阅读说明：本技术 用于减轻或治疗包括脆性X染色体综合征、Angelman综合征或Rett综合征的发育障碍的氨基甲酸酯化合物的用途 (Use of carbamate compounds for reducing or treating developmental disorders including fragile X syndrome, Angelman syndrome or Rett syndrome ) 是由 申蕙园 黄善宽 于 2018-11-13 设计创作，主要内容包括：本发明涉及由化学式1表示的氨基甲酸酯化合物,或其药学上可接受的盐,溶剂合物或水合物用于减轻或治疗包括脆性X染色体综合征、Angelman综合征或Rett综合征的发育障碍的用途。(The present invention relates to the use of a carbamate compound represented by chemical formula 1, or a pharmaceutically acceptable salt, solvate, or hydrate thereof for alleviating or treating developmental disorders including fragile X syndrome, Angelman syndrome, or Rett syndrome.)

1. A medicament for reducing or treating a developmental disorder comprising a therapeutically effective amount of a carbamate compound of formula 1, or a pharmaceutically acceptable salt, solvate, or hydrate thereof:

[ formula 1]

Wherein the content of the first and second substances,

R₁and R₂Each independently selected from hydrogen, halogen, C₁-C₈Alkyl, halo-C₁-C₈Alkyl radical, C₁-C₈Alkylthio and C₁-C₈An alkoxy group; and

A₁and A₂One is CH and the other is N.

2. A medicament according to claim 1, wherein the developmental disorder is fragile X syndrome, Angelman syndrome or Rett syndrome.

3. A medicament according to claim 1 for the prevention, alleviation or treatment of symptoms of developmental disorders.

4. The medicament according to claim 1, wherein the symptom of the developmental disorder is a delay in development, a loss of learning ability, a disorder or onset of social behavior.

5. The medicament according to any one of claims 1 to 4, wherein the therapeutically effective amount of the carbamate compound of formula 1 is administered once daily based on 50 mg to 500 mg in free form.

6. A medicament for reducing or treating fragile X syndrome comprising a therapeutically effective amount of a carbamate compound of formula 1, or a pharmaceutically acceptable salt, solvate, or hydrate thereof:

[ formula 1]

Wherein the content of the first and second substances,

R₁and R₂Each independently selected from hydrogen, halogen, C₁-C₈Alkyl, halo-C₁-C₈Alkyl radical, C₁-C₈Alkylthio and C₁-C₈An alkoxy group; and

A₁and A₂One is CH and the other is N.

7. The medicament according to claim 6, wherein the carbamate compound of formula 1 is (R) -1- (2-chlorophenyl) -2-tetrazol-2-yl-ethyl carbamate of the following formula 2:

[ formula 2]

。

8. A medicament according to claim 6 for the prevention, alleviation or treatment of symptoms of fragile X syndrome.

9. The medicament according to claim 8, wherein the symptom of fragile X syndrome is delayed development, learning deficit, social behavior disorder or onset.

10. The medicament according to claim 6, which is used for alleviating or treating an autism spectrum disorder caused by fragile X syndrome, or an autism spectrum disorder showing symptoms similar to fragile X syndrome.

11. The medicament according to any one of claims 6 to 10, wherein the therapeutically effective amount of the carbamate compound of formula 1 is 50 to 500 mg, based on the free form, administered once daily.

12. A medicament for reducing or treating Angelman syndrome comprising a therapeutically effective amount of a carbamate compound of formula 1, or a pharmaceutically acceptable salt, solvate or hydrate thereof:

[ formula 1]

Wherein the content of the first and second substances,

R₁and R₂Each independently selected from hydrogen, halogen, C₁-C₈Alkyl, halo-C₁-C₈Alkyl radical, C₁-C₈Alkylthio and C₁-C₈An alkoxy group; and

A₁and A₂One is CH and the other is N.

13. The medicament according to claim 12, wherein the carbamate compound of formula 1 is (R) -1- (2-chlorophenyl) -2-tetrazol-2-yl-ethyl carbamate of the following formula 2:

[ formula 2]

。

14. A medicament according to claim 12 for the prevention, alleviation or treatment of symptoms of Angelman syndrome.

15. A medicament according to claim 14, wherein the symptom of Angelman syndrome is developmental delay, learning deficit, social behaviour disorder or onset.

