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Fluorescent probe for screening drugs acting on ryanodine receptor

A technology of ryanodine receptors and fluorescent probes, applied in the field of fluorescent probes, can solve the problem of not being able to judge whether the drug is selective or not

Active Publication Date: 2020-10-23
TIANJIN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

At present, in order to screen drugs that act on insect ryanodine receptors, the method of testing insect cell calcium ion flow is generally used. In this method, very expensive calcium ion binding indicators are used, such as: Fura-2, Fura-4, etc., Whether the drug acts on the calcium ion channel of the insect can be judged according to the change of the calcium ion flow in the cell, but the disadvantage of this method is that it cannot judge whether the drug selectively acts on the ryanodine receptor of the insect, because the calcium ion concentration of the insect cell is regulated. In addition to RyR, there are voltage-gated calcium ion channels, metabotropic ion channels, G protein-coupled receptors, and 1,4,5-trisphosphate receptor IP3R (Apiculture of China, 2011 October-December, Volume 62, P12-15)

Method used

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  • Fluorescent probe for screening drugs acting on ryanodine receptor
  • Fluorescent probe for screening drugs acting on ryanodine receptor
  • Fluorescent probe for screening drugs acting on ryanodine receptor

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0049] A fluorescent probe for screening drugs acting on ryanodine receptors, made by the following method:

[0050]

[0051] 1) Preparation of compound 2-(tert-butylcarbamoyl)benzoic acid (intermediate S-1-1):

[0052] Disperse phthalic anhydride (1.48g) in 12ml of anhydrous dichloromethane, and slowly add (A-1)-NH 2 (0.73g) and stirred for 3h. The resulting precipitate was filtered and washed with petroleum ether and ethyl acetate to obtain 1.83 g of a white solid.

[0053] Yield 83%.

[0054] 2) Preparation of fluorescent probe I-A1:

[0055]2-(tert-Butylcarbamoyl)benzoic acid (500mg) was dissolved in 2.3ml of acetic anhydride, at 30°C, 0.28ml of perchloric acid was slowly added to the resulting suspension and stirred for 4h. The resulting precipitate was filtered and washed with ether. The white precipitate (540 mg) was dissolved in 7 ml of anhydrous THF, 7-amino-4-methylcoumarin (374 mg) and 0.74 ml of anhydrous triethylamine were added, and the reaction mixture w...

Embodiment 2

[0060] A fluorescent probe for screening drugs acting on ryanodine receptors, made by the following method:

[0061]

[0062] 1) Preparation of compound 2-(tert-amylcarbamoyl)benzoic acid (intermediate S-2-1):

[0063] Disperse phthalic anhydride (592 mg) in 4.7 ml of anhydrous dichloromethane, and slowly add (A-2)-NH 2 (348mg) and stirred for 3h. After the reaction was completed, dichloromethane was spin-dried under reduced pressure, purified by silica gel chromatography (petroleum ether: ethyl acetate = 2:1), and 489 mg of a white solid was obtained.

[0064] Yield 52%.

[0065] 2) Preparation of fluorescent probe I-A2:

[0066] 2-(tert-Amylcarbamoyl)benzoic acid (258mg) was dissolved in 1.4ml of acetic anhydride, and 0.14ml of perchloric acid was slowly added to the resulting suspension at 30°C and stirred for 4h. The resulting precipitate was filtered and washed with ether. The white precipitate (286 mg) was dissolved in 3.9 ml of anhydrous THF, 7-amino-4-methylcou...

Embodiment 3

[0071] A fluorescent probe for screening drugs acting on ryanodine receptors, made by the following method:

[0072]

[0073] 1) Preparation of compound 2-(2,4,4-trimethylpentan-2-ylcarbamoyl)benzoic acid (intermediate S-3-1):

[0074] Disperse phthalic anhydride (1.48g) in 12ml of anhydrous dichloromethane, and slowly add (A-3)-NH 2 (1.29g) and stirred for 3h. After the reaction was completed, dichloromethane was spin-dried under reduced pressure, and purified by silica gel chromatography (dichloromethane:methanol=50:1) to obtain 1.71 g of a white solid.

[0075] Yield 62%.

[0076] 2) Preparation of fluorescent probe I-A3:

[0077] Dissolve 2-(2,4,4-trimethylpentan-2-ylcarbamoyl)benzoic acid (500 mg) in 2.3 ml of acetic anhydride, and slowly add 0.28 ml of Perchloric acid and stirred for 4h. The resulting precipitate was filtered and washed with ether. The white precipitate (500 mg) was dissolved in 6.5 ml of anhydrous THF, 7-amino-4-methylcoumarin (292 mg) and 0.58...

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PUM

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Abstract

The invention discloses a fluorescent probe for screening drugs acting on a ryanodine receptor. The structural formula of the probe is shown as a formula (I) which is described in the specification. The fluorescent probe for screening the drug acting on the ryanodine receptor can directly and specifically bind to a ryanodine receptor existing in a cell system of an insect, and can be replaced by other drugs binding to the ryanodine receptor of the insect, so the fluorescent probe can be used for screening drugs interacting with the ryanodine receptor of the insect.

Description

technical field [0001] The invention belongs to the field of fluorescent probes, in particular to a fluorescent probe for screening drugs acting on ryanodine receptors. [0002] technical background [0003] The ryanodine receptors distributed on the endoplasmic reticulum / sarcoplasmic reticulum (ER / SR) membrane in the cytoplasm are the main channels responsible for the release of calcium ions. In mammals, it is divided into three subtypes, namely RyR1, RyR2 and RyR3, which are mainly located in skeletal muscle, cardiac muscle and brain tissue respectively. In contrast to mammals, birds, amphibians and fish have only two ryanodine receptors, RyRA and RyRB. RyRA receptors are similar to the mammalian RyR1 subtype, while RyRB are more closely related to the RyR3 subtype. There is only one kind of ryanodine receptor in insects: RyR. After research, it is found that the amino acid sequence of ryanodine receptors in different insects is very similar, but there are great differenc...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D311/16C09K11/06G01N21/64
CPCC07D311/16C09K11/06G01N21/6428C09K2211/1007C09K2211/1088
Inventor 高清志李子真刘胜男姜恒
Owner TIANJIN UNIV
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