Polybromo-N-phenyl-5-o-hydroxyphenylpyrazole-3-carboxamides and their preparation methods and applications

Abstract

The present invention relates to the field of microbial control, and discloses polybrominated N-phenyl-5-o-hydroxyphenylpyrazole-3-carboxamides, a preparation method thereof, and an application thereof. The compound has a chemical structure shown in formula (I), wherein R 1 and R 2 each independently selected from hydrogen, halogen or methyl, R 3 , R 4 , R 5 each independently selected from hydrogen, halogen, methyl, methoxy, trifluoromethyl or trifluoromethoxy. The polybrominated N-phenyl-5-o-hydroxyphenylpyrazole-3-carboxamides of the present invention have high cyanobacteria inhibitory activity and are suitable for use as algicides.

Description

Technical Field

[0001] The present invention relates to the field of microbial control, and particularly relates to polybrominated N-phenyl-5-o-hydroxyphenylpyrazole-3-carboxamides, a preparation method thereof, and an application thereof. Background Art

[0002] Lake cyanobacterial blooms caused by eutrophication of water bodies are major water environment problems globally, which have brought serious impacts on human production and life. On the one hand, it destroys the water area landscape and affects the normal operation of the tourism industry; on the other hand, cyanobacteria cover the water surface and isolate the air, resulting in a decrease in the oxygen content in the water body and endangering the survival of other aquatic animals and plants in the water body. However, global warming and the increasing frequency of extreme weather have further increased the probability of cyanobacterial blooms, making cyanobacterial blooms exist for a long time in the future. Therefore, the prevention and control of cyanobacterial blooms is the key to solving the current water environment problem. At present, the treatment of cyanobacterial blooms mainly starts from three aspects: physical, biological, and chemical. The physical method has the advantage of being environmentally friendly but is not easy to operate; the biological method is environmentally friendly and convenient, but has too long a cycle and there is also a risk of disrupting the ecological balance; the chemical method is convenient, fast, and effective. Therefore, in the hot summer when cyanobacteria break out in large numbers, using chemical algicides to inhibit the growth of cyanobacteria or kill cyanobacteria is an important prevention and control means to quickly and effectively solve the problem of cyanobacterial blooms. The commonly used chemical algicides are not many, such as hydrogen peroxide, diuron, p-hydroxybenzoic acid, amine and bromine algicides, etc., all of which have the advantage of high efficiency, but none of them are specific algicides designed for cyanobacteria and have the disadvantage of poor selectivity when used. Therefore, obtaining an algicide with high selectivity is an important practical problem that needs to be solved urgently in the research and development of modern chemical algicides.

[0003] The marine natural product pseudilin and its analogues have significant inhibitory activity against the IspD enzyme, and there are many reports as new herbicides and antibacterial and antimalarial drugs (ACS Chem. Biol. 2017, 12, 2132.), but there is still no report on the lead structure optimization and algicidal activity research targeting the cyanobacterial IspD enzyme. In past research, there have been a large number of reports on the application of commercial herbicides as algicides, and there is great development space for the research of new algicides based on the natural product pseudilin. Research shows that there have been reports on the co-crystal structures of the IspD enzymes of Arabidopsis thaliana and multiple genera of bacteria and their inhibitors, laying a foundation for the research on inhibitors targeting the cyanobacterial IspD enzyme. Based on the core skeleton structure of active natural products, carrying out the research and development of new algicides may obtain new, highly efficient and highly selective chemical algicides. Summary of the Invention

[0004] The purpose of the present invention is to provide polybrominated N-phenyl-5-o-hydroxyphenylpyrazole-3-carboxamides, a preparation method thereof, and an application thereof.

[0005] To achieve the above object, on the one hand, the present invention provides polybrominated N-phenyl-5-o-hydroxyphenylpyrazole-3-carboxamides, wherein the compound has a chemical structure shown in formula (I).

[0006]

[0007] Wherein, R 1 and R 2 each independently selected from hydrogen, halogen or methyl, and R 3 , R 4 , R 5 each independently selected from hydrogen, halogen, methyl, methoxy, trifluoromethyl or trifluoromethoxy.

[0008] On the second aspect, the present invention provides a preparation method of polybrominated N-phenyl-5-o-hydroxyphenylpyrazole-3-carboxamides shown in formula (I), wherein the method comprises the following steps:

[0009] (1) The o-hydroxyacetophenone-based compound shown in formula (1) and dimethyl oxalate shown in formula (2) are successively subjected to a cyclization reaction and a hydrolysis reaction to obtain a compound shown in formula (3);

[0010] (2) The compound shown in formula (3) is subjected to an amidation reaction with a substituted aniline to obtain a compound shown in formula (4);

[0011] (3) The compound shown in formula (4) is subjected to a ring transformation reaction with hydrazine hydrate to obtain a compound shown in formula (5);

[0012] (4) The compound shown in formula (5) is subjected to a bromination reaction with a brominating agent,

[0013]

[0014] Wherein, the definitions of R 1 , R 2 , R 3 , R 4 and R 5 are the same as those described above.

[0015] On the third aspect, the present invention provides the application of the above polybrominated N-phenyl-5-o-hydroxyphenylpyrazole-3-carboxamides as algicides.

[0016] The polybrominated N-phenyl-5-o-hydroxyphenylpyrazole-3-carboxamides according to the present invention have high cyanobacteria inhibitory activity. Specifically, most of the polybrominated N-phenyl-5-o-hydroxyphenylpyrazole-3-carboxamides provided by the present invention have excellent cyanobacteria inhibitory activity against FACHB905 (at a test concentration of 10 μM), and the inhibitory activity exceeds 95%. Most of the compounds have a cyanobacteria inhibitory activity of more than 90% against PCC6803, and some compounds have high cyanobacteria inhibitory activity against both FACHB905 and PCC6803.

[0017] Other advantages and features of the present invention will be described in detail in the following specific embodiments section. Specific Embodiments

[0018] The following provides a detailed description of the specific embodiments of the present invention. It should be understood that the specific embodiments described herein are only for the purpose of illustrating and explaining the present invention, and are not intended to limit the present invention.

[0019] In the ranges disclosed herein, the endpoints and any values are not limited to the exact ranges or values, and these ranges or values should be understood to include values close to these ranges or values. For numerical ranges, between the endpoint values of each range, between the endpoint values of each range and individual point values, and between individual point values, they can be combined with each other to obtain one or more new numerical ranges, and these numerical ranges should be regarded as specifically disclosed herein.

[0020] The polybrominated N-phenyl-5-o-hydroxyphenylpyrazole-3-carboxamides according to the present invention have the chemical structure shown in formula (I),

[0021]

[0022] wherein, R 1 and R 2 each independently selected from hydrogen, halogen or methyl, R 3 , R 4 , R 5 each independently selected from hydrogen, halogen, methyl, methoxy, trifluoromethyl or trifluoromethoxy.

[0023] In a preferred case, in formula (I), R 1 is hydrogen or fluorine, R 2 is halogen or methyl, R 3 is hydrogen or halogen, R 4 is halogen or trifluoromethyl, R 5 is halogen, methoxy or trifluoromethoxy.

[0024] Further preferably, in formula (I), R 1 is hydrogen, or fluorine, R2 is fluorine, chlorine, bromine or methyl, R 3 is hydrogen, fluorine or chlorine, R 4 is hydrogen, chlorine or trifluoromethyl, R 5 is hydrogen, fluorine, chlorine, bromine, methoxy or trifluoromethoxy.

