Salt-n-2-(tetrahydrolipstatin)-malosolenoj acid

 

(57) Abstract:

Usage: in the chemistry of heterocyclic compounds as substances having a depressing effect on the Central nervous system. The inventive product is a salt of N-2-(tetrahydrolipstatin)malosolenoj acid of formula 1:

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where n = 1, where M is Li or n = 2, when M is Zn. The output 63 is 72.5 %. The compound (1) produced by interaction of N-(2 - tetrahydroindazole)-malosolenoj acid or with metallic Li in the presence of methanolate sodium, where M is Li, or sulphate of zinc, when M is Zn. 5 table.

The invention relates to the synthesis of new chemical compounds having a depressing effect on the Central nervous system, and having the formula:

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Analogues for action are chlorpromazine and phenobarbital (as chlorpromazine has a specific, and phenobarbital nonspecific depressant effect on the Central nervous system).

The purpose of the invention to create a more effective and less toxic compared with chlorpromazine and phenobarbital compounds having a depressing effect on the Central nervous system.

Lithium salt of N-2-(tetrahydrolipstatin)-malosolenoj acid was obtained according to the scheme:

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The yield of the target product was 63 Received soy is N-2-(tetrahydrolipstatin)-malosolenoj acid was obtained according to the scheme:

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The yield of the target product was 72.5 Received connection - crystalline substance is yellow, not soluble in water.

The structure of the synthesized compounds are confirmed by the data of elemental analysis and IR spectra, the individuality by thin-layer chromatography (see tab. 1).

Acute toxicity of the synthesized compounds and Comparators were determined in experiments on white mice weighing 18 to 22 g by the method of [1] the Compounds were administered intraperitoneally in the form of a suspension, stabilized by tween-80. LD50compound I is 1100 mg/kg, compound 2 1900 mg/kg

To identify the inhibitory action of the proposed compounds used complex conventional methods (hazura centuries 1974): the latent period and the duration of eleminal-sodium sleep, antagonism with camphor, the change in pain threshold, the test "open field".

Study of action of lithium and zinc salts of N-2-(tetrahydrolipstatin)-malosolenoj acid on the duration of the latent period Atamanova sleep were performed on Wistar rats weighing 180 to 200 g of the Investigated compounds were administered at a dose of 1/10 LD50, intraperitoneally as a suspension with tween-80. Prepuce to be judged by the decrease in the latent period Atamanova sleep. The effect of compounds 1 and 2 on the latent period of eleminal-sodium sleep are presented in table. 2.

The impact of the proposed connection on the duration of eleminal-sodium sleep was studied by the method of [4] the Rats of the first group were administered compound 1, the second connection 2 at a dose of 1/10 LD50and after 30 min eleminal-sodium at a dose of 30 mg/kg Animals of the third group was administered chlorpromazine dose of 5 mg/kg, and after 30 min eleminal-sodium. The control group received only eleminal-sodium. About the duration of eleminal-sodium sleep judged on the time during which the animals were housed in an upright position. From the data table. 2 shows that the proposed compounds 1 and 2 reduce the latent period Atamanova sleep in 5.13 and 4.45 times, respectively, chlorpromazine in 2.19 times and increase the duration Atamanova sleep in 1.5 and 1.1 times as compared with control and in 1.6 and 1.2 times compared with chlorpromazine. Thus, compounds 1 and 2 exceed the comparator drug chlorpromazine influence on latent period eleminal-sodium sleep in 2.3 and 2 times, respectively, and the effect on the duration Atamanova sleep at 1.6 and 1.2 times, respectively. In addition, as can be seen from the table. 2 the proposed connection 1 11 times, and the connection 2 19 times mineah on white outbred rats weighing 150 to 200 g on their ability to prevent, called camphor, tonic-clonic convulsions and death of animals. Camphor oil was injected at a dose of 0.5 g/kg [3] intraperitoneally 30 min after the introduction of the investigated compounds. As the comparison drug used phenobarbital at a dose of 1/10 LD50(60 mg/kg). The control group of animals received only the camphor oil. About the effectiveness was judged to increase the latent period of tonic-clonic seizures and the number of surviving animals (protected believed animals that survived for 24 h after injection of camphor oil).

From the data table. 5 shows that the proposed connection 2 increases the latent period, called camphor, tonic-clonic seizures in 4.3 times, and phenobarbital 1.1 times. The survival of animals in connection 2 increases 2.5 times in comparison with control and 1.1 times as compared with phenobarbital. The proposed compound 1 decreased the latent period tonico-clonic seizures in 1.2 times, but increased when the survival of animals in 1,5 times in comparison with control. Thus, the proposed connection 2 exceeds the comparator drug phenobarbital, the effect on the latent period of tonic-clonic seizures in 3.9 times and the effect on survival of animals is in mink and at the edge of the platform, the number of washings and stevani on hind paws [2] the compounds were administered 30 min before the start of the experiment at a dose of 1/10 LD50, chlorpromazine 5 mg/kg As can be seen from the table. 3 connections 1 and 2 are statistically significantly reduced locomotor and exploratory activity of animals on test open field compared to control.

It was also studied the impact of the proposed connection on the change in pain threshold, electro-dermal sensitivity. The compounds were administered 30 min before the start of the experiment, the dose of 1/10 LD50, intraperitoneally as a suspension with tween-80. As the comparison drug used analgin, which was administered at a dose of 1/10 LD50(167 mg/kg). The threshold of pain electro-dermal irritation was determined before injection and 30 min after injection. Analysis of the results showed that compound 2 increased the threshold of pain sensitivity in 1.7 times, connection 1 to 1.1 times the reference product in 2.6 times (see tab. 4).

Thus, lithium and zinc salts of N-2-(tetrahydrolipstatin)-malosolenoj acids have a strong depressing effect on the Central nervous system. Connection 1 is superior to the chlorpromazine influence on latent period and duration this is the 2 has a pronounced anticonvulsant activity exceeds the comparison drug (phenobarbital) to increase the latent period cramps, called camphor, 3.8 times and increase the number of surviving animals in 1.1 times.

It is also agreed that the proposed compounds were increased threshold of pain electro-dermal irritation and reduced the estimated responses in the open-field test (p < 0.05).

Salt-N-2-(tetrahydrolipstatin)-malosolenoj acid formula

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where n is 1 when M is Li or n is 2 when M is Zn.

 

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,

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