Benzoazaindolone compound as well as preparation method and application thereof

Abstract

The invention relates to the technical field of organic luminescent materials and tumor drugs, in particular to a benzaza # imgabs0 # indolone compound as well as a preparation method and application thereof. A one-step synthesis strategy is adopted, the method is simple, conditions are mild, substrate sources are low in price and wide in source, the conversion yield is high, a simple and green synthesis thought is provided for synthesis of the benzaza # imgabs3 # indolone compound, and the benzaza # imgabs3 # indolone compound is suitable for industrial production. And the target compound (benzaza # imgabs4 # indolone compound) has very good fluorescence luminescence property and biocompatibility, and can be directly applied to fluorescence imaging and I-type photodynamic therapy of cancer cells.

Description

Technical Field

[0001] The present invention relates to the technical field of organic luminescent materials and tumor drugs, in particular to a benzazepine Indole ketone compounds, preparation methods and applications thereof. Background Art

[0002] Cancer is one of the major intractable diseases facing human society today. Compared with traditional cancer treatment methods, photodynamic therapy, by exposing the lesion to specific light, has shown great potential in clinical applications due to its significant advantages such as non-invasiveness, high specificity, spatiotemporal controllability and low side effects. Photodynamic therapy is divided into two types: Type I and Type II photodynamic therapy according to the different sensitization mechanisms of photosensitizers. Type II photodynamic therapy is highly dependent on oxygen, and the effect of phototherapy is limited in the hypoxic tumor microenvironment. Type I photodynamic therapy excites triplet photosensitizers to transfer electrons with surrounding molecules (such as lipids, proteins, oxygen, etc.), generating highly toxic free radicals (such as: ·O2 - , ·OH), breaking through the limitations of traditional PDT in hypoxic tumor microenvironments. Therefore, the development of high-performance type I photosensitizers has important scientific significance and research value for improving the efficacy of phototherapy in complex tumor microenvironments.

[0003] Currently, Type I photosensitizers still have relatively simple structures, generally requiring multi-step synthesis. Many of them are conjugated aromatic ring structures with poor water solubility. The development of Type I photodynamic photosensitizers with novel structures, excellent biocompatibility, and efficient luminescence properties has important scientific significance and research value for improving the diagnosis and efficacy of phototherapy in complex tumor microenvironments. Summary of the Invention

[0004] The purpose of the present invention is to provide a benzazepine Indole ketone compounds and their preparation method, and their use in the preparation of cell imaging or type I photodynamic therapy drugs.

[0005] To achieve the above object, the present invention provides the following solutions:

[0006] One of the technical solutions of the present invention is a benzazepine Indole ketone compounds, the structural formula is shown in formula (3):

[0007]

[0008] In formula (3), R 1 、R 2 、R 3 、R 4 Each of the following is independently selected from hydrogen, halogen, cyano, nitro, C1-C6 straight-chain alkyl or alkoxy, and OH;

[0009] R 5 、R 6 、R 7 、R 8 Each of the following is independently hydrogen, halogen, C1-C6 straight chain alkyl or alkoxy.

[0010] The second technical solution of the present invention is a benzazepine The preparation method of indole ketone compounds comprises the following steps: under acidic conditions, a compound represented by formula (1) and a compound represented by formula (2) are subjected to a cyclization reaction to obtain a benzazepine represented by formula (3). Indole ketone compounds; specifically comprising the following steps:

[0011] The compound represented by formula (1), the compound represented by formula (2) and an acid are added to an organic solvent for reaction to obtain the benzazepine Indolinone compounds;

[0012]

[0013] R in formula (1) 1 、R 2 、R 3 、R 4 The same as R in claim 1 1 、R 2 、R 3 、R 4 ;

[0014] R in formula (2) 5 、R 6 、R 7 、R 8 The same as R in claim 1 5 、R 6 、R 7 、R 8 ;

[0015] R in formula (2) 9 is a halogen (F, Cl, Br, I);

[0016] R in formula (2) 10 is halogen (F, Cl, Br, I), OH or SH.

