阅读说明：本技术 一类2-亚氨基噻唑烷酮烯酯类化合物及其制备方法与应用 (2-iminothiazolidinone alkenyl ester compounds and preparation method and application thereof ) 是由 郑绿茵 邓凌 郭维 范小林 于 2021-08-16 设计创作，主要内容包括：本发明提供了一类2-亚氨基噻唑烷酮烯酯类化合物,属于药物化学技术领域,本发明的2-亚氨基噻唑烷酮烯酯类化合物,具有杀死血吸虫成虫的作用,克服了现有抗血吸虫病药物长期用药产生的抗药导致的疗效差或治疗无效的技术问题,对寻找新的抗血吸虫病药物具有重要的科学价值和研究价值。(The 2-iminothiazolidone alkene ester compound has the effect of killing schistosome adult insects, overcomes the technical problem of poor curative effect or ineffective treatment caused by drug resistance generated by long-term drug administration of the existing anti-schistosomiasis drugs, and has important scientific value and research value for searching new anti-schistosomiasis drugs.)

1. The 2-iminothiazolidone alkene ester compound is characterized in that the structure of the 2-iminothiazolidone alkene ester compound is shown as the general formula I:

wherein R is₁Is aryl or nitrogen-containing alkyl, R₂Is a halogen-substituted aryl group or an alkyl-substituted aryl group.

2. 2-iminothiazolidinone alkenyl esters according to claim 1, wherein R is₁Is composed of

Any one of them.

3. 2-iminothiazolidinone alkenyl esters according to claim 1, wherein R is₂Is composed of

Any one of them.

4. The 2-iminothiazolidinone alkene ester compound according to claim 1, wherein the 2-iminothiazolidinone alkene ester compound is any one of:

5. a process for preparing 2-iminothiazolidinone alkene ester compounds according to any one of claims 1 to 4, wherein the process is obtained by the following reaction scheme:

wherein R is₃Is halogen or alkyl.

6. According to claimThe process according to claim 5, wherein R is₁-NH₂The R is₃The molar ratio of the substituted phenyl isothiocyanate to the diethyl acetylenedicarboxylate is 1:1: 1.

7. The use of 2-iminothiazolidinone alkene ester compounds according to any one of claims 1 to 4 for the preparation of anti-schistosome drugs.

8. The use according to claim 7, wherein the use is for killing adult schistosomes.

9. An anti-schistosome drug is characterized in that the active ingredients of the anti-schistosome drug are one or more of the 2-iminothiazolidinone alkene ester compounds according to any one of claims 1 to 4.

10. The medicament of claim 9, further comprising a pharmaceutically acceptable salt.

Technical Field

The invention relates to the technical field of medicinal chemistry, in particular to 2-iminothiazolidinone alkene ester compounds and a preparation method and application thereof.

Background

Schistosomiasis remains as an important zoonosis seriously harming human health up to now, and is an epidemic disease caused by infecting six main schistosomiasis species including Schistosoma mansoni, Schistosoma Egypti, Schistosoma japonicum, Schistosoma meibomiae, Schistosoma malabaricum and Schistosoma intermediums. Schistosomiasis is prevalent in more than 70 countries, both tropical and subtropical, with approximately 20 million people dying from schistosomiasis each year.

Because no effective vaccine for resisting schistosomiasis infection exists at present, the elimination of an infection source through chemotherapy becomes an irreplaceable means for blocking the epidemic of schistosomiasis. The research on schistosomiasis treatment drugs has been continuously progressed in the last century, and the drugs for schistosomiasis treatment include potassium antimonium tartrate, furylamine, nitrothiocyanamide, imitriptolide, cyclosporine, lucanthone, pyranthrone and oxaniquine, and the drugs play a certain role in schistosomiasis treatment, but have large side effects and insignificant curative effect, so that the drugs are eliminated quickly. In the 70 s of the 20 th century, the emergence of praziquantel is an important milestone in the development history of schistosomiasis treatment medicines, and has the advantages of high efficiency, low toxicity, oral administration, short curative effect and the like, so that the praziquantel can quickly replace all the previous schistosomiasis treatment medicines which are popularized and used all over the world and become the only medicine for schistosomiasis treatment, and because the praziquantel is widely and chronically used, the schistosomiasis generation drug resistance risk is increased, and the cure rate of the praziquantel is lower. Therefore, the research on novel anti-schistosome drugs which have high efficiency and low toxicity and can replace praziquantel has very important significance for schistosomiasis control work.

Disclosure of Invention

The invention aims to provide a 2-iminothiazolidone alkenyl ester compound, and the novel 2-iminothiazolidone alkenyl ester compound has a killing effect on adult schistosomes.

In order to achieve the above object, the present invention provides the following technical solutions:

the invention provides 2-iminothiazolidone alkene ester compounds, wherein the 2-iminothiazolidone alkene ester compounds have a structure shown in a general formula I:

wherein R is₁Is aryl or nitrogen-containing alkyl, R₂Is a halogen-substituted aryl group or an alkyl-substituted aryl group.

Preferably, said R is₁Is composed of

Any one of them.

Preferably, said R is₂Is composed of

Any one of them.

Preferably, the 2-iminothiazolidinone alkene ester compound is any one of the following:

the invention also provides a preparation method of any one 2-iminothiazolidinone alkene ester compound, which is obtained by the following reaction scheme:

wherein R is₃Is halogen or alkyl.

Preferably, said R is₁-NH₂The R is₃The molar ratio of the substituted phenyl isothiocyanate to the diethyl acetylenedicarboxylate is 1:1: 1.

The invention also provides an application of any 2-iminothiazolidone alkene ester compound in preparing anti-schistosome drugs.

Preferably, the application is used for killing adult schistosomes.

The invention also provides an anti-schistosome drug, wherein the active component of the anti-schistosome drug is one or more of any 2-iminothiazolidinone alkene ester compounds.

Preferably, the medicament further comprises a pharmaceutically acceptable salt.

Compared with the prior art, the technical scheme of the invention has the following beneficial effects:

(1) the invention provides 2-iminothiazolidone alkene ester compounds for the first time, which can be used for preparing medicaments for treating schistosomiasis, have killing effect on schistosomiasis japonica adults and overcome the technical problem of poor curative effect or ineffective treatment caused by drug resistance generated by long-term administration of the existing anti-schistosomiasis medicaments.

(2) The preparation method of the 2-iminothiazolidinone alkene ester compound is simple and convenient to operate and high in yield.