16. A medicament according to claim 12 for use in the alleviation or treatment of autism spectrum disorders caused by Angelman syndrome, or autism spectrum disorders showing symptoms similar to Angelman syndrome.

17. The medicament according to any one of claims 12 to 16, wherein the therapeutically effective amount of the carbamate compound of formula 1 is 50 to 500 mg, based on the free form, administered once daily.

18. A medicament for reducing or treating Rett syndrome comprising a therapeutically effective amount of a carbamate compound of formula 1, or a pharmaceutically acceptable salt, solvate, or hydrate thereof:

[ formula 1]

Wherein the content of the first and second substances,

R₁and R₂Each independently selected from hydrogen, halogen, C₁-C₈Alkyl, halo-C₁-C₈Alkyl radical, C₁-C₈Alkylthio and C₁-C₈An alkoxy group; and

A₁and A₂One is CH and the other is N.

19. The medicament according to claim 18, wherein the carbamate compound of formula 1 is (R) -1- (2-chlorophenyl) -2-tetrazol-2-yl-ethyl carbamate of formula 2 below:

[ formula 2]

。

20. A medicament according to claim 18 for the prevention, alleviation or treatment of symptoms of Rett syndrome.

21. A medicament according to claim 20, wherein the symptoms of Rett syndrome are developmental delay, learning deficit, social behavioral disorders or onset.

22. A medicament according to claim 18 for use in the alleviation or treatment of autism spectrum disorders caused by Rett syndrome, or autism spectrum disorders exhibiting symptoms similar to Rett syndrome.

23. The medicament according to any one of claims 18 to 22, wherein the therapeutically effective amount of the carbamate compound of formula 1 is 50 to 500 mg, based on the free form, administered once daily.

Technical Field

The present invention relates to the use of a carbamate compound of formula 1 below, or a pharmaceutically acceptable salt, solvate, or hydrate thereof, for reducing or treating developmental disorders including fragile X syndrome, Angelman syndrome, or Rett syndrome.

[ formula 1]

Wherein the content of the first and second substances,

R₁、R₂、A₁and A₂As defined herein.

Background

Treatment of developmental disorders such as Fragile X Syndrome (FXS), Rett syndrome and Angelman syndrome is limited.

Fragile X Syndrome (FXS) is a genetic disorder that is the most common monogenic cause of autism, particularly the genetic cause of mental disability in boys. Fragile X syndrome is caused by a mutation in the X mental retardation 1 fragment (Fmr1) gene located on the X chromosome. Fmr1 gene is the first autism related gene identified and encodes fragment X mental retardation protein (FMRP), an RNA binding protein that regulates translation. That is, the protein FMRP is produced from the Fmr1 gene, which is essential for normal brain development, and this protein is not produced sufficiently in fragile X syndrome (origin: center of disease control and prevention). This loss of functionality typically occurs when a CGG trinucleotide repeat is amplified in the 5' untranslated region of the Fmr1 gene. This amplification appears as a weak or "fragile-like" end on the X chromosome.

According to another report, the disorder occurs in 1/4600 men and 1/8000 women (from Genetics Home Reference, National L university of Medicine).

Symptoms of fragile X syndrome include delayed development, learning deficit, and social behavior disorders (eye mismatch, anxiety, attention problems, clapping hands, lack of thought to speak or act, hyperactivity). Men have moderate to severe intellectual disabilities, some women have normal range of intellectual disabilities or some women have intellectual disabilities. Autism spectrum disorders often occur in people with fragile X syndrome (source: center for Disease Control and Prevention). Furthermore, there is a risk of Seizures (seizure) in Fragile X Syndrome, and it is known that about 14% of men and about 4% of women experience Seizures (Berry-Kravis et al, 2010, "seizurs in Fragile X Synthesis: Characteristics and Comobind diagnostics," Am J inner Dev Disabl. 115 (6): 461-72).

To diagnose fragile X syndrome, Fmr1 gene abnormalities were diagnosed by blood DNA testing.

To date, there is no fundamental treatment for FXS. Adequate education can help, and sometimes medications are used to alleviate behavioral disorders and seizures.

Angelman syndrome is a disease that occurs when a specific gene on chromosome 15 is not inherited. Symptoms of Angelman syndrome include developmental delay, intellectual disability, social behavioral disorders (excitable personality, hyperactivity, attention problems) and seizures.