[0017] The third technical solution of the present invention is that the above-mentioned benzazepine Application of indolinone compounds in the preparation of drugs for cell imaging or type I photodynamic therapy.

[0018] The present invention discloses the following technical effects:

[0019] The present invention adopts a one-step synthesis strategy with simple method, mild conditions, cheap and extensive substrate sources, and high conversion yield. The synthesis of indole ketone compounds provides a simple and green synthesis idea, and the target compound (benzazepine Indolinone compounds) have very good fluorescence properties and biocompatibility and can be directly applied to fluorescence imaging and type I photodynamic therapy of cancer cells. BRIEF DESCRIPTION OF THE DRAWINGS

[0020] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the following briefly introduces the drawings required for use in the embodiments. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying any creative work.

[0021] Figure 1 The compound prepared by the present invention is benzazepine The hydrogen spectrum of indole was measured using a Bruker 400 MHz NMR spectrometer, with deuterated chloroform as the solvent.

[0022] Figure 2 The compound prepared by the present invention is benzazepine The carbon spectrum of indole was measured by Bruker 400MHz NMR spectrometer, and the solvent was deuterated chloroform.

[0023] Figure 3 The compound prepared by the present invention is benzazepine Schematic diagram of the crystal structure of indolinone.

[0024] Figure 4 The compound prepared by the present invention is benzazepine Schematic diagram of indole absorption and emission.

[0025] Figure 5 The compound prepared by the present invention is benzazepine Schematic diagram of the test for reactive oxygen species generated by indole.

[0026] Figure 6 The compound prepared by the present invention is benzazepine Confocal fluorescence imaging of HeLa cells treated with indole.

[0027] Figure 7 The compound prepared by the present invention is benzazepine Photodynamic therapy outcomes with indole.

[0028] Figure 8 The compound prepared by the present invention is benzazepine The effect of indole on the generation of a type of reactive oxygen species (superoxide anion). DETAILED DESCRIPTION

[0029] Various exemplary embodiments of the present invention will now be described in detail. This detailed description should not be considered as limiting the present invention, but rather as a more detailed description of certain aspects, features, and embodiments of the present invention.

[0030] It should be understood that the terms described herein are intended only to describe particular embodiments and are not intended to limit the present invention. In addition, for numerical ranges herein, it should be understood that each intermediate value between the upper and lower limits of the range is also specifically disclosed. The intermediate value within any stated value or stated range, and each smaller range between any other stated value or intermediate value within the stated range, is also encompassed within the present invention. The upper and lower limits of these smaller ranges may be independently included or excluded within the scope.

[0031] Unless otherwise indicated, all technical and scientific terms used herein have the same meaning as commonly understood by those skilled in the art. Although only preferred methods and materials are described herein, any methods and materials similar or equivalent to those described herein may also be used in the practice or testing of the present invention. All documents mentioned in this specification are incorporated by reference to disclose and describe the methods and / or materials associated with the documents. In the event of any conflict with any incorporated document, the contents of this specification shall prevail.

[0032] It will be apparent to those skilled in the art that various modifications and variations may be made to the specific embodiments described herein without departing from the scope or spirit of the invention. Other embodiments will be apparent to those skilled in the art from the description of the invention. The description and examples are intended to be exemplary only.

[0033] The words “include,” “including,” “have,” “contain,” etc. used in this document are open-ended terms, meaning including but not limited to.

[0034] The present invention is directed to the existing benzazepine The complex preparation process of indole ketone compounds provides an efficient single-step synthetic strategy to prepare benzazepines. Indolinone compounds have excellent luminescence properties and good biocompatibility, and can be directly applied to confocal imaging of HeLa cells. Furthermore, the materials can also function as Type I photosensitizers, demonstrating excellent photodynamic therapy effects at the cellular level. The Type I photosensitizers of the present invention have a novel structure, a cheap and widely available substrate, mild reaction conditions, and a simple preparation method, promising application prospects.