[0025] In a specific embodiment, the polybrominated N-phenyl-5-o-hydroxyphenylpyrazole-3-carboxamide compounds described in the present invention are at least one of the following compounds:

[0026] Compound I-1: R 1 is F, R 2 is Br, R 3 is Cl, R 4 is H, R 5 is Cl;

[0027] Compound I-2: R 1 is F, R 2 is Br, R 3 is H, R 4 is Cl, R 5 is Br;

[0028] Compound I-3: R 1 is F, R 2 is Br, R 3 is H, R 4 is -CF3, R 5 is H;

[0029] Compound I-4: R 1 is F, R 2 is Br, R 3 is H, R 4 is Cl, R 5 is -OCH3;

[0030] Compound I-5: R 1 is F, R 2 is Br, R 3 is F, R 4 is H, R 5 is F;

[0031] Compound I-6: R 1 is F, R 2 is Br, R 3 is H, R 4 is H, R 5 is -OCF3;

[0032] Compound I-7: R 1 is H, R 2 is F, R 3 is Cl, R4 is H, R 5 is Cl;

[0033] Compound I-8: R 1 is H, R 2 is F, R 3 is H, R 4 is Cl, R 5 is Br;

[0034] Compound I-9: R 1 is H, R 2 is F, R 3 is H, R 4 is -CF3, R 5 is H;

[0035] Compound I-10: R 1 is H, R 2 is F, R 3 is H, R 4 is Cl, R 5 is -OCH3;

[0036] Compound I-11: R 1 is H, R 2 is F, R 3 is F, R 4 is H, R 5 is F;

[0037] Compound I-12: R 1 is H, R 2 is F, R 3 is H, R 4 is H, R 5 is -OCF3;

[0038] Compound I-13: R 1 is H, R 2 is Cl, R 3 is Cl, R 4 is H, R 5 is Cl;

[0039] Compound I-14: R 1 is H, R 2 is Cl, R 3 is H, R 4 is Cl, R 5 is Br;

[0040] Compound I-15: R 1 is H, R 2 is Cl, R 3 is H, R 4 is -CF3, R 5is H;

[0041] Compound I-16: R 1 is H, R 2 is Cl, R 3 is H, R 4 is Cl, R 5 is -OCH3; Compound I-17: R 1 is H, R 2 is Cl, R 3 is F, R 4 is H, R 5 is F;

[0042] Compound I-18: R 1 is H, R 2 is Cl, R 3 is H, R 4 is H, R 5 is -OCF3;

[0043] Compound I-19: R 1 is H, R 2 is Br, R 3 is Cl, R 4 is H, R 5 is Cl;

[0044] Compound I-20: R 1 is H, R 2 is Br, R 3 is H, R 4 is Cl, R 5 is Br;

[0045] Compound I-21: R 1 is H, R 2 is Br, R 3 is H, R 4 is -CF3, R 5 is H;

[0046] Compound I-22: R 1 is H, R 2 is Br, R 3 is H, R 4 is Cl, R 5 is -OCH3; Compound I-23: R 1 is H, R 2 is Br, R 3 is F, R 4 is H, R 5 is F;

[0047] Compound I-24: R 1 is H, R 2is Br, R 3 is H, R 4 is H, R 5 is -OCF3;

[0048] Compound I-25: R 1 is H, R 2 is -CH3, R 3 is Cl, R 4 is H, R 5 is Cl;

[0049] Compound I-26: R 1 is H, R 2 is -CH3, R 3 is H, R 4 is Cl, R 5 is Br;

[0050] Compound I-27: R 1 is H, R 2 is -CH3, R 3 is H, R 4 is -CF3, R 5 is H; Compound I-28: R 1 is H, R 2 is -CH3, R 3 is H, R 4 is Cl, R 5 is -OCH3; Compound I-29: R 1 is H, R 2 is -CH3, R 3 is F, R 4 is H, R 5 is F;

[0051] Compound I-30: R 1 is H, R 2 is -CH3, R 3 is H, R 4 is H, R 5 is -OCF3.

[0052] The above specific compounds I-1 to I-30 refer to the compounds in which the substituent groups R 1 , R 2 , R 3 , R 4 and R 5 are respectively the above groups.

[0053] The present invention also provides a method for preparing the polybrominated N-phenyl-5-(o-hydroxyphenyl)pyrazole-3-carboxamide compounds represented by the above formula (I), and the method includes the following steps:

[0054] (1) The o-hydroxyacetophenone-based compound shown in formula (1) and dimethyl oxalate shown in formula (2) are subjected to a cyclization reaction and a hydrolysis reaction in sequence to obtain the compound shown in formula (3);

[0055] (2) The compound shown in formula (3) and a substituted aniline are subjected to an amidation reaction to obtain the compound shown in formula (4);

[0056] (3) The compound shown in formula (4) and hydrazine hydrate are subjected to a ring transformation reaction to obtain the compound shown in formula (5);

[0057] (4) The compound shown in formula (5) and a brominating reagent are subjected to a bromination reaction,

[0058]

[0059] wherein, R 1 , R 2 , R 3 , R 4 and R 5 are defined the same as those described previously.

[0060] In the present invention, by synthesizing various N-phenyl-5-o-hydroxyphenylpyrazole-3-carboxamide compounds and further performing a bromination reaction, bromine substituents are introduced at different substitution positions to obtain a class of polybrominated N-phenyl-5-o-hydroxyphenylpyrazole-3-carboxamide compounds. These compounds exhibit significant growth inhibitory activity against the model cyanobacteria PCC6803 and FACHB 905. Therefore, the polybrominated N-phenyl-5-o-hydroxyphenylpyrazole-3-carboxamide compounds of the present invention can be developed into novel algicides acting on the IspD enzyme target.

[0061] In step (1), preferably, the molar ratio of the amount of the o-hydroxyacetophenone-based compound shown in formula (1) to the amount of dimethyl oxalate shown in formula (2) is 1:3 - 4.

[0062] Preferably, the cyclization reaction is carried out in the presence of a basic compound and a first organic solvent. As the basic compound used in the above cyclization reaction, various strong bases used in the art can be used. Specifically, the basic compound is selected from one or more of sodium hydride, sodium methoxide, and sodium ethoxide, and preferably sodium hydride.

[0063] The first organic solvent used in the above cyclization reaction can be a conventional selection in the art. Specifically, the first organic solvent is tetrahydrofuran and / or dichloromethane, and preferably tetrahydrofuran. The first organic solvent adopted in the present invention is an ultra-dry solvent with a water content ≤ 50 ppm.

[0064] In the specific embodiment, the conditions of the cyclization reaction in step (1) may include: the temperature is the reflux temperature (i.e., the temperature of the cyclization reaction is based on observing the reflux of the first organic solvent), and the time is 1.5 - 3 h.

[0065] In step (1), the hydrolysis reaction is carried out in the presence of an acidic solution. Specifically, the acidic solution is hydrochloric acid and / or sulfuric acid, preferably hydrochloric acid.

[0066] Preferably, the conditions of the hydrolysis reaction include: the temperature is 15 - 40 °C (room temperature), and the time is 0.5 - 3 h.

[0067] In the present invention, the o-hydroxyacetophenone-based compound and dimethyl oxalate used in the cyclization reaction are both well-known in the art and can be obtained through commercial purchase.

[0068] In addition, the method for reacting the o-hydroxyacetophenone-based compound with dimethyl oxalate to obtain the compound shown in formula (3) can also be carried out according to the method reported in J. Org. Chem. 2015, 80, 3, 1632 - 1643.

