CN115806555B - Indoloazepinone derivatives, their preparation and their use for controlling plant viruses, for killing parasites and for killing bacteria - Google Patents

Abstract

The present invention relates to indoloazepinone derivatives and their preparation methods and applications in preventing and controlling plant viruses, killing insects and sterilizing bacteria. The meanings of the groups in the general formula are shown in the specification. The indoloazepinone derivatives of the present invention have excellent anti-plant virus activity and also have broad-spectrum sterilization and insecticidal activities.

Description

Indoloazepinone derivatives and their preparation and application in preventing and controlling plant viruses, killing insects, and killing bacteria

Technical Field

The invention relates to indoloazepinone derivatives and their preparation and application in preventing and controlling plant viruses, killing insects and sterilizing bacteria, and belongs to the technical field of agricultural protection.

Background technique

In 1985, the Schmitz research group at the University of Oklahoma first isolated the pyrrololactam alkaloid Aldisin from the Guam sponge Hymeniacidon aldis delaubenfels (J.Nat.Prod.1985,48,47-53). In 1990, the Pettit research group reported that two alkaloids with the Aldisin structure, Hymenialdisin and Debromohymenialdisin, had an inhibitory effect on P388 lymphocytic leukemia (Can.J.Chem.1990,68,1621-1624.). In 2012, the Fouad research group of Mia University in Egypt conducted a study on the biological activity of alkaloids with the structure of Aldisin and found that 12-N-methyl stevensine, Hymenialdisin, Debromohymenialdisin and Latonduine A had significant in vitro activity against the mouse lymphoma cell line L5187Y, with EC ₅₀ values of 3.5, 1.8, 2.1 and 9.0 mg/mL, respectively (Tetrahedron, 2012, 68, 10176-10179.). Inspired by this, we tried to study Aldisine as a lead compound. In order to enhance the stability of the structure and improve its solubility, we designed and synthesized a series of derivatives using Indoloazepinone as the skeleton. So far, there is no report on the synthesis method of Indoloazepinone derivatives I-1 to I-26 and their application in preventing and controlling plant viruses, insecticides and sterilization.

Summary of the invention

In view of the shortcomings of the prior art, the present invention provides indoloazepinone derivatives and their preparation methods and applications in controlling plant viruses, killing insects and sterilizing bacteria. The indoloazepinone derivatives of this patent have good plant virus control, insecticidal activity, and broad-spectrum sterilizing activity.

The indoloazepinone derivative of the present invention is a compound having a structure shown in the following general formula:

^R1 represents H, substituted or unsubstituted benzyl, tert-butyloxycarbonyl, benzyloxycarbonyl; ^R2 represents H, X band represents O, NOR ⁴ , N-NH-R ⁵ ;

R ³ represents an alkyl group of 1 to 4 carbon atoms or a benzyl group;

R ⁴ represents an alkyl group with 3 to 4 carbon atoms, an allyl group, a phenyl group,

R ⁵ represents a substituted or unsubstituted phenyl group; the substituents of the substituted phenyl group are each independently selected from one or more of methyl, methoxy, chlorine, bromine, and trifluoromethyl;

R ⁶ represents isobutyl, allyl, substituted or unsubstituted phenyl, 1-naphthyl, furan-2-yl; the substituents of the substituted phenyl are each independently selected from one or more of methyl, methoxy, chloro, trifluoromethyl.

The present invention provides a preparation method 1 of the above-mentioned indoloazepinone derivatives, which comprises: using indoloazepinone and NH ₂ OR ⁴ as reactants, sodium acetate as a base, and methanol as a solvent, under heating reflux conditions, to obtain compounds I-1 to I-5;

The present invention provides a second preparation method of the above-mentioned indoloazepinone derivative, which comprises: first, using indoloazepinone and NH ₂ OH as reactants, sodium acetate as a base, and methanol as a solvent, under heating reflux conditions to obtain compound A; then, using compound A as a raw material, dichloromethane as a solvent, and triethylamine as a base, adding acyl chloride dropwise thereto under ice bath conditions, and then restoring to room temperature to obtain compounds I-6 to I-17;

The present invention provides a third method for preparing the above-mentioned indoloazepinone derivatives, which comprises: using indoloazepinone and NH ₂ NHR ⁵ as reactants and ethanol as solvent, under heating and reflux conditions, to obtain compounds I-18 and I-19;

The present invention provides a fourth method for preparing the above-mentioned indoloazepinone derivative, which comprises: using indoloazepinone and Boc ₂ O as reactants, 4-dimethylaminopyridine as a catalyst, and acetonitrile as a solvent, at room temperature to obtain compound I-20;

The present invention provides a fifth preparation method of the above-mentioned indoloazepinone derivative, which comprises: first, using indoloazepinone and benzyl bromide as reactants, potassium carbonate as a base, and N,N- _{dimethylformamide} as a solvent, at room temperature to obtain compound B; then, using compound B and _BrCH2CO2R3 as raw materials, potassium carbonate as a base, and N,N-dimethylformamide as a solvent, at room temperature to obtain compounds I- ²¹ to I-24;

The present invention provides a sixth method for preparing the above-mentioned indoloazepinone derivatives, which comprises: first, using indoloazepinone and benzyl bromide as reactants, potassium carbonate as a base, and N,N-dimethylformamide as a solvent, at room temperature to obtain a compound with a benzyl group on the indole nitrogen; then, using sodium acetate as a base and methanol as a solvent, under heating reflux conditions, to obtain compounds I-25 and I-26.

The indoloazepinone derivatives of the general formula of the present invention exhibit good activity against pepper mild mottle virus.

The indoloazepinone derivatives of the general formula of the present invention have the activity of killing diamondback moth and mosquito larvae.

The indoloazepinone derivatives of the general formula of the present invention exhibit fungicidal activity against eight pathogens, including cucumber wilt, peanut brown spot, apple ring pattern, wheat leaf blight, tomato early blight, rice blast, pepper phytophthora and rape sclerotia.

Detailed ways

The present invention provides an indoloazepinone derivative, which is a compound represented by the general formula:

^R1 represents H, substituted or unsubstituted benzyl, tert-butyloxycarbonyl, benzyloxycarbonyl; ^R2 represents H, X band represents O, NOR ⁴ , N-NH-R ⁵ ;

R ³ represents an alkyl group of 1 to 4 carbon atoms or a benzyl group;

R ⁴ represents an alkyl group with 3 to 4 carbon atoms, an allyl group, a phenyl group,

R ⁵ represents a substituted or unsubstituted phenyl group; the substituents of the substituted phenyl group are each independently selected from one or more of methyl, methoxy, chlorine, bromine, and trifluoromethyl;

R ⁶ represents isobutyl, allyl, substituted or unsubstituted phenyl, 1-naphthyl, furan-2-yl; the substituents of the substituted phenyl are each independently selected from one or more of methyl, methoxy, chloro, trifluoromethyl.