[0035] The first aspect of the present invention provides a benzazepine Indole ketone compounds, the structural formula is shown in formula (3):

[0036]

[0037] In formula (3), R 1 、R 2 、R 3 、R 4 Each of the following is independently selected from hydrogen, halogen, cyano, nitro, C1-C6 straight-chain alkyl or alkoxy, and OH;

[0038] R 5 、R 6 、R 7 、R 8 Each of the following is independently hydrogen, halogen, C1-C6 straight chain alkyl or alkoxy.

[0039] In the present invention, the C1-C6 alkyl group may specifically be: methyl, ethyl, propyl, isopropyl, butyl, isobutyl, pentyl or hexyl.

[0040] The C1-C6 alkoxy group may specifically include methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, pentyloxy or hexyloxy.

[0041] In a preferred embodiment of the present invention, R 1 、R 2 、R 3 、R 4 Each of the following groups is independently one of hydrogen, Cl, Br, cyano, nitro, -Me, -Et, -OMe, -OEt, and OH;

[0042] R 5 、R 6 、R 7 、R 8 Independently, they are hydrogen, halogen, and -Me.

[0043] In a preferred embodiment of the present invention, the benzazepine The structural formula of the indole ketone compound is one of the following structural formulas:

[0044]

[0045] In a further preferred embodiment of the present invention, the benzazepine The structural formula of the indole ketone compound is one of the following structural formulas:

[0046]

[0047]

[0048]

[0049] The second aspect of the present invention provides a benzazepine The preparation method of indole ketone compounds comprises the following steps: under acidic conditions, a compound represented by formula (1) and a compound represented by formula (2) are subjected to a cyclization reaction to obtain a benzazepine represented by formula (3). Indole ketone compounds; specifically comprising the following steps:

[0050] The compound represented by formula (1), the compound represented by formula (2) and an acid are added to an organic solvent for reaction to obtain the benzazepine Indolinone compounds;

[0051]

[0052] R in formula (1) 1 、R 2 、R 3 、R 4 The same as R in claim 1 1 、R 2 、R 3 、R 4 ;

[0053] R in formula (2) 5 、R 6 、R 7 、R 8 The same as R in claim 1 5 、R 6 、R 7 、R 8 ;

[0054] R in formula (2) 9 is a halogen (F, Cl, Br, I);

[0055] R in formula (2) 10 is halogen (F, Cl, Br, I), OH or SH.

[0056] From the perspective of improving the reactivity between the reaction compounds, preferably, R 1 、R 2 、R 3 、R 4 are independently hydrogen, methyl, ethyl, propyl, methoxy, ethoxy, propoxy and halogen; further preferably, R 1 、R 2 、R 3 、R 4 Each of the following groups is independently selected from hydrogen, Br, methyl or methoxy.

[0057] From the perspective of improving the reactivity between the reaction compounds, preferably, R5 、R 6 、R 7 、R 8 is independently methyl, ethyl, propyl, benzyl or phenyl.

[0058] In some specific embodiments of the present invention, the compound represented by formula (1) can be one of formula (1-1) to formula (1-6):

[0059] Formula (1-1): R 1 、R 2 、R 3 、R 4 All are H;

[0060] Formula (1-2): Formula (1-3):

[0061] Formula (1-4): Formula (1-5):

[0062] Formula (1-6): R 1 、R 2 、R 3 、R 4 One of them is Cl or Br, and the others are H, for example:

[0063]

[0064] Formula (1-6): R 1 、R 2 、R 3 、R 4 One of them is -NO2 and the others are H, for example:

[0065] In some specific embodiments of the present invention, the compound represented by formula (2) can be one of formula (2-1) to formula (2-8):

[0066] Formula (2-1): R 5 、R 6 、R 7 、R 8 Both H, R 9 is F;

[0067] Formula (2-2): R 5 、R 6 、R 7 、R 8 All are methyl, R 9 For F.