In addition, autism spectrum disorders often occur in people with Angelman syndrome. To date, there is no fundamental treatment for Angelman syndrome. Appropriate education can help, and sometimes medications, to alleviate the symptoms of the Angelman syndrome described above.

Rett syndrome is a disease caused by a genetic mutation in MECP2 gene. Symptoms of Rett syndrome include developmental delay, intellectual disability, social behavioral disorders (excitable personality, hyperactivity, attention problems) and onset.

Furthermore, people with Rett syndrome exhibit symptoms similar to autism spectrum disorders. To date, there is no fundamental treatment for Rett syndrome. Appropriate education can help, and sometimes medications, to alleviate the symptoms of Rett syndrome as described above.

Namely, fragile X syndrome, Angelman syndrome and Rett syndrome have common symptoms of developmental delay, intellectual disability, social behavioral disorder (social dysfunction), seizure and autism spectrum disorder (or the like). In addition, fragile X syndrome, Angelman syndrome and Rett syndrome have no fundamental treatment and thus have a common feature that administration is aimed at alleviating their symptoms.

Disclosure of Invention

Technical problem to be solved

The present invention aims to provide a method for alleviating or treating developmental disorders.

The present invention is also directed to the use of a therapeutically effective amount of a carbamate compound of formula 1 below, or a pharmaceutically acceptable salt, solvate, or hydrate thereof for alleviating or treating a developmental disorder:

[ formula 1]

Wherein the content of the first and second substances,

R₁、R₂、A₁and A₂As defined herein.

The present invention is directed to methods for reducing or treating fragile X syndrome.

The present invention is also directed to providing the use of the carbamate compound of formula 1 above, or a pharmaceutically acceptable salt, solvate, or hydrate thereof for alleviating or treating fragile X syndrome.

The present invention is also directed to methods for alleviating or treating Angelman syndrome.

The present invention is also directed to providing the use of the carbamate compound of formula 1 above, or a pharmaceutically acceptable salt, solvate, or hydrate thereof for alleviating or treating Angelman syndrome.

The present invention also aims to provide methods for reducing or treating Rett syndrome.

The present invention is also directed to providing the use of the carbamate compound of formula 1 above, or a pharmaceutically acceptable salt, solvate, or hydrate thereof for alleviating or treating Rett syndrome.

[ solution to problems ]

The present invention provides a medicament for reducing or treating a developmental disorder comprising a therapeutically effective amount of a carbamate compound of formula 1, or a pharmaceutically acceptable salt, solvate, or hydrate thereof:

[ formula 1]

Wherein the content of the first and second substances,

R₁and R₂Each independently selected from hydrogen, halogen, C₁-C₈Alkyl, halo-C₁-C₈Alkyl radical, C₁-C₈Alkylthio and C₁-C₈An alkoxy group; and

A₁and A₂One is CH and the other is N.

In addition, the present invention provides a method for reducing or treating a developmental disorder in a subject, comprising administering to the subject a therapeutically effective amount of a carbamate compound of formula 1 above, or a pharmaceutically acceptable salt, solvate, or hydrate thereof.

In addition, the present invention provides a use of the carbamate compound of formula 1 above, or a pharmaceutically acceptable salt, solvate, or hydrate thereof for alleviating or treating a developmental disorder.

In addition, the present invention provides a medicament for reducing or treating fragile X syndrome, comprising a therapeutically effective amount of the carbamate compound of formula 1 above, or a pharmaceutically acceptable salt, solvate, or hydrate thereof.

In addition, the present invention provides a method for reducing or treating fragile X syndrome in a subject, which comprises administering to the subject a therapeutically effective amount of a carbamate compound of formula 1 above, or a pharmaceutically acceptable salt, solvate, or hydrate thereof.

In addition, the present invention provides a use of the carbamate compound of formula 1 above, or a pharmaceutically acceptable salt, solvate, or hydrate thereof for alleviating or treating fragile X syndrome.

In addition, the present invention provides a medicament for reducing or treating Angelman syndrome, which comprises a therapeutically effective amount of a carbamate compound of formula 1 above, or a pharmaceutically acceptable salt, solvate or hydrate thereof.