In a preferred embodiment of the present invention, the compound represented by the general formula is selected from one of the compounds represented by the following formulae:

The present invention provides a preparation method 1 of the above-mentioned indoloazepinone derivatives, which comprises: using indoloazepinone and NH ₂ OR ⁴ as reactants, sodium acetate as a base, and methanol as a solvent, under heating reflux conditions, to obtain compounds I-1 to I-5;

The present invention provides a second preparation method of the above-mentioned indoloazepinone derivative, which comprises: first, using indoloazepinone and NH ₂ OH as reactants, sodium acetate as a base, and methanol as a solvent, under heating reflux conditions to obtain compound A; then, using compound A as a raw material, dichloromethane as a solvent, and triethylamine as a base, adding acyl chloride dropwise thereto under ice bath conditions, and then restoring to room temperature to obtain compounds I-6 to I-17;

The present invention provides a third method for preparing the above-mentioned indoloazepinone derivatives, which comprises: using indoloazepinone and NH ₂ NHR ⁵ as reactants and ethanol as solvent, under heating and reflux conditions, to obtain compounds I-18 and I-19;

The present invention provides a fourth method for preparing the above-mentioned indoloazepinone derivative, which comprises: using indoloazepinone and Boc ₂ O as reactants, 4-dimethylaminopyridine as a catalyst, and acetonitrile as a solvent, at room temperature to obtain compound I-20;

The present invention provides a fifth preparation method of the above-mentioned indoloazepinone derivative, which comprises: first, using indoloazepinone and benzyl bromide as reactants, potassium carbonate as a base, and N,N- _{dimethylformamide} as a solvent, at room temperature to obtain compound B; then, using compound B and _BrCH2CO2R3 as raw materials, potassium carbonate as a base, and N,N-dimethylformamide as a solvent, at room temperature to obtain compounds I- ²¹ to I-24;

The present invention provides a sixth method for preparing the above-mentioned indoloazepinone derivatives, which comprises: first, using indoloazepinone and benzyl bromide as reactants, potassium carbonate as a base, and N,N-dimethylformamide as a solvent, at room temperature to obtain a compound with a benzyl group on the indole nitrogen; then, using sodium acetate as a base and methanol as a solvent, under heating reflux conditions, to obtain compounds I-25 and I-26.

The selection of each substituent is as described above, and the present invention will not be repeated here.

The present invention provides the application of the above-mentioned indoloazepinone derivatives in terms of anti-plant virus activity.

The indoloazepinone derivatives provided by the invention have excellent anti-plant virus activity, and the indoloazepinone derivatives shown in the general formula show good anti-pepper mild mottle virus activity.

The indoloazepinone derivative provided by the invention has high killing activity against diamondback moth and mosquito larvae.

The present invention provides the application of the above-mentioned Indoloazepinone derivatives in sterilization.

The indoloazepinone derivatives provided by the present invention have high fungicidal activity, especially against one or more pathogens causing cucumber wilt, peanut brown spot, apple ring spot, wheat leaf blight, tomato early blight, rice blast, pepper phytophthora and rape sclerotia.

The invention also provides a method for killing insects by using the indoloazepinone derivatives as anti-plant virus agents.

The invention also provides a method for killing insects by using the indoloazepinone derivatives as insecticides.

The invention also provides a method for sterilizing by using the indoloazepinone derivative as a bactericide.

The following examples and biological test results can be used to further illustrate the present invention, but are not intended to limit the present invention.

Example 1: Synthesis of Indoloazepinone Derivatives I-1 to I-5

Synthesis of I-1: A mixture of compound Indoloazepinone (0.29 mmol), NH ₂ OC ₄ H ₉ (0.59 mmol), AcONa (48 mg, 0.59 mmol) in 10 ml CH ₃ OH was heated to reflux for 5 hours. The reaction mixture was cooled to room temperature and the solvent was evaporated. The residue was dissolved in EtOAc and water, and the aqueous layer was extracted 3 times with EtOAc. The combined organic phases were washed with brine, dried over anhydrous Na ₂ SO ₄ and filtered. The filtrate was concentrated and the residue was purified by silica gel column chromatography (PE: EA 1: 1 elution) to obtain a light yellow solid. Yield 66%, melting point 188-190°C. ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 11.93 (s, 1H), 8.40 (t, J=5.2 Hz, 1H), 8.24 (d, J=8.0 Hz, 1H), 7.48 (d, J=8.0 Hz, 1H), 7.31-7.24 (m, 1H), 7.19-7.12 (m, 1H), 4.19 (t, J=6.4 Hz, 2H), 3.37-3.28 (m, 2H), 3.05-2.93 (m, 2H), 1.75-1.65 (m, 2H), 1.47-1.36 (m, 2H), 0.94 (t, J=7.2 Hz, 3H). ¹³ C NMR (100 MHz, DMSO-d ₆ )δ164.0, 1534.0, 136.2, 130.3, 124.6, 124.4, 124.1, 120.9, 112.2, 111.4, 73.2, 37.3, 31.0, 30.6, 18.7, 13.8. HRMS (ESI), calculated for C ₁₆ H ₂₀ N ₃ O ₂ ⁺ [M+H] ⁺ 286.1556, found 286.1553.

Synthesis of I-2: The synthesis method is the same as that of I-1. Pale yellow solid, yield 66%, melting point 189-191°C. ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 11.92 (s, 1H), 8.41 (s, 1H), 8.26 (d, J=8.0 Hz, 1H), 7.49 (d, J=8.4 Hz, 1H), 7.28 (t, J=7.6 Hz, 1H), 7.17 (d, J=8.0 Hz, 1H), 4.52-4.38 (m, 1H), 3.33 (d, J=4.8 Hz, 2H), 3.02-2.92 (m, 2H), 1.32 (d, J=6.4 Hz, 6H). ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 164.0, 153.5, 136.2, 130.2, 124.6, 124.4, 124.0, 120.9, 112.2, 111.7, 74.9, 37.3, 30.5, 21.7. HRMS (ESI), calculated for C ₁₅ H ₁₈ N ₃ O ₂ ⁺ [M+H] ⁺ 272.1399, found 272.1392.

