RU1806137C - 2-[n,n-dimethyl- n(2-propylpentanoyloxymethyl) -ammoniomethyl] -3-(n,n-demethyl- carbomoyloxy) pyridinium chloride showing deratization action - Google Patents

Abstract

Use: as a deratization agent for controlling mice and rats. SUMMARY OF THE INVENTION: M-Dimethyl-Shch2-propyl-pentoyloxymethyl) ammonium-methyl-3- (M, M-dimethylcarbamoyloxy) - pyridinium chloride Yield 55-60%, BF CaoNm No. 04C1. Mp 99-99 ° C, LD 0.54-0.76 mg / kg (mouse), 3.72-3.96 mg / kg (rat). Reagent 1; aminostigmine base. Reagent 2: dipropylacetic acid chloro ester chloride. Reaction conditions: at a temperature of 45-50 ° C for 50 hours in anhydrous chloroform. 2 tab.

Description

The invention relates to the field of chemistry of pyridine derivatives, namely, N-dimethyl-M- (Ј-propylpentoyloxymethyl) ammoniomethyl-3- (M, M-dimethylcarbamoyloxy) pyridinium chloride of the formula I

pCON (

N CH2N

СН2ОСОСН (СН7УИС1 ЬНЫ2

possessing a deratization effect, which can be used to control mouse rodents in residential premises, hospitals, warehouses and on ships.

The aim of the invention is you. in a series of pyridine derivatives of a derivative having a deratization effect, but providing a delayed onset of intoxication while maintaining high toxicity for mice and rats with the rapid onset of animal death (acute effect).

This goal is achieved by the proposed compound 1, which is obtained by alkylation of aminostigmine (a substance produced by the domestic industry in Novokuznetsk) with dipropylacetic acid chloroformate.

Example 1 preparation of compound I. t In a flask in anhydrous chloroform (10-15 ml), 0.003 mol of aminostigmine base (P) was dissolved, 5-10% more carefully purified chlorophenyl ether dipropylacetic acid was added.

ate with

00

about

Os

from VI

with

acid obtained from the corresponding acid chloride. and formaldehyde. The aminostigmine alkylation process was carried out at a temperature of 45-50 ° C for 50 hours. Then, chloroform was distilled off in vacuo. Ether is added to the residue, in which it gradually solidifies. The solid mass is triturated and filtered. Crystallized either from dry ethyl acetate or from methyl ethyl ketone. The product yield after crystallization is 55-60% of the initial weight. The melting point of the obtained compound is 96-99 ° C. Elementary analysis: found CI8.75; 8.80. Gross formula: С2оНз4№з04С1, mol.m.415.9b. Calculated in%: CI-8.52. An admixture of aminostigmine is absent. The resulting compound is a white crystalline powder without taste or odor.

The structure of compound I was confirmed by the data of 1H NMR spectra. In the 1H NMR spectrum recorded on an RS 2310 device, 60 MHz in OG there are signals characteristic of the compound I / d, ppm /: 3.20 / N + (CH3) 2, s /; 4.53 / N f-CH2-C, s /; 5.27 / N f-CH2-0, s /. Compound I is readily soluble in water. In crystalline form, stable during storage. In aqueous solutions it undergoes slow hydrolysis, which accelerates sharply in an alkaline environment, in particular at a pH characteristic of rat intestinal contents. The decomposition with the release of aminostigmine was confirmed by the change in time of the NMR spectra of its solutions in a deuterophosphate buffer with a pH of 8.2. A decrease in the intensity of the N - CH2-0 and N + - (CHa) 2 signals of the protons of the starting compound 1 is observed, with the simultaneous appearance of the 1M + - (CH3) 2, 53.12 signal corresponding to the protonated amynostigmine. The rate constant for the hydrolytic cleavage of salt 1 in the pH-stating mode, 05.37 ° C, KS, 05 M / is Khydr. / 9.17 ± 1.34 / x10 3 min 1.

Thus, the claimed compound indeed undergoes hydrolysis in an alkaline medium, releasing aminostigmine.

The severity of the toxic effect is judged by the value of the average lethal dose (LD 50) when the substance is introduced into the stomach through an tube. Each LD 50 value was determined per 25 animals. The results are shown in table 1.

According to the table, the connection

I practically does not differ from the compound

II in toxicity for mice and lower in toxicity for rats 2 times.

When converted to a whole animal, the average lethal doses of I are 0.013-0.017 mg / mouse and 0.98-1.02 mg / rat.

- Thus, the toxicity of the claimed compound remains extremely high. A kilogram of substances is enough to kill 1 million mice or 250 thousand rats.

The rates of the toxic process and the completeness of the deratization effect were investigated as follows. Animals / white outbred mice and rats / are placed in plastic boxes providing relatively free movement. Mice were tested from cells with constantly replenished food, rats after starvation for 24 hours, in two series. In experiments with aminostigmine, rats were previously twice placed in experimental boxes and fed, accustomed to a new environment and bait. Cottage cheese was used as a bait for mice, and sweet liver powder was used for rats. The results are shown in table.2.

5 According to the data obtained, 100% mortality of mice is achieved without any preliminary preparation and starvation. Rats eat the bait only if they have previously starved.

0. In mice, when replacing aminostigmine with proaminostigmine, a slowdown in the time of occurrence of the first symptoms of poisoning by 7-11 minutes and time was recorded; no deaths for 8-22 minutes. There was no significant change in the behavior of animals before poisoning and in the clinical picture of intoxication,

Rats pre-accustomed to the experimental box ate the bait immediately after being placed in it. Unaccustomed - 5-10 minutes after the first test. As a result, 100% death is achieved when aminostigmine is used only in trained animals.

5 When using proaminostigmine, all animals died even in those experiments in which they fell into the seed box for the first time. The differences in efficiency of 0.2% and 0.5% are

0 some change in the rate of intoxication. Compared to aminostigmine, the time of onset of the first symptoms in the case of using compound I is delayed by 10-15 minutes, and the time

5 deaths - for 45-50 minutes,

When analyzing the materials shown in the table, it was found that the results obtained in experiments with mice in series 1-2 have the reliability of the difference in the average time of occurrence of the first symptoms.

poisoning, 001 and at the time of the onset of death -, 005. In experiments with rats in series 3-4 with one and the other assessment -, 001; in series x 5-6. with both estimates -, 001; in series 3-5, characterizing baits with different contents, yes, the error of the difference in the time of occurrence of symptoms and in the time of death -, 4.

Thus, the slowing down of the onset of seizures and death when replacing aminostigmine with proaminostigmine is absolutely reliable. Differences when using 0.2 and 0.5% of the content in the bait are not significant.

Thus, the proposed compound I can improve the effectiveness of the fight against mice and rats with obtaining

100% death without first accustoming the animals to the bait.

Claims (1)

Claims 2- {M, M-dimethyl M- (2-propylpentanoyloxymethyl) ammoniomethyl-3- (M, Y-dimethylcarbamoyloxy) pyridinium chloride of the formula 10 C1 OCON ( (f5f ChH  -HI N CH2N-CH2OC-CHCH2CH2CH3 15 Cg-C II 1 0 C3H, twenty possessing a deratization effect. Table 1 Medium (total doses of compound I / proaminostigmine) and compound II (aminostigmine) for mice and rats by intragastric administration. The range of doses within the error in mg / kg is given. Table 2 The time of the onset of the first symptoms of poisoning and the onset of death in mice and rats / rats starving 24 hours / after being placed in an animal box with a bait containing compound I / proaminostigmine / or compound II / aminostigmine /. The range of time fluctuations within the arithmetic mean error is given.