[0069] In the specific embodiment, in step (2), the molar ratio of the amount of the compound shown in formula (3) to the substituted aniline can be 1:1 - 2.

[0070] Preferably, in step (2), the amidation reaction is carried out in the presence of a second organic solvent.

[0071] The second organic solvent used in the above amidation reaction can be a conventional choice in the art. Specifically, the second organic solvent is N,N-dimethylformamide and / or tetrahydrofuran, preferably an N,N-dimethylformamide solution. The second organic solvent adopted in the present invention is an ultra-dry solvent with a water content ≤ 50 ppm.

[0072] The substituted aniline used in the amidation reaction is commonly used in the art and can be obtained through commercial purchase; among them, the definition and position of the substituents in the substituted aniline are the same as those of R 3 、R 4 and R 5 in the compound shown in formula (I).

[0073] Step (2) specifically includes: reacting the compound shown in formula (3) with phosphorus oxychloride (POCl3) at room temperature, and then reacting the obtained reaction solution with the substituted aniline to obtain the compound shown in formula (4).

[0074] In the specific embodiment, the conditions of the amidation reaction may include: the temperature is 110 - 130 °C, and the time is 2 - 3 h.

[0075] In addition, the method for obtaining the compound represented by formula (4) by amidation of the compound represented by formula (3) can be carried out according to the method reported in Tetrahedron Letters, 52.48 (2011) 6446-6449.

[0076] In step (3), preferably, the molar ratio of the compound represented by formula (4) to the amount of hydrazine hydrate used can be 1:1 to 2.

[0077] In a specific embodiment, the hydrazine hydrate can be used in the form of an aqueous solution. The hydrazine hydrate aqueous solution used in the amidation reaction is common in the art and can be obtained by commercial purchase. The concentration of the hydroxylamine aqueous solution can be 30-60% by weight, preferably 60% by weight.

[0078] In step (3), the ring transformation reaction is carried out in the presence of a third organic solvent.

[0079] The third organic solvent used in the above ring transformation reaction can be a conventional choice in the art. Specifically, the third organic solvent can be ethanol and / or methanol, preferably ethanol.

[0080] Preferably, the conditions of the ring transformation reaction can include: the temperature is the reflux temperature (that is, the temperature of the ring transformation reaction is based on observing the reflux of the third organic solvent), and the time is 1-2 h.

[0081] In addition, the method for obtaining the compound represented by formula (5) by ring transformation of the compound represented by formula (4) can also be carried out according to the method reported in ChemMedChem, 2015, 10, 1655-1671.

[0082] In step (4), preferably, the molar equivalent ratio of the compound represented by formula (5) to the amount of the brominating reagent used is 1:3 to 5.

[0083] Specifically, the brominating reagent used in the bromination reaction can be N-bromosuccinimide and / or pyridinium tribromide, preferably pyridinium tribromide.

[0084] The brominating reagent used in the bromination reaction can be conventionally used in the art and can be obtained by commercial purchase.

[0085] In step (4), the bromination reaction is carried out in the presence of a fourth organic solvent.

[0086] The fourth organic solvent used as the bromination reaction can be methanol and / or ethanol, preferably methanol.

[0087] In a specific embodiment, the conditions of the bromination reaction in step (4) can include: the temperature is 15-40 °C, and the time is 1-4 h.

[0088] The method for obtaining the brominated compound of formula (I) from the compound shown in formula (5) can also be carried out according to the method reported in European Journal of Organic Chemistry 2014.21(2014):4487 - 4505.

[0089] The present invention also provides the application of the above-mentioned polybrominated N-phenyl-5-o-hydroxyphenylpyrazole-3-carboxamides as algicides.

[0090] The present invention will be described in detail below through examples, but the present invention is not limited to the following examples.

[0091] The compounds used in the following examples are all obtained through commercial purchase unless otherwise specified.

[0092] In the following examples, the nuclear magnetic data was measured using a Varian Mercury 400 / 600M nuclear magnetic resonance spectrometer, and the high-resolution mass spectrometry (HRMS) was determined by an Agilent Technologies 6530 Accurate-Mass Q-TOF mass spectrometer.

[0093] The synthetic routes of the following examples are shown as follows:

[0094]

[0095] In the above synthetic route, the substituents in each general formula compound used in each example are shown in Table 1 below.

[0096] Table 1

[0097]

[0098]

[0099] Examples 1 - 30

[0100] This example is used to illustrate the preparation method of the polybrominated N-phenyl-5-o-hydroxyphenylpyrazole-3-carboxamide compound of the present invention.

[0101] (1) Synthesis of the compound shown in formula (3)

[0102] In a dry 25 mL two-necked flask, dimethyl oxalate (1.1 mmol) and NaH (4.0 mmol) were dissolved in 10 mL of ultra-dry tetrahydrofuran (THF), and the mixture was stirred magnetically for 10 min. At room temperature, a solution of o-hydroxyacetophenone (1.0 mmol) dissolved in 2 mL of ultra-dry tetrahydrofuran was slowly added dropwise to the above mixture using a constant-pressure dropping funnel. After the addition was complete, the mixture was heated to reflux and reacted for 2 h, and the reaction progress was monitored by TLC until the reaction was completed. The reaction mixture was cooled to room temperature, concentrated hydrochloric acid was added and stirred for 30 min, and then extracted with ethyl acetate (3 × 50 mL). The organic phases were combined, washed with saturated brine (3 × 50 mL), dried over anhydrous sodium sulfate, and concentrated by rotary evaporation to obtain the crude product. The compound shown in formula (3) was obtained by column chromatography using petroleum ether / ethyl acetate (2:1, v / v).

[0103] (2) Synthesis of the compound shown in formula (4)

[0104] In a dry 50 mL two-necked flask, the compound shown in formula (3) prepared in step (1) (1.0 mmol) and 10 mL of ultra-dry DMF (N,N-dimethylformamide) were added and dissolved by magnetic stirring at room temperature. Subsequently, POCl3 (0.1 mL, 1.1 mmol) was added, and the mixture was stirred at room temperature for an additional 0.5 h. Substituted aniline (1.1 mmol) was added to the above reaction mixture, and the mixture was heated at 120 °C for 2 h, and the reaction progress was monitored by TLC until the reaction was complete. The reaction mixture was cooled to room temperature, water was added to precipitate a solid, and the solid was collected by filtration to obtain the compound shown in formula (4).

[0105] (3) Synthesis of the compound shown in formula (5)

[0106] In a 50 mL two-necked flask, the compound shown in formula (4) prepared in step (2) (1.0 mmol) and 10 mL of ethanol were added and dissolved by magnetic stirring. Hydrazine hydrate solution (0.1 mL, 1.5 mmol, concentration 60%) was added, and the mixture was heated to reflux for 1 h, and the reaction progress was monitored by TLC until the reaction was complete. The reaction mixture was cooled to room temperature, water was added to precipitate a solid, and the solid was collected by filtration and dried in vacuo to obtain the compound shown in formula (5).