Synthesis of I-3: The synthesis method is the same as that of I-1. White solid, yield 66%, melting point 193-195°C. ¹ H NMR (400 MHz, CDCl ₃ ) δ10.47 (s, 1H), 8.44 (d, J=8.0 Hz, 1H), 7.56-7.50 (m, 2H), 7.39-7.33 (m, 1H), 7.30-7.22 (m, 2H), 3.50 (dd, J=10.8, 5.2 Hz, 2H), 3.18-3.11 (m, 2H), 1.46 (s, 9H). ¹³ C NMR (100 MHz, CDCl 3 ) δ166.3, 152.2, 136.6, 128.2, 125.6, 125.5, 125.1, 121.6, 115.2, 112.0, 79.0, 38.9, 30.0, 28.0. HRMS (ESI), calculated for C ₁₆ H ₂₀ N ₃ O ₂ ⁺ [M+H] ⁺ 286.1556, found 286.1549.

Synthesis of I-4: The synthesis method is the same as that of I-1. Pale yellow solid, yield 97%, melting point 155-156°C. ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 11.94 (s, 1H), 8.41 (t, J = 5.2 Hz, 1H), 8.22 (d, J = 8.0 Hz, 1H), 7.46 (d, J = 8.4 Hz, 1H), 7.27 (t, J = 7.6 Hz, 1H), 7.13 (t, J = 7.6 Hz, 1H), 6.17-6.03 (m, 1H), 5.37 (dd, 1H), 5.26 (d, J = 10.4 Hz, 1H), 4.71 (d, J = 5.6 Hz, 2H), 3.35-3.28 (m, 2H), 3.05-2.95 (m, 2H). ¹³ C NMR (100 MHz, DMSO-d ₆ )δ164.4, 155.0, 136.7, 135.5, 130.9, 125.0, 124.9, 124.6, 121.4, 117.8, 112.7, 111.6, 74.9, 37.7, 31.1. HRMS (ESI), calculated for C ₁₅ H ₁₆ N ₃ O ₂ ⁺ [M+H] ⁺ 270.1243, found 270.1240.

Synthesis of I-5: The synthesis method is the same as that of I-1. Light brown solid, yield 83%, melting point 190-192°C. ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 12.17 (s, 1H), 8.54 (d, J = 3.2 Hz, 1H), 8.31 (d, J = 8.0 Hz, 1H), 7.52 (d, J = 8.0 Hz, 1H), 7.42 (t, J = 6.8 Hz, 2H), 7.36-7.28 (m, 3H), 7.27-7.22 (m, 1H), 7.07 (t, J = 6.6 Hz, 1H), 3.41 (s, 2H), 3.27 (s, 2H). ¹³ C NMR (101 MHz, DMSO-d ₆ ) δ 164.1, 159.5, 158.9, 136.7, 132.3, 130.1, 125.2, 124.9, 124.1, 122.6, 122.1, 114.9, 113.0, 37.6, 31.5. HRMS (ESI), calculated for C ₁₈ H ₁₆ N ₃ O ₂ ⁺ [M+H] ⁺ 306.1243, found 306.1239.

Example 2: Synthesis of Indoloazepinone Derivatives I-6 to I-17

Synthesis of A: A mixture of compound Indoloazepinone (0.29 mmol), NH ₂ OH (0.59 mmol), AcONa (48 mg, 0.59 mmol) in 10 ml CH ₃ OH was heated to reflux for 5 hours. The reaction mixture was cooled to room temperature and the solvent was evaporated. The residue was dissolved in EtOAc and water, and the aqueous layer was extracted 3 times with EtOAc. The organic phases were combined and washed with brine, dried over anhydrous Na ₂ SO ₄ and filtered. The solution was concentrated and the residue was purified by silica gel column chromatography (PE: EA 1: 1 elution) to obtain a light brown solid with a yield of 91% and a melting point of 165-167°C. ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 11.81 (s, 1H), 11.13 (s, 1H), 8.36 (s, 1H), 8.22 (d, J=8.0 Hz, 1H), 7.46 (d, J=8.0 Hz, 1H), 7.26 (t, J=7.6 Hz, 1H), 7.12 (t, J=7.6 Hz, 1H), 3.33 (s, 2H), 2.98 (s, 2H). ¹³ C NMR (100 MHz, DMSO-d ₆ )δ164.7, 154.1, 149.7, 136.7, 130.1, 125.2, 124.9, 124.6, 124.6, 121.1, 112.9, 112.7, 37.9, 30.6. HRMS (ESI), calculated for C ₁₂ H ₁₂ N ₃ O ₂ ⁺ [M+H] ⁺ 230.0930, found 230.0928.

Synthesis of I-6: Triethylamine (16.5 mmol) and acyl chloride (15 mmol) were added dropwise to a solution of compound B (16.5 mmol) in CH ₂ Cl ₂ (75 mL) at 0°C under nitrogen protection. After stirring at room temperature for 2 hours, the solvent in the reaction mixture was evaporated and then diluted with EtOAc. The solution was washed with 1M KHSO ₄ aqueous solution, H ₂ O and brine in sequence. The organic phase was dried over Na ₂ SO ₄ and evaporated to obtain a crude product, which was then purified by silica gel chromatography (PE: EA 1: 1 elution) to obtain a yellow solid with a yield of 24% and a melting point of 228-230°C. ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 12.25 (s, 1H), 8.63-8.49 (m, 1H), 8.45-8.27 (m, 1H), 7.58-7.46 (m, 1H), 7.40-7.14 (m, 2H), 3.42 (s, 2H), 3.16 (s, 2H), 2.90-2.68 (m, 1H), 1.31-1.15 (m, 6H). ¹³ C NMR (100 MHz, DMSO-d ₆ )δ173.6, 163.9, 162.6, 136.5, 133.0, 125.3, 125.1, 124.8, 122.0, 112.9, 110.0, 37.5, 32.9, 31.8, 19.3. HRMS (ESI), calculated for C ₁₆ H ₁₈ N ₃ O ₃ ⁺ [M+H] ⁺ 300.1348. found 300.1345.

Synthesis of I-7: The synthesis method is the same as that of I-6. Yellow solid, yield 53%, melting point 202-203°C. ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 12.25 (s, 1H), 8.54 (t, J=4.8 Hz, 1H), 8.37 (d, J=8.0 Hz, 1H), 7.51 (d, J=8.4 Hz, 1H), 7.32 (t, J=7.6 Hz, 1H), 7.22 (t, J=7.6 Hz, 1H), 6.60-6.48 (m, 1H), 6.45-6.31 (m, 1H), 6.15-6.02 (m, 1H), 3.37 (s, 2H), 3.25-3.13 (m, 2H). ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 163.3, HRMS( _ESI ), calculated for _{C15H14N3O3 +} ^[ M+H] ⁺ 284.1035, found _284.1031 .