Drawings

FIG. 1 is a general formula I of 2-iminothiazolidinone alkene ester compounds

FIG. 2 is an infrared spectrum of Compound 1;

FIG. 3 is an infrared spectrum of Compound 2;

FIG. 4 is an infrared spectrum of Compound 3;

FIG. 5 is an infrared spectrum of Compound 4;

FIG. 6 is an infrared spectrum of Compound 5;

FIG. 7 is an infrared spectrum of Compound 6;

FIG. 8 is an infrared spectrum of Compound 7;

FIG. 9 is an infrared spectrum of Compound 8;

FIG. 10 is an infrared spectrum of Compound 9;

FIG. 11 is an infrared spectrum of Compound 10;

FIG. 12 is an infrared spectrum of Compound 11;

FIG. 13 is an infrared spectrum of Compound 12;

FIG. 14 is an infrared spectrum of Compound 13;

FIG. 15 is an infrared spectrum of Compound 14;

FIG. 16 is an infrared spectrum of Compound 15;

FIG. 17 is an infrared spectrum of Compound 16;

FIG. 18 is an infrared spectrum of Compound 17;

FIG. 19 is an infrared spectrum of Compound 18;

FIG. 20 is an infrared spectrum of Compound 19;

FIG. 21 is an infrared spectrum of Compound 20;

FIG. 22 is an infrared spectrum of Compound 21;

FIG. 23 is an infrared spectrum of Compound 22;

FIG. 24 is an infrared spectrum of Compound 23;

FIG. 25 is an infrared spectrum of Compound 24;

fig. 26 is an infrared spectrum of compound 25.

Detailed Description

The invention provides 2-iminothiazolidone alkene ester compounds, wherein the 2-iminothiazolidone alkene ester compounds have a structure shown in a general formula I:

wherein R is₁Is aryl or nitrogen-containing alkyl, R₂Is a halogen-substituted aryl group or an alkyl-substituted aryl group.

In the present invention, said R₁Preferably, it is

Any one of the above; the R is₂Preferably, it is

Any one of them.

The 2-iminothiazolidinone alkene ester compound is preferably any one of the following compounds:

the invention also provides a preparation method of any one 2-iminothiazolidinone alkene ester compound, which is obtained by the following reaction scheme:

wherein R is₃Is halogen or alkyl.

In the invention, the method specifically comprises the following steps: r substituted by amino in a molar ratio of 1:1:1₁-NH₂、R₃Mixing substituted phenyl isothiocyanate, diethyl acetylenedicarboxylate and 2mL ethanol, reacting for 12h at room temperature under white light, and separating by TLC separation method to obtain 2-iminothiazolidinone alkenyl ester compounds. The preparation method is simple and convenient to operate, and the yield of the obtained target compound is high.

The invention also provides an application of any 2-iminothiazolidone alkene ester compound in preparing anti-schistosome drugs.

In the present invention, the application is preferably used for killing adult schistosomes.

The invention also provides an anti-schistosome drug, wherein the active component of the anti-schistosome drug is one or more of any 2-iminothiazolidinone alkene ester compounds.

In the present invention, the medicament preferably further comprises a pharmaceutically acceptable salt; the mass percentage content of the 2-iminothiazolidinone alkene ester compound in the medicine is preferably 0.05-99%, and more preferably 0.1-70%; the medicament is preferably in the form of tablets, granules, powder, solutions, emulsions, suspensions, syrups, injections or capsules.

In the present invention, all the raw material components are commercially available products well known to those skilled in the art unless otherwise specified.

The technical solution of the present invention will be clearly and completely described below with reference to the embodiments of the present invention. It is to be understood that the described embodiments are merely exemplary of the invention, and not restrictive of the full scope of the invention. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.

Example 1

(1) Preparation of Compound 1

0.25mmol of 1-1 of the compound, 0.25mmol of phenyl isothiocyanate, 0.25mmol of diethyl acetylenedicarboxylate and 2mL of ethanol were mixed, reacted at room temperature for 12 hours under white light, and separated by TLC separation to obtain 24.9mg of 1 compound with a yield of 23.9%. Compound 1 was analyzed and characterized:

IR(KBr,cm^-1)2935.40,2794.11,1720.01,1638.86,1592.61,1388.60,1314.82,1190.96,1028.20,854.21,762.15,695.75,476.40；¹H NMR(400MHz,CDCl₃)δ＝7.34(t,J＝7.9Hz,2H),7.15(t,J＝7.5Hz,1H),6.94(d,J＝7.3Hz,2H),6.87(s,1H),4.23(q,J＝7.1Hz,2H),4.03(t,J＝7.1Hz,2H),2.45(t,J＝7.0Hz,10H),2.24(s,3H),1.94(dd,J＝14.1,7.1Hz,2H),1.28(t,J＝7.1Hz,3H).¹³C NMR(100MHz,CDCl₃)δ＝165.9(s),165.0(s),151.1(s),147.3(s),141.6(s),129.3(s),125.1(s),121.0(s),116.1(s),61.6(s),55.8(s),55.0(s),53.0(s),45.9(s),41.7(s),24.2(s),14.1(s).HRMS(ESI):calcd.for C₂₁H₂₈N₄O₃S[M+H]⁺417.19549, found417.19727. the identification data indicate successful preparation of Compound 1.

(2) Preparation of Compound 2

0.25mmol of compound 2-1, 0.25mmol of phenyl isothiocyanate, 0.25mmol of diethyl acetylenedicarboxylate and 2mL of ethanol were mixed, reacted at room temperature for 12 hours under white light, and separated by TLC separation to obtain 21mg of compound 2 with a yield of 24.2%. Analysis and profile characterization of compound 2:

IR(KBr,cm^-1)2942.38,2770.36,1721.20,1641.43,1593.41,1388.39,1315.85,1193.33,1027.68,858.91,764.30,646.49；¹H NMR(400MHz,CDCl₃)δ＝7.35(dd,J＝8.2,7.6Hz,2H),7.17(t,J＝7.5Hz,1H),6.97(d,J＝7.3Hz,2H),6.89(s,1H),4.24(q,J＝7.1Hz,2H),4.10(t,J＝6.7Hz,2H),2.69(t,J＝6.7Hz,2H),2.31(s,6H),1.29(t,J＝7.1Hz,3H).¹³C NMR(100MHz,CDCl₃)δ＝166.0(s),165.0(s),151.0(s),147.3(s),141.5(s),129.3(s),125.1(s),121.0(s),116.4(s),61.6(s),56.0(s),45.6(s),40.8(s),14.1(s).HRMS(ESI):calcd.for C₁₇H₂₁N₃O₃S[M+H]⁺348.13764, found 348.13747. the data indicate successful preparation of Compound 2.