[0107] (4) Synthesis of the target compound

[0108] In a 50 mL round-bottom flask, the compound shown in formula (5) (1.0 mmol) and 15 mL of methanol were added and dissolved by magnetic stirring. 3.1 equiv of the brominating reagent Py .HBr3 (pyridinium tribromide), continue stirring at room temperature for 4 h, and monitor the reaction progress by TLC until the reaction is complete. Transfer to a separatory funnel, add 20 mL of water and 50 mL of ethyl acetate, and separate the organic layer. Extract the aqueous layer with ethyl acetate (3 × 50 mL), combine the organic phases, and wash with saturated brine (3 × 50 mL). Dry the organic phase over anhydrous sodium sulfate, remove the solvent by rotary evaporation to obtain the crude product. Use petroleum ether / ethyl acetate (2:1, v / v) column chromatography to obtain the target compounds I-1 to I-30 shown in Table 1.

[0109] The molecular structure data of compounds I-1 to I-30 are as follows:

[0110] Compound I-1: Gray solid, 1 H NMR (600 MHz, DMSO-d6) δ 14.16 (s, 1H), 10.82 (d, J = 195.4 Hz, 1H), 9.73 (d, J = 21.0 Hz, 1H), 8.12 (dd, J = 19.2, 9.0 Hz, 1H), 7.86–7.64 (m, 2H), 7.49 (d, J = 8.4 Hz, 1H). 13 C NMR (100 MHz, DMSO-d6) δ 158.7, 157.94, 157.49, 156.68, 155.05, 153.77, 134.76, 133.63, 128.97, 127.87, 126.18, 124.88, 104.47, 100.58, 97.67, 96.12, 95.22, 94.24.

[0111] HRMS (Dual ESI): Calcd for C 16 H7Br3Cl2FN3O2 [M-H] - 597.7377. Found 597.7379.

[0112] Compound I-2: Brown solid, 1 H NMR (600 MHz, DMSO-d6) δ 14.10 (s, 1H), 10.61 (s, 2H), 8.23 (s, 1H), 8.12–7.21 (m, 3H). 13 C NMR (100 MHz, DMSO-d6) δ 159.6, 157.43, 154.99, 153.75, 139.48, 133.68, 133.50, 132.90, 121.28, 120.39, 114.81, 100.60, 97.67, 95.16.

[0113] HRMS (Dual ESI): Calcd for C16 H7Br4ClFN3O2[M-H] - 641.6872.Found 641.6874.

[0115] Compound I-3: Grey solid, 1 H NMR(600MHz,DMSO-d6)δ14.11(s,1H),10.64(s,2H),8.35(s,1H),8.10(d,J = 7.8Hz,1H),7.73(d,J = 7.8Hz,1H),7.59(t,J = 7.8Hz,1H),7.45(d,J = 7.2Hz,1H). 13 C NMR(100MHz,DMSO-d6)δ159.7,157.43,154.99,153.76(d,J = 3.0Hz),139.54,133.51,129.81,129.53,129.22,125.52,123.77,122.81,119.88,116.28(d,J = 4.0Hz),100.60(d,J =

[0116] 22.9Hz),97.67(d,J = 23.1Hz),95.11.

[0117] HRMS(Dual ESI):Calcd for C 17 H8Br3F4N3O2[M-H] - 597.8030.Found 597.8029.

[0119] Compound I-4: White solid, 1 H NMR(600MHz,DMSO-d6)δ14.02(s,1H),10.66(s,1H),10.32(s,1H),7.99(s,1H),7.73(t,J = 9.6Hz,2H),7.15(d,J = 9.0Hz,1H),3.85(s,3H). 13 C NMR(100MHz,DMSO-d6)δ159.1,157.38,154.95,153.75(d,J = 3.0Hz),150.77,142.14,133.43,132.40,121.77,120.47,120.11,115.07,112.77,100.57(d,J = 22.8Hz),97.65(d,J = 23.0Hz),94.82,56.21.

[0120] HRMS (Dual ESI): Calcd for C 16 H7Br4ClFN3O2 [M-H] - 593.7872. Found 593.7879.

[0122] Compound I-5: Yellow solid, 1 H NMR (600 MHz, DMSO-d6) δ 14.04 (s, 1H), 10.65 (s, 1H), 9.89 (s, 1H), 7.73 (dd, J = 19.8, 7.8 Hz, 2H), 7.37 (t, J = 8.4 Hz, 1H), 7.13 (t, J = 7.8 Hz, 1H). 13 C NMR (100 MHz, DMSO-d6) δ 160.5, 159.11, 158.12 (d, J = 11.6 Hz), 157.42, 156.66 (d, J = 12.6 Hz), 154.99, 154.18 (d, J = 12.8 Hz), 153.77 (d, J = 3.0 Hz), 133.48, 127.26 (d, J = 11.9 Hz), 121.96 (d, J = 12.2 Hz), 114.94, 111.18 (d, J = 18.6 Hz), 104.95–102.93, 100.56 (d, J = 22.8 Hz), 97.64 (d, J = 23.2 Hz), 95.06.

[0123] HRMS (Dual ESI): Calcd for C 16 H7Br3F3N3O2 [M-H] - 565.7968. Found 565.7966.

[0125] Compound I-6: Brown solid, 1 H NMR (400 MHz, DMSO-d6) δ 14.05 (s, 1H), 10.65 (s, 1H), 10.50 (s, 1H), 7.95 (d, J = 9.2 Hz, 2H), 7.72 (d, J = 8.0 Hz, 1H), 7.36 (d, J = 8.8 Hz, 2H). 13CNMR(100MHz, DMSO-d6) δ 159.4, 157.40, 154.97, 153.76(d, J = 2.9Hz), 146.19, 143.85, 142.35, 137.92, 133.45, 127.18, 121.64, 121.56, 121.46, 118.89, 115.03, 100.58(d, J = 23.0Hz), 97.65(d, J = 23.1Hz), 94.97.

[0126] HRMS(Dual ESI): Calcd for C 17 H8Br3F4N3O3[M - H] - 613.7979. Found 613.7977.

[0128] Compound I - 7: White solid, 1 H NMR(400MHz, DMSO-d6) δ 10.92(s, 1H), 9.75(s, 2H), 8.12(d, J = 8.8Hz, 1H), 7.74(d, J = 2.4Hz, 1H), 7.70(dd, J = 8.0, 3.2Hz, 1H), 7.50(dd, J = 8.8, 2.4Hz, 1H), 7.31(dd, J = 8.8, 3.2Hz, 1H). 13 C NMR(100MHz, DMSO-d6) δ 158.7, 155.81, 153.42, 148.88(d, J = 2.4Hz), 140.40(d, J = 144.2Hz), 133.64, 129.06, 128.89, 127.89, 126.29, 124.98, 121.16(d, J =

[0129] 25.4Hz), 118.07(d, J = 9.2Hz), 117.14(d, J = 23.6Hz), 112.23(d, J = 10.8Hz), 94.78.

[0130] HRMS(Dual ESI): Calcd for C 16 H8Br2Cl2FN3O2[M - H] - 519.8272. Found 519.8274.

[0131] Compound I - 8: White solid, 11H NMR (400 MHz, DMSO-d6) δ 14.11 (s, 1H), 10.61 (s, 1H), 9.74 (s, 1H), 8.23 (d, J = 1.6 Hz, 1H), 7.77 (dd, J = 8.8, 2.0 Hz, 1H), 7.74 (s, 1H), 7.72–7.65 (m, 1H), 7.31 (dd, J = 8.4, 2.8 Hz, 1H). 13 13C NMR (100 MHz, DMSO-d6) δ 159.7, 155.83, 153.44, 148.86 (d, J = 2.4 Hz), 142.12, 139.51, 133.70, 132.92, 121.27, 121.06 (d, J = 25.8 Hz), 120.38, 118.26 (d, J = 9.2 Hz), 117.14 (d, J = 22.9 Hz), 114.82, 112.26 (d, J = 10.4 Hz), 94.69.