Synthesis of I-8: The synthesis method is the same as that of I-6. Light yellow solid, yield 76%, melting point 253-254°C. ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 12.30 (s, 1H), 8.60 (t, J = 4.8 Hz, 1H), 8.47 (d, J = 8.0 Hz, 1H), 8.13 (d, J = 7.2 Hz, 2H), 7.74 (t, J = 7.6 Hz, 1H), 7.62 (t, J = 7.6 Hz, 2H), 7.54 (d, J = 8.4 Hz, 1H), 7.35 (t, J = 7.2 Hz, 1H), 7.25 (t, J = 7.6 Hz, 1H), 3.44-3.35 (m, 4H). ¹³ C NMR (100 MHz, DMSO-d ₆ )δ163.9, 163.5, 163.4, 136.6, 134.2, 133.3, 129.8, 129.5, 129.2, 125.3, 125.1, 124.9, 122.2, 113.0, 109.9, 37.5, 32.0. HRMS (ESI), calculated for C ₁₉ H ₁₆ N ₃ O ₃ ⁺ [M+H] ⁺ 334.1192, found 334.1188.

Synthesis of I-9: The synthesis method is the same as that of I-6. White solid, yield 67%, melting point 255-257°C. ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 12.26 (s, 1H), 8.57 (t, J = 5.2 Hz, 1H), 8.45 (d, J = 8.0 Hz, 1H), 8.01 (d, J = 8.0 Hz, 2H), 7.53 (d, J = 8.4 Hz, 1H), 7.41 (d, J = 8.0 Hz, 2H), 7.34 (t, J = 7.2 Hz, 1H), 7.24 (t, J = 7.6 Hz, 1H), 3.45-3.39 (m, 2H), 3.33 (s, 2H), 2.43 (s, 3H). ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 163.9, 163.4163.3, _144.6 , 136.6, 133.2, 130.0, 129.8, 126.4, 125.3 _, 125.1, 124.9, 122.1, 113.0, 110.0, 37.5 _, 32.0, 21.7. HRMS (ESI), calculated for _C20H18N3O3 ⁺ [M+H] ⁺ 348.1348, found 348.1344.

Synthesis of I-10: The synthesis method is the same as that of I-6. Yellow solid, yield 56%, melting point 218-220°C. ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 12.28 (s, 1H), 8.58 (t, J = 4.8 Hz, 1H), 8.39 (d, J = 8.0 Hz, 1H), 7.81 (d, J = 7.2 Hz, 1H), 7.61 (t, J = 7.2 Hz, 1H), 7.53 (d, J = 8.0 Hz, 1H), 7.34 (t, J = 7.6 Hz, 1H), 7.22 (dd, J = 7.6, 4.8 Hz, 2H), 7.10 (t, J = 7.6 Hz, 1H), 3.90 (s, 3H), 3.41 (s, 2H), 3.25 (d, J = 4.0 Hz, 2H). ¹³ C NMR (100 MHz, DMSO-d ₆ )δ163.3, 162.5, 158.2, 136.1, 133.8, 132.7, 130.8, 124.8, 124.6, 124.4, 121.6, 120.3, 119.0, 112.6, 112.4, 109.2, 55.9, 37.0, 31.6. HRMS (ESI), calculated for C ₂₀ H ₁₈ N ₃ O ₄ ⁺ [M+H] ⁺ 364.1297, found 364.1288.

Synthesis of I-11: The synthesis method is the same as that of I-6. Pale yellow solid, yield 51%, melting point 212-213°C. ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 12.29 (s, 1H), 8.59 (s, 1H), 8.45 (d, J = 8.0 Hz, 1H), 7.71 (d, J = 7.6 Hz, 1H), 7.59 (s, 1H), 7.53 (t, J = 7.6 Hz, 2H), 7.37-7.28 (m, 2H), 7.25 (d, J = 7.2 Hz, 1H), 3.87 (s, 3H), 3.46-3.35 (m, 4H). ¹³ C NMR (100 MHz, DMSO-d ₆ )δ163.4, 163.1, 162.7, 159.4, 136.1, 132.8, 130.2, 130.1, 124.8, 124.6, 124.4, 121.7, 121.5, 119.4, 114.2, 112.5, 109.4, 55.4, 37.0, 31.5. HRMS (ESI), calculated for C ₂₀ H ₁₈ N ₃ O ₄ ⁺ [M+H] ⁺ 364.1297, found 364.1292.

Synthesis of I-12: The synthesis method is the same as that of I-6. Light yellow solid, yield 62%, melting point 231-233°C. ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 12.29 (s, 1H), 8.59 (d, J = 5.2 Hz, 1H), 8.48 (d, J = 8.0 Hz, 1H), 8.08 (d, J = 8.8 Hz, 2H), 7.55 (d, J = 8.4 Hz, 1H), 7.35 (t, J = 7.2 Hz, 1H), 7.25 (t, J = 7.6 Hz, 1H), 7.12 (d, J = 8.8 Hz, 2H), 3.87 (s, 3H), 3.45-3.39 (m, 4H). ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 163.4, 162.6, 162.5, 136.1, 132.6, 131.4, 124.8, 124.6, 124.4, 121.6, 120.7, 114.2, 112.4, 109.6, 55.5, 37.1, 31.5. HRMS (ESI), calculated for C ₂₀ H ₁₈ N ₃ O ₄ ⁺ [M+H] ⁺ 364.1297 found 364.1292.

Synthesis of I-13: The synthesis method is the same as that of I-6. Light yellow solid, yield 73%, melting point 232-234°C. ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 12.31 (s, 1H), 8.60 (t, J = 5.2 Hz, 1H), 8.44 (d, J = 8.0 Hz, 1H), 8.15-8.01 (m, 2H), 7.85-7.77 (m, 1H), 7.65 (t, J = 8.4 Hz, 1H), 7.54 (d, J = 8.0 Hz, 1H), 7.35 (t, J = 7.2 Hz, 1H), 7.25 (t, J = 7.6 Hz, 1H), 3.41 (d, J = 4.8 Hz, 4H). ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 163.5, ^{HRMS (ESI), calculated for C19H15ClN3O3+} _{[ M +} H] ⁺ 368.0802, _found 368.0800.

Synthesis of I-14: The synthesis method is the same as that of I-6. Light yellow solid, yield 62%, melting point 258-260°C. ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 12.31 (s, 1H), 8.60 (t, J=5.2 Hz, 1H), 8.44 (d, J=8.0 Hz, 1H), 8.14-8.11 (m, 2H), 7.70-7.66 (m, 2H), 7.54 (d, J=8.4 Hz, 1H), 7.36-7.32 (m, 1H), 7.27-7.22 (m, 1H), 3.40 (s, 4H). ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 163.3, 163.2, 162.1, 138.6, 136.1, 132.8, 131.2, 129.1, 127.5, 124.8, 124.6, 124.3, 121.7, 112.5, 109.3, 37.0, 31.5. HRMS (ESI), calculated for C ₁₉ H ₁₅ ClN ₃ O ₃ ⁺ [M+H] ⁺ 368.0802, found 368.0800.

