Trichloroethanol derivatives and uses thereof

Abstract

The application belongs to the technical field of medicines, and particularly relates to a trichloroethanol derivative and application thereof. The trichloroethanol derivative has low stimulation, high sleep rate and long sleep time, and has potential multi-scene clinical application value.

Description

TECHNICAL FIELD

[0001] The present application belongs to the technical field of medicine, and particularly relates to a trichloroethanol derivative, a preparation method and application thereof. BACKGROUND

[0002] The main pharmacological effect of sedative-hypnotics is sedation and hypnosis. At present, the commonly used sedative-hypnotics in China include aldehydes, benzodiazepines, barbiturates and the like. Chloral hydrate is a hydrate of trichloroacetaldehyde, which belongs to central sedative drugs and can inhibit the ascending activating system of the reticular formation of the brain stem, has no obvious influence on the balance of sleep phase, fast wave sleep and slow wave sleep, has an effect similar to physiological sleep, and has no discomfort and no lag effect and accumulation after waking up. It is a relatively safe hypnotic, sedative and anticonvulsant drug, and is suitable for patients with difficulty falling asleep, but has large drug stimulation, bitter taste, poor stability, short duration and the like, and is limited in clinical application scenarios. Benzodiazepines can enhance the neurotransmission of inhibitory synapses, cause positive allosteric modulation to be enhanced, and thus cause the effect of chloride ion flux to be enhanced, and have hypnotic and sedative effects; among them, midazolam and oxazepam have fast onset and short action time, and belong to short-acting tranquilizers in clinical application, but are difficult to fall asleep after early and sudden waking up, and thus are limited in clinical application for insomniac patients who need long-acting sedation. Phenobarbital is a long-acting barbiturate, and has central inhibitory effects varying with the dose, has sedative, hypnotic and anticonvulsant effects, has an action time of 6-8 hours, and is suitable for intractable insomnia, but is limited in clinical application for patients who need rapid and short-acting and have difficulty falling asleep before falling asleep. In addition, benzodiazepines and barbiturates can produce tolerance and addiction when repeatedly taken or continuously taken in a short period, and are not suitable for long-term use.

[0003] Therefore, a sedative, hypnotic and anticonvulsant drug with small stimulation, good stability, fast sedation, relatively long duration and high safety is developed to improve the clinical application scenarios and has great market prospects. SUMMARY

[0004] In order to solve at least one of the technical problems existing in the prior art, the present application provides a new trichloroethanol derivative to reduce stimulation, improve drug efficacy and prolong the action time.

[0005] In one aspect, the present application provides a compound shown in formula (I) or a stereoisomer thereof:

[0006]

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

[0008] Further, R1 is selected from hydrogen; R2 is selected from sucrosyl, glucosyl, fructosyl, glyceryl, maltitolyl, sorbitolyl, mannitolyl, xylitolyl, erythritolyl, maltosyl, isomaltulosyl, or chlorosucrosyl; or R1 and R2 are connected to form a five- or six-membered heterocyclic ring.

[0009] Further, R1 is selected from hydrogen; R2 is selected from sucrosyl, glucosyl, fructosyl, glyceryl, maltitolyl, sorbitolyl, mannitolyl, xylitolyl, erythritolyl, maltosyl, isomaltulosyl, or chlorosucrosyl; or R1 and R2 are connected to form a five- or six-membered heterocyclic ring.

[0010] Further, the compound is selected from:

[0011] or .

[0012] Further, at least one hydrogen in the structure of any of the compounds or stereoisomers thereof described above can be replaced by deuterium.

[0013] In a second aspect, the present application provides a pharmaceutical composition comprising any of the compounds or stereoisomers thereof described above, and a pharmaceutically acceptable carrier and / or excipient.

[0014] Further, the pharmaceutical composition can be used for preparing tablets, capsules, syrups, oral solutions, injection solutions, small water injections, powder injections, or enemas; preferably syrups, oral solutions, or enemas.

[0015] In a third aspect, the present application provides use of any of the compounds or stereoisomers thereof described above in the preparation of a sedative, hypnotic, anxiolytic, or anticonvulsant drug.