In addition, the present invention provides a method for reducing or treating Angelman syndrome in a subject, which comprises administering to the subject a therapeutically effective amount of a carbamate compound of formula 1 above, or a pharmaceutically acceptable salt, solvate or hydrate thereof.

In addition, the present invention provides the use of the carbamate compound of formula 1 above, or a pharmaceutically acceptable salt, solvate, or hydrate thereof for alleviating or treating Angelman syndrome.

In addition, the present invention provides a medicament for reducing or treating Rett syndrome, which comprises a therapeutically effective amount of a carbamate compound of formula 1 above, or a pharmaceutically acceptable salt, solvate, or hydrate thereof.

In addition, the present invention provides a method for reducing or treating Rett syndrome in a subject, comprising administering to the subject a therapeutically effective amount of a carbamate compound of formula 1 above, or a pharmaceutically acceptable salt, solvate, or hydrate thereof.

In addition, the present invention provides the use of the carbamate compound of formula 1 above, or a pharmaceutically acceptable salt, solvate, or hydrate thereof for alleviating or treating Rett syndrome.

According to one embodiment of the present invention, in the above formula 1, R₁And R₂Each independently selected from hydrogen, halogen and C₁-C₈An alkyl group.

In one embodiment of the invention, halo C₁-C₈Alkyl is perfluoroalkyl.

According to another embodiment of the present invention, the carbamate compound of the above formula 1 is (R) -1- (2-chlorophenyl) -2-tetrazol-2-yl-ethyl carbamate of the following formula 2:

[ formula 2]

。

The carbamate compounds of the above formulae 1 and 2 can be easily prepared by one of ordinary skill in the art of compound synthesis using known compounds or compounds that can be easily prepared therefrom. In particular, methods for preparing the compounds of formula 1 above are described in detail in international publication nos. WO2006/112685a1, WO2010/150946a1 and WO2011/046380a2, the disclosures of which are incorporated herein by reference. The compound of the above formula 1 can be chemically synthesized by any method described in the above documents, but these methods are merely exemplary methods, and the order of unit operations and the like can be selectively changed if necessary. Accordingly, the above methods are not intended to limit the scope of the present invention.

The carbamate compounds of formula 1 above may be used to alleviate or treat developmental disorders including fragile X syndrome, Angelman syndrome or Rett syndrome.

The carbamate compounds of formula 1 above may be used for preventing, alleviating or treating symptoms of developmental disorders including fragile X syndrome, Angelman syndrome or Rett syndrome.

Symptoms of developmental disorders include developmental delay, learning deficit, and social behavior disorders (eye mismatch, anxiety, attention problems, clapping hands, talking or moving without thinking, hyperactivity) or seizures.

Symptoms of fragile X syndrome include delayed development, learning deficit, and social behavior disorders (eye mismatch, anxiety, attention problems, clapping hands, lack of thought to speak or act, hyperactivity). Men have moderate to severe intellectual disabilities, some women have normal range of intellectual disabilities or some women have intellectual disabilities. Autism spectrum disorders often occur in people with fragile X syndrome (source: center for Disease Control and Prevention). Furthermore, there is a risk of seizures in Fragile X Syndrome, and it is known that about 14% of men and about 4% of women experience seizures (Berry-Kravis et al, 2010, "Seizuresin framework X Synthesis: transactions and Commobid diagnostics," Am JIntellect Dev Disabl. 115 (6): 461-72).

Symptoms of Angelman syndrome and Rett syndrome include developmental delay, intellectual disability, social behavioral disorders (excitable personality, hyperactivity, attention problems) and episodes.

Therefore, the drugs and pharmaceutical compositions according to the present invention can be used for preventing, alleviating or treating symptoms of developmental disorders including fragile X syndrome, Angelman syndrome or Rett syndrome, and symptoms including, but not limited to, developmental delay, learning disability, social behavior disorder (socioehavial disorder) and onset.

In addition, the medicament according to the present invention can be used for alleviating or treating autism spectrum disorders caused by fragile X syndrome, Angelman syndrome and Rett syndrome, or autism spectrum disorders showing symptoms similar to fragile X syndrome, Angelman syndrome and Rett syndrome.