Synthesis of I-15: The synthesis method is the same as that of I-6. White solid, yield 76%, melting point 257-259°C. ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 12.33 (s, 1H), 8.61 (t, J = 4.8 Hz, 1H), 8.45 (d, J = 8.0 Hz, 1H), 8.32 (d, J = 7.2 Hz, 2H), 7.98 (d, J = 8.4 Hz, 2H), 7.54 (d, J = 8.0 Hz, 1H), 7.35 (t, J = 7.6 Hz, 1H), 7.26 (t, J = 7.6 Hz, 1H), 3.47-3.37 (m, 4H). ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 163.6, 163.3, 161.9, 136.1, 133.0, 132.6, 130.2, 125.9, 124.9, 124.6, 124.3, 121.7, 112.5, 109.2, 37.0, 31.6. ¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ -61.63 (s). HRMS (ESI), calculated for C ₂₀ H ₁₅ F ₃ N ₃ O ₃ ⁺ [M+H] ⁺ 402.1066, found 402.1064.

Synthesis of I-16: The synthesis method is the same as that of I-6. Yellow solid, yield 66%, melting point 252-254°C. ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 12.30 (s, 1H), 8.81 (s, 1H), 8.61 (s, 1H), 8.49 (d, J = 8.0 Hz, 1H), 8.22 (d, J = 8.0 Hz, 1H), 8.13 (s, 2H), 8.08 (d, J = 8.0 Hz, 1H), 7.75-7.66 (m, 2H), 7.54 (d, J = 8.4 Hz, 1H), 7.35 (t, J = 7.2 Hz, 1H), 7.27 (d, J = 8.0 Hz, 1H), 3.45 (s, 4H). ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ _HRMS (ESI) _, calculated for _C23H18N3O3 ⁺ [M ₊ H] ⁺ 384.1348, found 384.1247.

Synthesis of I-17: The synthesis method is the same as that of I-6. Light yellow solid, yield 46%, melting point 252-254°C. ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 12.27 (s, 1H), 8.56 (s, 1H), 8.40 (d, J=8.0 Hz, 1H), 8.05 (s, 1H), 7.58-7.47 (m, 2H), 7.32 (t, J=7.6 Hz, 1H), 7.23 (t, J=7.6 Hz, 1H), 6.76 (s, 1H), 3.41 (s, 2H), 3.30 (s, 2H). ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ 163.3, 163.1, 155.3, 148.3, 142.4, 136.1, 132.8, 124.9, 124.6, 124.3, 121.7, 119.2, 112.5, 109.2, 37.0, 31.4. HRMS (ESI), calculated for C ₁₇ H ₁₄ N ₃ O ₄ ⁺ [M+H] ⁺ 324.0984, found 324.0976.

Example 3: Synthesis of Indoloazepinone Derivatives I-18 to I-19

Synthesis of I-18: In a 25 mL two-necked round-bottom flask equipped with Dean-stark and a condenser, a solution of indoloazepinone (1.0 mmol) in EtOH (15 mL) was added, and 4-chlorophenylhydrazine hydrochloride (4.0 mmol) was added to the reaction mixture. Heat and reflux for 8 hours. The solvent was removed by distillation under reduced pressure. The crude product was purified by column chromatography (PE: EA 1: 1 elution) to obtain an orange-yellow solid with a yield of 40% and a melting point of 242-244°C. ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 11.85 (s, 1H), 8.47-8.38 (m, 2H), 8.13 (s, 1H), 7.65-7.60 (m, 1H), 7.49 (d, J=8.0 Hz, 1H), 7.42-7.35 (m, 2H), 7.30 (t, J=7.2 Hz, 1H), 7.22 (t, J=7.6 Hz, 1H), 6.86 (td, J=7.6, 1.2 Hz, 1H), 3.47-3.41 (m, 2H), 3.12-3.04 (m, 2H). ¹³ C NMR (100 MHz, DMSO-d ₆ )δ164.9,147.9,142.2,136.8,130.2,129.8,128.8,125.3, 124.9,124.2,121.4,120.5,117.9,115.1,114.5,112.8,37.8,32.3. HRMS (ESI), calculated for C ₁₈ H ₁₆ ClN ₄ O ⁺ [M+H] ⁺ 339.1013, found 339.1010.

Synthesis of I-19: The synthesis method is the same as that of I-18. Orange-yellow solid, yield 46%, melting point 132-134°C. ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 11.86 (s, 1H), 8.42 (t, J = 7.8 Hz, 2H), 8.01 (s, 1H), 7.62-7.54 (m, 2H), 7.49 (d, J = 8.0 Hz, 1H), 7.41 (t, J = 7.6 Hz, 1H), 7.30 (t, J = 7.6 Hz, 1H), 7.22 (t, J = 7.6 Hz, 1H), 6.81 (t, J = 7.2 Hz, 1H), 3.45 (d, J = 4.4 Hz, 2H), 3.07 (d, J = 4.0 Hz, 2H). ¹³ C NMR (100 MHz, DMSO-d ₆ )δ164.86, 147.5, 143.0, 136.8, 132.9, 130.2, 129.4, 125.2, 124.9, 124.2, 121.4, 121.2, 115.0, 114.7, 112.8, 108.1, 37.8, 32.3. HRMS (ESI), calculated for C ₁₈ H ₁₆ BrN ₄ O ⁺ [M+H] ⁺ 383.0507, found 383.0506.

Example 4: Synthesis of Indoloazepinone Derivative I-20

A solution of indoloazepinone (1.0 mmol), di-tert-butyl dicarbonate (2 mmol) and a catalytic amount of DMAP in acetonitrile (5 mL) was stirred at room temperature for 24 hours. After the solvent was removed under reduced pressure, the residue was purified by column chromatography (PE: EA 1: 1 elution) to obtain a white solid with a yield of 24% and a melting point of 230-231°C. ¹ H NMR (400 MHz, CDCl ₃ ) δ9.94 (s, 1H), 8.46 (d, J=8.0 Hz, 1H), 7.52 (d, J=8.4 Hz, 1H), 7.45-7.39 (m, 1H), 7.38-7.33 (m, 1H), 4.31-4.22 (m, 2H), 3.06-3.00 (m, 2H), 1.60 (s, 9H). ¹³ C NMR (100 MHz, CDCl ₃ )δ195.0,161.8,151.7,135.9,132.3,126.9,126.6,124.3,124.2,115.5,112.0,84.4,43.6,42.1,28.1.HRMS(ESI), calculated for C ₁₇ H ₁₉ N ₂ O ₄ ⁺ [M+H] ⁺ 315.1345, found 315.1342.