[0068] Formula (2-3): R 5 、R6 、R 7 、R 8 All are ethyl, R 9 is a halogen;

[0069] Formula (2-4): Formula (2-5):

[0070] Formula (2-6): Formula (2-7): Formula (2-8):

[0071] In some specific embodiments of the present invention, the compound represented by formula (3) can be one of formula (3-1) to formula (3-5):

[0072] Formula (3-1): R 1 、R 2 、R 3 、R 4 Both H, R 5 、R 6 、R 7 、R 8 All are H;

[0073] Formula (3-2): R 1 、R 2 、R 3 、R 4 As set in formula (1-2), R 5 、R 6 、R 7 、R 8 Set as formula (2-2);

[0074] Formula (3-3): R 1 、R 2 、R 3 、R 4 As set in formula (1-3), R 5 、R 6 、R 7 、R 8 Set as formula (2-3);

[0075] Formula (3-4): R 1 、R 2 、R 3 、R 4 As set in formula (1-4), R 5 、R 6 、R 7 、R 8 Set as formula (2-4);

[0076] Formula (3-5): R 1 、R 2 、R 3 、R 4 As set in formula (1-5), R 5 、R 6 、R 7 、R 8 Set as shown in formula (2-5).

[0077] In the present invention, the molar amounts of the compound represented by formula (1) and the compound represented by formula (2) can vary within a wide range. In order to enable a more complete reaction and improve the utilization rate of raw materials, preferably, the molar ratio of the compound represented by formula (1) to the compound represented by formula (2) is 1:(0.5-3.0); more preferably, it is 1:(2-2.5).

[0078] In the present invention, the acid can be various protonic acids, such as one or more of an organic acid and an inorganic acid. Preferably, the acid is one or more of benzoic acid (PhCOOH), acetic acid, trifluoroacetic acid, hydrochloric acid, sulfuric acid, trifluoromethanesulfonic acid, and p-toluenesulfonic acid, more preferably one or more of benzoic acid, hydrochloric acid, and trifluoroacetic acid. When the acid is one or more of benzoic acid, hydrochloric acid, and trifluoroacetic acid, the compound represented by formula (3) can be obtained in a higher yield.

[0079] The present invention has no particular limitation on the amount of the acid, as long as it can provide sufficient acidic conditions for the reaction (cycloaddition reaction). Preferably, the molar ratio of the compound represented by formula (1) to the acid is 1:(1-5).

[0080] In the present invention, the organic solvent can be various solvents conventionally used in the field of cyclization reaction. With respect to the specific raw materials of the present invention, in order to improve the reaction yield, preferably, the solvent is one or more of toluene, DMF, acetonitrile, dichloromethane, isopropanol, dimethyl sulfoxide, 1,4-dioxane, 1,2-dichloroethane, ethyl acetate, 1,2-dichloroethyl ether and N-methylpyrrolidone.

[0081] The amount of the organic solvent can vary within a wide range. Preferably, the ratio of the compound represented by formula (1) to the organic solvent is 1 mmol: 3-10 mL; more preferably, the ratio of the compound represented by formula (1) to the organic solvent is 1 mmol: 5-7 mL.

[0082] In a preferred embodiment of the present invention, the reaction temperature is 40-120° C., preferably 60-100° C., and the reaction time is 0.5-10 hours, preferably 2-4 hours. Stirring can also be performed during the reaction at a rate of 300-1000 rpm.

[0083] In a preferred embodiment of the present invention, the reaction further comprises the steps of extraction, washing and purification.

[0084] According to the present invention, although the compound prepared in a single step can be characterized by low-resolution mass spectrometry with a high yield, and the scope of the present invention also includes this situation, in order to obtain a purer final product, it is preferred to purify the cycloaddition product to obtain a higher purity final product. For example, the product can be extracted (for example, with ethyl acetate), washed (first with a saturated sodium carbonate solution and then with saturated brine), concentrated and separated by silica gel column chromatography (for example, using a mixture of ethyl acetate and petroleum ether with a volume ratio of 1:8 as eluent) to obtain a relatively pure compound represented by formula (3).

[0085] The third aspect of the present invention provides the above-mentioned benzazepine Application of indolinone compounds in the preparation of drugs for cell imaging or type I photodynamic therapy.

