Trichloroethanol derivative and application thereof

Abstract

The invention belongs to the technical field of medicines, and particularly relates to a trichloroethanol derivative and application thereof. The trichloroethanol derivative disclosed by the invention is small in irritation, high in sleep rate and long in sleep time, and has potential multi-scene clinical application value. # imgabs0 #

Description

Technical Field

[0001] The invention belongs to the technical field of medicines, and in particular relates to a trichloroethanol derivative and a preparation method and application thereof. Background Art

[0002] The main pharmacological effects of sedative hypnotics are sedation and hypnosis. At present, commonly used sedative hypnotics in China include aldehydes, benzodiazepines, barbiturates, etc. Chloral hydrate is a hydrate of trichloroacetaldehyde, which is a central nervous system sedative that can inhibit the ascending activation system of the brainstem reticular formation. It has no obvious effect on sleep phases and the balance between rapid-wave sleep and slow-wave sleep. The effect is similar to physiological sleep, with no discomfort after waking up, no lag effect and accumulation. It is a relatively safe hypnotic, sedative, and anticonvulsant, suitable for patients who have difficulty falling asleep, but the drug is highly irritating, bitter, has poor stability, and is of short duration, so its clinical application scenarios are limited. Benzodiazepines, this class of drugs enhances the neurotransmission of inhibitory synapses, which enhances the positive allosteric regulation, thereby enhancing the effect of chloride ion flux, and has hypnotic and sedative effects; among them, midazolam, oxazepam, etc. have a fast onset and short duration of action, and are clinically short-acting tranquilizers, but they are difficult to fall asleep after early awakening and awakening, so their clinical application is limited for insomnia patients who need long-term sedation. Phenobarbital is a long-acting barbiturate drug, whose central inhibitory effect varies with dose, has sedative, hypnotic, and anticonvulsant effects, and has an action time of 6-8 hours. It is suitable for refractory insomnia, but for patients who need fast and short-term effects and have difficulty falling asleep, its clinical application is limited. In addition, repeated or continuous use of benzodiazepines and barbiturates in a short period of time can produce tolerance and addiction, and are not suitable for long-term use.

[0003] Based on this, developing a sedative, hypnotic, and anticonvulsant drug with low stimulation, good stability, fast sedation, relatively long duration, and high safety to improve clinical application scenarios will have huge market prospects. Summary of the invention

[0004] In order to solve at least one technical problem existing in the prior art, the present invention provides a new trichloroethanol derivative to reduce irritation, improve efficacy, and prolong the duration of action.

[0005] In one aspect, the present invention provides a compound represented by formula (I) or a stereoisomer thereof: Wherein, R1 and R2 are independently selected from hydrogen, sucrose, glucose, fructosyl, glycerol, maltitol, sorbitol, mannitol, xylitol, erythritol, maltosyl, isomaltulose or sucralose; or the above R1 and R2 are connected to form a five-membered or six-membered heterocyclic ring.

[0006] Furthermore, the above R1 is selected from hydrogen; R2 is selected from sucrose, glucose, fructosyl, glycerol, maltitol, sorbitol, mannitol, xylitol, erythritol, maltosyl, isomaltulose or sucralose; or the above R1 and R2 are connected to form a five-membered or six-membered heterocyclic ring.

[0007] Furthermore, the above R1 is selected from hydrogen; R2 is selected from sucrose, glucose, fructose, glycerol, maltitol, sorbitol, mannitol, xylitol, erythritol or sucralose; or the above R1 and R2 are connected to form a five-membered or six-membered heterocyclic ring.

[0008] Furthermore, the above compound is selected from: or .

[0009] Furthermore, at least one hydrogen in the structure of any of the above compounds or stereoisomers thereof may be substituted by deuterium.

[0010] In a second aspect, the present invention provides a pharmaceutical composition comprising any one of the above compounds or stereoisomers thereof, and a pharmaceutically acceptable carrier and / or excipient. Furthermore, the above-mentioned pharmaceutical composition can be used to prepare tablets, capsules, syrups, oral solutions, injections, small water injections, powder injections or enemas; preferably syrups, oral solutions or enemas.

[0011] In a third aspect, the present invention provides use of any of the above compounds or stereoisomers thereof in the preparation of sedative, hypnotic, antianxiety or anticonvulsant drugs. Furthermore, the present invention provides use of any of the above compounds or their stereoisomers in the preparation of sedatives and / or hypnotic drugs.