Example 5: Synthesis of Indoloazepinone Derivatives I-21 to I-24

Synthesis of B: K ₂ CO ₃ (3 equivalents) was added to a solution of Indoloazepinone 3 (2.33 mmol) in DMF (5 mL) at 0°C and stirred for 15 minutes. Benzyl bromide (1 equivalent) was then added dropwise thereto and the reaction mixture was heated under reflux for 8 hours. After the reaction was completed, the reaction mixture was cooled to room temperature and poured onto crushed ice. The organic layer was further extracted with EtOAc and concentrated to dryness, and then purified by column chromatography (PE: EA 1: 1 elution) to obtain an orange solid with a yield of 72% and a melting point of 170-172°C. ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.54-8.46 (m, 1H), 7.40-7.33 (m, 3H), 7.27-7.23 (m, 3H), 7.09 (d, J=6.8 Hz, 3H), 5.89 (s, 2H), 3.58-3.51 (m, 2H), 2.97-2.91 (m, 2H). ¹³ C NMR (100 MHz, CDCl ₃ ) δ 195.6, 163.7, 138.4, 137.4, 132.6, 128.7, 127.5, 126.5, 126.0, 125.5, 123.9, 117.1, 110.9, 48.7, 45.1, 37.7. HRMS (ESI), calculated for C ₁₉ H ₁₇ N ₂ O ₂ ⁺ [M+H] ⁺ 305.1290, found 305.1287.

Synthesis of I-21: A DMF (5 mL) solution of compound B (1.0 mmol), methyl bromoacetate (1.05 equivalents) and potassium carbonate (1.5 equivalents) was stirred at room temperature overnight. After the reaction was completed, an appropriate amount of water was added and extracted with EtOAc three times. The organic phases were then combined, washed with brine, dried over anhydrous Na ₂ SO ₄ , filtered and concentrated under reduced pressure. Further purification was performed by column chromatography (PE: EA 1: 2 elution) to obtain a yellow solid with a yield of 72% and a melting point of 143-145°C. ¹ H NMR (400 MHz, CDCl ₃ ) δ8.46-8.42 (m, 1H), 7.35-7.31 (m, 3H), 7.26-7.19 (m, 3H), 7.13-7.10 (m, 2H), 5.79 (s, 2H), 4.39 (s, 2H), 3.74 (s, 3H), 3.65 (s, 2H), 3.10-3.04 (m, 2H). ¹³ C NMR (100 MHz, CDCl ₃ ) δ195.6, _HRMS (ESI), calculated for _{C22H21N2O4 +} [M ⁺ H] ₊ 377.1501 ^, found 377.1499.

Synthesis of I-22: The synthesis method is the same as that of I-21. Orange-yellow solid, yield 94%, melting point 52-53°C. ¹ H NMR (400 MHz, CDCl ₃ ) δ8.46-8.41 (m, 1H), 7.34-7.29 (m, 3H), 7.25-7.17 (m, 3H), 7.11 (d, J=6.8 Hz, 2H), 5.79 (s, 2H), 4.37 (s, 2H), 4.20 (q, J=7.2 Hz, 2H), 3.78 (s, 2H), 3.10-3.01 (m, 2H), 1.26 (t, J=7.2 Hz, 3H). ¹³ C NMR (100 MHz, CDCl ₃ ) δ195.6, 168.8, 162.0, 138.3, 137.3, 133.4, 128.7, 127.5, 126.6, 125.9, 125.3, 123.9, 123.7, 116.6, 111.0, 77.5, 77.4, 77.2, 76.8, 61.7, 50.2, 48.9, 46.4, 43.7, 14.2. HRMS (ESI), calculated for C ₂₃ H ₂₃ N ₂ O ₄ ⁺ [M+H] ⁺ 391.1658, found: 391.1658.

Synthesis of I-23: The synthesis method is the same as that of I-21. Light yellow solid, yield 86%, melting point 118-120°C. ¹ H NMR (400 MHz, CDCl ₃ ) δ8.49-8.39 (m, 1H), 7.36-7.30 (m, 3H), 7.23 (m, 3H), 7.11 (d, J=6.8 Hz, 2H), 5.81 (s, 2H), 4.29 (s, 2H), 3.78 (s, 2H), 3.07 (s, 2H), 1.46 (s, 9H). ¹³ C NMR (100 MHz, CDCl ₃ ) δ195.7, 167.9, 161.9, 138.3, 137.3, 133.6, 128.7, 127.5, 126.6, 125.9, 125.3, 123.8, 123.7, 116.5, 111.0, 82.5, 77.4, 77.1, 76.8, 51.0, 48.9, 46.4, 43.7, 28.1. HRMS (ESI), calculated for C _{2 5} H _{2 7} N ₂ O ₄ ⁺ [M+H] ⁺ 419.1971, found 419.1968.

Synthesis of I-24: The synthesis method is the same as that of I-21. Orange-yellow oily liquid, yield 87%. ¹ H NMR (400 MHz, CDCl ₃ ) δ8.47-8.42 (m, 1H), 7.33 (dd, J=6.4, 2.8 Hz, 8H), 7.24 (dd, J=5.8, 1.6 Hz, 3H), 7.13-7.09 (m, 2H), 5.77 (s, 2H), 5.18 (s, 2H), 4.42 (s, 2H), 3.78 (s, 2H), 3.07-3.01 (m, 2H). ¹³ C NMR (100 MHz, CDCl ₃ ) δ195.6, 168.7, 162.1, 138.3, 137.2, 135.1, 133.4, 128.7, 128.6, 128.5, 127.5, 126.6, 126.0, 125.3, 123.9, 123.7, 116.6, 111.0, 67.4, 50.2, 49.0, 46.4, 43.6. HRMS (ESI), calculated for C ₂₈ H ₂₅ N ₂ O ₄ ⁺ [M+H] ⁺ 453.1814, found 453.1813.

Example 6: Synthesis of Indoloazepinone Derivatives I-25 to I-26

Benzyl is added to the indole nitrogen. The synthesis method is the same as in Example 5. Light yellow solid, yield 42%, melting point 135-137°C. ¹ H NMR (400 MHz, CDCl ₃ ) δ8.54-8.47 (m, 1H), 7.36 (dq, J=2.8, 2.0 Hz, 3H), 7.25-7.21 (m, 2H), 7.05 (d, J=8.4 Hz, 2H), 6.90 (t, J=6.0 Hz, 1H), 5.83 (s, 2H), 3.60-3.54 (m, 2H), 2.99-2.93 (m, 2H). ¹³ C NMR (100 MHz, CDCl ₃ ) δ195.5, 163.6, 138.3, 135.9, 133.3, 132.4, 128.9, 128.0, 126.24, 125.5, 124.1, 117.2, 110.7, 48.2, 45.1, 37.7. HRMS (ESI), calculated for C ₁₉ H ₁₆ ClN ₂ O ₂ ⁺ [M+H] ⁺ 339.0900, found: 339.0899.