[0086] Unless otherwise specified, the technical solutions described in the present invention are all conventional solutions in the field, and the reagents or raw materials used, unless otherwise specified, are purchased from commercial channels or have been disclosed.

[0087] The technical solutions provided by the present invention are described in detail below with reference to the embodiments, but they should not be construed as limiting the scope of protection of the present invention.

[0088] Example 1

[0089] This example is used to illustrate the benzazepine Synthesis of indole ketone compounds:

[0090]

[0091] (1) As shown in the above reaction formula, the compound represented by formula (1-1) (0.5 mmol), the compound represented by formula (2-1) (1.25 mmol) and 2.5 mmol of hydrochloric acid were added to 3 mL of 1,2-dichloroethane, and reacted at an oil bath temperature of 100°C and a stirring speed of 600 rpm for 4 hours. The mixture was extracted three times with ethyl acetate, washed with saturated sodium carbonate solution and saturated brine in sequence, concentrated and separated and purified by silica gel column chromatography (ethyl acetate / petroleum ether mixture with a volume ratio of 1:8 as eluent) to obtain the compound of formula (3-1) - benzazepine Indole.

[0092] Formula (3-1): 1H NMR(400MHz, CDCl3)δ7.20(d,J=7.2Hz,1H),7.46(t,J=7.6Hz,2H),7.29–7.22(m,2H), 7.16(d,J=7.2Hz,1H),6.91–6.86(m,3H),3.98(t,J=4.8Hz,2H),3.23(t,J=5.6Hz,2H). 13 C NMR (101MHz, CDCl3) δ186.1,152.4,139.9,136.1,135.9,133.8,132.7,130.0,128.4,127.3,124.9,120.8,119.3,111.3,108.3,44.4,36.2.

[0093] Example 2

[0094] This example is used to illustrate the benzazepine Indolinones for bioimaging and photodynamic therapy.

[0095] (1) Biological imaging experiments

[0096] Hela cells were seeded into confocal microplates and cultured for 24 hours until they adhered to the wall. Indole was dispersed into the cell culture medium in the form of a solution. After incubation for 6 hours, 4% paraformaldehyde fixative was used to maintain cell morphology and change cell permeability. Commercial Hoechst33342 dye was then used to stain the cell nuclei to achieve colocalization. Finally, laser confocal microscopy was used for biological imaging.

[0097] (2) Cytotoxicity assay

[0098] Evaluation of benzazepines by CCK-8 assay The effects of indole on cytotoxicity and photodynamic therapy of Hela cells are as follows:

[0099] HeLa cells were cultured at a density of 5×10 4 The cells were inoculated into 96-well plates, 100 μL per well, and cultured for 24 hours until adhered to the wall. The indolinone culture medium was added to the well plate in the form of replacement medium and cultured for another 24 hours. Excess material was washed with PBS and 100 μL of CCK-8 working solution was added to each well. The cells were incubated at 37°C for another hour and the absorbance at 450 nm was measured using a microplate reader.

[0100] (3) Photodynamic performance test

[0101] HeLa cells were cultured at a density of 5×104 The cells were inoculated into 96-well plates, 100 μL per well, and cultured for 24 hours until adhered to the wall. Subsequently, different concentrations of benzazepine-containing The indole culture medium was added to the well plate in the form of liquid replacement and culture was continued for 6 hours; irradiated under 470nm laser for half an hour, placed in the incubator and incubated for 3 hours, and the cell viability was detected by CCK-8 method, using the same method as above.

[0102] To further verify the Indole phototoxicity effect, HeLa cells were seeded into 35 mm culture dishes and cultured for 24 h; 1×10 5 cells, containing benzazepines Indolinone 50 μM was added to the culture medium as a replacement, and the cells were cultured for another 6 hours. The cells were irradiated with a 470 nm laser for half an hour and then incubated for another 3 hours. The cells were stained with a Calcein / PI cell viability and cytotoxicity assay kit according to the manufacturer's instructions, and apoptosis was observed using an inverted fluorescence microscope. The excitation wavelengths for AM and PI were 488 nm and 559 nm, respectively.

