KR20190031221A - Insecticidal composition comprising halogenated N-hetero compound and method for killing the insect using thereby - Google Patents

Abstract

The present invention relates to an insecticidal composition for preventing pests, and a method for killing insects using the same. The insecticidal composition for preventing pests can be used as an insecticide replacing conventional avermectin or abamectin. In addition, the insecticidal composition for preventing pests and the method for killing insects using the same are capable of destroying nematodes, are inexpensive, and provide an environmentally-friendly mechanism.

Description

[0001] The present invention relates to an insecticidal composition comprising a halogenated N-heterocyclic compound and a halogenated N-heterocyclic compound, and an insecticidal method using the halogenated N-

The present invention relates to an insecticidal composition comprising a halogenated N-hetero compound and a method of insecticidal use using the same.

One of the pine nematodes known to cause serious environmental damage to the pine forest ecosystem, pine reeves, is a nematode of parasites in the migratory birds. Pine nematodes cause pine wilt disease (PWD), which is a serious concern in many parts of Asia, Europe and North America. The pine wilt disease was first reported in 1988 in Busan, and rapidly destroyed the domestic pine forest. The disease spread not only to Korea but also to other Asian countries and Europe, and destroyed many kinds of pine trees. Most of the pine species affected by the pine wilt disease are pine, ginseng, pine, shoreline, european ginseng, and rataeta pine. This pine wilt disease is an epidemic, a powerful disease that kills pine trees within a few weeks or months after infection.

Common methods used to combat pine wilt disease include chemical treatments that inject pesticides into fumigants or stems of wood. The most commonly used insecticides are abamectin and emamectin benzoate belonging to the avermectin family. Insecticides containing these chemicals are considered highly effective and environmentally safe for certain pine wines, but they are expensive. However, repeated use of pesticides such as abamectin and avermectin, as evidenced by some pests such as Colorado potato beetles, cabbage moths and nematode nematodes, results in selective pressures and resistance to pesticides. Therefore, regular inspections of resistance patterns should be conducted to eliminate pine wilt disease, and screening should be continuously conducted to find alternative, cost-effective and environmentally friendly methods.

Abamectin is the most commercially used insecticide and its method of action is partly revealed. It won the Nobel Prize in 2015 for its incredible activity against most parasitic infections. Avermectin and abamectin are known to paralyze and kill pine nematodes, the cause of pine wilt disease, which causes rapid destruction of pine forests worldwide. However, the rapid evolution of nematode resistance to avermectin and abamectin can replace evermectin-based insecticides to eradicate pine wilt disease, and an inexpensive eco-friendly method is needed.

The present application provides an insecticidal composition comprising a halogenated N-hetero compound which can replace conventional avermectin and is inexpensive and environmentally friendly.

The present application provides a pest insecticidal method using the insecticidal composition.

The present application relates to an insecticidal composition for preventing pests. Exemplary insecticidal compositions of the present application comprise a compound of formula (I) or a pharmaceutically acceptable salt thereof; And pharmaceutically acceptable excipients.

The present application relates to a pest insecticide method. According to an exemplary pest insecticidal method of the present application, a compound of formula (I) or a pharmaceutically acceptable salt thereof; And an effective amount of an insecticidal composition comprising a pharmaceutically acceptable excipient, to a pest or a locus thereof.

The present application relates to an insecticidal combination for preventing pests. According to another aspect of the present invention, there is provided an insecticidal combination comprising a compound of formula (I) or a pharmaceutically acceptable salt thereof; And avermectin or a pharmaceutically acceptable salt thereof.

The present application relates to a kit for preventing pests. According to another embodiment of the kit, the compound of the formula (1) or a pharmaceutically acceptable salt thereof; And a medicament containing avermectin or a pharmaceutically acceptable salt thereof.

The present application relates to a pest insecticide method. According to a pest insecticidal method which is another embodiment of the present exemplary embodiment, the compound of the formula (1) or a pharmaceutically acceptable salt thereof; And a step of treating avermectin or a pharmaceutically acceptable salt thereof to a pest or a locus thereof, wherein the compound of formula (I) or a pharmaceutically acceptable salt thereof; And a step wherein the avermectin or a pharmaceutically acceptable salt thereof is separately treated as a single agent or as an individual agent simultaneously or at different times.