[0016] Further, the present application provides use of any of the compounds or stereoisomers thereof described above in the preparation of a sedative and / or hypnotic drug.

[0017] In a fourth aspect, the present application provides use of any of the compounds or stereoisomers thereof described above in the detection of drug quality.

[0018] Beneficial effects: The present application provides a brand-new trichloroethanol derivative, the compound has a small stimulation, a high sedation rate, and a relatively long sedation time, which proves to have a better sedative effect, and has a strong potential for clinical application. DETAILED DESCRIPTION

[0019] The schemes of the present application will be explained below with reference to examples. Those skilled in the art will understand that the examples below are only for illustration of the present application and should not be considered as limiting the scope of the present application. The specific techniques or conditions not mentioned in the examples are carried out according to the techniques or conditions described in the literature in the art or according to the product instructions. The reagents or instruments not mentioned by the manufacturer are all conventional products available on the market.

[0020] Example 1: Preparation of Compound 1 and Compound 2

[0021]

[0022] Sucrose (34.23 g, 1.00 eq.) and trichloroacetaldehyde (14.74 g, 1.00 eq.) were added into 300 ml trifluoroacetic acid, the reaction mixture was warmed to 40℃ and stirred overnight, the reaction solution was cooled to 0-10℃, 500 ml purified water was slowly added dropwise into the reaction solution, dichloromethane was used to control the low temperature condition of 0~10℃, extraction and washing were carried out for three times, 800 ml was used each time, and the aqueous phase was collected. The aqueous phase was purified by reversed-phase preparative separation chromatography, and 1.50 g of target compound 1 with a purity of 97.5% and 1.32 g of target compound 2 with a purity of 96.8% were obtained, respectively.

[0023] Structure confirmation of Compound 1: MS-ESI(+), m / z: 506.1 (M+NH4 + ), 1 H NMR: (400 MHz, D2O) δ 5.18 (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) δ 105.12, 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.

[0024] Structure confirmation of Compound 2: MS-ESI(+), m / z: 506.1 (M+NH4 + ), 1H NMR: (400 MHz, D20) δ 5.18 (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, D20) δ 104.53, 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.

[0025] Wherein the chemical shift of compound 1 carbon spectrum 80.58 and 65.61 and the chemical shift of compound 2 carbon spectrum 81.98 and 67.00 are compared, respectively, to further confirm the connection position of compound 1 and compound 2.

[0026] Example 2: Preparation of compound 3 and compound 4

[0027]

[0028] According to the preparation method in example 1, compound 3 with purity of 98.7% and compound 4 with purity of 98.2% can be prepared by replacing sucrose with glucose.

[0029] Structure confirmation of compound 3: MS-ESI(+), m / z: 344.0 (M+NH4 + ), 1 H NMR: (400 MHz, D20) δ 5.12 (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 result shows that the hydrogen of chemical shift 5.08 ppm and the carbon of chemical shift 95.00 appear cross peaks, which indicates that the connection position of the compound is at the glycosidic bond, which is the target compound 3.

[0030] Structure confirmation of compound 4: MS-ESI(+), m / z: 344.0 (M+NH4 + ), 1H NMR: (400 MHz, D20) δ 5.07 (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 2D NMR result showed that the hydrogen of chemical shift 3.47 - 3.43 ppm and the carbon of chemical shift 96.80 appeared cross peak, indicating that the connecting position of the compound was primary alcohol hydroxyl group, which was the target compound 4.

[0031] Example 3: Preparation of compound 5 and compound 6

[0032]

[0033] According to the preparation method in Example 1, sucrose is replaced by fructose to obtain compound 5 with a purity of 98.7% and compound 6 with a purity of 98.2%.

[0034] Structure confirmation of compound 5: MS-ESI(+), m / z: 344.0 (M+NH4 + ), 1 H NMR: (400 MHz, D20) δ 5.07 (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 2D NMR result showed that the hydrogen of chemical shift 3.47 - 3.43 ppm and the carbon of chemical shift 96.80 appeared cross peak, indicating that the connecting position of the compound was primary alcohol hydroxyl group, which was the target compound 4.

