Unlock instant, AI-driven research and patent intelligence for your innovation.

3,4-dihydroxyphenylethyl alcohol fenofibric acid ester and its preparation method and application

A technology of dihydroxyphenylethanol and fenofibrate ester, which is applied in the field of 3,4-dihydroxyphenylethanol fenofibrate ester and its preparation, can solve the problem of decreased glucose transport capacity of fat cells, insulin secretion disorder, Reduced insulin sensitivity and other problems, to achieve the effect of reducing triglyceride levels and total cholesterol levels, improving oxidative stress, and significantly reducing blood sugar activity

Inactive Publication Date: 2018-07-17
XI AN JIAOTONG UNIV
View PDF9 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The ectopic deposition of FFA in muscle and liver tissue leads to a significant reduction in the glucose transport capacity of adipocytes and a decrease in insulin sensitivity. Excessive deposition in islets can trigger and accelerate the apoptosis of islet β cells; FFA stimulates the production of excessively accumulated adipose tissue And release excessive tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6) and other inflammatory factors, these inflammatory factors combine with the receptors of adipose tissue and other tissue cells, interfere with the body's normal glycolipids Metabolism; excessive accumulation of FFA in the target tissues of insulin action, such as liver and skeletal muscle, leads to insulin resistance; ectopic deposition in pancreatic beta cells causes damage to pancreatic beta cells and insulin secretion disorders, eventually leading to the occurrence and aggravation of diabetes

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • 3,4-dihydroxyphenylethyl alcohol fenofibric acid ester and its preparation method and application
  • 3,4-dihydroxyphenylethyl alcohol fenofibric acid ester and its preparation method and application
  • 3,4-dihydroxyphenylethyl alcohol fenofibric acid ester and its preparation method and application

Examples

Experimental program
Comparison scheme
Effect test

preparation example Construction

[0033] The present invention provides a new compound 3,4-dihydroxyphenethyl fenofibrate (HT-Fen) and a preparation method thereof. The present invention also provides that the compound is used in the preparation of the compound for the treatment of diabetes and hyperlipidemia. disease use.

[0034] The invention discloses a new compound 3,4-dihydroxyphenethyl fenofibrate (I), chemical name is 2-methyl-2-[4-(4-chlorobenzoyl)phenoxy ] Propionate-2-(3,4-dihydroxyphenyl)ethyl ester, referred to as 3,4-dihydroxyphenylethanol fenofibric ester (hydroxytyrosol fenofibric ester, HT-Fen).

[0035]

[0036]The hypoglycemic effect of HT-Fen of the present invention is achieved by the hypoglycemic effect of HT-Fen on the streptozotocin (STZ)-induced diabetes mouse model; the antioxidant effect of HT-Fen is achieved by reducing the streptozotocin (STZ) ( The lipid peroxidation product MDA of STZ)-induced diabetes mouse model was achieved; the lipid-lowering effect of HT-Fen was achieved...

Embodiment 1

[0044] Example 1: Preparation of HT-Fen

[0045] 3,4-Dihydroxyphenethyl alcohol (1.00g, 6.50mmol) and potassium carbonate (3.60g, 26.09mmol) were dissolved in acetone (25mL), benzyl bromide (1.40ml, 14.95mmol) was added, and the reaction was heated under reflux for 24h, After completion of the reaction, suction filtration and concentration. Column chromatography separation (developing solvent: petroleum ether and ethyl acetate) gave 1.46 g of 3,4-dibenzyloxyphenethyl alcohol as a pale yellow solid with a yield of 67.12%.

[0046] 3,4-Dibenzyloxyphenethyl alcohol (1.00g, 3.26mmol), fenofibric acid (1.56g, 4.89mmol) and DMAP (0.08g, 0.65mmol) were added to DMF (20mL), stirred for 5min and then added EDC·HCl (0.94g, 4.89mmol), stirred at room temperature, detected by thin layer plate, the reaction was completed, and the reactant was added with 5% NaHCO 3 The solution and saturated brine were washed twice in turn, and anhydrous Na 2 SO 4 Dry and concentrate to obtain 2.13 g of...

Embodiment 2

[0049] Example 2: Hypoglycemic effect and antioxidant effect of HT-Fen

[0050] Preparation of 0.1mmol / L pH4.5 citrate buffer:

[0051] Preparation of solution A (0.1 mol / L citric acid aqueous solution): 2.10 g of citric acid was added to distilled water to make 100 ml. Preparation of liquid B (0.1 mol / L trisodium citrate aqueous solution): add 2.94 g of trisodium citrate to 100 ml of distilled water. The 0.1 mol / L citric acid aqueous solution and the 0.1 mol / L trisodium citrate aqueous solution are mixed in a volume ratio of 1:1.44 to prepare a 0.1 mmol / L pH4.5 citric acid buffer.

[0052] STZ solution preparation: dissolve in 0.1mmol / L pH 4.5 citric acid buffer to prepare a 20mg / ml solution, ice bath, avoid light, and complete the injection within half an hour.

[0053] Establishment of diabetic mouse model: Mice were adaptively fed for 3 days, fasted for 12 hours, and injected intraperitoneally with STZ (using 0.1mol / L, pH4.5 citrate buffer, 200mg / kg) for 72 hours, fastin...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

No PUM Login to View More

Abstract

The invention discloses 3,4-dihydroxyphenylethanol fenofibrate acid ester as well as a preparation method and an application thereof, and belongs to the technical field of drug preparation. The 3,4-dihydroxyphenylethanol fenofibrate acid ester disclosed by the invention is a novel multi-efficacy active compound, can be used for treating diabetes and hyperlipidaemia, can be used for effectively reducing glucose and lipid (triglyceride and cholesterol), can resist lipid peroxidation, and can improve oxidative stress effect under diabetes and hyperlipidaemia states. The invention further discloses a preparation method for the 3,4-dihydroxyphenylethanol fenofibrate acid ester. The preparation method comprises the following steps: protecting 3,4-dihydroxyl of 3,4-dihydroxyl phenethyl alcohol with benzyl; enabling the 3,4-dihydroxyl phenethyl alcohol to condense with fenofibrate acid to synthesize an ester; then, removing the benzyl under the action of hydrogen and palladium / carbon, thereby preparing the 3,4-dihydroxyphenylethanol fenofibrate acid ester. The preparation method is simple to operate, is low in equipment requirement, and is environmentally friendly.

Description

technical field [0001] The invention belongs to the technical field of pharmaceutical preparation, and particularly relates to a 3,4-dihydroxyphenethyl fenofibrate ester and a preparation method and application thereof. Background technique [0002] Diabetes has become a major public health problem threatening human health. There are 415 million diabetic patients in the world, and more than 100 million diabetic patients in my country, and the incidence rate is increasing year by year. Among them, 90% to 95% are type 2 diabetes (non-diabetes). Insulin-dependent diabetes mellitus, T2DM). The main hazard of diabetes is the occurrence and rapid development of multi-system and multi-organ complications induced by hyperglycemia and insulin resistance, of which cardiovascular and cerebrovascular diseases account for more than 80%. T2DM is a metabolic disorder syndrome characterized by hyperglycemia, hyperlipidemia and insulin resistance. It is a common risk factor for cardiovascula...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
Patent Type & Authority Patents(China)
IPC IPC(8): C07C69/738C07C67/297A61P3/10A61P3/06
CPCC07C41/16C07C67/08C07C67/297C07C69/738C07C43/23
Inventor 边晓丽谢允东杨广德李义平张继业林蓉陆文芳杨亚萍许艳红陈建刚
Owner XI AN JIAOTONG UNIV