(3) Preparation of Compound 3

0.25mmol of compound 3-1, 0.25mmol of phenyl isothiocyanate, 0.25mmol of diethyl acetylenedicarboxylate and 2mL of ethanol were mixed, reacted at room temperature for 12 hours under white light, and separated by TLC separation to obtain 26.4mg of compound 3 with a yield of 28.2%. Analysis and profile characterization of compound 3:

IR(KBr,cm^-1)2967.95,2800.00,1720.33,1639.22,1593.52,1315.51,1191.92,1028.45,762.48,696.10,470.69；¹H NMR(400MHz,CDCl₃)δ＝7.37–7.32(m,2H),7.18–7.13(m,1H),6.99–6.94(m,2H),6.88(s,1H),4.26–4.20(m,2H),4.07–4.02(m,2H),2.83–2.78(m,2H),2.58(q,J＝7.1Hz,4H),1.31–1.27(m,3H),1.04–0.99(m,6H).¹³C NMR(100MHz,CDCl₃)δ＝166.0(s),164.9(s),151.0(s),147.4(s),141.6(s),129.3(s),125.1(s),121.0(s),116.2(s),61.6(s),49.0(s),47.3(s),40.9(s),14.1(s),12.2(s).HRMS(ESI):calcd.for C₁₉H₂₅N₃O₃S[M+H]⁺376.16894, found 376.17009. the data indicate successful preparation of Compound 3.

0.25mmol of 4-1 of the compound, 0.25mmol of phenyl isothiocyanate, 0.25mmol of diethyl acetylenedicarboxylate and 2mL of ethanol were mixed, reacted at room temperature for 12 hours under white light, and separated by TLC separation to obtain 28.1mg of the compound 4 with a yield of 31.1%. Analysis and profile characterization of compound 4:

IR(KBr,cm^-1)2934.58,2822.43,1728.97,1644.86,1591.59,1384.11,1314.02,1201.87,1025.23,862.62,758.88,702.80；¹H NMR(400MHz,CDCl₃)δ＝7.37–7.32(m,2H),7.19–7.14(m,1H),6.99–6.94(m,2H),6.89(s,1H),4.24(q,J＝7.1Hz,2H),4.06–4.00(m,2H),2.39(t,J＝7.2Hz,2H),2.24(s,6H),1.94(dt,J＝14.4,7.2Hz,2H),1.29(t,J＝7.1Hz,3H).¹³C NMR(100MHz,CDCl₃)δ＝166.0(s),165.0(s),151.0(s),147.4(s),141.5(s),129.3(s),125.1(s),121.0(s),116.3(s),61.6(s),56.9(s),45.3(s),41.5(s),29.7(s),29.3(s),25.4(s),14.1(s).HRMS(ESI):calcd.for C₁₈H₂₃N₃O₃S[M+H]⁺362.15329, found 362.15312. The identification data indicates that compound 4 was successfully prepared.

(5) Preparation of Compound 5

0.25mmol of compound 5-1, 0.25mmol of phenyl isothiocyanate, 0.25mmol of diethyl acetylenedicarboxylate and 2mL of ethanol were mixed, reacted at room temperature for 12 hours under white light, and separated by TLC separation to obtain 32.3mg of compound 5, the yield was 32.1%. Analysis and profile characterization of compound 5:

IR(KBr,cm^-1)2956.02,2853.75,1720.01,1640.64,1593.11,1315.78,1193.18,1117.64,1027.53,862.33,762.45,696.74；¹H NMR(400MHz,CDCl₃)δ＝7.37–7.31(m,2H),7.18–7.13(m,1H),6.94(dt,J＝8.5,1.7Hz,2H),6.87(s,1H),4.28–4.18(m,2H),4.09–4.00(m,2H),3.69–3.62(m,4H),2.47–2.40(m,6H),1.95(p,J＝6.9Hz,2H),1.28(t,J＝7.1Hz,3H).¹³C NMR(100MHz,CDCl₃)δ＝165.9(s),165.0(s),151.1(s),147.3(s),141.6(s),129.3(s),125.1(s),120.9(s),116.2(s),66.9(s),61.6(s),56.3(s),53.6(s),41.6(s),23.8(s),14.1(s).HRMS(ESI):calcd.for C₂₀H₂₅N₃O₄S[M+H]⁺404.16385, found 404.16444. the data indicate successful preparation of Compound 5.

0.25mmol of compound 6-1, 0.25mmol of phenyl isothiocyanate, 0.25mmol of diethyl acetylenedicarboxylate and 2mL of ethanol were mixed, reacted at room temperature for 12 hours under white light, and separated by TLC separation to obtain 24.5mg of compound 6 with a yield of 25.2%. Compound 6 was analyzed and characterized:

IR(KBr,cm^-1)2957.62,2853.52,2809.39,1720.56,1641.54,1593.13,1444.62,1383.60,1315.97,1117.13,1028.22,858.42,763.9,697.31；¹H NMR(400MHz,CDCl₃)δ＝7.35(t,J＝7.9Hz,2H),7.17(t,J＝8.5Hz,1H),6.95(d,J＝7.3Hz,2H),6.89(s,1H),4.25(q,J＝7.1Hz,2H),4.11(t,J＝6.4Hz,2H),3.68–3.64(m,4H),2.74(t,J＝6.4Hz,2H),2.56(s,4H),1.30(t,J＝7.1Hz,3H).¹³C NMR(100MHz,CDCl3)δ＝166.0(s),165.0(s),151.1(s),147.3(s),141.5(s),129.4(s),125.2(s),121.0(s),116.4(s),77.3(s),77.0(s),76.7(s),67.0(s),61.7(s),55.2(s),53.6(s),39.8(s),29.8(s),14.1(s).HRMS(ESI):calcd.for C₁₉H₂₃N₃O₄S[M+H]⁺390.14820, found 390.14796. the data indicate successful preparation of Compound 6.