[0012] In a fourth aspect, the present invention provides use of any of the above compounds or stereoisomers thereof in drug quality testing.

[0013] Beneficial effects: The present invention provides a new trichloroethanol derivative, which has low irritation, high sedation rate and relatively long sedation time, and has been proven to have better sedative effect and strong clinical application potential. DETAILED DESCRIPTION

[0014] The scheme of the present invention will be explained below in conjunction with the embodiments. It will be appreciated by those skilled in the art that the following embodiments are only used to illustrate the present invention and should not be considered as limiting the scope of the present invention. The specific techniques or conditions not indicated in the embodiments are carried out according to the techniques or conditions described in the literature in this area or according to the product specification. The reagents or instruments used that do not indicate the manufacturer are conventional products obtained through commercial purchase.

[0015] Example 1: Preparation of Compound 1 and Compound 2 Sucrose (34.23g, 1.00eq.) and trichloroacetaldehyde (14.74g, 1.00eq.) were added to 300ml trifluoroacetic acid, the reaction mixture was heated to 40°C and stirred overnight, the reaction solution was cooled to 0-10°C, 500ml purified water was slowly added to the reaction solution, and dichloromethane was used to extract and wash three times at a low temperature of 0-10°C, 800ml each time, and the extracted aqueous phase was combined and collected. The aqueous phase was purified by reverse phase preparative separation chromatography to obtain 1.50g of target compound 1 with a purity of 97.5%, and 1.32g of target compound 2 with a purity of 96.8%, respectively.

[0016] Structural confirmation of compound 1: MS-ESI(+), m / z: 506.1 (M+NH4 + ), 1 H NMR: (400 MHz, D2O) δ5.18 (s, 1H), 5.10 (d, 1H), 4.18 – 4.07 (m, 2H), 4.02 – 3.96 (m, 2H), 3.93 –3.85 (m, 2H), 3.82 – 3.60 (m, 5H), 3.57 – 3.44 (m, 2H). 13 C NMR: (100 MHz, D2O) δ105.12, 101.03, 100.78, 93.11, 80.58, 77.07, 76.16, 74.65, 74.40, 72.02,70.37, 65.61, 63.22, 61.74.

[0017] Structural confirmation of compound 2: MS-ESI(+), m / z: 506.1 (M+NH4 + ), 1H NMR: (400 MHz, D2O) δ5.18 (s, 1H), 5.10 (d, 1H),, 4.15 – 4.04 (m, 2H), 4.00 – 3.90 (m, 2H), 3.87 –3.77 (m, 2H), 3.76 – 3.59 (m, 6H), 3.51 – 3.46 (m, 1H). 13 C NMR: (100 MHz, D2O) δ104.53, 101.03, 100.76, 93.36, 81.98, 77.13, 75.66, 74.73, 74.63, 73.04,71.03, 67.00, 63.22, 62.43.

[0018] The carbon spectrum chemical shifts 80.58 and 65.61 of compound 1 were compared with the chemical shifts 81.98 and 67.00 of compound 2 to further confirm the connection position of compound 1 and compound 2.

[0019] Example 2: Preparation of Compound 3 and Compound 4 According to the preparation method in Example 1, sucrose was replaced with glucose to obtain compound 3 with a purity of 98.7% and compound 4 with a purity of 98.2%. Structural confirmation of compound 3: MS-ESI (+), m / z: 344.0 (M+NH4 + ), 1 H NMR: (400 MHz, D2O) δ5.12 (s, 1H), 5.08 (d, 1H), 3.66 – 3.63 (m, 2H), 3.47 – 3.43 (m, 2H), 3.30 (dd, 1H), 3.13 – 3.09 (m, 1H). HMBC two-dimensional nuclear magnetic results showed that the hydrogen with a chemical shift of 5.08ppm and the carbon with a chemical shift of 95.00 had a cross peak, indicating that the connection position of the compound was the glycosidic bond, which was the target compound 3.