[0103] Fluorescence microscopy was used to detect the generation of intracellular reactive oxygen species. A commercial DHE fluorescent probe was used as a ROS probe. Hela cells were seeded into 35 mm culture dishes at 1 × 10 cells per well. 5 The cells were cultured for 24 hours until they adhered to the wall; then 50 μM benzazepine was added as a replacement medium. Indole medium; after culturing the cells for 6 hours, irradiate the cells with 470nm laser for 5 minutes, add DHE fluorescent probe and incubate for 30 minutes, discard the fluorescent probe and add commercial Hoechst33342 dye to dye the cell nucleus to achieve colocalization, and finally observe the fluorescence of the reactive oxygen species probe under a fluorescence microscope.

[0104] Figure 1 The compound prepared by the present invention is benzazepine The hydrogen spectrum of indole was measured using a Bruker 400 MHz NMR spectrometer, with deuterated chloroform as the solvent.

[0105] Figure 2 The compound prepared by the present invention is benzazepine The carbon spectrum of indole was measured by Bruker 400MHz NMR spectrometer, and the solvent was deuterated chloroform.

[0106] Figure 3 The compound prepared by the present invention is benzazepine Schematic diagram of the crystal structure of indolinone.

[0107] Figure 4 The compound prepared by the present invention is benzazepine Schematic diagram of indole absorption and emission, Figure 4 It is known that benzazepine The maximum absorption wavelength of indolinone is 490 nm, and the maximum fluorescence emission wavelength is 520 nm.

[0108] Figure 5 The compound prepared by the present invention is benzazepine Schematic diagram of the test for the generation of reactive oxygen species by indole Figure 5 It is known that benzazepine The fluorescence intensity of indole did not increase significantly after interaction with SOSG probe after illumination, indicating that no type II reactive oxygen species were generated.

[0109] Figure 6 The compound prepared by the present invention is benzazepine Confocal fluorescence imaging of Hela cells by indole Figure 6 It is known that benzazepine Indole has good luminescence and imaging effects, and plays a role in diagnosing cancer cells.

[0110] Figure 7 The compound prepared by the present invention is benzazepine The results of photodynamic therapy with indole (in the figure, "PBS" refers to phosphate buffered saline, "PBS+L" refers to phosphate buffered saline + laser light treatment, and "50μM" refers to a solution concentration of 50μM benzazepine Indole solution, "50μM+L" refers to a solution concentration of 50μM benzazepine Indole solution + laser irradiation treatment. The four groups were operated under the same test conditions; the "PBS", "PBS+L", and "50μM" groups were control groups, and the "50μM+L" group was the experimental group. A commercial live-dead staining kit was used to determine the photodynamic therapy effect of the compound at 50μM. Living cells were marked with green fluorescence, and dead cells were marked with red fluorescence. When Hela cells were only treated with the drug and incubated for 6 hours, the Hela cells hardly died, indicating that benzazepine Indole has good biocompatibility with Hela cells; after incubation for 6 hours, Hela cells were treated with 470nm laser for 30 minutes, and many cells died and the cell survival rate was very low. This result shows that benzazepine Indole has good biocompatibility and photodynamic therapy activity.

[0111] Figure 8 The compound prepared by the present invention is benzazepine The effect of indole on the generation of a type of reactive oxygen species (superoxide anion) (in the figure, "PBS" refers to phosphate buffered saline, benzazepine The concentration of indole solution was 50 μM. The two groups were operated under the same test conditions. The commercial DHE fluorescent probe was used to detect benzazepines. Indole generates reactive oxygen species in cells. HeLa cells were seeded into 35 mm culture dishes at 1 × 10 cells per well. 5 The cells were cultured for 24 hours until they adhered to the wall; then PBS and 50 μM benzazepine were added as the medium for replacement. Indole medium; after culturing the cells for 6 hours, the cells were irradiated with a 470nm laser for 5 minutes, and DHE fluorescent probe was added and incubated for 30 minutes. After discarding the fluorescent probe, commercial Hoechst33342 dye was added to stain the cell nucleus to achieve co-localization. Finally, the fluorescence of the reactive oxygen species probe was observed under a fluorescence microscope. The results showed that DHE was oxidized after binding to superoxide anions in the cell, entering the cell nucleus and binding to DNA to emit red fluorescence; compared with the non-irradiated group, red fluorescence was clearly observed in the cell nucleus of the illuminated group, which well illustrates that benzazepine Indole generates superoxide anions under laser irradiation and has photodynamic therapeutic effect.