0.25mmol of compound 7-1, 0.25mmol of phenyl isothiocyanate, 0.25mmol of diethyl acetylenedicarboxylate and 2mL of ethanol were mixed, reacted at room temperature for 12 hours under white light, and separated by TLC separation to obtain 29.9mg of compound 7 with a yield of 31%. Analysis and profile characterization of compound 7:

IR(KBr,cm^-1)2928.12,2787.11,1721.58,1642.04,1315.85,1193.5,1028.2,763.66,697.11；¹H NMR(400MHz,CDCl₃)δ＝7.37–7.32(m,2H),7.16(t,J＝7.5Hz,1H),6.96(d,J＝7.3Hz,2H),6.88(s,1H),4.24(q,J＝7.1Hz,2H),4.05(t,J＝7.1Hz,2H),2.61(dd,J＝15.9,8.3Hz,6H),2.04–1.99(m,2H),1.81–1.75(m,4H),1.28(d,J＝7.1Hz,3H).¹³C NMR(100MHz,CDCl₃)δ＝165.9(s),165.0(s),151.1(s),147.3(s),141.5(s),129.3(s),125.2(s),121.0(s),116.3(s),54.1(s),53.7(s),41.6(s),29.7(s),26.4(s),23.4(s),14.1(s).HRMS(ESI):calcd.for C₂₀H₂₅N₃O₃S[M+CH₃OH H]⁺420.19515, found 420.19438. the data indicate successful preparation of Compound 7.

0.25mmol of compound 8-1, 0.25mmol of phenyl isothiocyanate, 0.25mmol of diethyl acetylenedicarboxylate and 2mL of ethanol were mixed, reacted at room temperature for 12 hours under white light, and separated by TLC separation to obtain 27mg of compound 8 with a yield of 29%. Analysis and profile characterization of compound 8:

IR(KBr,cm^-1)2961.34,2792.04,1722.32,1643.16,1593.46,1383.87,1315.7,1193.43,1027.88,763.12,696.59；¹H NMR(400MHz,CDCl₃)δ＝7.35(t,J＝7.9Hz,2H),7.16(t,J＝7.5Hz,1H),6.96(d,J＝7.3Hz,2H),6.89(s,1H),4.27–4.22(m,2H),4.13(t,J＝6.8Hz,2H),2.86(t,J＝6.8Hz,2H),2.63(t,J＝6.6Hz,4H),1.80–1.76(m,4H),1.30(d,J＝7.1Hz,3H).¹³C NMR(100MHz,CDCl₃)δ＝166.0(s),165.0(s),151.0(s),147.4(s),141.6(s),129.3(s),125.1(s),121.0(s),116.3(s),61.6(s),54.3(s),52.8(s),41.9(s),23.6(s),14.1(s).HRMS(ESI):calcd.for C₁₉H₂₃N₃O₃S[M+CH₃OH H]⁺406.17950, found 406.17862. the data indicate successful preparation of Compound 8.

(9) Preparation of Compound 9

0.25mmol of compound 9-1, 0.25mmol of phenyl isothiocyanate, 0.25mmol of diethyl acetylenedicarboxylate and 2mL of ethanol were mixed, reacted at room temperature for 12 hours under white light, and separated by TLC to obtain 22mg of compound 9 with a yield of 22.7%. Compound 9 was analyzed and characterized:

IR(KBr,cm^-1)2934.27,2852.60,2799.31,1721.27,1641.61,1593.59,1443.34,1315.62,1193.19,1123.81,1028.27,859.61,763.34,696.40；¹H NMR(400MHz,CDCl₃)δ＝7.36–7.31(m,2H),7.15(t,J＝7.5Hz,1H),6.95(d,J＝7.3Hz,2H),6.88(s,1H),4.23(q,J＝7.1Hz,2H),4.10(t,J＝6.8Hz,2H),2.68(t,J＝6.8Hz,2H),2.48(s,4H),1.53(dt,J＝10.9,5.6Hz,4H),1.40(dd,J＝11.2,5.9Hz,2H),1.28(t,J＝7.1Hz,3H).¹³C NMR(100MHz,CDCl₃)δ＝165.9(s),164.9(s),151.0(s),147.4(s),141.6(s),129.3(s),125.0(s),121.0(s),116.1(s),61.5(s),55.3(s),54.6(s),40.3(s),26.0(s),24.2(s),14.1(s).HRMS(ESI):calcd.for C₂₀H₂₅N₃O₃S[M+H]⁺388.16894, found 388.17091. the data indicate successful preparation of Compound 9.

0.25mmol of compound 10-1, 0.25mmol of phenyl isothiocyanate, 0.25mmol of diethyl acetylenedicarboxylate and 2mL of ethanol were mixed, reacted at room temperature for 12 hours under white light, and separated by TLC separation to obtain 36.6mg of compound 10 with a yield of 40%. Analysis and profile characterization of compound 10:

IR(KBr,cm^-1)3418.16,2980.4,1770.2,1642.58,1383.8,1316.36,1194.65,1028.7,760.11,697.09,532.42；¹H NMR(400MHz,CDCl₃,ppm)δ＝7.53-7.51(d,J＝8Hz,2H),7.37-7.28(m,5H),7.18-7.15(t,J＝8Hz,1H),6.97-6.95(d,J＝8Hz,2H),6.90(s,1H),5.14(s,2H),4.26-4.21(q,J＝8Hz,2H),1.30-1.27(t,J＝8Hz,3H)；¹³C NMR(100MHz,CDCl₃,ppm)δ＝165.9(s),164.9(s),150.8(s),147.2(s),141.4(s),135.6(s),129.4(s),129.1(s),128.6(s),128.1(s),125.2(s),121.1(s),116.6(s),61.7(s),46.2(s),14.2(s).HRMS(ESI):calcd.for C₂₀H₁₈N₂O₃S[M+H]⁺367.11109, found 367.11072. the data indicate successful preparation of Compound 10.

