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

PTP1B (Protein Tyrosine Phosphatase 1B) inhibitor, synthesis and application thereof in preparation of drugs for treating type 2 diabetes mellitus

A technology of inhibitors and compounds, applied in the field of biomedicine, can solve the problems of poor chemical and biological stability, not much, high electronegativity, etc., achieve good industrial production prospects, simple process operation, and reduce reaction costs

Inactive Publication Date: 2011-04-20
INST OF OCEANOLOGY - CHINESE ACAD OF SCI
View PDF2 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] There are not many studies on PTP1B inhibitors in the world, mainly in the following categories: (1) Peptides: peptide substrates containing phosphorylated tyrosine residues (pTyr) have a higher affinity with PTP1B, But its chemical and biological stability are poor; (2), naphthoquinones Naphthnoquinone: inhibit the activity of enzyme by modifying the active site of PTPase; (3), thiazolidinediones Azolidinediones: increase the insulin sensitivity of target organ Improve blood sugar control, mainly including ciglitazone, troglitazone and rosiglitazone, but due to severe liver toxicity, ciglitazone has been withdrawn from the market; (4), Benzo[b]naphthol[2,3-d]furans and thiophenes: benzbromarone (PTP1B inhibitor, IC 50 =26μM) as the lead compound designed and synthesized as a series of Benzo[b]naphthol[2,3-d]furans and thiophenes compounds, which showed good hypoglycemic activity in mice, but it still needs to be used as a drug for treating diabetes. Overcoming many obstacles, such as high electronegativity, poor cell membrane permeability, and poor selective specificity, all of which make these inhibitors less druggable

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
  • PTP1B (Protein Tyrosine Phosphatase 1B) inhibitor, synthesis and application thereof in preparation of drugs for treating type 2 diabetes mellitus
  • PTP1B (Protein Tyrosine Phosphatase 1B) inhibitor, synthesis and application thereof in preparation of drugs for treating type 2 diabetes mellitus
  • PTP1B (Protein Tyrosine Phosphatase 1B) inhibitor, synthesis and application thereof in preparation of drugs for treating type 2 diabetes mellitus

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0030] Example 1 Chemical synthesis and structure identification of "bis-(2,3,6-tribromo-4,5-dimethoxy-phenyl)-methane"

[0031] (1) Chemical synthesis and structure identification of Bis-(3,4-dimethoxy-phenyl)-methanone 3

[0032] Add 22.08g (120mmol) veratrol (compound 1), 16.92g (120mmol) veratrol (compound 2) and 100g polyphosphoric acid into a 250ml three-necked reaction flask according to the molar ratio of 1:1, and stir at 80°C for reaction 1h; cool to 60°C and add 250ml of ice water dropwise to the reactant within 30min, at this time, a large amount of water-insoluble pink solid precipitates out of the reactant; after removing water by filtration, dissolve the obtained solid in 100ml of dichloromethane , washed three times with an equal volume of 3% sodium hydroxide solution and distilled water successively; after drying the dichloromethane phase with anhydrous sodium sulfate, concentrate under reduced pressure to obtain a pink solid; wash the solid with petroleum ethe...

Embodiment 2

[0042] Example 2 Determination of protein tyrosine phospholipase 1B inhibitory activity

[0043]Compounds 3, 4, 5, 6 and compound 7 to be tested were prepared into 20 μg / mL and 5 μg / mL test solution with DMSO respectively, and 2 μL of the test solution was added to the standard bioassay system (50 mM Tris-HCl, PH 6.5, 2mM pNPP, 2% DMSO, 30nMhGST-PTP1B), negative control: DMSO, positive control: sodium orthovanadate, the reaction temperature is 30°C, and the light absorption at the wavelength of 405nm is dynamically measured for 3 minutes , according to the following formula to calculate the inhibitory rate of compound PTP1B enzyme activity. Inhibition rate=(experimental group A value-negative control group A value) / (control group A value-negative control group A)×100%, the results are shown in Table 1.

[0044] Table 1 Inhibition rate of protein tyrosine phospholipase 1B (%)

[0045] Table 1 Inhibitory Ratio (%) of PTP1B

[0046]

[0047] When the comp...

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

PropertyMeasurementUnit
melting pointaaaaaaaaaa
Login to View More

Abstract

The invention relates to a chemical total synthesis method of a novel PTP1B (Protein Tyrosine Phosphatase 1B) inhibitor and application thereof in the drugs for treating the type 2 diabetes mellitus. The PTP1B inhibitor has the following chemical structural formula, wherein the groups connected with the 2,2', 3,3' and 6,6' carbons are bromine atoms; the 4,4' and 5,5' carbons are connected with methoxy groups; the novel PTP1B has the chemical English name of bis-(2,3.6-tribromo-4,5-dimethoxy-phenyl)-methane; and the compound can strengthen the sensibility of the insulin receptors through inhibiting the activity of the protein tyrosine phosphatase 1B, and has favorable therapeutic effect on the insulin resistant type 2 diabetes mellitus.

Description

technical field [0001] The present invention relates to biological medicine, specifically a brominated compound "bis-(2,3,6-tribromo-4,5-dimethoxy-phenyl)-methane" and its chemical total synthesis method, Pharmacological activity and pharmaceutical use. As an insulin sensitizer, the compound and its derivatives can be used for treating insulin-resistant type 2 diabetes. Background technique [0002] Diabetes (Diabetes Mellitus, DM) is a chronic endocrine and metabolic disease. Currently, the drugs used to treat type 2 diabetes (Type 2Diabetes Mellitus, T2DM) mainly include biguanides, sulfonylureas, α-glucosidase inhibitors and thiazolidinediones. Classes, etc., because most of them are designed for diseases rather than for molecular target drugs of etiology, there are various disadvantages. Therefore, the market is in urgent need of safe, effective, reasonably priced and safe hypoglycemic drugs that can be taken for a long time. [0003] Insulin resistance is a key factor...

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 Applications(China)
IPC IPC(8): C07C43/225C07C41/22A61K31/09A61P3/10
Inventor 史大永范晓李敬郭书举
Owner INST OF OCEANOLOGY - CHINESE ACAD OF SCI