[0112] The present invention also uses a preparation method similar to that of Example 1 to prepare the following benzazepine Indolinone compounds

[0113] For the above-mentioned benzazepine The same effect verification as in Example 1 was carried out on indole ketone compounds. The results showed that the above-mentioned benzazepine Indole ketone compounds can achieve the same Similar technical effects.

[0114] The embodiments described above are merely descriptions of preferred embodiments of the present invention and are not intended to limit the scope of the present invention. Without departing from the spirit of the present invention, various modifications and improvements made to the technical solutions of the present invention by persons skilled in the art should fall within the scope of protection defined by the claims of the present invention.

Claims

1. A benzazepine Indole ketone compounds, characterized in that The structural formula is shown in formula (3): In formula (3), R 1 、R 2 、R 3 、R 4 Each of the following is independently selected from hydrogen, halogen, cyano, nitro, C1-C6 straight-chain alkyl or alkoxy, and OH; R 5 、R 6 、R 7 、R 8 Each of the following is independently hydrogen, halogen, C1-C6 straight chain alkyl or alkoxy.

2. Benzazepine according to claim 1 Indole ketone compounds, characterized in that R 1 、R 2 、R 3 、R 4 is independently one of hydrogen, Cl, Br, cyano, nitro, -Me, -Et, -OMe, -OEt, and OH; R 5 、R 6 、R 7 、R 8 Independently, they are hydrogen, halogen, and -Me.

3. A benzazepine according to claim 1 The preparation method of indole ketone compounds is characterized in that: The following steps are involved: The compound represented by formula (1), the compound represented by formula (2) and an acid are added to an organic solvent for reaction to obtain the benzazepine Indolinone compounds; R in formula (1) 1 、R 2 、R 3 、R 4 The same as R in claim 1 1 、R 2 、R 3 、R 4 ; R in formula (2) 5 、R 6 、R 7 、R 8 The same as R in claim 1 5 、R 6 、R 7 、R 8 ; R in formula (2) 9 is a halogen; R in formula (2) 10 is halogen, OH or SH.

4. Benzazepine according to claim 3 The preparation method of indole ketone compounds is characterized in that: The molar ratio of the compound represented by formula (1) to the compound represented by formula (2) is 1:(0.5-3.0).

5. The benzazepine according to claim 3 The preparation method of indole ketone compounds is characterized in that: The acid is at least one of benzoic acid, acetic acid, trifluoroacetic acid, hydrochloric acid, sulfuric acid, trifluoromethanesulfonic acid and p-toluenesulfonic acid; the molar ratio of the compound represented by formula (1) to the acid is 1:(1-5).

6. The benzazepine according to claim 3 The preparation method of indole ketone compounds is characterized in that: The organic solvent is at least one of toluene, DMF, acetonitrile, dichloromethane, isopropanol, dimethyl sulfoxide, 1,4-dioxane, 1,2-dichloroethane, ethyl acetate, 1,2-dichloroethyl ether and N-methylpyrrolidone; the ratio of the compound represented by formula (1) to the organic solvent is 1 mmol: 3-10 mL.

7. The benzazepine according to claim 3 The preparation method of indole ketone compounds is characterized in that: The reaction temperature is 40-120° C., and the reaction time is 0.5-10 hours.

8. The benzazepine according to claim 3 The preparation method of indole ketone compounds is characterized in that: After the reaction is completed, the steps of extraction, washing and purification are further included.

9. The benzoazepine according to claim 1 Application of indolinone compounds in the preparation of drugs for cell imaging or type I photodynamic therapy.

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