[0020] Structural confirmation of compound 4: MS-ESI (+), m / z: 344.0 (M+NH4 + ), 1H NMR: (400 MHz, D2O) δ5.07 (s, 1H), 4.93 (d, 1H), 3.86 – 3.79 (m, 1H), 3.72 – 3.68 (m, 1H), 3.47 –3.43 (m, 2H) 3.30 (dd, 1H), 3.13 – 3.09 (m, 1H). HMBC two-dimensional nuclear magnetic results show that the hydrogen with a chemical shift of 3.47 – 3.43ppm and the carbon with a chemical shift of 96.80 have cross peaks, indicating that the connection position of the compound is the primary alcohol hydroxyl group, which is the target compound 4.

[0021] Example 3: Preparation of Compound 5 and Compound 6 According to the preparation method in Example 1, sucrose was replaced with fructose to obtain compound 5 with a purity of 98.7% and compound 6 with a purity of 98.2%. Structural confirmation of compound 5: MS-ESI (+), m / z: 344.0 (M+NH4 + ), 1 H NMR: (400 MHz, D2O) δ5.12 (s, 1H), 3.89 – 3.80 (m, 5H), 3.76 (d, 2H).

[0022] Structural confirmation of compound 6: MS-ESI (+), m / z: 344.0 (M+NH4 + ), 1 H NMR: (400 MHz, D2O) δ5.12 (s, 1H), 3.92 (d, 2H), 3.87 – 3.73 (m, 5H).

[0023] Among them, compound 5 and compound 6 showed a difference in chemical shift of d peak CH2, which further confirmed the connection position of compound 5 and compound 6.

[0024] Example 4: Preparation of Compound 7 and Compound 8 According to the preparation method in Example 1, the two title compounds can be prepared by replacing sucrose with maltitol, and the purities are 99.0% and 98.7%, respectively.

[0025] Structural confirmation of compound 7: MS-ESI (+), m / z: 490.1 (M+NH4 + ), 1H NMR: (400 MHz, D2O) δ5.08 (s, 1H), 5.00 (d, 1H), 4.51 – 4.49 (m, 1H), 4.08 (s, 1H), 4.06 – 4.02(m, 1H), 3.92 – 3.85 (m, 3H), 3.81 – 3.64 (m, 6H), 3.62 – 3.49 (m, 2H).

[0026] Structural confirmation of compound 8: MS-ESI (+), m / z: 490.1 (M+NH4 + ), 1 H NMR: (400 MHz, D2O) δ5.08 (s, 1H), 4.93 (d, 1H), 4.23 – 4.18 (m, 1H), 4.00 – 3.96 (m, 2H), 3.93 –3.74 (m, 5H), 3.74 – 3.59 (m, 4H), 3.58 – 3.49 (m, 2H).

[0027] The multiple peaks of the hydrogen spectrum chemical shift of compound 7 at 4.51-4.49 were compared with the hydrogen spectrum chemical shift of compound 8 at 4.23-4.18 to further confirm the connection position of compound 7 and compound 8.

[0028] Example 5: Preparation of Compound 9 and Compound 10 According to the preparation method in Example 1, two title compounds can be prepared by replacing sucrose with sorbitol, and the purities are 97.6% and 98.1%, respectively.

[0029] Structural confirmation of compound 9: MS-ESI (+), m / z: 346.1 (M+NH4 + ), 1 H NMR: (400 MHz, D2O) δ5.12 (s, 1H), 3.89 – 3.76 (m, 6H), 3.68 – 3.56 (m, 2H).

[0030] Structural confirmation of compound 10: MS-ESI (+), m / z: 328.1 (M+NH4 + ), 1H NMR: (400 MHz, D2O) δ5.08 (s, 1H), 4.22 – 4.20 (m, 1H), 4.05 (d, 1H), 3.90 – 3.80 (m, 2H), 3.77 –3.69 (m, 2H), 3.67 – 3.56 (m, 2H).

[0031] Example 6: Preparation of Compound 11 and Compound 12 According to the preparation method in Example 1, two title compounds can be prepared by replacing sucrose with mannitol, and the purities are 97.9% and 98.7%, respectively.

[0032] Structural confirmation of compound 11: MS-ESI (+), m / z: 346.1 (M+NH4 + ), 1 H NMR: (400 MHz, D2O) δ5.12 (s, 1H), 3.89 – 3.84 (m, 2H), 3.78 (d, 1H), 3.74 – 3.63 (m, 4H), 3.61 –3.55 (m, 1H).

