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

5-substituted methylene imidazolidine-2, 4-diketone derivative as well as pharmaceutical composition and application thereof

A technology of imidazolidine and benzylidene, which is applied in the field of organic chemical drug synthesis, and can solve unseen problems

Inactive Publication Date: 2014-08-20
TIANJIN MEDICAL UNIV
View PDF1 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] There are no reports of PTP1B inhibitors with imidazolidine-2,4-dione as the core

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
  • 5-substituted methylene imidazolidine-2, 4-diketone derivative as well as pharmaceutical composition and application thereof
  • 5-substituted methylene imidazolidine-2, 4-diketone derivative as well as pharmaceutical composition and application thereof
  • 5-substituted methylene imidazolidine-2, 4-diketone derivative as well as pharmaceutical composition and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0107] Preparation of 5-Hydroxybenzylmethyleneimidazolidine-2,4-dione (Ⅱ)

[0108]

[0109] Add 6.11 g (50 mmol) of hydroxybenzaldehyde and 5.5 g (55 mmol) of imidazolidine-2,4-dione into a 250 mL round bottom flask, add 10 mL of piperidine, install a reflux condenser and a drying tube above the flask, Place the flask in an oil bath to make the reaction solution level with the oil bath surface, heat to 130°C and keep for 30 minutes; generate a large number of bubbles and slightly boil; add 200 mL of distilled water at 60°C after cooling, stir with a glass rod until the solid dissolves, and obtain a red color solution and yellow flocculent insoluble matter, filtered to remove the insoluble matter, after the filtrate was cooled to room temperature, the filtrate was transferred to a beaker, and 20 mL of 10 N HCl solution was added dropwise while stirring; after standing at room temperature for 12 h, the The yellow precipitate was obtained by suction filtration through a Schnei...

Embodiment 2

[0114]

[0115] p-Chlorobenzyl chloride and 5-(4-p-hydroxybenzylidene) imidazolidine-2,4-dione reaction steps: Mixed 5-[4-p-hydroxybenzylidene] imidazolidine-2,4- Diketone (4.08g, 20mmol), p-chlorobenzyl chloride (3.24g, 20mmol), K 2 CO 3 (2.76g, 20mmol) and acetone (120mL) were refluxed for 24 h, TLC detected that the reaction of the raw materials was complete, and the reaction was stopped; after cooling, the inorganic salt was removed by filtration; I-1: white solid (0.46g, 14.00 %), m.p.255~258℃; I-2: light yellow solid (0.62 g, 27.15%), m.p.167~168℃; I-3: white solid ( 0.56 g, 28.83 %), m.p.129~132 ℃.

[0116] The compound structure and spectrum analysis are as follows:

[0117] I-1 : 5-[4-(p-Chlorobenzyloxy)benzylidene]imidazolidine-2,4-dione

[0118] Spectrum analysis:

[0119] 1 H-NMR (DMSO-d6, 400Hz), δ : 10.654(s, 1H, N 3 H); 9.895(s, 1H, N 1 H); 7.499(s, 2H, J =8.8Hz, Ar-H); 7.381-7.415(m, 2H, Ar-H); 7.303(d, 2H, J =8.4Hz, Ar-H); 6.786(d, 2H, J =8.8...

Embodiment 3-28

[0125] With reference to the operation of Example 2, the difference is that the product of Example 1 is replaced with a halogenated compound of different structure to obtain the compound of the following general formula I

[0126]

[0127]

[0128]

[0129] The measurement results of the hydrogen spectra and mass spectra of the above compounds are described below.

[0130] I-4: 5-(4-(phenylpropoxy)benzylidene)imidazolidine-2,4-dione

[0131] Spectrum analysis: 1 H-NMR (DMSO-d 6 , 400Hz), δ:10.519(s, 1H, N 3 H); 9.864(s, 1H, N 1 H); 7.485(d, 2H, J =8.4Hz, Ar-H); 7.143-7.284(m, 5H, Ar-H); 6.773(t, 2H, J =7.2Hz, Ar-H); 6.453(s, 1H, =CH); 3.486(t, 2H, J =7.2Hz, OCH 2 ); 2.586(t, 2H, J =7.2Hz, PhCH 2 ); 1.823-1.896(m, 2H, PhCH 2 CH 2 ). MS (m / z): 323.3 (M+1).

[0132] I-5: 1-phenylpropyl-5-(4-(phenylpropoxy)benzylidene)imidazolidine-2,4-dione

[0133] Spectrum analysis: 1 H-NMR (DMSO-d 6 , 400Hz), δ :10.422(s, 1H, NH); 7.635(d, 2H, J =8.6Hz, Ar-H); 7.40...

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 present invention also discloses a compound with the general formula I structure or a pharmaceutically acceptable salt thereof, wherein the definitions of R1, R2 and R3 are the same as those in the description. The present invention also discloses a pharmaceutical composition comprising the compound as the active ingredient I or a pharmaceutically acceptable salt thereof and one or more pharmaceutically acceptable carriers, excipients or diluents, especially as a therapeutic Medicinal use in diabetes.

Description

technical field [0001] The invention belongs to the technical field of organic chemical drug synthesis, and relates to the synthesis of chemical drugs for treating diabetes, more specifically, a new class of 5-substituted methylene imidazolidine-2,4-dione derivatives and their preparation methods, as well as pharmaceutical compositions containing them and their use as medicines. Background technique [0002] Diabetes and its chronic complications are very serious hazards to human health. With the improvement of the biological environment, the incidence rate in the world is increasing year by year. Hypoglycemia is the most important treatment. and side effects have very high requirements, therefore, new hypoglycemic agents have been the focus of people's development. Recently, inhibitors of protein tyrosine phosphatase 1B (PTP1B) were found to have favorable hypoglycemic effects. [0003] PTP1B is the most representative member of the protein tyrosine phosphatase family. Th...

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): C07D233/96C07D405/06C07D405/14C07D405/12C07D401/14A61K31/4174A61K31/4178A61K31/4439A61P3/10
Inventor 王润玲程先超孙素霞刘桂友
Owner TIANJIN MEDICAL UNIV