[0035] Structure confirmation of compound 6: MS-ESI(+), m / z: 344.0 (M+NH4 + ), 1 H NMR: (400 MHz, D20) δ 5.12 (s, 1H), 3.89 - 3.80 (m, 5H), 3.76 (d, 2H).

[0036] Compound 5 and compound 6 showed the difference of chemical shift of d-peak CH2, which further confirmed the connecting position of compound 5 and compound 6.

[0037] Example 4: Preparation of compound 7 and compound 8

[0038]

[0039] According to the preparation method in Example 1, sucrose is replaced by fructose to obtain compound 5 with a purity of 98.7% and compound 6 with a purity of 98.2%.

[0040] Structure confirmation of compound 7: MS-ESI(+), m / z: 490.1 (M+NH4+ 1 H NMR: (400 MHz, D2O) δ 5.08 (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).

[0041] Structure confirmation of compound 8: MS-ESI(+), m / z: 490.1 (M+NH4 + 1 H NMR: (400 MHz, D2O) δ 5.08 (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).

[0042] The multiplet of hydrogen spectrum chemical shift 4.51 - 4.49 of compound 7 is compared with the hydrogen spectrum chemical shift 4.23 - 4.18 of compound 8, which further confirms the connection position of compound 7 and compound 8.

[0043] Example 5: Preparation of compound 9 and compound 10

[0044]

[0045] According to the preparation method in Example 1, the two title compounds can be prepared by replacing sucrose with sorbitol, and the purities are 97.6% and 98.1%, respectively.

[0046] Structure confirmation of compound 9: MS-ESI(+), m / z: 346.1 (M+NH4 + 1 H NMR: (400 MHz, D2O) δ 5.12 (s, 1H), 3.89 - 3.76 (m, 6H), 3.68 - 3.56 (m, 2H).

[0047] Structure confirmation of compound 10: MS-ESI(+), m / z: 328.1 (M+NH4 + 1 ​​​​H NMR: (400 MHz, D20) δ 5.12 (s, 1H), 3.89 - 3.84 (m, 2H), 3.78 (d, 1H), 3.74 - 3.63 (m, 4H), 3.61 - 3.55 (m, 1H).

[0048] Example 6: Preparation of compound 11 and compound 12

[0049]

[0050] The two title compounds were prepared according to the preparation method in Example 1 by replacing sucrose with mannitol, and the purities were 97.9%, 98.7%, respectively.

[0051] Structure confirmation of compound 11: MS-ESI(+), m / z: 346.1 (M+NH4 + ), 1 H NMR: (400 MHz, D20) δ 5.12 (s, 1H), 3.89 - 3.84 (m, 2H), 3.78 (d, 1H), 3.74 - 3.63 (m, 4H), 3.61 - 3.55 (m, 1H).

[0052] Structure confirmation of compound 12: MS-ESI(+), m / z: 328.1 (M+NH4 + ), 1 H NMR: (400 MHz, D20) δ 5.08 (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).

[0053] Example 7: Preparation of compound 13 and compound 14

[0054]

[0055] The two title compounds were prepared according to the preparation method in Example 1 by replacing sucrose with xylitol, and the purities were 98.0%, 98.5%, respectively.

[0056] Structure confirmation of compound 13: MS-ESI(+), m / z: 316.1 (M+NH4 + ), 1H NMR: (400 MHz, D20) δ 5.12 (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).

[0057] Structure confirmation of compound 14: MS-ESI (+), m / z: 298.1 (M+NH4 + ), 1 H NMR: (400 MHz, D20) δ 5.08 (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).

[0058] Example 8: Preparation of compound 15 and compound 16

[0059]

[0060] The two title compounds were prepared according to the preparation method in Example 1, replacing sucrose with erythritol, and the purities were 98.2%, 98.4%, respectively.

[0061] Structure confirmation of compound 15: MS-ESI (+), m / z: 286.1 (M+NH4 + ), 1 H NMR: (400 MHz, D20) δ 5.12 (s, 1H), 3.88 (m, 1H), 3.81 - 3.69 (m, 3H), 3.68 - 3.53 (m, 2H).