[0132] HRMS (Dual ESI): Calcd for C 16 H8Br3ClFN3O2 [M-H] - 563.7766. Found 563.7764.

[0134] Compound I-9: White solid, 1 1H NMR (400 MHz, DMSO-d6) δ 14.12 (s, 1H), 10.66 (s, 1H), 9.76 (s, 1H), 8.36 (s, 1H), 8.10 (d, J = 8.0 Hz, 1H), 7.71 (dd, J = 8.0, 3.2 Hz, 1H), 7.60 (t, J = 8.0 Hz, 1H), 7.46 (d, J = 7.6 Hz, 1H), 7.32 (d, J = 6.4 Hz, 1H). 13 13C NMR (100 MHz, DMSO-d6) δ 159.9, 155.87, 153.48, 148.89 (d, J = 2.4 Hz), 140.60 (d, J = 344.6 Hz), 139.60, 129.85, 129.01 (dd, J = 81.6, 50.2 Hz), 125.56, 123.78, 122.85, 121.09 (d, J = 26.2 Hz), 119.93, 116.28 (d, J = 3.8 Hz), 112.25, 94.68.

[0135] HRMS (Dual ESI): Calcd for C 17 H9Br2F4N3O2 [M-H]- 519.8925.Found 519.8927.

[0137] Compound I-10: Brown solid, 1 H NMR(400MHz,DMSO-d6)δ14.03(s,1H),10.31(s,1H),10.09(s,1H),7.99(d,J = 2.4Hz,1H),7.82(d,J = 2.8Hz,1H),7.73(dd,J = 8.8,2.4Hz,1H),7.44(s,1H),7.14(d,J = 9.2Hz,1H),3.85(s,3H). 13 C NMR(100MHz,DMSO-d6)δ159.2,156.04,151.32,150.76,133.23,132.41,130.08,123.53,121.75,120.46,120.09,119.01,112.77,112.67,94.52,56.20.

[0138] HRMS(Dual ESI):Calcd for C 17 H 11 Br2ClFN3O2[M-H] - 5158767.Found 515.8766.

[0140] Compound I-11: White solid, 1 H NMR(400MHz,DMSO-d6)δ14.09(s,1H),10.09(s,1H),10.09(s,1H),9.89(s,1H),7.82(d,J = 2.8Hz,1H),7.74(dd,J = 15.2,8.8Hz,1H),7.44(s,1H),7.41–7.32(m,1H),7.13(t,J = 8.8Hz,1H). 13CNMR(100MHz, DMSO-d6) δ 160.6 (d, J = 11.2Hz), 159.14, 158.12 (d, J = 11.4Hz), 156.65 (d, J = 12.4Hz), 154.17 (d, J = 12.6Hz), 151.34, 133.31, 130.14, 127.24 (d, J = 10.0Hz), 123.52, 122.00 (dd, J = 12.2, 3.4Hz), 118.83, 112.67, 111.19 (dd, J = 22.0, 3.4Hz), 104.29 (dd, J = 26.6, 24.4Hz), 94.77.

[0141] HRMS (Dual ESI): Calcd for C 16 H8Br2F3N3O2 [M-H] - 487.8863. Found 487.8865.

[0143] Compound I-12: White solid, 1 H NMR (400MHz, DMSO-d6) δ 14.06 (s, 1H), 10.49 (s, 1H), 10.09 (s, 1H), 7.95 (d, J = 8.8Hz, 2H), 7.83 (d, J = 2.4Hz, 1H), 7.44 (s, 1H), 7.36 (d, J = 8.8Hz, 2H). 13 C NMR (100MHz, DMSO-d6) δ 159.5, 151.33, 143.86, 140.52 (d, J = 390.4Hz), 137.95, 133.28, 130.16, 127.03, 123.54, 123.26, 121.63, 121.48, 118.90, 116.36, 112.69, 94.67.

[0144] HRMS (Dual ESI): Calcd for C 17 H9Br2F4N3O2 [M-H] - 535.8874. Found 535.8878.

[0146] Compound I-13: White solid, 11H NMR (600 MHz, DMSO-d6) δ 14.18 (s, 1H), 10.10 (s, 1H), 9.75 (s, 1H), 8.11 (d, J = 8.4 Hz, 1H), 7.83 (s, 1H), 7.74 (s, 1H), 7.49 (d, J = 7.8 Hz, 1H), 7.45 (s, 1H). 13 13C NMR (100 MHz, DMSO-d6) δ 158.7, 151.33, 141.33, 139.24, 133.62, 133.39, 130.16, 129.04, 128.87, 127.87, 126.26, 124.95, 123.53, 118.64, 112.67, 94.92.

[0147] HRMS (Dual ESI): Calcd for C 16 H8Br2Cl3N3O2 [M-H] - 535.7976. Found 535.7973.

[0149] Compound I-14: Brown solid, 1 1H NMR (600 MHz, DMSO-d6) δ 14.11 (s, 1H), 10.58 (d, J = 27.6 Hz, 1H), 10.09 (s, 1H), 8.23 (s, 1H), 7.83 (d, J = 1.8 Hz, 1H), 7.75 (dd, J = 24.0, 8.4 Hz, 2H), 7.44 (s, 1H). 13 13C NMR (100 MHz, DMSO-d6) δ 159.6, 151.31, 144.38, 139.49, 134.41, 133.68, 133.30, 132.90, 130.13, 123.55, 121.27, 120.38, 118.84, 114.81, 112.69, 94.84.

[0150] HRMS (Dual ESI): Calcd for C 16 H8Br3Cl2N3O2 [M-H] - 579.7471. Found 579.7477.

[0152] Compound I-15: White solid, 11H NMR(600MHz, DMSO-d6) δ 14.11 (s, 1H), 10.65 (s, 1H), 10.11 (s, 1H), 8.35 (s, 1H), 8.10 (d, J = 7.2 Hz, 1H), 7.83 (s, 1H), 7.59 (t, J = 7.8 Hz, 1H), 7.46 (s, 2H). 13 13C NMR(100MHz, DMSO-d6) δ 159.8, 151.33, 139.56, 133.30, 130.15, 129.81, 129.39 (d, J = 31.4 Hz), 128.57 (d, J = 69.2 Hz), 125.52, 123.76, 123.56, 122.82, 119.90 (d, J = 3.2 Hz), 118.87, 116.27 (d, J = 4.0 Hz), 112.71, 94.79.

[0153] HRMS(Dual ESI): Calcd for C 17 H9Br2ClF3N3O2 [M - H] - 535.8629. Found 535.8628.

[0154] Compound I - 16: Gray solid, 1 1H NMR(600MHz, DMSO-d6) δ 14.04 (s, 1H), 10.31 (s, 1H), 10.09 (s, 1H), 7.99 (s, 1H), 7.82 (s, 1H), 7.74 (d, J = 7.2 Hz, 1H), 7.44 (s, 1H), 7.15 (d, J = 9.0 Hz, 1H), 3.85 (s, 3H). 13 13C NMR(100MHz, DMSO-d6) δ 159.3, 154.47, 151.32, 150.77, 133.23, 132.41, 130.22, 123.53, 121.75, 120.47, 120.09, 118.99, 117.63, 112.78, 112.67, 94.53, 56.20.

[0155] HRMS(Dual ESI): Calcd for C 17 H 11 Br2Cl2N3O2 [M - H] - 531.8472. Found 531.8471.