The efficacy of the compounds of formula 1 above for developmental disorders including fragile X syndrome, Angelman syndrome or Rett syndrome can be confirmed using known models. For example, the Fmr1 gene-deleted mouse model represents several clinical symptoms observed in developmental disorders such as fragile X syndrome, Angelman syndrome or Rett syndrome, and has been used as a means of validating drug efficacy for studying disease mechanisms and development of therapeutics (Bakker et al, 1994, "Fmr1knock out mice: A model to study fragment X structural recovery", Cell, 15; 78(1): 23-33). Typical phenotypes of this mouse model include auditory onset, excessive autonomic activity, cognitive deficits, attention problems, and the like.

The dosage of the carbamate compound of formula 1 for use in reducing or treating the above-mentioned diseases may generally vary depending on the severity, body weight and metabolic condition of the disease in the subject. A "therapeutically effective amount" for an individual patient refers to an amount of active compound sufficient to achieve the pharmacological effects described above (i.e., the therapeutic effects described above). A therapeutically effective amount of a compound of formula 1 is 50 to 500 mg, 50 to 400 mg, 50 to 300 mg, 100 to 400 mg, 100 to 300 mg, 50 to 200 mg, or 100 to 200 mg, in free form and administered once daily to a human.

The compounds of the present invention may be administered by any conventional method for administering therapeutic agents, for example, oral, parenteral, intravenous, intramuscular, subcutaneous, or rectal administration.

A medicament or pharmaceutical composition according to one embodiment of the present invention may comprise a therapeutically effective amount of a compound selected from the group consisting of the carbamate compounds of the present invention, pharmaceutically acceptable salts, solvates, hydrates thereof, and combinations thereof.

Examples of the pharmaceutically acceptable salts of the carbamate compounds of formula 1 above independently include acetate, benzenesulfonate, benzoate, bitartrate, calcium acetate, camphorsulfonate, carbonate, citrate, edetate, edisylate, etolate (estolate), ethanesulfonate, fumarate, glucoheptonate, gluconate, glutamate, glycolylated para-aminophenylarsenate, hexylresorcinate (hexylresorcinate), hydrabamine (hydrabamine), hydrobromide, hydrochloride, bicarbonate, hydroxynaphthoate (hydroxynaphthoate), iodide, isethionate, lactate, lactobionate (lactobionate), malate, maleate, mandelate, methanesulfonate, methylnitrate, methylsulfate, mucate (mucate), naphthalenesulfonate, nitrate, pamoate (pamoate), pantothenate, phosphate/diphosphate, calcium acetate, camphorate, menthyl nitrate, methyl sulfate, galactonate, napsylate (mucoate), napsylate (pamoate), pamoate, pantothenate, phosphate/diphosphate, and the like, Polygalacturonate, salicylate, stearate, subacetate, succinate or hemisuccinate, sulfate or hemisulfate, tannate, tartrate, oxalate or hemitartrate, theachlorate (teoclate), triiodonium, benzathine, chloroprocaine, choline, diethanolamine, ethylenediamine, meglumine, procaine, aluminum, ammonium, tetramethylammonium, calcium, lithium, magnesium, potassium, sodium, and zinc.

The medicament or pharmaceutical composition according to one embodiment of the present invention may be administered orally or parenterally. Parenteral administration may include intravenous injection, subcutaneous injection, intramuscular injection, intraperitoneal injection, endothelial administration, topical administration, intranasal administration, intravaginal administration, intrapulmonary administration, rectal administration, and the like. In the case of oral administration, the pharmaceutical composition according to one embodiment of the invention may be formulated as a plain tablet (uncoated tablet) or such that the active agent is coated or protected from degradation in the stomach. Furthermore, the composition can be administered by any device capable of transferring the active agent to the target cell. The route of administration may vary according to the general condition and age of the subject to be treated, the nature of the condition being treated and the active ingredient selected.

The appropriate dose of the drug or pharmaceutical composition according to one embodiment of the present invention may vary depending on factors such as formulation method, administration method, age, body weight and sex of the patient, pathological conditions, diet, administration times, administration route, excretion rate and response sensitivity, and a physician having ordinary skill can easily determine and prescribe a dose effective for the desired treatment or prevention. The pharmaceutical composition according to one embodiment may be administered in one or more doses, e.g., 1-4 times per day. A pharmaceutical composition according to one embodiment may comprise a compound of formula 1 in an amount of 50 to 500 mg, 50 to 400 mg, 50 to 300 mg, 100 to 400 mg, 100 to 300 mg, 50 to 200 mg, or 100 to 200 mg, preferably 50 to 300 mg, more preferably 50 to 200 mg, based on the free form.