[0062] Structure confirmation of compound 16: MS-ESI (+), m / z: 268.1 (M+NH4 + ), 1 H NMR: (400 MHz, D20) δ 5.08 (s, 1H), 3.89 - 3.86 (m, 1H), 4.05 - 3.78 (m, 3H), 3.68 - 3.54 (m, 2H).

[0063] Example 9: Preparation of compound 17

[0064]

[0065] Compound 17 was prepared according to the preparation method in Example 1 by replacing sucrose with maltose, purity 97.9%.

[0066] Structure confirmation of compound 17: MS-ESI(+), m / z: 506.1 (M+NH4 + ), 1 H NMR: (400 MHz, D2O) δ 5.18 (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).

[0067] Example 10: Preparation of compound 18 and compound 19

[0068]

[0069] The two title compounds were prepared according to the preparation method in Example 1 by replacing sucrose with isomaltulose, purities were 97.5%, 98.1% respectively.

[0070] Structure confirmation of compound 18: MS-ESI(+), m / z: 506.1 (M+NH4 + ), 1 H NMR: (400 MHz, D2O) δ 5.18 (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), HMBC two-dimensional nuclear magnetic result showed that the hydrogen with chemical shift 4.25-4.18 ppm and the carbon with chemical shift 206.67 and 93.15 appeared cross peaks at the same time, indicating that the compound was the target compound 18.

[0071] Structure confirmation of compound 19: MS-ESI(+), m / z: 506.1 (M+NH4 + ), 1H NMR: (400 MHz, D20) δ 5.18 (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), HMBC two-dimensional nuclear magnetic result shows that the hydrogen of chemical shift 4.02 - 3.93 ppm and the carbon of chemical shift 92.69 appear cross peaks, indicating that the compound is the target compound 19.

[0072] Example 11: Preparation of compound 20

[0073]

[0074] Compound 20 can be prepared according to the preparation method in Example 1, by replacing sucrose with trichlorosucrose, with a purity of 97.2%.

[0075] Structural confirmation of compound 20: MS-ESI (+), m / z: 560.1 (M+NH4 + ), 1 H NMR: (400 MHz, D20) δ 5.18 (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), HMBC two-dimensional nuclear magnetic result shows that the hydrogen of chemical shift 4.02 - 3.93 ppm and the carbon of chemical shift 92.69 appear cross peaks, indicating that the compound is the target compound 19.

[0076] Example 12: Preparation of compound 21

[0077]

[0078] Compound 21 can be prepared according to the preparation method in Example 1, by replacing sucrose with glycerol, with a purity of 98.0%.

[0079] Structural confirmation of compound 21: MS-ESI (+), m / z: 238.1 (M+NH4 + ), 1 H NMR: (400 MHz, D20) δ 5.08 (s, 1H), 4.23 - 4.21 (m, 1H), 4.06 (dd, 1H), 3.95 (dd, 1H), 3.74 (d, 2H).

[0080] Example 13: Preparation of compound 22 and compound 23

[0081]

[0082] Step one:

[0083] Glycerol (30.00 g, 1.00 eq.) was added with trichloroacetic acid (53.25 g, 1.00 eq.) into 200 ml dichloromethane, 1.5 eq. of dicyclohexyl carbodiimide (DCC) and 0.2 eq. of DMAP were added into the reaction solution, the reaction solution was heated to 30 °C and stirred overnight, the reaction solution was filtered, purified by reversed-phase preparative separation chromatography first, then purified by chiral chromatography, 1.1 g of compound 22-1 was obtained, with a purity of 92.5%, and 1.02 g of compound 23-1 was obtained, with a purity of 94.8%.

[0084] Structure 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).

[0085] Structure 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).

[0086] Step two:

[0087] Compound 22-1 (1.00 g, 1.00 eq.) was dissolved in tetrahydrofuran solvent under an argon atmosphere, the reaction solution was cooled to -78 °C, and then diisobutylaluminum hydride in toluene solution (DIBAL-H, 2.0 eq.) was added dropwise. The dropwise process lasted for 15 ~ 20 minutes. The reaction mixture was stirred at -78 °C for 2 ~ 3 hours, and then saturated potassium sodium tartrate aqueous solution was added to quench the reaction. The reaction solution was extracted and washed with dichloromethane three times, each time using 50 ml, and the lower aqueous phase was collected. Purified by reversed-phase preparative separation chromatography first, then purified by chiral chromatography, compound 22 was prepared, 210 mg, with a purity of 98.6%.