An insecticidal composition for preventing pests of the present application and a method for insect pest insect pest insecticidal composition according to the present invention can be used as an insecticide replacing conventional avermectin or abamectin. An insecticidal composition for preventing the insect pests and a insect pest insecticidal method using the insecticidal composition can provide a mechanism that can destroy nematodes, is inexpensive and environmentally friendly.

Figure 1 is a graph showing the effect of indole and abamectin on the survival of pine tree reeduces.
Figure 2 is an image and graph showing the effect of 5-iodoindole on the reproduction and locomotor activity of the pine tree creeper.
Fig. 3 is an image of the activity pattern of pine tree worms over time. Fig.
FIG. 4 is a graph and an image showing the effect of 5-iodoindene on hatching and larval destruction.
Fig. 5 is an image showing the effect of 5-Iodoindole and abamectin on the shape of the pine wilt.
Fig. 6 is an image showing the effect of 5-iodoindole on the morphology of eggs and transparent eggshells in the second larval stage.
Fig. 7 is an image showing the effect of 5-iodoindole on the development stage of various pine weevils.
Fig. 8 is an image showing a series of processes leading to the mechanism of vacuole formation and destruction of nematode.
Fig. 9 is an image showing the mechanism of methoosis of Pinus densiflora.
10 is an image showing the effect of 7-iodoindole on the pine wilt.
11 is an image showing the influence of 5-iodoindene on seed germination.
12 is a graph showing weight comparisons among groups of mice for 5-iodoindole and abamectin.
13 is a graph showing blood test results of rats against 5-iodoindole and abamectin.

The present application relates to an insecticidal composition for preventing pests. Can be used as an insecticidal composition or an insecticidal composition which can be administered in parallel by replacing conventional abortin or abamectin by using the insecticidal composition. The insecticidal composition is capable of destroying nematodes, providing an inexpensive and environmentally friendly mechanism. An insecticidal composition according to one embodiment of the present application is a compound of the following formula 1: or a pharmaceutically acceptable salt thereof; ≪ / RTI > and pharmaceutically acceptable excipients.

[Chemical Formula 1]

In Formula 1, R ¹ to R ⁶ represent hydrogen or halogen, and at least one of R ² to R ⁶ is F or I.

In Formula 1, R ¹ is hydrogen, and at least one of R ² to R ⁶ may be F or I, but is not limited thereto.

Wherein R ¹ , R ³ and R ⁵ are hydrogen; When R ² is I, R ⁴ is hydrogen, if R ² is hydrogen, R ⁴ is I, and; R ⁶ may be hydrogen or F, but is not limited thereto.

Wherein R ¹ to R ⁴ are hydrogen; R < ⁵ > is I; R ⁶ may be hydrogen, but is not limited thereto.

 The pharmaceutically acceptable salt means a formulation of a compound that does not cause serious irritation to the organism to which the compound is administered and does not impair the biological activity and properties of the compound. Such pharmaceutically acceptable salts include those acids which form non-toxic acid addition salts containing a pharmaceutically acceptable anion such as inorganic acids such as hydrochloric acid, sulfuric acid, nitric acid, phosphoric acid, hydrobromic acid, hydroiodic acid and the like, Organic carboxylic acids such as acetic acid, formic acid, citric acid, acetic acid, trichloroacetic acid, trifluoroacetic acid, gluconic acid, benzoic acid, lactic acid, fumaric acid, maleic acid and salicinic acid, methanesulfonic acid, ethanesulfonic acid, benzenesulfonic acid, p- But are not limited to, acid addition salts formed with sulfonic acids such as sulfonic acids and the like.

The pharmaceutically usable excipients include lactose, dextrose, sucrose, dextrates, mannitol, sorbitol, xylitol, sodium chloride, potassium chloride, magnesium chloride, calcium hydrogenphosphate, calcium phosphate, citric acid, microcrystalline cellulose, Hydroxypropylcellulose, butylhydroxytoluene, butylhydroxyanisole, glyceryl behenate, magnesium stearate, stearic acid, sodium stearyl fumarate or the like, or an aqueous solution of sodium carboxymethylcellulose, sodium carboxymethylcellulose, sodium carboxymethylcellulose, Light silicic acid, and may be mixed with, but not limited to, a water-soluble, sustained-release polymer for use in sustained release of the drug.