Synthesis of I-25: A mixture of compound B (0.29 mmol), NH ₂ OH (0.59 mmol), AcONa (0.59 mmol) in 10 ml CH ₃ OH was heated to reflux for 5 hours. The reaction mixture was cooled to room temperature and the solvent was evaporated. The residue was dissolved in EtOAc and water, and the aqueous layer was extracted 3 times with EtOAc. The combined organic phases were washed with brine, dried over anhydrous Na ₂ SO ₄ and filtered. The filtrate was concentrated and the residue was purified by silica gel column chromatography (PE: EA 1: 1 elution) to give a white solid with a yield of 49% and a melting point of 248-250°C. ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 11.31 (s, 1H), 8.48 (d, J = 5.6 Hz, 1H), 8.18-8.04 (m, 1H), 7.54 (d, J = 8.8 Hz, 1H), 7.33-7.15 (m, 5H), 7.09 (d, J = 8.0 Hz, 2H), 5.81 (s, 2H), 3.27 (d, J = 4.0 Hz, 2H), 2.92 (s, 2H). ¹³ C NMR (100 MHz, DMSO-d ₆ )δ164.0, 152.8, 138.4, 137.8, 129.6, 128.4, 127.0, 126.5, 124.7, 124.0, 123.3, 121.1, 114.0, 110.9, 46.9, 37.2, 32.6. HRMS (ESI), calculated for C ₁₉ H ₁₈ N ₃ O ₂ ⁺ [M+H] ⁺ 320.1399, found 320.1397.

Synthesis of I-26: The synthesis method is the same as that of I-25. Light yellow solid, yield 67%, melting point 129-132°C. ¹ H NMR (400 MHz, CDCl3) δ8.53-8.47 (m, 1H), 7.38-7.31 (m, 4H), 7.26-7.20 (m, 3H), 7.05 (d, J=8.4 Hz, 2H), 5.82 (s, 2H), 3.56-3.48 (m, 2H), 2.98-2.92 (m, 2H). ¹³ C NMR (100 MHz, DMSO- _d6 ) δ196.0, 162.4, 137.4, 136.9, 134.1, 131.8, 128.5, 128.4, 125.4, 124.8, 123.4, 122.9, 115.6, 111.4, 47.2, 45.0, 36.6. HRMS (ESI), calculated for C ₁₉ H ₁₇ ClN ₃ O ₂ ⁺ [M+H] ⁺ 354.1009, found 354.1007.

Example 7: Determination of activity against pepper mild mottle virus, the determination procedure is as follows:

1. In vivo protection:

(1) Weigh 2 mg of each of the experimental drugs I-1 to I-26, and 2 mg of each of the control drugs Ningnanmycin and Ribavirin.

(2) The sample to be tested was fully dissolved in 40uL of dimethyl sulfoxide (DMSO), and 30uL of the drug solution was taken out and added with 3mL of 1% Tween 80 to dilute to the required concentration.

(3) Select healthy heart-leaf tobacco leaves at the 4-8 leaf stage, evenly sprinkle 320-mesh quartz sand on the leaves to be inoculated, and inoculate the drug solution on the right half of the heart-leaf tobacco leaves by friction inoculation. After 12 to 18 hours, evenly apply the virus solution on the heart-leaf tobacco leaves. Inoculate 3 to 4 leaves for each treatment, and repeat three times.

(4) After inoculation, the leaves were placed in an artificial climate chamber at 28°C for 3 days, and then the number of necrotic spots on the leaves was counted and the inhibition rate was calculated according to the following formula: Inhibition rate (%) = [(number of necrotic spots in control - number of necrotic spots in treatment) / number of necrotic spots in control] × 100%.

2. In vivo therapeutic effect:

(1) Weigh 2 mg of each of the experimental drugs I-1 to I-26, and 2 mg of each of the control drugs Ningnanmycin and Ribavirin.

(2) Select healthy heart-leaf tobacco plants at the 4-8 leaf stage, evenly sprinkle 320-mesh quartz sand on the leaves to be inoculated, and use the friction inoculation method to inoculate the entire leaf with a 100% diluted virus solution. After 0.5 h, rinse the quartz sand, use paper to absorb the water droplets on the leaves, and inoculate the right half of the leaf with 500 ppm solution as a control. Inoculate 3-4 leaves for each treatment, and repeat three times.

(4) After inoculation, the leaves were placed in an artificial climate chamber at 25-28°C for 3 days, and then the number of necrotic spots on the leaves was counted and the inhibition rate was calculated according to the following formula: Inhibition rate (%) = [(number of necrotic spots in control - number of necrotic spots in treatment) / number of necrotic spots in control] × 100%.

3. In vivo passivation effect:

(1) Weigh 2 mg of each of the experimental drugs I-1 to I-26, and 2 mg of each of the control drugs Ningnanmycin and Ribavirin.

(2) Dissolve the sample in 40uL dimethyl sulfoxide (DMSO), take 20uL of the solution and add 1mL of 1% Tween 80 to dilute to the required concentration.

(3) Add the 50-fold diluted virus solution, mix the virus solution and the drug solution at a ratio of 1:1 to obtain a 100-fold diluted mixed solution, and react at room temperature for 30 minutes.

(4) Select healthy heartleaf tobacco leaves at the 4-8 leaf stage, sprinkle 320-mesh quartz sand evenly on the leaves to be inoculated, and use the friction inoculation method to inoculate the right half of the leaf with the drug mixture solution and the left half of the leaf with the 100-fold diluted virus solution as a control. Inoculate 3-4 leaves for each treatment and repeat 2 times.

(5) After inoculation, the leaves were placed in an artificial climate chamber at 25-28°C for 3 days, and then the number of necrotic spots on the leaves was counted and the inhibition rate was calculated according to the following formula: Inhibition rate (%) = [(number of necrotic spots in control - number of necrotic spots in treatment) / number of necrotic spots in control] × 100%.

Table 1 Test results of the activity of indoloazepinone derivatives against pepper mild mottle virus (PMMoV)

As can be seen from the data in Table 1, at 500 μg/mL, most of the indoloazepinone derivatives showed good anti-PMMoV activity, among which compounds I-2, I-7, I-12, I-13, I-15, I-18, I-19, I-24 and I-26 had active protection and therapeutic effects on PMMoV comparable to those of commercial ribavirin, while I-9, I-11, I-14, I-17 and I-18 had passivation activity comparable to that of ribavirin on PMMoV.