(11) Preparation of Compound 11

0.25mmol of compound 11-1, 0.25mmol of phenyl isothiocyanate, 0.25mmol of diethyl acetylenedicarboxylate and 2mL of ethanol were mixed, reacted at room temperature for 12 hours under white light, and separated by TLC separation to obtain 31.2mg of compound 11 with a yield of 26.2%. Compound 11 was analyzed and characterized:

IR(KBr,cm^-1)3063.55,2924.28,2853.30,1719.51,1641.24,1593.17,1391.5,1315.50,1192.88,1028.05,857.01,763.55,696.78；¹H NMR(400MHz,CDCl₃)δ＝7.35(t,J＝7.9Hz,2H),7.31(d,J＝4.4Hz,4H),7.24(d,J＝4.3Hz,1H),7.17(t,J＝6.9Hz,1H),6.95(d,J＝7.3Hz,2H),6.89(s,1H),4.24(q,J＝7.1Hz,2H),4.05–3.96(m,2H),3.50(s,2H),2.89(d,J＝11.3Hz,2H),1.96(t,J＝10.9Hz,2H),1.78(d,J＝9.1Hz,2H),1.71(dd,J＝13.4,6.6Hz,2H),1.30(t,J＝7.1Hz,6H).¹³C NMR(100MHz,CDCl₃)δ＝165.9(s),164.9(s),150.9(s),147.3(s),141.5(s),138.3(s),129.3(s),129.2(s),128.1(s),126.9(s),125.1(s),121.0(s),116.3(s),63.3(s),61.6(s),53.6(s),41.0(s),34.0(s),33.5(s),32.0(s),29.7(s),14.1(s).HRMS(ESI):calcd.for C₂₇H₃₁N₃O₃S[M+H]⁺478.21589, found 478.21621. the data indicate successful preparation of Compound 11.

0.25mmol of compound 1-1, 0.25mmol of 12-1, 0.25mmol of diethyl acetylenedicarboxylate and 2mL of ethanol were mixed, reacted at room temperature for 12 hours under white light, and separated by TLC to obtain 17.9mg of compound 12 with a yield of 16.1%. Analysis and profile characterization of compound 12:

IR(KBr,cm^-1)2934.93,2794.48,1720.54,1640.77,1507.48,1388.91,1314.89,1192.25,1029.56,859.81,756.07；¹HNMR(400MHz,CDCl₃)δ＝7.17(d,J＝8.4Hz,2H),6.90–6.85(m,3H),4.24(q,J＝7.1Hz,2H),4.03(t,J＝7.1Hz,2H),2.64(q,J＝7.6Hz,2H),2.46(t,J＝7.0Hz,10H),2.24(s,3H),1.95(p,J＝7.0Hz,2H),1.31–1.24(m,6H).¹³C NMR(100MHz,CDCl₃)δ＝166.0(s),165.1(s),150.7(s),145.0(s),141.9(s),141.2(s),128.7(s),120.9(s),116.0(s),61.6(s),55.8(s),55.0(s),53.0(s),45.9(s),41.7(s),28.3(s),24.3(s),15.5(s),14.1(s).HRMS(ESI):calcd.for C₂₃H₃₃N₄O₃S[M+H]⁺445.22679, found 445.22643. the data indicate successful preparation of Compound 12.

0.25mmol of compound 1-1, 0.25mmol of 13-1, 0.25mmol of diethyl acetylenedicarboxylate and 2mL of ethanol were mixed, reacted at room temperature for 12 hours under white light, and separated by TLC to obtain 20mg of compound 13 with a yield of 18%. Compound 13 was analyzed and characterized:

IR(KBr,cm^-1)2936.57,2794.57,1718.56,1637.13,1505.44,1390.13,1244.47,1193.11,1031.94,834.00,761.03,556.79；¹H NMR(400MHz,CDCl₃)δ＝6.95–6.82(m,5H),4.24(q,J＝7.1Hz,2H),4.02(t,J＝7.1Hz,2H),3.80(s,3H),2.45(t,J＝7.0Hz,10H),2.23(s,3H),1.99–1.89(m,2H),1.29(t,J＝7.1Hz,3H).¹³C NMR(100MHz,CDCl₃)δ＝166.0(s),165.0(s),157.2(s),150.7(s),141.8(s),140.5(s),122.2(s),1156.0(s),114.6(s),61.6(s),55.8(s),55.5(s),55.1(s),53.1(s),46.0(s),41.7(s),24.3(s),14.1(s).HRMS(ESI):calcd.for C₂₂H₃₀N₄O₄S[M+H]⁺447.20605, found447.20567. the data indicate successful preparation of compound 13.

0.25mmol of compound 1-1, 0.25mmol of compound 14-1, 0.25mmol of diethyl acetylenedicarboxylate and 2mL of ethanol were mixed, reacted at room temperature for 12 hours under white light, and separated by TLC separation to obtain 17.2mg of compound 14 with a yield of 15%. Analysis and profile characterization of compound 14: IR (KBr, cm)^-1)2934.07,2794.63,1725.57,1642.33,1584.15,1458.37,1315.67,1193.50,1030.17,758.62；¹H NMR(400MHz,CDCl₃)δ＝7.42(dd,J＝8.0,1.3Hz,1H),7.23(td,J＝7.7,1.4Hz,1H),7.10(td,J＝7.8,1.6Hz,1H),6.94(dd,J＝7.8,1.5Hz,1H),6.91(s,1H),4.24(q,J＝7.1Hz,2H),4.06(t,J＝7.0Hz,2H),2.48(t,J＝6.9Hz,10H),2.24(s,3H),2.00(dd,J＝14.1,7.0Hz,2H),1.29(t,J＝7.1Hz,3H).¹³C NMR(100MHz,CDCl3)δ＝165.9(s),165.0(s),153.0(s),144.5(s),141.3(s),130.2(s),127.6(s),126.5(s),126.1(s),121.7(s),116.7(s),61.7(s),55.8(s),55.0(s),52.9(s),45.9(s),41.8(s),24.2(s),14.1(s).HRMS(ESI):calcd.for C₂₁H₂₇N₄O₃SCl[M+H]⁺451.15652, found 451.15629 data, indicating successful preparation of Compound 14.

0.25mmol of compound 1-1, 0.25mmol of compound 15-1, 0.25mmol of diethyl acetylenedicarboxylate and 2mL of ethanol were mixed, reacted at room temperature for 12 hours under white light, and separated by TLC separation to obtain 16.3mg of compound 15 with a yield of 13%. Analysis and profile characterization of compound 15:

IR(KBr,cm^-1)2936.43,2793.81,1723.87,1696.71,1641.46,1579.92,1465.83,1315.63,1193.23,1027.82,758.99；¹H NMR(400MHz,CDCl₃)δ＝7.58(dd,J＝8.0,1.3Hz,1H),7.29–7.24(m,1H),7.01(td,J＝7.8,1.5Hz,1H),6.94–6.87(m,2H),4.22(q,J＝7.1Hz,2H),4.04(t,J＝7.1Hz,2H),2.61–2.29(m,10H),2.22(s,3H),1.98(dd,J＝14.0,7.0Hz,2H),1.27(t,J＝7.1Hz,3H).¹³C NMR(100MHz,CDCl₃)δ＝165.8(s),164.9(s),152.9(s),145.9(s),141.3(s),133.2(s),128.2(s),126.3(s),121.4(s),116.6(d,J＝11.1Hz),61.7(s),55.8(s),55.0(s),52.9(s),45.9(s),41.8(s),24.3(s),14.1(s).HRMS(ESI):calcd.for C₂₁H₂₇N₄O₃SBr[M+H]⁺495.10600, found 495.10582. the data indicate successful preparation of Compound 15.