In an insecticidal composition for preventing pests, the insect pests may be nematodes, and in particular, they may be, but not limited to, pine wilt.

The present application relates to a pest insecticide method. According to an exemplary pest insecticidal method of the present application, there is provided a compound of the following general formula (1): or a pharmaceutically acceptable salt thereof; And an effective amount of an insecticidal composition comprising a pharmaceutically acceptable excipient, to a pest or a locus thereof.

 [Chemical Formula 1]

In Formula 1, R ¹ to R ⁶ represent hydrogen or halogen, and at least one of R ² to R ⁶ is F or I.

The method for insect pest insecticides can be applied to nematodes, larvae or adults, but is not limited thereto.

In addition, contents overlapping with those described in the above-described insecticidal composition will be omitted.

The present application relates to an insecticidal combination for preventing pests. According to another aspect of the present invention, there is provided an insecticidal combination comprising a compound of formula (I) or a pharmaceutically acceptable salt thereof; And avermectin or a pharmaceutically acceptable salt thereof.

 [Chemical Formula 1]

In Formula 1, R ¹ to R ⁶ represent hydrogen or halogen, and at least one of R ² to R ⁶ is F or I.

The avermectin may include abamectin, emamectin benzoate, ivermectin, doramectin or eprinomectin, and more specifically, abarone, such as abamectin, emamectin benzoate, ivermectin, doramectin or eprinomectin, But are not limited to, abamectin.

In addition, contents overlapping with those described in the above-described insecticidal composition will be omitted.

The present application relates to a kit for preventing pests. According to another embodiment of the present invention, there is provided a kit comprising: a compound represented by the following general formula (1): or a pharmaceutically acceptable salt thereof; ≪ / RTI > and a pharmaceutical comprising avermectin or a pharmaceutically acceptable salt thereof.

 [Chemical Formula 1]

In Formula 1, R ¹ to R ⁶ represent hydrogen or halogen, and at least one of R ² to R ⁶ is F or I.

In addition, contents overlapping with those described in the above-described insecticidal composition will be omitted.

The term " co-agent "means that the insecticidal composition comprises two different kinds of active ingredients and can be used simultaneously or separately.

The term "kit " means that the insecticide composition is formed independently, for example in the form of particles, granules or pellets, and made into a form that can be used simultaneously.

The present application relates to a pest insecticide method. According to a pest insecticide method which is another embodiment of the present exemplary application, a compound of the following general formula (1) or a pharmaceutically acceptable salt thereof; And a step of treating avermectin or a pharmaceutically acceptable salt thereof to a pest or a locus thereof, wherein the compound is represented by the following formula (1) or a pharmaceutically acceptable salt thereof; And a step wherein the avermectin or a pharmaceutically acceptable salt thereof is separately treated as a single agent or as an individual agent simultaneously or at different times.

 [Chemical Formula 1]

In Formula 1, R ¹ to R ⁶ represent hydrogen or halogen, and at least one of R ² to R ⁶ is F or I.

In addition, contents overlapping with those described in the above-described insecticidal composition will be omitted.

Hereinafter, the present invention will be described in more detail with reference to the following examples, reference examples and comparative examples, but the scope of the present application is not limited by the following description.

Example  1. 5- Iodoindole

4.86 μg, 12.15 μg and 24.3 μg of 5-iodoindole (Sigma-Aldrich, USA) were dissolved in dimethyl sulfoxide (DMSO; Sigma-Aldrich, USA) And diluted.

0.05 mM and 0.1 mM of 5-iodoindole were pretreated with adult nematodes and cultured at 22 ° C for 24 hours. After 24 hours, approximately 10 female and male nematodes were randomly picked and placed in the center of the Vortiris cinerea plate and grown and propagated for 8 days. When the Borytis cinerea was completely consumed by the nematode, nematodes were extracted from the plate using sterilized distilled water. Nematodes were diluted using sterile distilled water and the number of nematodes in 100 μl suspension was counted using iRiS ™ digital cell imaging system (iRiS ™ Digital Cell Imaging System, Logos Bio Systems, Korea). The regeneration rate (P _f / P _i ) of the nematode was calculated. Where P _f = final nematode population, and P _i = initial nematode population.