[0033] Structural confirmation of compound 12: MS-ESI (+), m / z: 328.1 (M+NH4 + ), 1 H NMR: (400 MHz, D2O) δ5.08 (s, 1H), 4.05 – 4.01 (m, 1H), 4.00 – 3.98 (m, 1H), 3.89 – 3.84 (m, 1H), 3.80 (d, 1H), 3.70 – 3.55 (m, 4H).

[0034] Example 7: Preparation of Compound 13 and Compound 14 According to the preparation method in Example 1, two title compounds can be prepared by replacing sucrose with xylitol, and the purities are 98.0% and 98.5%, respectively.

[0035] Structural confirmation of compound 13: MS-ESI (+), m / z: 316.1 (M+NH4 + ), 1H NMR: (400 MHz, D2O) δ5.12 (s, 1H), 3.92 – 3.88 (m, 1H), 3.88 – 3.83 (m, 1H), 3.81 – 3.74 (m, 2H), 3.74 – 3.54 (m, 3H).

[0036] Structural confirmation of compound 14: MS-ESI (+), m / z: 298.1 (M+NH4 + ), 1 H NMR: (400 MHz, D2O) δ5.08 (s, 1H), 4.12 – 4.08 (m, 1H), 4.03 – 4.01 (m, 1H), 3.79 – 3.74 (m, 1H), 3.88 – 3.82 (m, 2H), 3.72 – 3.65 (m, 1H), 3.60– 3.55 (m, 1H).

[0037] Example 8: Preparation of Compound 15 and Compound 16 According to the preparation method in Example 1, the two title compounds can be prepared by replacing sucrose with erythritol, and the purities are 98.2% and 98.4%, respectively.

[0038] Structural confirmation of compound 15: MS-ESI(+), m / z: 286.1 (M+NH4 + ), 1 H NMR: (400 MHz, D2O) δ5.12 (s, 1H), 3.88 (m, 1H), 3.81 – 3.69 (m, 3H), 3.68 – 3.53 (m, 2H).

[0039] Structural confirmation of compound 16: MS-ESI (+), m / z: 268.1 (M+NH4 + ), 1 H NMR: (400 MHz, D2O) δ5.08 (s, 1H), 3.89 – 3.86 (m,1H), 4.05 – 3.78 (m, 3H), 3.68 – 3.54 (m, 2H).

[0040] Example 9: Preparation of Compound 17 According to the preparation method in Example 1, compound 17 with a purity of 97.9% can be prepared by replacing sucrose with maltose.

[0041] Structural confirmation of compound 17: MS-ESI (+), m / z: 506.1 (M+NH4 + ), 1 H NMR: (400 MHz, D2O) δ5.18 (s, 1H), 5.07 (d, 1H), 4.75 (d, 1H), 3.90–3.73 (m,7H), 3.72–3.68 (m,1H), 3.67–3.65(m,1H),3.65–3.63(m,1H), 3.54–3.48(m,2H).

[0042] Example 10: Preparation of Compound 18 and Compound 19 According to the preparation method in Example 1, the two title compounds can be prepared by replacing sucrose with isomaltulose, and the purities are 97.5% and 98.1%, respectively.

[0043] Structural confirmation of compound 18: MS-ESI(+), m / z: 506.1 (M+NH4 + ), 1 H NMR: (400 MHz, D2O) δ5.18 (s, 1H), 4.75 (d, 1H), 4.25 – 4.18 (m, 3H), 3.98 – 3.95 (m, 1H), 3.91–3.65(m, 5H), 3.65 – 3.61 (m, 2H), 3.59 – 3.55 (m, 1H), 3.51 – 3.47 (m, 1H). The HMBC two-dimensional nuclear magnetic resonance results showed that hydrogen with a chemical shift of 4.25 – 4.18 ppm and carbon with chemical shifts of 206.67 and 93.15 simultaneously showed cross peaks, indicating that the compound was the target compound 18.

[0044] Structural confirmation of compound 19: MS-ESI (+), m / z: 506.1 (M+NH4 + ), 1H NMR: (400 MHz, D2O) δ5.18 (s, 1H), 4.69 (d, 1H), 4.24 – 4.21 (m, 1H), 4.11 – 4.07 (m, 2H), 4.02 –3.93 (m, 3H), 3.89 – 3.85 (m,1H), 3.81 – 3.65 (m, 4H) 3.64 – 3.60 (m, 1H),3.51 – 3.47 (m, 1H). The results of HMBC two-dimensional nuclear magnetic resonance showed that the hydrogen with a chemical shift of 4.02 – 3.93 ppm and the carbon with a chemical shift of 92.69 had a cross peak, indicating that the compound was the target compound 19.