Example 8: Insecticidal activity test, the determination procedure is as follows:

Diamondback moth: The test method is leaf dipping. Dip corn leaves in the acetone solution for 5-6 seconds, take them out, and after the solution dries, add 10 3rd-instar diamondback moth larvae. The main effects are stomach poison and contact killing. At the same time, observe the feeding phenomenon of the larvae. Check the mortality rate after 72 hours.

Each compound was tested three times and the average value was calculated.

Mosquito larvae: Culex pipiens subspecies pallens, normal population raised indoors. Select 10 3rd instar Culex pipiens larvae and place them in a 100mL beaker containing the test solution of the required concentration. Place them in a standard treatment room and check the mortality rate after 72 hours. Test each compound twice and calculate the average. Use an aqueous solution containing 1mL of the test solvent as a blank control.

Mortality rate (%) = [(number of control insects - number of surviving insects) / number of control insects] × 100%

Table 2 Insecticidal activity test results of indoloazepinone derivatives against diamondback moth and mosquito larvae

As can be seen from the data in Table 2, most of the indoloazepinone derivatives showed activity against diamondback moth and mosquito larvae, among which compounds I-3, I-4 and I-19 had excellent insecticidal activity against diamondback moth; in addition, compounds I-8, I-12, I-13, I-14, I-15 and I-16 also had good insecticidal activity against mosquito larvae.

Example 9: Antibacterial activity test, the determination procedure is as follows:

Bacterial growth rate determination method (plate method): dissolve the test compound in acetone, and then add 200μg/mL emulsifier aqueous solution to prepare the test solution of the required concentration. Pipette 1mL of the test solution into the culture dish, add 9mL of culture medium, stir evenly to make a 50μg/mL drug-containing plate, and prepare a plate with only 1mL of sterilized water as a blank control. Use a 4mm diameter puncher to cut the bacterial disk along the outer edge of the hyphae and move it to the drug-containing plate and the control plate. Repeat the same operation 3 times. Finally, place the culture dish in a constant temperature incubator. After 48 hours, measure the colony diameter, and compare the average of the 3 measurements with the blank control to calculate the relative inhibition rate.

Relative inhibition rate (%) = [(control colony diameter - test colony diameter) / control colony diameter] × 100%

Table 3 In vitro bactericidal activity test results of indoloazepinone derivatives

From the data in Table 3, it can be seen that under the condition of 50 μg/mL, indoloazepinone derivatives I-1 to I-26 showed broad-spectrum inhibitory activity against 8 tested bacteria, among which compound I-4 had an inhibitory activity against apple ring rot pathogen of 98±2.8, compound I-14 had an inhibitory activity against rice blast of 91±2.3, and compound I-6 had an inhibitory rate against pepper phytophthora of 97±1.1.

Claims (10)

1. A Indoloazepinone derivative, which Indoloazepinone derivative is a compound represented by the general formula:

R ¹ represents H, benzyl, t-butoxycarbonyl, benzyloxycarbonyl; r ² represents H, X represents O, N-O-R ⁴、N-NH-R⁵; and is not a compound/>

R ³ represents alkyl of 1 to 4 carbons, benzyl;

r ⁴ represents an alkyl group having 3 to 4 carbon atoms, an allyl group, a phenyl group,

R ⁵ represents a substituted or unsubstituted phenyl group; the substituent groups of the substituted phenyl groups are respectively and independently selected from one or more of methyl, methoxy, chlorine, bromine and trifluoromethyl;

r ⁶ represents isobutyl, allyl, substituted or unsubstituted phenyl, 1-naphthyl, furan-2-yl; the substituent groups of the substituted phenyl groups are each independently selected from one or more of methyl, methoxy, chlorine and trifluoromethyl.

2. The Indoloazepinone derivative according to claim 1, which is one of the compounds of the following formula:

3. A process for preparing a Indoloazepinone derivative according to claim 2, which comprises: indoloazepinone and NH ₂OR⁴ are used as reactants, sodium acetate is used as alkali, methanol is used as solvent, and oxime ether compound is obtained under the condition of heating reflux

R ⁴ is substituent groups at corresponding positions of I-1 to I-5.

4. A process for preparing a Indoloazepinone derivative according to claim 2, which comprises: firstly, indoloazepinone and NH ₂ OH are taken as reactants, sodium acetate is taken as alkali, methanol is taken as solvent, a compound A is obtained under the condition of heating and refluxing, then, the compound A is taken as raw material, dichloromethane is taken as solvent, triethylamine is taken as alkali, acyl chloride is dropwise added into the compound A under the ice bath condition, and then, the temperature is restored to the room temperature, thus obtaining oxime ester compound

R ⁶ is substituent groups at corresponding positions of I-6 to I-17.

5. A process for preparing a Indoloazepinone derivative according to claim 2, which comprises: indoloazepinone and NH ₂NHR⁵ are used as reactants, ethanol is used as solvent, and hydrazone compound is obtained under the condition of heating refluxR ⁵ is substituent groups at corresponding positions of I-18 to I-19.

6. A process for preparing a Indoloazepinone derivative according to claim 2, which comprises: by using Indoloazepinone and (Boc) ₂ O as reactants, 4-dimethylaminopyridine as a catalyst and acetonitrile as a solvent, the compound with R ¹ as tert-butoxycarbonyl is obtained under the room temperature condition

7. A process for preparing a Indoloazepinone derivative according to claim 2, which comprises: firstly, indoloazepinone and benzyl bromide are used as reactants, potassium carbonate is used as alkali, N-dimethylformamide is used as solvent, under the condition of room temperature, a compound B is obtained, then, the compound B and BrCH ₂CO₂R³ are used as raw materials, potassium carbonate is used as alkali, N-dimethylformamide is used as solvent, under the condition of room temperature, R ¹ is benzyl, R ² isIs a compound of formula (I)

R ³ is a substituent group at the corresponding position of I-21 to I-24.

8. A process for preparing a Indoloazepinone derivative according to claim 2, which comprises: firstly, indoloazepinone and benzyl bromide are used as reactants, potassium carbonate is used as alkali, N-dimethylformamide is used as solvent, under the condition of room temperature, a compound of benzyl on indole nitrogen is obtained, then sodium acetate is used as alkali, methanol is used as solvent, and under the condition of heating reflux, an oxime compound is obtained

9. Use of Indoloazepinone derivatives according to any one of claims 1 to 2 for the treatment of plant viral diseases, characterized in that the series of derivatives has activity in inhibiting pepper's light mottle virus.

10. Use of Indoloazepinone derivatives according to any one of claims 1 to 2 for the sterilization, characterized in that the series of derivatives has inhibitory activity against one or more of cucumber wilt, peanut brown spot, apple ring, wheat sharp eyespot, tomato early blight, rice blast, phytophthora capsici and sclerotium bacteria.