Example  2. 7- Fluoro -5- Iodoindole

The same procedure was followed except that 5.2 g, 13.1 g and 26.1 g of 7-fluoro-5-iodoindole were used instead of the 5-iodoindole of Example 1.

Example  3. 7- Iodoindole

The same procedure was followed except that 243,, 364.5 및 and 486 의 of 7-iodoindole were used instead of the 5-iodoindole of Example 1.

Example 4 . 4- Fluoroindole

Except that 13.5 占 퐂, 67.5 占 퐂 and 135 占 퐂 of 4-fluoroindole were used instead of 5-iodoindole of Example 1.

Reference example  One. Abamectin

The same procedure was followed except that 5 μg and 10 μg of abamectin were used instead of the 5-iodoindole of Example 1.

Comparative Example  One. Untreated group

* The same procedure was followed except that the diluted 5-iodoindole of Example 1 was not used.

Test Example  One. On pine tree  About Insecticide  Measure

Figure 1 is a graph showing the effect of indole and abamectin on the survival of pine tree reeduces. The graph was averaged after three measurements and N / D was not detected.

The indole of Figure 1A showed significant pesticidal activity at 1.5 mM and complete pesticide activity at 2 mM. Further analyzes were performed to confirm the survival rate of the pine reeves at lower concentrations (0, 0.02, 0.05, 0.1, and 0.5 mM). The 4-fluoroindole of Figure 1B showed 50% pesticidal activity at 0.5 mM concentration and the 7-iodoindole of Figure 1C achieved complete pesticide activity at 1.5 mM. The 5-iodoindole of FIG. 1 D showed the greatest reduction in survival rate of pine re-growth at 0.05 mM and all nematodes were killed at 0.1 and 0.5 mM. As shown in Fig. 1D and Fig. 1E, the survival rates of pine reovirus were 61 ± 2% and 36 ± 4%, respectively, when treated with 0.05 mM of 5-iodoindole and 10 μg / mL of abamectin of Reference Example 1 . In FIGS. 1D and 1E, 5-iodoindole 0.05 mM (12.15 g / mL) and abamectin (10 g / mL) showed similar effects on survival of the pine tree line. In addition, 5-iodoindole and abamectin increased the mortality rate of pine tree creeper. As expected, as shown in FIG. 1 E, abamectin killed pine reorganization in a dose-dependent manner at a maximum inhibition of 50 μg / mL, but significant reductions in pine rehabilitation survival were observed at 10 μg / mL and 20 μg / mL . As shown in FIG. 1 F, when the 5-iodoindole and abamectin were used in combination at 0.05 mM and 10 μg / mL, respectively, an improved activity was observed with about 11 ± 5% survival. When 0.05 mM of 5-iodoindole and 20 μg / mL of abamectin were used in combination, it was confirmed that the survival rate of the pine reovirus was 0%. As shown in Fig. 1G, the survival rate of pine woodworms was 0.02 mM in 7-fluoro-5-iodoindole, which was 51%, which was 43% at 0.05 mM and 11% at 0.1 mM. At 0.5mM, the survival rate of the pine tree creeper was 0%. When 7-fluoro-5-iodoindole and 7-fluoro-5-iodoindole were compared, it was found that at the same low concentration of 0.02 mM and 0.05 mM, 7-fluoro- Activity was confirmed to be superior.

Figure 2 is an image and graph showing the effect of 5-iodoindole on the reproduction and locomotor activity of the pine tree creeper. The graph was averaged after three measurements and N / D was not detected.

To characterize the effects of 5-iodoindole and abamectin on fertility and reproductive activity, 5-iodoindole and abamectin were treated and after 8 days, Botrytis cinerea cinerea ) were counted in the area of mycelium. On the surface of the fully grown bacterium Cineera hyphae, the pine bug was first inoculated.