[0045] Example 11: Preparation of Compound 20 According to the preparation method in Example 1, compound 20 can be prepared by replacing sucrose with sucralose, with a purity of 97.2%. Structural confirmation of compound 20: MS-ESI (+), m / z: 560.1 (M+NH4 + ), 1 H NMR: (400 MHz, D2O) δ5.12 (s, 1H), 5.01 (d, 1H), 4.39 – 4.32 (m, 2H), 4.21 – 4.13 (m, 2H), 4.09 –4.03 (m, 2H), 4.00 – 3.75 (m, 7H).

[0046] Example 12: Preparation of Compound 21 According to the preparation method in Example 1, compound 21 can be prepared by replacing sucrose with glycerol, with a purity of 98.0%.

[0047] Structural confirmation of compound 21: MS-ESI(+), m / z: 238.1 (M+NH4 + ), 1 H NMR: (400 MHz, D2O) δ5.08 (s, 1H), 4.23 – 4.21 (m, 1H), 4.06 (dd, 1H), 3.95 (dd, 1H), 3.74 (d,2H).

[0048] Example 13: Preparation of Compound 22 and Compound 23 Step 1: Glycerol (30.00 g, 1.00 eq.) and trichloroacetic acid (53.25 g, 1.00 eq.) were added to 200 ml of dichloromethane. 1.5 eq of dicyclohexylcarbodiimide (DCC) and 0.2 eq of DMAP were added to the reaction solution. The reaction solution was heated to 30°C and stirred overnight. The reaction solution was filtered and purified by reverse phase preparative separation chromatography and then by chiral chromatography to obtain 1.1 g of compound 22-1 with a purity of 92.5% and 1.02 g of compound 23-1 with a purity of 94.8%, respectively.

[0049] Structural confirmation of compound 22-1: MS-ESI(+), m / z: 254.1 (M+NH4 + ), 1 H NMR (400 MHz, DMSO- d6 ) δ 4.42 – 4.33 (m, 2H), 4.08 (t , 1H), 3.75 – 3.55 (m, 3H), 3.52 (d,1H).

[0050] Structural confirmation of compound 23-1: MS-ESI(+), m / z: 254.1 (M+NH4 + ), 1 H NMR (400 MHz, DMSO- d6 ) δ 4.42 – 4.33 (m, 2H), 4.08 (t , 1H), 3.75 – 3.55 (m, 3H), 3.52 (d,1H).

[0051] Step 2: Under an argon atmosphere, compound 22-1 (1.00 g, 1.00 eq) was dissolved in tetrahydrofuran solvent, and the reaction solution was cooled to -78 °C, and a toluene solution of diisobutylaluminum hydride (DIBAL-H, 2.0 eq) was added dropwise for 15 to 20 minutes. The reaction mixture was stirred at -78 °C for 2 to 3 hours, and a saturated aqueous solution of potassium sodium tartrate was added to the reaction solution to quench the reaction. The mixture was extracted and washed three times with dichloromethane, each time using 50 ml, and the lower aqueous phase was collected. The mixture was first purified by reverse phase preparative separation chromatography, and then purified by chiral chromatography to obtain compound 22, 210 mg, with a purity of 98.6%.

[0052] According to the preparation method of step 2, compound 23 can be prepared by replacing compound 22-1 with compound 23-1, with a purity of 98.5%.

[0053] Structural confirmation of compound 22: MS-ESI(+), m / z: 256.1 (M+NH4 + ),1 H NMR: (400 MHz, D2O) δ5.14 (s, 1H), 3.77 – 3.67 (m, 3H), 3.54 – 3.48 (m, 1H), 3.47 – 3.37 (m, 1H).

[0054] Structural confirmation of compound 23: MS-ESI(+), m / z: 256.1 (M+NH4 + ), 1 H NMR: (400 MHz, D2O) δ5.14 (s, 1H), 3.76 – 3.64 (m, 3H), 3.58 – 3.49 (m, 2H).

[0055] The configurations of compounds 22 and 23 were confirmed by circular dichroism calculations.