0.25mmol of compound 1-1, 0.25mmol of 16-1, 0.25mmol of diethyl acetylenedicarboxylate and 2mL of ethanol were mixed, reacted at room temperature for 12 hours under white light, and separated by TLC to obtain 16.5mg of compound 16 with a yield of 13.6%. Analysis and profile characterization of compound 16:

IR(KBr,cm^-1)2937.53,2795.521726.68,1644.29,1579.07,1371.70,1264.02,1194.74,1130.11,1033.22,859.82,761.80；¹H NMR(400MHz,CDCl₃)δ7.36–7.31(m,2H),7.15(t,J＝7.5Hz,1H),6.95(d,J＝7.3Hz,2H),6.88(s,1H),4.23(q,J＝7.1Hz,2H),4.10(t,J＝6.8Hz,2H),2.68(t,J＝6.8Hz,2H),2.48(s,4H),1.53(dt,J＝10.9,5.6Hz,4H),1.40(dd,J＝11.2,5.9Hz,2H),1.28(t,J＝7.1Hz,3H).¹³C NMR(100MHz,CDCl₃)δ165.3(d,J＝107.3Hz),164.8(s),152.6(s),145.5(s),141.0(s),132.8(s),126.8(dd,J＝10.5,5.3Hz),124.8(d,J＝18.6Hz),122.2(t,J＝30.2Hz),121.6(d,J＝61.7Hz),116.9(s),61.7(s),55.7(s),55.0(s),52.8(s),45.9(s),41.8(s),24.1(s),14.0(s).HRMS(ESI):calcd.for C₂₂H₂₇N₄O₃F₃S[M+H]⁺485.18287, found 485.18233. the data indicate successful preparation of Compound 16.

0.25mmol of compound 1-1, 0.25mmol of 17-1, 0.25mmol of diethyl acetylenedicarboxylate and 2mL of ethanol were mixed, reacted at room temperature for 12 hours under white light, and separated by TLC to obtain 18mg of compound 17 with a yield of 15.9%. Compound 17 was analyzed and characterized:

IR(KBr,cm^-1)2937.53,2795.07,1723.72,1642.36,1460.29,1316.24,1194.28,1028.99,865.13,694.65；¹H NMR(400MHz,CDCl₃)δ＝7.25(dd,J＝9.5,6.4Hz,1H),7.14–7.10(m,1H),6.93(t,J＝2.0Hz,1H),6.88(s,1H),6.81(ddd,J＝7.9,2.0,1.0Hz,1H),4.23(q,J＝7.1Hz,2H),3.99(t,J＝7.1Hz,2H),2.43(t,J＝6.9Hz,10H),2.22(s,3H),1.96–1.87(m,2H),1.27(d,J＝7.1Hz,3H).¹³C NMR(100MHz,CDCl₃)δ＝165.8(s),164.9(s),152.2(s),148.5(s),141.1(s),134.8(s),130.3(s),125.1(s),121.4(s),119.1(s),116.7(s),61.7(s),55.8(s),55.0(s),53.0(s),45.9(s),41.7(s),24.2(s),14.1(s).HRMS(ESI):calcd.for C₂₁H₂₇N₄O₃SCl[M+H]⁺451.15652, found 451.15644. the data indicate successful preparation of Compound 17.

0.25mmol of compound 1-1, 0.25mmol of 18-1, 0.25mmol of diethyl acetylenedicarboxylate and 2mL of ethanol were mixed, reacted at room temperature for 12 hours under white light, and separated by TLC to obtain 17.3mg of compound 18 with a yield of 14%. Analysis and profile characterization of compound 18:

IR(KBr,cm^-1)2936.52,2795.27,1721.28,1641.73,1581.67,1467.78,1370.53,1194.51,1021.65,864.15,784.15,695.01；¹H NMR(400MHz,CDCl₃)δ＝7.31–7.27(m,1H),7.20(t,J＝7.9Hz,1H),7.10(t,J＝1.9Hz,1H),6.90(s,1H),6.89–6.85(m,1H),4.24(t,J＝7.1Hz,2H),4.00(t,J＝7.1Hz,2H),2.44(t,J＝6.9Hz,10H),2.25(s,3H),1.97–1.88(m,2H),1.29(t,J＝7.1Hz,3H).¹³C NMR(100MHz,CDCl₃)δ＝165.8(s),164.9(s),152.3(s),148.7(s),141.1(s),130.6(s),128.0(s),124.2(s),122.9(s),119.6(s),116.7(s),61.7(s),55.8(s),55.0(s),53.0(s),45.9(s),41.7(s),24.2(s),14.1(s).HRMS(ESI):calcd.for C₂₁H₂₇N₄O₃SBr[M+H]⁺495.10600, found495.10574. the identification data indicates that compound 18 was successfully prepared.

0.25mmol of 1-1, 0.25mmol of 19-1, 0.25mmol of diethyl acetylenedicarboxylate and 2mL of ethanol were mixed, reacted at room temperature for 12 hours under white light, and separated by TLC to obtain 16.4mg of 19, the yield of which was 13.3%. Compound 19 was analyzed and characterized:

IR(KBr,cm^-1)2936.17,2794.92,1721.70,1638.95,1483.26,1315.47,1193.55,1009.94,828.97,761.68；¹H NMR(400MHz,CDCl₃)δ＝7.49–7.44(m,2H),6.89(s,1H),6.86–6.81(m,2H),4.25(q,J＝7.1Hz,2H),4.01(t,J＝7.1Hz,2H),2.45(t,J＝7.0Hz,10H),2.25(s,3H),1.94(dd,J＝14.1,7.0Hz,2H),1.31(d,J＝7.1Hz,3H).¹³C NMR(100MHz,CDCl₃)δ＝165.9(s),164.9(s),151.9(s),146.4(s),141.1(s),132.4(s),122.8(s),118.3(s),116.7(s),61.7(s),55.8(s),55.0(s),53.0(s),45.9(s),41.7(s),24.2(s),14.1(s).HRMS(ESI):calcd.for C₂₁H₂₇N₄O₃SBr[M+H]⁺495.10600, found495.10655. the identification data indicates that compound 19 was successfully prepared.