As shown in Fig. 2A < RTI ID = 0.0 > i., ≪ / RTI > the Borytis cinerea mycelium was consumed by the nematode. However, as shown in FIG. 2A ii and iii, in plates treated with 0.05 mM 5-iodoindole or 10 μg / mL of avamectin, similar effects of both agents at similar concentrations were observed in the bacteriocinera mycelium , And the number of nematodes decreased similarly. Specifically, as shown in Fig. 2A, the pine reeves, in the presence of 0.1 mM 5-iodoindole, did not consume Bactritis cinerea hyphae at all. 2C, when the number of nematodes in the plate was counted, it was found that 0.05 mM 5-iodoindole or 10 μg / mL abamectin (2.9 x 10 ⁵ ± 0.1) Decreased the number of nematodes to 1.4 x 10 ⁵ ± 0.1 and 1.5 x 10 ⁵ ± 0.1, respectively.

Nematodes are characterized by rapid special movements and intense thrashing behavior under the control of motor motor neurons. As can be seen in Figures 2B and 2D, the frequency of nematode thrashing was reduced to 2 +/- 1.50 < RTI ID = 0.0 > thrashes / min < / RTI > for 0.05 mM 5-iodoindole compared to 30 +/- 2.25 thrashes / min for Comparative Example 1, 10 μg / mL of abamectin was significantly reduced to 2 ± 1.25 thrashes / min. As shown in Figure 2D, 0.1 mM of 5-iodoindole completely destroyed thrashing.

Fig. 3 is an image of the activity pattern of pine tree worms over time. Fig. The scale bar is 20 占 퐉.

(A) Comparative Example 1, (B) Abamectin (C) at 10 / / mL 0.05 mM 5-iodoindole (D) A mixture of 10 / / mL of avamectin and 0.05 mM 5-iodoindole The images of the motile activity of the treated pine creeper were shown.

As shown in FIG. 2B and FIG. 3, the motion of 5-iodoindole and abamectin-treated pine tree reptiles tended to decrease in the images of the motility activity over time.

FIG. 4 is a graph and an image showing the effect of 5-iodoindene on hatching and larval destruction. The graph was averaged after three measurements and N / D was not detected. The scale bar is 50 탆.

As shown in Fig. 4A, 0.05 mM of 5-iodoindole or 10 μg / mL of abamectin significantly inhibited the hatching of pine creeper eggs. Comparative Example 1 showed a hatching rate of 91 ± 2%, whereas 0.05 mM 5-iodoindole reduced the hatching rate to 25 ± 2%, and the hatching rate of 10 μg / mL abamectin was 44 ± 3% Respectively. Al (L2) at the second larval stage treated with 0.1 mM 5-iodoindole did not hatch. In addition, as shown in Figs. 4B and 4D, 5-iodoindole and abamectin adversely affected the fertility of adult nematodes. As shown in FIG. 4B, the female of Comparative Example 1 gave 10 ± 2 eggs within 12 hours, while the treatment with 0.05 mM 5-iodoindole or 10 μg / ml of avamectin was 4.3 ± 0.5 and And decreased to 4.3 ± 1.5 eggs.

As shown in FIG. 4C, the second larval stage (L2) of the pine reeves treated with 0.05 mM of 5-iodine greatly reduced the survival rate of the pine reeves, and 0.1 mM 5-iodoindole was the second The larval stage (L2) was destroyed. As shown in FIG. 4D, the result of visualization with a microscope confirmed that nematodes could not lay eggs and eggs were accumulated in nematodes. Also in Fig. 4D iii, a second larval stage (L2) was observed inside the nematode suggesting internal molting.

Fig. 5 is an image showing the effect of 5-Iodoindole and abamectin on the shape of the pine wilt. The scale bar is 50 탆.

Accumulation of fluid due to osmotic imbalance causes cell swelling following vacuole swelling in other animals. Several morphological changes were visible in the nematodes and eggs treated with 5-iodoindole, but not in abamectin or in Comparative Example 1. As shown in FIG. 5A, when treated with 0.05 mM or 0.1 mM of 5-iodoindole, vacuoles occurred rapidly in nematodes and several medium- to large-sized vacuoles were produced. As shown in Fig. 5B, the nematode of the male adult, the egg of the first larval stage (Fig. 6), the third larval stage (L3), the fourth larval stage (L4) Interestingly, many large vacuoles were found but not in the second larval stage (L2) (see FIG. 7). In addition, the egg shell membrane in which 0.1 mM 5-iodine stromal-fetal transfer occurred was remarkably destroyed (see FIG. 6). The presence of multiple vacuoles of the larva in the first larval stage (L1) and the second larval stage (L2) eggs showed that the 5-iodine stone destroys the osmotic barrier properties of the egg shell.