[0056] Experimental Example 1: Study on the sedative effect of different compounds on mice KM mice were selected and randomly divided into groups, with 10 mice in each group, half male and half female. Each group of mice was intraperitoneally injected with the corresponding drug or positive control drug (chloral hydrate), the dosage of chloral hydrate was 0.36 mg / g, and other compounds were calculated on an equimolar basis. The injection volume for each mouse was 0.1 ml / 10 g. The blank control group was injected with the same volume of saline. Before injecting the drug, the weight of each mouse was weighed and recorded; after injecting the drug, the mice were placed on a heating blanket (adjusted to 37 ° C) for the experiment, and the sleeping conditions of each group of mice after the injection of the corresponding drug were observed and recorded. The number of mice in each group who fell asleep and the sleeping time were recorded, and the sleeping rate of each group of mice was calculated. This experiment was repeated 3 times, and the groups were randomly divided again each time, with an interval of 7 days between each experiment.

[0057] Judgment criteria: Loss of righting reflex: refers to the mouse lying on its back with its limbs facing up and not turning over within 1 minute, which means it has entered the stage of loss of righting reflex; recovery of righting reflex: refers to the mouse being able to freely turn over from the supine position to the prone position; sleep latency: refers to the time from the injection of the drug to the disappearance of the righting reflex. Sleep time: refers to the time from the disappearance of the righting reflex to the recovery of the righting reflex; the loss of the righting reflex for more than 1 minute is the judgment standard for falling asleep. Average sleep time: is the arithmetic mean of the sleep time of each sleeping animal in the group. The percentage of sleep occurrence, that is, the sleep rate (%) = number of sleeping animals / total number of animals × 100%; average sleep rate: the arithmetic mean of the three sleep rates.

[0058] The experimental results are as follows: Note: Compared with the positive control group, *: P < 0.05; **: P < 0.01.

[0059] It can be seen that compared with the positive control drug, the compounds 1-16, 20, 22 and 23 of the present invention have higher sleep onset rate and longer sleep time, which are significantly different; in particular, the sleep onset rate and sleep time of compound 1-6 are far better than those of the positive control drug, and both have significant differences, and are expected to have good clinical sedation and hypnosis potential.

[0060] The above embodiment is only one of the preferred implementation modes of the present invention and should not be used to limit the protection scope of the present invention. Any changes or modifications that are made to the main design concept and spirit of the present invention and have no substantive significance, and the technical problems they solve are still consistent with the present invention, should be included in the protection scope of the present invention.

Claims

1. A compound represented by formula (I) or a stereoisomer thereof: in, R1 and R2 are independently selected from hydrogen, sucrose, glucose, fructosyl, glycerol, maltitol, sorbitol, mannitol, xylitol, erythritol, maltosyl, isomaltulose or sucralose; or R1 and R2 are connected to form a five-membered or six-membered heterocyclic ring.

2. The compound according to claim 1 or its stereoisomer, characterized in that: The R1 is selected from hydrogen; R2 is selected from sucrose, glucose, fructosyl, glycerol, maltitol, sorbitol, mannitol, xylitol, erythritol, maltosyl, isomaltulose or sucralose; or R1 and R2 are connected to form a five-membered or six-membered heterocyclic ring.

3. The compound according to claim 1 or its stereoisomer, characterized in that: The R1 is selected from hydrogen; R2 is selected from sucrose, glucose, fructosyl, glycerol, maltitol, sorbitol, mannitol, xylitol, erythritol or sucralose; or R1 and R2 are connected to form a five-membered or six-membered heterocyclic ring.

4. The compound according to claim 1 or its stereoisomer, characterized in that: The compound is selected from: or .

5. The compound or stereoisomer thereof according to any one of claims 1 to 4, characterized in that: At least one hydrogen in the compound may be substituted with deuterium.

6. A pharmaceutical composition comprising the compound according to any one of claims 1 to 4 or a stereoisomer thereof, and a pharmaceutically acceptable carrier and / or excipient.

7. Use of the pharmaceutical composition according to claim 6 for preparing tablets, capsules, syrups, oral solutions, injections, small water injections, powder injections or enemas.

8. Use of the compound according to any one of claims 1 to 4 or its stereoisomers in the preparation of sedative, hypnotic, antianxiety or anticonvulsant drugs.

9. Use of the compound according to any one of claims 1 to 4 or its stereoisomers in the preparation of sedatives and / or hypnotic drugs.

10. Use of the compound according to any one of claims 1 to 4 or its stereoisomers in drug quality testing.

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