[0156] Compound I - 17: Yellow solid, 11H NMR (600 MHz, DMSO-d6) δ 14.10 (s, 1H), 10.10 (s, 1H), 9.90 (s, 1H), 7.82 (d, J = 2.4 Hz, 1H), 7.73 (dd, J = 15.0, 8.4 Hz, 1H), 7.44 (s, 1H), 7.37 (t, J = 9.0 Hz, 1H), 7.13 (t, J = 7.8 Hz, 1H). 13 13C NMR (100 MHz, DMSO-d6) δ 160.5 (d, J = 11.4 Hz), 159.16, 158.11 (d, J = 11.4 Hz), 156.64 (d, J = 12.8 Hz), 154.72–153.68 (m), 151.33, 133.30, 130.11, 127.23 (d, J = 10.4 Hz), 123.51, 121.99 (dd, J = 12.2, 3.4 Hz), 118.88, 112.66, 111.20 (d, J = 22.0 Hz), 105.36–102.45 (m), 94.76.

[0157] HRMS (Dual ESI): Calcd for C 16 H8Br2ClF2N3O2 [M-H] - 503.8567. Found 503.8568.

[0158] Compound I-18: White solid, 1 1H NMR (600 MHz, DMSO-d6) δ 14.08 (s, 1H), 10.50 (s, 1H), 10.10 (s, 1H), 7.95 (d, J = 8.4 Hz, 2H), 7.83 (d, J = 1.8 Hz, 1H), 7.45 (s, 1H), 7.36 (d, J = 8.4 Hz, 2H). 13 13C NMR (100 MHz, DMSO-d6) δ 159.5, 151.33, 143.87, 137.94, 133.26, 130.11, 123.98, 123.54, 121.62, 121.47, 118.90, 116.36, 112.68, 94.66.

[0159] HRMS (Dual ESI): Calcd for C 17 H9Br2ClF3N3O3 [M-H] - 551.8578. Found 551.8574.

[0160] Compound I-19: White solid, 11H NMR (400 MHz, DMSO-d6) δ 14.18 (s, 1H), 10.10 (s, 1H), 9.74 (s, 1H), 8.11 (d, J = 8.8 Hz, 1H), 7.83 (d, J = 2.0 Hz, 1H), 7.74 (s, 1H), 7.49 (d, J = 8.4 Hz, 1H), 7.44 (s, 1H). 13 13C NMR (100 MHz, DMSO-d6) δ 158.6, 153.66, 151.73, 136.01, 133.62, 132.95, 131.99, 129.49, 129.04, 128.87, 127.88, 126.27, 124.97, 118.50, 113.05, 110.71, 110.51, 105.71, 94.95.

[0161] HRMS (Dual ESI): Calcd for C 16 H8Br3Cl2N3O2 [M-H] - 579.7471. Found 579.7475.

[0163] Compound I-20: White solid, 1 1H NMR (400 MHz, DMSO-d6) δ 14.03 (d, J = 57.6 Hz, 1H), 10.60 (s, 1H), 10.10 (s, 1H), 8.23 (s, 1H), 7.93 (d, J = 2.4 Hz, 1H), 7.74 (t, J = 8.4 Hz, 2H), 7.52 (d, J = 6.0 Hz, 1H). 13 13C NMR (100 MHz, DMSO-d6) δ

[0164] 159.8, 154.91, 151.71, 142.19, 139.50, 135.93, 133.68, 132.91, 121.27, 120.38, 118.12, 114.80, 113.07, 110.73, 109.62, 94.88.

[0165] HRMS (Dual ESI): Calcd for C 16 H8Br4ClN3O2 [M-H] - 623.6966. Found 623.6961.

[0167] Compound I-21: Grey solid, 11H NMR (400 MHz, DMSO-d6) δ 14.10 (s, 1H), 10.64 (s, 1H), 10.12 (s, 1H), 8.35 (s, 1H), 8.10 (d, J = 8.4 Hz, 1H), 7.93 (d, J = 2.4 Hz, 1H), 7.58 (dd, J = 16.0, 8.0 Hz, 2H), 7.45 (d, J = 7.6 Hz, 1H). 13 13C NMR (100 MHz, DMSO-d6) δ 159.8, 151.73, 139.56, 135.92, 132.95, 129.81, 129.39 (d, J = 31.4 Hz), 125.52, 123.76, 122.82, 119.89, 119.43, 116.27 (d, J = 4.0 Hz), 113.08, 110.73, 94.83.

[0168] HRMS (Dual ESI): Calcd for C 17 H9Br3F3N3O2 [M-H] - 579.8124. Found 579.8129.

[0170] Compound I-22: Purple solid, 1 1H NMR (400 MHz, DMSO-d6) δ 14.02 (s, 1H), 10.30 (s, 1H), 10.11 (s, 1H), 7.99 (d, J = 2.4 Hz, 1H), 7.92 (d, J = 2.4 Hz, 1H), 7.74 (dd, J = 8.8, 2.4 Hz, 1H), 7.54 (s, 1H), 7.14 (d, J = 9.2 Hz, 1H), 3.85 (s, 3H). 13 13C NMR (100 MHz, DMSO-d6) δ 159.2, 154.91, 151.71, 150.76, 135.85, 132.88, 132.41, 121.75, 120.46, 120.09, 119.50, 113.04, 112.77, 110.70, 94.54, 56.20.

[0171] HRMS (Dual ESI): Calcd for C 17 H 11 Br3ClN3O3 [M-H] - 575.7966. Found 575.7965.

[0173] Compound I-23: White solid, 11H NMR (400 MHz, DMSO-d6) δ 14.08 (s, 1H), 10.11 (s, 1H), 9.89 (s, 1H), 7.92 (d, J = 2.4 Hz, 1H), 7.74 (dd, J = 15.2, 8.8 Hz, 1H), 7.54 (d, J = 1.6 Hz, 1H), 7.44–7.31 (m, 1H), 7.13 (t, J = 8.8 Hz, 1H). 13 13C NMR (100 MHz, DMSO-d6) δ 160.5 (d, J = 11.6 Hz), 159.18, 158.11 (d, J = 11.6 Hz), 156.64 (d, J = 12.8 Hz), 154.91, 154.16 (d, J = 12.5 Hz), 151.73, 135.91, 132.91, 127.22 (d, J = 9.8 Hz), 122.00 (dd, J = 12.0, 3.4 Hz), 119.44, 113.03, 111.18 (dd, J = 22.0, 3.4 Hz), 110.69, 104.28 (dd, J = 26.8, 24.2 Hz), 94.79.

[0174] HRMS (Dual ESI): Calcd for C 16 H8Br3F2N3O2 [M-H] - 547.8062. Found 547.8061.

[0176] Compound I-24: Brown solid, 1 1H NMR (400 MHz, DMSO-d6) δ 14.06 (s, 1H), 10.49 (s, 1H), 10.11 (s, 1H), 7.95 (d, J = 9.2 Hz, 2H), 7.92 (d, J = 2.4 Hz, 1H), 7.54 (s, 1H), 7.36 (d, J = 8.8 Hz, 2H). 13 13C NMR (100 MHz, DMSO-d6) δ 159.5, 151.73, 143.86, 137.94, 135.88, 132.92, 123.64 (d, J = 69.4 Hz), 121.63, 121.55, 121.47, 119.49, 118.90, 116.36, 113.06, 110.71, 94.69.

[0177] HRMS (Dual ESI): Calcd for C 17 H9Br3F3N3O3 [M-H] - 595.8073. Found 595.8072.