0.25mmol of compound 1-1, 0.25mmol of 20-1, 0.25mmol of diethyl acetylenedicarboxylate and 2mL of ethanol were mixed, reacted at room temperature for 12 hours under white light, and separated by TLC separation to obtain 19.2mg of compound 20 with a yield of 17%. Analysis and profile characterization of compound 20:

IR(KBr,cm^-1)2937.00,2795.57,1721.91,1638.59,1588.12,1486.44,1316.10,1194.18,1012.66,834.77,760.89,525.38；¹HNMR(400MHz,CDCl₃)δ＝7.34–7.28(m,2H),6.91–6.85(m,3H),4.24(q,J＝7.1Hz,2H),4.01(t,J＝7.1Hz,2H),2.44(t,J＝7.0Hz,10H),2.24(s,3H),1.97–1.89(m,2H),1.29(t,J＝7.1Hz,3H).13C NMR(100MHz,CDCl₃)δ＝165.8(s),164.9(s),151.9(s),145.9(s),141.1(s),130.6(s),129.4(s),122.4(s),116.6(s),61.7(s),55.8(s),55.0(s),53.0(s),45.9(s),41.7(s),24.2(s),14.1(s).HRMS(ESI):calcd.for C₂₁H₂₇N₄O₃SCl[M+H]⁺451.15652, found 451.15633. the data indicate successful preparation of Compound 20.

0.25mmol of 1-1, 0.25mmol of 21-1, 0.25mmol of diethyl acetylenedicarboxylate and 2mL of ethanol were mixed, reacted at room temperature for 12 hours under white light, and separated by TLC to obtain 19.3mg of 21, 15.9% yield. Compound 21 was analyzed and characterized:

IR(KBr,cm^-1)2933.34,2796.34,1725.74,1643.23,1459.60,1322.66,1194.69,1065.69,848.81,758.88,615.89,514.95；¹H NMR(400MHz,CDCl₃)δ＝7.60(d,J＝8.3Hz,2H),7.03(d,J＝8.2Hz,2H),6.90(s,1H),4.23(t,J＝7.1Hz,2H),4.02(t,J＝7.1Hz,2H),2.46(t,J＝6.9Hz,10H),2.24(s,3H),1.93(dd,J＝14.1,7.0Hz,2H),1.28(t,J＝7.1Hz,3H).¹³C NMR(100MHz,CDCl₃)δ165.8(s),164.9(s),151.4(d,J＝196.1Hz),140.9(s),127.1(d,J＝32.8Hz),126.8–126.4(m),121.3(s),116.9(s),61.8(s),55.8(s),55.0(s),52.9(s),45.9(s),41.7(s),24.2(s),14.1(s).HRMS(ESI):calcd.for C₂₂H₂₇N₄O₃F₃S[M+H]⁺485.18287, found 485.18292. the data indicate successful preparation of Compound 21.

(22) Preparation of Compound 22

0.25mmol of compound 1-1, 0.25mmol of 22-1, 0.25mmol of diethyl acetylenedicarboxylate and 2mL of ethanol were mixed, reacted at room temperature for 12 hours under white light, and separated by TLC to obtain 18.2mg of compound 22 with a yield of 16.8%. Analysis and profile characterization of compound 22:

IR(KBr,cm^-1)2937.45,2795.83,1721.72,1640.48,1503.27,1389.46,1316.09,1193.21,1029.18,841.07,761.20；¹H NMR(400MHz,CDCl₃)δ＝7.03(t,J＝8.6Hz,2H),6.94–6.86(m,3H),4.24(q,J＝7.1Hz,2H),4.01(t,J＝7.1Hz,2H),2.45(t,J＝7.0Hz,10H),2.25(s,3H),1.97–1.89(m,2H),1.28(t,J＝7.1Hz,3H).¹³C NMR(100MHz,CDCl₃)δ165.9(s),164.9(s),160.3(d,J＝244.1Hz),151.7(s),143.4(d,J＝2.9Hz),141.3(s),122.4(d,J＝8.2Hz),116.3(d,J＝22.8Hz),116.0(s),61.7(s),55.8(s),55.0(s),52.9(s),45.8(s),41.7(s),24.2(s),14.1(s).HRMS(ESI):calcd.for C₂₁H₂₇N₄O₃FS[M+H]⁺435.18607, found 435.18588. the data indicate successful preparation of Compound 22.

0.25mmol of 1-1, 0.25mmol of 23-1, 0.25mmol of diethyl acetylenedicarboxylate and 2mL of ethanol were mixed, reacted at room temperature for 12 hours under white light, and separated by TLC to obtain 14.9mg of 23, which is 13.2% yield. Compound 23 was analyzed and characterized:

IR(KBr,cm^-1)2934.58,2795.10,1728.57,1643.85,1613.50,1496.18,1386.03,1316.22,1194.58,1027.99,861.51,761.53；¹H NMR(400MHz,CDCl₃)δ＝7.03(td,J＝9.3,4.9Hz,1H),6.89(s,1H),6.82–6.75(m,1H),6.66(ddd,J＝9.2,6.3,3.1Hz,1H),4.22(q,J＝7.1Hz,2H),4.01(t,J＝6.9Hz,2H),2.42(t,J＝6.8Hz,10H),2.19(s,3H),1.92(dd,J＝13.7,6.9Hz,2H),1.27(t,J＝7.1Hz,3H).¹³C NMR(100MHz,CDCl₃)δ165.7(s),164.8(s),158.5(dd,J＝243.9,2.5Hz),154.4(s),149.8(dd,J＝242.7,2.9Hz),140.8(s),136.0(dd,J＝14.8,9.9Hz),117.1(d,J＝9.6Hz),117.0–116.8(m),112.1(dd,J＝23.9,7.5Hz),109.7(d,J＝25.4Hz),61.7(s),55.8(s),55.0(s),53.4(d,J＝96.3Hz),45.9(s),41.8(s),23.9(s),14.0(s).HRMS(ESI):calcd.for C₂₁H₂₆N₄O₃F₂S[M+Na]⁺475.15859, found 475.15750. the data indicate successful preparation of compound 23.

