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

Halogenated adamantane amide derivatives, preparation method and use thereof

A compound and substituent technology, applied in the field of diabetes-related drugs, can solve problems such as undiscovered weight gain

Inactive Publication Date: 2016-03-30
江苏天凤源食品有限公司
View PDF4 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Clinical results show that this type of drug has a good hypoglycemic effect, and no adverse reactions such as weight gain and hypoglycemia, which are common in other diabetes drugs, have been found

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
  • Halogenated adamantane amide derivatives, preparation method and use thereof
  • Halogenated adamantane amide derivatives, preparation method and use thereof
  • Halogenated adamantane amide derivatives, preparation method and use thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0028]

[0029] In a 100mL round bottom flask, add 2.28g (10mmol) compound II-1, 3.21g (10mmol) compound III, 2.06g (10mmol) N, N'-dicyclohexylcarbodiimide (DCC) and 1.22g (10mmol) 4-dimethylaminopyridine (DMAP), dissolved in 20mL of dry THF, stirred at room temperature overnight, TLC showed that the reaction was almost complete. The reaction mixture was suction filtered to remove the solid, the filtrate was evaporated to dryness on a rotary evaporator, and the residue was purified by column chromatography to obtain compound IV-1 as a white solid, ESI-MS, m / z=550 ([M+NH 4 ] + ).

[0030] 3.19 g (6 mmol) of compound IV-1 was dissolved in 30 mL THF, 0.10 g of 10% Pd / C was added, and catalytic hydrogenolysis was carried out at room temperature, and the reaction was completed within 12 hours. The reaction mixture was suction filtered to remove the catalyst, and the filtrate was concentrated on a rotary evaporator, poured into 200 mL of water, stirred, and extracted with 50 mL...

Embodiment 2-4

[0034] Using the same method as in Example 1, the following compounds could be prepared.

[0035]

[0036]

Embodiment 5

[0037] Embodiment 5 compound measures the inhibition of DPP-IV enzyme

[0038] Using the fluorescent DPP4 activity detection kit of BPS Bioscience Company, the inhibitory activity of the compound of the present invention on DPP-IV enzyme was determined.

[0039] Dilute the samples successively according to the concentration of 5, 10, 30, 100 and 200ng / kg, and add the samples in the following table in the fluorescence reaction 96-well plate:

[0040]

[0041] Place in a water bath at 22°C for 10 minutes, use a SpectraMaxM5 type fluorescence detector with an excitation light of 350nm, and measure the absorbance with 450nm fluorescence. Calculation of IC from the concentration-fluorescence intensity curve 50 values, see the table below.

[0042] IC of compounds for inhibition of DPP-IV enzymes 50 value

[0043]

[0044]

[0045] It can be seen from the above table that the compound of the present invention has a strong inhibitory effect on DPP-IV enzyme.

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 relates to the field of drugs relates to diabetes, in particular to a dipeptidyl peptidase-IV inhibitor with a general formula I, a preparing method of the inhibitor, and an application of the inhibitor to preparation of the diabetes drugs. The inhibitor contains a halogen-substituted adamantane amide structure. Please see the formula in the specification, wherein R1 is selected from a halogen-substituted group.

Description

technical field [0001] The invention relates to the field of medicine related to diabetes. Specifically, the present invention relates to a dipeptidyl peptidase-IV inhibitor containing a halogenated adamantane amide structure that has a therapeutic effect on diabetes, a preparation method thereof, a pharmaceutical composition containing them and a drug for treating diabetes. Background technique [0002] According to statistics, there were approximately 250 million diabetic patients in the world in 2007, most of whom were type II (ie, non-insulin-dependent) diabetic patients. The antidiabetic drugs currently in clinical use mainly include sulfonylureas, metformin and insulin drugs. In recent years, insulin sensitizers and α-glucosidase inhibitors have also been marketed. These drugs have good therapeutic effects, but severe side effects such as hypoglycemia are common, and there are safety problems in long-term treatment, such as liver toxicity and weight gain. [0003] Di...

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): C07D207/16A61K31/4025A61P3/10
CPCY02P20/55
Inventor 蔡子洋
Owner 江苏天凤源食品有限公司