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Pyrazine compounds, and medicinal application thereof

A compound and drug technology, applied in the field of novel small molecule fluorescent compounds, to achieve the effect of good brain-penetrating ability and enhanced fluorescence intensity

Active Publication Date: 2016-10-12
SICHUAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, there are few research reports on fluorescent compounds targeting Aβ plaques or neurofibrillary tangles at home and abroad, and it is still in its infancy.

Method used

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  • Pyrazine compounds, and medicinal application thereof
  • Pyrazine compounds, and medicinal application thereof
  • Pyrazine compounds, and medicinal application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0026] Embodiment one: the synthesis of the compound shown in formula (I)

[0027] The synthetic route of the compound represented by the formula (I) of the present invention is as follows: figure 1 shown.

[0028] Synthetic PB-1

[0029]

[0030] Dissolve 2-methylpyrazine (282.3 mg, 3 mmol) and 4-N,N dimethylaminocinnamaldehyde (175.4 mg, 1 mmol) in 20 mL of dry tetrahydrofuran, add potassium tert-butoxide (448.8 mg, 4 mmol ), heated to reflux at 80°C for 2 hours, and the solvent was removed by rotary evaporation; 20 mL of water was added to precipitate a solid, and after suction filtration, the resulting solid was separated by column chromatography to obtain 105.8 mg of PB-1, with a yield of 42.1%. The structure is as follows: 1 H-NMR (400 MHz, CDCl 3 ): δ 8.50 (s, 1H), 8.47 (s, 1H), 8.30 (s,1H), 7.51 (dt, J = 36.4, 18.2 Hz, 1H), 7.38 (d, J = 8.5 Hz, 2H), 6.83 (d, J =7.0 Hz, 1H),6.81 (d, J = 4.1 Hz, 1H), 6.70 (d, J = 7.7 Hz, 1H), 6.61 (s, 1H),6.58 (s, 1H), 3.00 (s...

Embodiment 2

[0031] Embodiment two: the synthesis of the compound shown in formula (II)

[0032] The synthetic route of the compound represented by the formula (II) of the present invention is as follows: figure 1 shown.

[0033] Synthetic QB-1

[0034]

[0035] Dissolve 2-methylquinoxaline (288 mg, 2 mmol) and 4-N,N dimethylaminocinnamaldehyde (175.4 mg, 1 mmol) in 15 mL of sodium hydroxide solution (5mol / L), add Aliquat 336 (43 mg, 0.1 mmol), heated to reflux at 100°C for 10 hours, cooled, filtered, and the resulting solid was separated by column chromatography to obtain 91.0 mg of QB-1, with a yield of 30.2%. The structure is as follows: 1 H-NMR (400 MHz, CDCl 3 ): δ 8.90 (s, 1H), 8.03-7.99 (m, 1H), 7.73-7.63 (m, 4H),7.40 (d, 2H, J = 8.8 Hz), 6.89 (d, 2H, J = 8.0 Hz ), 6.81 (d, 1H, J = 15.6Hz), 6.70 (d, 2H, J = 8.8 Hz), 3.02 (s, 6H).

Embodiment 3

[0036] Embodiment three: the mensuration of optical parameter

[0037] 1. Determination of maximum absorption wavelength and molar absorption coefficient

[0038] Using dichloromethane as solvent, prepare compounds with a certain concentration gradient, such as 1, 5, 10, 20, and 25 μM solutions, scan the ultraviolet absorption spectrum with a UV-visible spectrophotometer, and record the maximum absorption wavelength (λ abs ) and absorbance, and calculate the molar absorption coefficient ε (M -1 cm -1 ). The maximum absorption wavelengths and molar absorption coefficients of some compounds in the examples of the present invention are shown in Table 1.

[0039] 2. Determination of fluorescence excitation wavelength and fluorescence emission wavelength

[0040] The compounds of the present invention have good fluorescence properties. In order to investigate the fluorescence properties of the compounds of the present invention, the specific implementation steps are: accurate...

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Abstract

The invention provides fluorescence-labeled pyrazine compounds for beta-amyloid plaques and neurofibrillary tangles. The general structural formula of the compounds is as shown in a formula (I) or a formula (II) which is described in the specification. In the formula, n is 1, 2 or 3. The invention also provides a preparation method and application of the compounds. The compounds can be directly used as a developer for detecting or developing beta-amyloid plaques or neurofibrillary tangles in the tissue of animal or human bodies. The compounds are especially applicable to preparation of developers or diagnosis medicines used for direct detection and diagnosis of beta-amyloid deposit diseases or neurofibrillary tangle diseases including the Alzheimer disease.

Description

technical field [0001] The present invention relates to the field of specific molecular recognition diagnostic reagents, more specifically, to a class of novel small-molecule fluorescent compounds with high affinity to β-amyloid plaques and neurofibrillary tangles, and the preparation of such compounds for detection Or use in imaging agents for imaging beta-amyloid deposition diseases or neurofibrillary tangle diseases. Background technique [0002] Alzheimer's Disease (AD) is a progressive and fatal neurodegenerative disease. At present, my country has entered an aging society ahead of schedule, and about 6 million people suffer from AD, ranking first in the world, and the number of patients is increasing at a rate of more than 300,000 per year. The prevalence rate of people over 65 years old in my country is 7.2%, and AD patients are becoming younger. AD has become the fourth leading cause of death among the elderly after heart disease, cancer and stroke. AD not only ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D241/12C07D241/42A61K49/00A61K49/04A61K49/06A61K49/22
CPCA61K49/00A61K49/04A61K49/06A61K49/22C07D241/12C07D241/42A61K49/0021
Inventor 程妍
Owner SICHUAN UNIV
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