[0179] Compound I-25: White solid, 1 H NMR(400MHz,DMSO-d6)δ14.09(s,1H),9.73(s,1H),9.47(s,1H),8.15(d,J = 8.8Hz,1H),7.74(d,J = 2.4Hz,1H),7.52(s,1H),7.49(dd,J = 8.8,2.4Hz,1H),7.14(s,1H),2.27(s,3H). 13 C NMR(100MHz,DMSO-d6)δ158.9,153.16,149.64,141.34,140.41,134.63,133.70,131.14,130.23,128.88,127.91,126.00,124.68,117.24,111.73,94.51,19.56.

[0180] HRMS(Dual ESI):Calcd for C 17 H 11 Br2Cl2N3O2[M-H] - 515.8522.Found 515.8529.

[0182] Compound I-27: Yellow solid, 1 H NMR(400MHz,DMSO-d6)δ14.02(s,1H),10.63(s,1H),9.47(s,1H),8.36(s,1H),8.10(d,J = 8.4Hz,1H),7.59(t,J = 8.0Hz,1H),7.52(d,J = 1.6Hz,1H),7.45(d,J = 7.6Hz,1H),7.16(s,1H),2.28(s,3H). 13 C NMR(100MHz,DMSO-d6)δ159.9,149.64,142.07,139.65,134.50,131.11,130.23,129.84,129.40(d,J = 31.4Hz),128.60(d,J = 66.0Hz),125.57,123.74,122.86,119.89,117.58,116.25(d,J = 4.1Hz),111.75,94.35,19.56.

[0183] HRMS(Dual ESI):Calcd for C 18 H 12Br2F3N3O2[M-H] - 515.9176.Found 515.9175.

[0185] Compound I-28: Grey solid, 1 H NMR(400MHz,DMSO-d6)δ13.93(s,1H),10.29(s,1H),9.43(s,1H),8.00(s,1H),7.75(d,J=8.0Hz,1H),7.51(s,1H),7.15(s,1H),7.13(s,1H),3.85(s,3H),2.27(s,3H). 13 C NMR(100MHz,DMSO-d6)δ159.5,150.69,149.62,142.53,139.82,134.48,132.55,131.17,130.22,121.72,120.45,120.06,117.57,112.76,111.76,94.12,56.20,19.56.

[0186] HRMS(Dual ESI):Calcd for C 18 H 14 Br2ClN3O3[M-H] - 511.9018.Found 511.9019.

[0188] Compound I-29: White solid, 1 H NMR(400MHz,DMSO-d6)δ13.97(s,1H),9.87(s,1H),9.47(s,1H),7.75(td,J=8.8,6.4Hz,1H),7.52(d,J=1.6Hz,1H),7.37(ddd,J=10.8,9.2,2.8Hz,1H),7.20–6.98(m,2H),2.27(s,3H). 1313C NMR (100 MHz, DMSO-d6) δ 160.5 (d, J = 11.6 Hz), 159.33, 158.09 (d, J = 11.6 Hz), 156.62 (d, J = 12.6 Hz), 154.14 (d, J = 12.6 Hz), 149.65, 140.90 (d, J = 111.8 Hz), 134.52, 131.09, 130.20, 127.17 (dd, J = 9.6, 2.6 Hz), 122.11 (dd, J = 12.0, 3.6 Hz), 117.54, 111.70, 111.21 (dd, J = 22.0, 3.4 Hz), 104.31 (dd, J = 26.6, 24.2 Hz), 94.34, 19.58.

[0189] HRMS (Dual ESI): Calcd for C 17 H 11 Br2F2N3O2 [M-H] - 483.9113. Found 483.9117.

[0191] Compound I-30: Yellow solid, 1 1H NMR (400 MHz, DMSO-d6) δ 13.97 (s, 1H), 10.47 (s, 1H), 9.46 (s, 1H), 7.95 (d, J = 9.2 Hz, 2H), 7.52 (d, J = 1.6 Hz, 1H), 7.36 (d, J = 8.8 Hz, 2H), 7.15 (s, 1H), 2.28 (s, 3H). 13 13C NMR (100 MHz, DMSO-d6) δ 159.7, 149.63, 143.83, 138.04, 134.47, 131.10, 130.20, 124.00, 121.59, 121.51, 118.92, 117.61, 116.38, 111.71, 94.22, 19.55. HRMS (Dual ESI): Calcd for C 18 H 12 Br2F3N3O3 [M-H] - 531.9125. Found 531.9124.

[0192] Test Example 1

[0193] This test example is used to illustrate the cyanobacteria inhibitory activity of the polybrominated N-phenyl-5-o-hydroxyphenylpyrazole-3-carboxamide compounds described in the present invention.

[0194] Test cyanobacteria: Synechocystis sp. PCC 6803; Microcystis aeruginosa FACHB 905.

[0195] Subculture of experimental algal species: Under sterile conditions, 1 mL of the original algal solution was inoculated into 100 mL of sterile BG11 medium respectively, sealed with sealing film and cultured (culture conditions: temperature 26 - 28 °C, humidity 50%, light intensity 35 mol photons / m 2 / s, light / dark = 14 h / 10 h). Ensure that before the cyanobacteria inhibition test, the initial cyanobacteria concentration OD 680 = 0.02 ± 0.005.

[0196] Preparation of inhibitors: Weigh a certain mass of the test compound and dissolve it with DMSO to prepare a 10 mM concentrated solution for use. Select CuSO4 as the control and dilute it with DMSO to the required different concentration gradients before use.

[0197] Test method: The whole process of the test requires sterile conditions. Take a 96-well plate, add 2 μL of inhibitor to each well, and repeat the experiment in three groups for each inhibitor. Then add 198 μL of cyanobacteria cell culture solution with an initial concentration OD 680 = 0.02 ± 0.005 to each well to make the test system 200 μL, seal it with sealing film, and transfer it to an artificial climate chamber for 6 days. Use an enzyme-linked immunosorbent assay (ELISA) reader to measure the OD 680 value and calculate its inhibition rate. Inhibition rate = (OD of blank control 680 - OD of experimental group 680 ) / OD of blank control 680 (inhibition rate, %). Calculate the effective concentration with 50% inhibitory activity based on the inhibition rate of cyanobacteria growth at different inhibitory concentrations, and express it with EC 50 (μM). The test results are shown in Table 2.

[0198] Table 2

[0199]

[0200]

[0201] As can be seen from Table 2, most compounds have good inhibitory activity against cyanobacteria. Among them, compounds I-2, I-8, and I-20 have very excellent inhibitory activity against both algae, which is better than the control CuSO4. Generally speaking, the inhibitory activity of the target compounds against FACHB905 is better than that against PCC 6803.

[0202] For the inhibition of PCC 6803, 12 compounds showed good inhibitory activity, and their EC 50 were all lower than 10 μM. Among them, compound I-2 (EC 50 = 1.23 μM), I-8 (EC50 = 1.28 μM), and I-20 (EC 50 = 1.14 μM) showed excellent inhibitory activity and was higher than the control CuSO4 (EC 50 = 1.79 μM). Comprehensive analysis of the structural characteristics of these three compounds revealed that the R 3 substituents on the benzene ring of these compounds were all 3-Cl, 4-Br groups, which might be an effective group for the inhibition of cyanobacteria.

