C2C12 myoblasts under normal condit...

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Abstract

The invention belongs to the technical field of drug synthesis, and particularly relates to a synthesis method for a compound and application thereof in field of medicines used for improving insulin resistance. The invention provides the synthesis method of SN159. The synthesis method comprises the following steps: brominating a raw material, namely 2,4-dihydroxy benzaldehyde, protecting para-hydroxyl groups by using methoxymethyl groups, performing methylating by using dimethyl sulfate or methyl iodide, and carrying out a Claisen-Schmidt condensation reaction under an alkaline or acidic condition, thereby enhancing the yield of the finally produced compound from 18.9% in the prior art to 68% or above. According to the invention, column chromatographic purification is not needed in the preparation process, and the finally produced compound with a purity of 99% or above can be obtained only through recrystallization; and the method is suitable for large-scale / industrial production. According to the synthesis method of the compound and the application of the compound in the field of preparation of medicines used for improving insulin resistance, the technical defects that SN159 is low in synthesis yield and complex in purification in the prior art are overcome.

Description

technical field [0001] The invention belongs to the technical field of medicine synthesis, and in particular relates to a compound synthesis method and its application in the field of medicines for improving insulin resistance. Background technique [0002] Studies have found that insulin resistance is the basis of obesity, diabetes and cardiovascular disease, and is the main pathophysiological feature of type 2 diabetes. The natural product Licochalcone E has the functions of improving blood sugar level, regulating lipid metabolism and improving insulin resistance, and its structurally modified derivatives, Hereinafter referred to as SN159, it is a dual partial agonist of PPARα / γ, which can increase the glucose uptake of C2C12 myoblasts under normal conditions and insulin resistance conditions, and promote insulin-mediated phosphorylation of insulin receptor (IR) and Akt, thereby increasing Insulin activation of the IR-Akt axis increases insulin sensitivity; SN159 can pro...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07C47/565C07C45/63C07C45/64C07C47/575C07C221/00C07C225/22A61K31/136A61P5/50A61P3/10
CPCC07C45/63C07C45/64C07C221/00A61K31/136A61P5/50A61P3/10C07C47/565C07C47/575C07C225/22Y02P20/55
Inventor 曹永凯张子理千胜勋曹永亮
Owner SHENZHEN LINGLAN BIO PHARMA TECH CO LTD
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