In addition, as shown in Figures 5C i and iii, the macropore was observed in dead nematodes treated with 0.1 mM 5-iodoindole and was mostly localized to the terminal. Along with the macropore, 5-iodoindole also causes internal organs damage, which is associated with the vacancies in the head, body and tail regions. In FIG. 5C iv, v, vi, no macropores and voids were observed in Comparative Example 1 or in abamectin treated nematodes.

FIG. 6 is an image showing the effect of 5-iodoindole on the eggshell and transparent egg shells in the second larval stage (L2). The scale bar is 50 탆.

Morphological analysis of eggs from the second larval stage (L2) showed that vacuole was formed in all samples treated with 5-iodoindole. (i) Comparative Example 1, (ii) Abamectin of 10 占 퐂 / mL, (iii) 0.0.5 mM of 5-iodoindole and (iv) 0.1 mM of 5-iodoindole . (v) Transparent shells usually left in the second larval stage (L2) during the hatching process are seen intact in Comparative Example 1, (vi) eggs of the 5-iodoindole administration group in which the rupture and release of the contents are evident It is an image showing the shell. Here, the blue arrow indicates the vacuole and the red arrow indicates the rupture.

Fig. 7 is an image showing the effect of 5-iodoindole on the development stage of various pine weevils. The scale bar is 50 탆.

Multiple vacuoles, indicated by black arrows, were observed in the third larval stage (L3), the fourth larval stage (L4), and adult pine reeves. All 5-Iodoindole-treated pine reworkers died within 12 hours, but not in the second larval stage (L2).

Fig. 8 is an image showing a series of processes leading to the mechanism of vacuole formation and destruction of nematode. The scale bar is 50 탆.

As shown in Fig. 8, agglomeration and rupture of vacuoles also appeared in 5-iodoindole treated nematodes and were visualized by nematode flexion and vacuole release into the external environment. This observation supports the involvement of fluid accumulation, destruction of osmotic pressure, and reversible cell damage (RCI) in the process of liquidation and methotosis.

Fig. 9 is an image showing the mechanism of methoosis of Pinus densiflora. The scale bar is 50 탆.

Figure 9 shows the sequential process of methuotic death in the pine tree creeper. Methoose is not a type of apoptosis associated with the accumulation of prominent cytoplasmic vacuoles. The morphological defects observed in the pine tree rehabilitation were closely related to the mechanism of methuosis. Microscopic images at different times indicate that 0.1 mM of 5-iodoindene forms a macropore 20 hours later. After 8 hours of treatment, microfilaments were observed and it was confirmed that the number increased after 12 hours. Several large vacuoles were observed after 14 hours. After 12 hours to 16 hours of treatment, several fused vacuoles were clearly visible. This suggests that liquid foam melting has a bottom at the base of methosocyst. At 20 hours several large vacuoles formed throughout nematodes were observed. This observation constitutes the first mechanism of methuosis in our knowledge and nematode.

10 is an image showing the effect of 7-iodoindole on the pine wilt. The scale bar is 50 탆.

The effects of 2mM 7-Iodine stone on the mortality of pine tree rehabilitate and the results of the formation of multiple vacuoles in the eggs, third larval stage (L3), fourth larval stage (L4) and adult stage of pine tree rehabilitate.

11 is an image showing the influence of 5-iodoindene on seed germination. Germination and germination of the seeds of Brassica oleracea and Western radishes on MS agar medium with or without abamectin or 5-iodoindole. Germination was recorded after 3 days of incubation at 22 ° C.

As shown in Fig. 11, an experiment was conducted to evaluate the toxic effects of 5-iodoindole on seed germination of Brassica oleracea and P. falciparum. 0.05 mM or 0.1 mM of 5-iodoindole or 10 μg / mL of abamectin did not affect or neglect initial blight and germination. In addition, no similar difference was observed between the germination rates of Comparative Example 1, 5-iodoindole or abamectin-treated seeds. The effects on the number of primary root elongation and number of side roots formed were negligible, but side root development was slightly delayed by 1 mM 5-iodoindole (10 times more active concentration). These results indicate that 5-iodoindole is not toxic to plant cells at the tested concentrations and does not interfere with the plant development process.