[0088] Compound 23 was prepared according to the procedure of Step 2 by replacing compound 22-1 with compound 23-1. The purity was 98.5%.

[0089] Compound 22 was confirmed by structure: MS-ESI(+), m / z: 256.1 (M+NH4 + ), 1 H NMR: (400 MHz, D2O) δ 5.14 (s, 1H), 3.77 - 3.67 (m, 3H), 3.54 - 3.48 (m, 1H), 3.47 - 3.37 (m, 1H).

[0090] Compound 23 was confirmed by structure: MS-ESI(+), m / z: 256.1 (M+NH4 + ), 1 H NMR: (400 MHz, D2O) δ 5.14 (s, 1H), 3.76 - 3.64 (m, 3H), 3.58 - 3.49 (m, 2H).

[0091] The configuration of compound 22 and compound 23 was confirmed by the computational method of circular dichroism.

[0092] Test Example 1: Study on the sedative effect of different compounds on mice

[0093] KM mice were selected and randomly divided into groups, 10 mice in each group, half male and half female. Each group of mice was injected intraperitoneally with the corresponding drug or positive control drug (chloral hydrate). The dose of chloral hydrate was 0.36 mg / g, and the other compounds were calculated according to the same molar. The injection volume of each mouse was 0.1 ml / 10g. The blank control group was injected with the same volume of normal 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 (the temperature was adjusted to 37°C) for the experiment. The sleep condition of each group of mice after injecting the corresponding drug was observed and recorded, and the number of sleeping mice and sleep time of each group of mice were recorded. The sleep rate of each group of mice was calculated. This experiment was repeated 3 times, and each experiment was randomly divided into groups. The interval between each experiment was 7 days.

[0094] Judgment criteria: righting reflex disappearance: refers to the mouse four limbs supine 1 minute without turning over, that is, into the righting reflex disappearance stage; righting reflex recovery: refers to the mouse can be free to turn from the supine position to the prone position; sleep latency: refers to the time used between the start of injecting the drug and the disappearance of the righting reflex. Sleep time: refers to the time used from the disappearance of the righting reflex to the recovery of the righting reflex; more than 1 minute of righting reflex disappearance is the judgment standard of falling asleep. Average sleep time: the arithmetic mean of the sleep time of each animal falling asleep in the group. Sleep occurrence percentage, i.e. sleep rate (%) = number of animals falling asleep / total number of animals x 100%; average sleep rate: the arithmetic mean of three sleep rates.

[0095] The experimental results are as follows:

[0096]

[0097] Note: compared with the positive control group, *: P<0.05; **: P<0.01.

[0098] It can be seen that the sleep rate of the compounds 1-16, 20, 22 and 23 of the present application is higher and the sleep time is longer compared with the positive control drug, and there is a significant difference; especially the sleep rate and sleep time of the compound 1-6 are far superior to the positive control drug, and both have a significant difference, and are expected to have good clinical sedation and hypnotic potential.

[0099] The above examples are only one of the preferred embodiments of the present application, and should not be used to limit the protection scope of the present application, but any modification or polishing without substantial meaning made in the main design idea and spirit of the present application, the technical problems solved are still consistent with the present application, and should be included in the protection scope of the present application.

Claims

1. A compound selected from the group consisting of: , or .

2. A compound selected from the group consisting of: , or .

3. A pharmaceutical composition comprising a compound according to claim 1 or 2, and a pharmaceutically acceptable excipient.

4. Use of the pharmaceutical composition according to claim 3 for the preparation of tablets, capsules, syrups, oral solutions, injectable solutions, powders for injection or enemas.

5. Use of a compound according to claim 1 or 2 for the preparation of a sedative, hypnotic, anxiolytic or anticonvulsant medicament.

6. Use of a compound according to claim 1 or 2 for the preparation of a sedative and / or hypnotic medicament.

7. Use of a compound according to claim 1 or 2 for the detection of the quality of a medicament.

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