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Benzimidazole hERG potassium ion channel small-molecular fluorescent probe and preparation method and applications thereof

A technology of potassium ion channels and benzimidazoles, applied in fluorescence/phosphorescence, chemical instruments and methods, luminescent materials, etc., can solve the problem of few applications

Active Publication Date: 2015-09-16
SHANDONG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

At present, fluorescent probes related to potassium ion channels mainly use fluorescent protein labeling technology, immunofluorescence technology, voltage-sensitive fluorescent probes, etc., and the application of small molecule fluorescent probes with high selectivity and high sensitivity in the field of potassium ion channels less

Method used

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  • Benzimidazole hERG potassium ion channel small-molecular fluorescent probe and preparation method and applications thereof
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  • Benzimidazole hERG potassium ion channel small-molecular fluorescent probe and preparation method and applications thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0032] Embodiment 1: Preparation of coumarin-based fluorophore probes:

[0033]

[0034] Concrete synthetic route is as follows:

[0035]

[0036] (1) Preparation of Intermediate 1:

[0037] Add 30ml of acetonitrile and potassium hydroxide (2.62g, 46.6mmol) to 2-chlorobenzimidazole (5g, 32.7mmol), heat to 80°C, stir for 30min, the solution is clear; after cooling to room temperature, add p-fluorobenzyl bromide ( 9.29g, 49.1mmol), heated to 80°C and refluxed for 5h, the reaction solution was a white turbid solution; the reaction solution was extracted three times with dichloromethane (100mL×3), washed with distilled water, combined organic layers, dried over anhydrous magnesium sulfate, pumped Filter and concentrate to obtain a white solid, which is recrystallized with acetone / petroleum ether, refrigerated, suction filtered, and dried to obtain a white solid with a yield of 91.1%. 1H-NMR (300MHz, DMSO): δ=7.64(d, J=6.6Hz, 2H), 7.32-7.24(m, 4H), 7.19(t, J=4.9Hz, 2H), 5.5...

Embodiment 2

[0053] Example 2: Preparation of naphthalene diimide fluorophore probes

[0054]

[0055] Concrete synthetic route is as follows:

[0056]

[0057] In the synthetic route of this example, the preparation method of intermediate 1-3 is the same as that of intermediate 1-3 in Example 1.

[0058] (1) Preparation of Intermediate 4:

[0059] Add 4 mL of glacial acetic acid and 20 mL of pyridine to 4-amino-1,8-naphthalene diimide (2 g, 9.3 mmol), and reflux for 1 h. Then 30mL of acetic anhydride was added, and the reaction was refluxed for 5h. After the reaction solution was cooled to room temperature, it was poured into 200 mL of ice water, filtered with suction, and the filter cake was washed with water to obtain a crude brown solid with a yield of 71.3%.

[0060] (2) Preparation of intermediate 5:

[0061] Intermediate 4 (1.7g, 6.66mmol) and 4-amino-1-butanol (0.71g, 7.96mmol) were dissolved in absolute ethanol and refluxed for 5h. The reaction solution was concentrated...

Embodiment 3

[0066] Example 3: Determination of Optical Activity

[0067] Table 1: Optical characteristics of probe molecules

[0068]

[0069]

[0070] Note: All the above optical properties were measured in phosphate buffer at pH = 7.4.

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Abstract

The invention relates to a benzimidazole hERG potassium ion channel small-molecular fluorescent probe and a preparation method and applications thereof; the fluorescent probe has the structural general formula represented by the formula (I), wherein in the formula, R1 is hydroxyl, halogen, alkyl or alkoxy monosubstituent or polysubstituent, R2 is fluorophore, n is 1-6, particularly, R1 is p-halogen, and R2 is coumarin, naphthalene diimide, NBD, Cy5 or fluorescein isothiocyanate fluorophore. The invention discloses the applications of the probe in marking of hERG potassium ion channels and high-expression tumor cells or tissues, high-throughput screening of hERG potassium ion channel inhibitors, evaluation of new drug cardiotoxicity, use as a probe for identification of the hERG potassium ion channels and studies on hERG potassium ion channel physiological, pathological and related diseases.

Description

technical field [0001] The invention belongs to the technical field of medicines, and in particular relates to a small-molecule fluorescent probe of a benzimidazole hERG potassium ion channel and a preparation method and application thereof. Background technique [0002] The human ether-a-go-go related gene (hERG) is isolated and identified from the human hippocampal gene, and has homology with the Drosophila EAG gene. The hERG gene encodes the cardiac rapid activation delayed rectifier (I kr ) The α subunit of the potassium ion channel, which mainly exists in the heart tissue and the nervous system, and plays an important role in the repolarization of the cardiac action potential. Recently, it has been found that hERG is highly expressed in many tumor cells and has a regulatory effect on the proliferation and apoptosis of tumor cells. When hERG gene mutation or hERG channel is blocked, it will cause hereditary or acquired long QT syndrome (LQTS), which will lead to torsad...

Claims

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Application Information

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IPC IPC(8): C09K11/06C07D405/14C07D401/14C07D401/12C07D493/10G01N21/64
Inventor 杜吕佩李敏勇汪蓓蕾
Owner SHANDONG UNIV
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