Test Example  2. Toxicity to animals

12 is a graph showing weight comparisons among groups of mice for 5-iodoindole and abamectin.

5-iodoindole and abamectin were orally administered to rats. As a result, abamectin had LD50 = 13.5 mg / kg (or 14-24 mg / kg) 1M) showed no difference in weight change.

13 is a graph showing blood test results of rats against 5-iodoindole and abamectin.

The results of this study suggest that hepatic toxicity may not be caused by administration of 100 mg / kg 5-iodoindole in TP and ALB, hepatocyte damage index, ALT and AST, and TG, a liver function indicator.

In addition, BUN and CRE, which are indicators of kidney damage, and GLU, which is an indicator of insulin secretion function of pancreas, have been observed as a whole, so that it can be deduced that there is no toxicity to other organs or organs.

Claims (12)

Claims 1. A compound of the formula (I): And
An insecticidal composition for preventing nematodes comprising a pharmaceutically usable excipient:
[Chemical Formula 1]

In Formula 1,
R ¹ and R ² are hydrogen,
R ³ to R ⁶ each independently represent hydrogen, F or I, with the proviso that at least one of R ³ to R ⁶ is F or I. The method according to claim 1,
R ¹ , R ² , R ⁴ , R ⁵ and R ⁶ are hydrogen; Wherein R < ³ > is F. The method according to claim 1,
R ¹ , R ² , R ³ and R ⁵ are hydrogen;
R ⁴ is I;
And R < ⁶ > is hydrogen or F. The method according to claim 1,
R ¹ to R ⁵ are hydrogen;
And R < ⁶ > is I. Claims 1. A compound of the formula (I): And
A method for insecticidal insecticidal treatment comprising treating an effective amount of an insecticidal composition for preventing nematodes comprising a pharmaceutically usable excipient to a nematode or a habitat thereof:
[Chemical Formula 1]

In Formula 1,
R ¹ and R ² are hydrogen,
R ³ to R ⁶ each independently represent hydrogen, F or I, with the proviso that at least one of R ³ to R ⁶ is F or I. 6. The method of claim 5,
R ¹ , R ² , R ⁴ , R ⁵ and R ⁶ are hydrogen; Wherein R ³ is F. 6. The method of claim 5,
R ¹ , R ² , R ³ and R ⁵ are hydrogen;
R ⁴ is I;
Wherein R < ⁶ > is hydrogen or F. 6. The method of claim 5,
R ¹ to R ⁵ are hydrogen;
Wherein R < ⁶ > is I. 6. The method of claim 5,
Wherein the insecticidal composition for preventing nematodes is treated with eggs, larvae or adults of nematodes. Claims 1. A compound of the formula (I): And a combinatorial insecticidal composition for preventing nematodes comprising avermectin or a pharmaceutically acceptable salt thereof:
[Chemical Formula 1]

In Formula 1,
R ¹ and R ² are hydrogen,
R ³ to R ⁶ each independently represent hydrogen, F or I, with the proviso that at least one of R ³ to R ⁶ is F or I. Claims 1. A compound of the formula (I): And a pest insecticidal kit comprising an insecticidal agent comprising avermectin or a pharmaceutically acceptable salt thereof:
[Chemical Formula 1]

In Formula 1,
R ¹ and R ² are hydrogen,
R ³ to R ⁶ each independently represent hydrogen, F or I, with the proviso that at least one of R ³ to R ⁶ is F or I. Claims 1. A compound of the formula (I): And avermectin or a pharmaceutically acceptable salt thereof to a nematocide or a locus thereof,
Claims 1. A compound of the formula (I): And a method of insect nematode in which avermectin or a pharmaceutically acceptable salt thereof is treated separately as a single agent or individually or simultaneously as a separate agent:
[Chemical Formula 1]

In Formula 1,
R ¹ and R ² are hydrogen,
R ³ to R ⁶ each independently represent hydrogen, F or I, with the proviso that at least one of R ³ to R ⁶ is F or I.

Images