(24) Preparation of Compound 24

0.25mmol of compound 1-1, 0.25mmol of compound 24-1, 0.25mmol of diethyl acetylenedicarboxylate and 2mL of ethanol were mixed, reacted at room temperature for 12 hours under white light, and separated by TLC to obtain 19.7mg of compound 24 with a yield of 16.2%. Analysis and profile characterization of compound 24:

IR(KBr,cm^-1)2936.41,2795.27,1724.46,1639.69,1583.51,1467.67,1371.06,1315.87,1194.32,1027.22,871.03,758.88；¹H NMR(400MHz,CDCl₃)δ＝7.40(d,J＝8.5Hz,1H),7.05(d,J＝2.4Hz,1H),6.90(s,1H),6.80(dd,J＝8.5,2.5Hz,1H),4.25(q,J＝7.1Hz,2H),3.99(t,J＝7.1Hz,2H),2.43(t,J＝6.9Hz,10H),2.23(s,3H),1.91(p,J＝7.0Hz,2H),1.29(t,J＝7.1Hz,3H).¹³C NMR(100MHz,CDCl₃)δ＝165.8(s),164.8(s),152.8(s),146.8(s),140.7(s),133.1(s),131.0(s),128.7(s),123.1(s),120.5(s),117.0(s),61.8(s),55.8(s),55.0(s),53.0(s),45.9(s),41.7(s),24.2(s),21.0(s),14.1(s).HRMS(ESI):calcd.for C₂₁H₂₆N₄O₃SCl₂[M+H]⁺485.11754, found 485.11710. the data indicate successful preparation of Compound 24.

(25) Preparation of Compound 25

0.25mmol of compound 1-1, 0.25mmol of compound 25-1, 0.25mmol of diethyl acetylenedicarboxylate and 2mL of ethanol were mixed, reacted at room temperature for 12 hours under white light, and separated by TLC to obtain 20.2mg of compound 25 with a yield of 14.6%. Analysis and profile characterization of compound 25:

IR(KBr,cm^-1)2938.16,2796.82,1729.72,1641.45,1458.92,1317.12,1279.33,1137.41,1028.83,890.04,761.68,703.57,613.08；¹H NMR(400MHz,CDCl₃)δ＝7.67(s,1H),7.37(s,2H),6.94(s,1H),4.25(q,J＝7.1Hz,2H),4.02(t,J＝7.1Hz,2H),2.61–2.35(m,10H),2.25(s,3H),1.98–1.90(m,2H),1.28(d,J＝7.1Hz,3H).¹³C NMR(100MHz,CDCl₃)δ165.6(s),164.7(s),154.0(s),148.8(s),140.1(s),132.8(q,J＝33.6Hz),127.1(s),124.3(s),121.6(s),121.4(s),118.7–118.3(m),117.8(s),62.0(s),55.7(s),54.9(s),52.9(s),45.8(s),41.8(s),29.5(d,J＝38.3Hz),24.1(s),14.0(s).HRMS(ESI):calcd.for C₂₃H₂₆N₄O₃F₆S[M+H]⁺553.17026, found 553.17020. the data indicate successful preparation of Compound 25.

Example 2: in vitro adult killing activity test

(1) In vitro adult killing activity test

Collecting living 45-day schistosoma japonicum adults, placing the living 45-day schistosoma japonicum adults in RPMI-1640 culture solution (10 strips/3 mL/dish), adding 3 mu L of each compound into each dish, wherein the final concentration of each compound is 0.5mmol/L, 0.1mmol/L and 0.05mmol/L, adding 3 mu L of DMSO into a control group, fully shaking up after adding drugs, placing the control group in a 37 ℃ and 5% CO2 incubator, washing the schistosoma japonicum by using physiological saline for 3 times after culturing for 16h, adding fresh culture solution, observing the vitality state of the schistosoma japonicum cultured for 24-72 h under a stereoscopic microscope, wherein praziquantel is a positive control, namely adding 3 mu L of 50 mu mol/mL praziquantel solution into 3mL culture solution to obtain 50 mu mol/L praziquantel liquid medicine; negative control is 3. mu.L of solvent DMSO added to the culture medium; blank controls did not add any reagents to the culture. The results are shown in Table 1.

TABLE 1 Effect of 1-25 Compounds on killing adult schistosoma japonicum katsurada in 45 days

Compound (I)	Grade of death	Compound (I)	Grade of death
				1	B	14	A
2	B	15	A
				3	B	16	A
4	B	17	A
				5	D	18	B
6	C	19	A
				7	C	20	A
8	C	21	A
				9	C	22	A
10	C	23	A
				11	C	24	A
12	C	25	A
				13	B	Praziquantel	A
Blank control	D	Negative control	D

In the death grade shown in the table 1, when the medicine concentration is 0.05mmol/L, the death rate of the adult within 72h is 100 percent; b is that when the drug concentration is 0.1mmol/L, the death rate of the adult within 72h is 100 percent; c is that when the concentration of the medicine is 0.5mmol/L, the death rate of the adult within 72h is 100 percent; d is the death rate of the adult within 72h when the drug concentration is 0.5 mmol/L.

Example 3: in vivo anti-schistosome adult action

Culturing 12 mice infected with 50 cercaria for 35 days, dividing into A, B, C, D groups, weighing 3 mice, weighing compound 1, compound 2, and compound 3, respectively weighing 120mg, and ultrasonic dissolving with 5mL edible oil to obtain 24mg/mL compound 1, compound 2, and compound 3 solutions.

The mice in group A were administered compound 1 at a dose of 400mg/kg, the mice in group B were administered compound 2 at a dose of 400mg/kg, the mice in group C were administered compound 3 at a dose of 400mg/kg, the mice in group D were administered the corresponding volume of edible oil as a control group, and the administration was continued for 3 days, and the mice were sacrificed at day 45 after infection for anatomical observation of the insect-reducing effect and the pathological characteristics of the livers and spleens of the mice, and the results are shown in Table 3.

TABLE 3 Effect of Compounds 1-3 against adult schistosomiasis in vivo

As can be seen from table 3, the insect-reducing rates of compounds 1 to 3 were 67.6%, 29%, and 61.7%, respectively, and showed high activity of killing adult insects in vivo.

The foregoing is only a preferred embodiment of the present invention, and it should be noted that, for those skilled in the art, various modifications and decorations can be made without departing from the principle of the present invention, and these modifications and decorations should also be regarded as the protection scope of the present invention.