[0203] For the inhibition of FACHB 905, 19 compounds showed good inhibitory activity, and the EC 50 was all lower than 10 μM. 15 compounds had excellent inhibitory activity, and the inhibitory activity EC 50 was all lower than 1 μM. Among them, the inhibitory activities of compounds I-11 (EC 50 = 0.14 μM) and I-15 (EC 50 = 0.13 μM) were the best, about 10 times that of the control CuSO4 (EC 50 = 1.79 μM). In subsequent studies, it is worth further exploring the mechanism of action of the inhibition of cyanobacteria.

[0204] Overall analysis of the above data shows that the polybrominated N-phenyl-5-o-hydroxyphenylpyrazole-3-carboxamide compounds described in the present invention have good inhibitory activity against both FACHB 905 and PCC 6803, and are suitable for use as algicides.

[0205] The preferred embodiments of the present invention have been described in detail above. However, the present invention is not limited thereto. Within the scope of the technical concept of the present invention, various simple modifications can be made to the technical solutions of the present invention, including any other suitable combination of each technical feature. These simple modifications and combinations should also be regarded as the content disclosed by the present invention and fall within the protection scope of the present invention.

Claims

1. Polybrominated N -phenyl-5-o-hydroxyphenylpyrazole-3-carboxamides compounds, characterized in that, The compound has a chemical structure represented by formula (I), Formula (I) wherein, the compound is at least one of the following compounds: Compound I-2: R 1 is F, R 2 is Br, R 3 is H, R 4 is Cl, R 5 is Br; Compound I-3: R 1 is F, R 2 is Br, R 3 is H, R 4 is -CF3, R 5 is H; Compound I-4: R 1 is F, R 2 is Br, R 3 is H, R 4 is Cl, R 5 is -OCH3; Compound I-5: R 1 is F, R 2 is Br, R 3 is F, R 4 is H, R 5 is F; Compound I-6: R 1 is F, R 2 is Br, R 3 is H, R 4 is H, R 5 is -OCF3; Compound I-7: R 1 is H, R 2 is F, R 3 is Cl, R 4 is H, R 5 is Cl; Compound I-8: R 1 is H, R 2 is F, R 3 is H, R 4 is Cl, R 5 is Br; Compound I-10: R 1 is H, R 2 is F, R 3 is H, R 4 is Cl, R 5 is -OCH3; Compound I-11: R 1 is H, R 2 is F, R 3 is F, R 4 is H, R 5 is F; Compound I-15: R 1 is H, R 2 is Cl, R 3 is H, R 4 is -CF3, R 5 is H; Compound I-16: R 1 is H, R 2 is Cl, R 3 is H, R 4 is Cl, R 5 is -OCH3; Compound I-17: R 1 is H, R 2 is Cl, R 3 is F, R 4 is H, R 5 is F; Compound I-20: R 1 is H, R 2 is Br, R 3 is H, R 4 is Cl, R 5 is Br; Compound I-21: R 1 is H, R 2 is Br, R 3 is H, R 4 is -CF3, R 5 is H; Compound I-22: R 1 is H, R 2 is Br, R 3 is H, R 4 is Cl, R 5 is -OCH3; Compound I-23: R 1 is H, R 2 is Br, R 3 is F, R 4 is H, R 5 is F; Compound I-26: R 1 is H, R 2 is -CH3, R 3 is H, R 4 is Cl, R 5 is Br; Compound I-27: R 1 is H, R 2 is -CH3, R 3 is H, R 4 is -CF3, R 5 is H; Compound I-28: R 1 is H, R 2 is -CH3, R 3 is H, R 4 is Cl, R 5 is -OCH3; Compound I-29: R 1 is H, R 2 is -CH3, R 3 is F, R 4 is H, R 5 is F; Compound I-30: R 1 is H, R 2 is -CH3, R 3 is H, R 4 is H, R 5 is -OCF3.

2. The method for preparing the compound according to claim 1, characterized in that, The method comprises the following steps: (1) successively carrying out a cyclization reaction and a hydrolysis reaction on the o-hydroxyacetophenone compound represented by formula (1) and dimethyl oxalate represented by formula (2) to obtain the compound represented by formula (3); (2) carrying out an amidation reaction on the compound represented by formula (3) and a substituted aniline to obtain the compound represented by formula (4); (3) carrying out a ring transformation reaction on the compound represented by formula (4) and hydrazine hydrate to obtain the compound represented by formula (5); (4) carrying out a bromination reaction on the compound represented by formula (5) and a brominating reagent to obtain the compound of formula (I), Formula (I) Formula (1) Formula (2) Formula (3) Formula (4) Formula (5) Among them, R 1 , R 2 , R 3 , R 4 and R 5 are defined in the same way as in claim 1.

3. The method according to claim 2, wherein In step (1), the molar ratio of the amounts of the o-hydroxyacetophenone compound represented by formula (1) and dimethyl oxalate represented by formula (2) is 1:3 to 4.

4. The method according to claim 3, characterized in that The cyclization reaction is carried out in the presence of a basic compound and a first organic solvent.

5. The method according to claim 4, characterized in that The basic compound is selected from one or more of sodium hydride, sodium methoxide and sodium ethoxide.

6. The method according to claim 4, characterized in that, The first organic solvent is tetrahydrofuran and / or dichloromethane.

7. The method according to any one of claims 2-6, characterized in that The conditions of the cyclization reaction include: the temperature is the reflux temperature and the time is 1.5 to 3 h.

8. The method according to claim 2, wherein In step (1), the hydrolysis reaction is carried out in the presence of an acidic solution.

9. The method according to claim 8, wherein The acidic solution is hydrochloric acid and / or sulfuric acid.

10. The method according to claim 8 or 9, characterized in that, The conditions of the hydrolysis reaction include: the temperature is 15 to 40 °C and the time is 0.5 to 3 h.

11. The method according to claim 2, wherein In step (2), the molar ratio of the amounts of the compound represented by formula (3) and the substituted aniline is 1:1 to 2.

12. The method according to claim 11, characterized in that, In step (2), the amidation reaction is carried out in the presence of a second organic solvent.

13. The method according to claim 12, wherein The second organic solvent is N,N -dimethylformamide and / or tetrahydrofuran.

14. The method according to any one of claims 11-13, characterized in that, In step (2), the conditions of the amidation reaction include: the temperature is 110 to 130 °C and the time is 2 to 3 h.

15. The method according to claim 2, wherein In step (3), the molar ratio of the amounts of the compound represented by formula (4) and the hydrazine hydrate is 1:1 to 2.

16. The method according to claim 15, wherein The ring transformation reaction is carried out in the presence of a third organic solvent.

17. The method according to claim 16, wherein The third organic solvent is ethanol and / or methanol.

18. The method according to any one of claims 15 - 17, characterized in that, The conditions of the ring transformation reaction include: the temperature is the reflux temperature and the time is 1 to 2 h.

19. The method according to claim 2, wherein In step (4), the molar equivalent ratio of the amounts of the compound represented by formula (5) and the brominating reagent is 1:3 to 4.

20. The method according to claim 19, wherein The bromination reagent is N N-bromosuccinimide and / or pyridinium tribromide.

21. The method according to claim 19, wherein The bromination reaction is carried out in the presence of a fourth organic solvent.

22. The method according to claim 21, wherein The fourth organic solvent is methanol and / or ethanol.

23. The method according to any one of claims 19-22, characterized in that, The conditions of the bromination reaction in step (4) include: the temperature is 15 to 40 °C and the time is 1 to 4 h.

24. Use of the polybromo- N -phenyl-5-o-hydroxyphenylpyrazole-3-carboxamide compound as an algicide.

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