The medicament or pharmaceutical composition according to one embodiment of the present invention may be formulated according to methods that can be easily performed by those having ordinary skill in the art, using pharmaceutically acceptable carriers and/or excipients, so as to be prepared in unit dosage form, or contained in a multi-dose container. The above formulation may be a solution, suspension or emulsion (emulsified solution), extract, powder, granule, tablet or capsule in an oil or aqueous medium, and may further include a dispersing or stabilizing agent. In addition, the pharmaceutical composition may be administered in the form of suppositories, sprays, ointments, emulsions, gels, inhalants or skin patches. The pharmaceutical compositions may also be prepared for administration to a mammal, more preferably for administration to a human.

The pharmaceutically acceptable carrier may be a solid or a liquid, and may be one or more selected from the group consisting of fillers, antioxidants, buffers, bacteriostats, dispersants, adsorbents, surfactants, binders, preservatives, disintegrants, sweeteners, flavoring agents, glidants, release control agents, wetting agents, stabilizers, suspending agents, and lubricants. In addition, the pharmaceutically acceptable carrier may be selected from the group consisting of saline, sterile water, ringer's solution, buffered saline, dextrose solution, maltodextrin solution, glycerol, ethanol, and mixtures thereof.

In one embodiment, suitable fillers include, but are not limited to, sugars (e.g., glucose, sucrose, maltose, and lactose), starches (e.g., corn starch), sugar alcohols (e.g., mannitol, sorbitol, maltitol, erythritol, and xylitol), starch hydrolysates (e.g., dextrins and maltodextrins), cellulose or cellulose derivatives (e.g., microcrystalline cellulose), or mixtures thereof.

In one embodiment, suitable binders include, but are not limited to, povidone, copovidone, methylcellulose, hydroxypropylmethylcellulose, hydroxypropylcellulose, hydroxyethylcellulose, gelatin, gums, sucrose, starch, or mixtures thereof.

In one embodiment, suitable preservatives include, but are not limited to, benzoic acid, sodium benzoate, benzyl alcohol, butylated hydroxyanisole, butylated hydroxytoluene, chlorobutanol, gallates, hydroxybenzoate, EDTA, or mixtures thereof.

In one embodiment, suitable disintegrants include, but are not limited to, sodium starch glycolate, cross-linked polyvinylpyrrolidone, cross-linked carboxymethylcellulose, starch, microcrystalline cellulose, or a mixture thereof.

In one embodiment, suitable sweeteners include, but are not limited to, sucralose (sucralose), saccharin, sodium saccharin, potassium saccharin, calcium saccharin, potassium acesulfame or sodium cyclamate, mannitol, fructose, sucrose, maltose, or mixtures thereof.

In one embodiment, suitable glidants include, but are not limited to, silicon dioxide, colloidal silicon dioxide, talc, and the like.

In one embodiment, suitable lubricants include, but are not limited to, long chain fatty acids and salts thereof, such as magnesium stearate and stearic acid, talc, glyceride waxes, or mixtures thereof.

As used herein, the terms "preventing", "preventing" and "prevention" refer to reducing or eliminating the likelihood of disease.

As used herein, the terms "alleviate", "alleviating" and "alleviating" refer to ameliorating, in whole or in part, a disease and/or its attendant symptoms.

As used herein, the terms "treating", "treating" and "treatment" refer to the complete or partial elimination of a disease and/or its attendant symptoms.

As used herein, the term "subject" refers to an animal, preferably a mammal (e.g., primate (e.g., human), cow, sheep, goat, horse, dog, cat, rabbit, rat, mouse, etc.), most preferably a human, who is the subject of treatment, observation or experiment.

As used herein, the term "therapeutically effective amount" refers to the amount of active compound or pharmaceutical agent that elicits the biological or medical response in a system, animal or human that is being sought by a researcher, veterinarian, medical doctor or other clinician, including alleviation of the symptoms of the disease or disorder being treated.

As used herein, the term "composition" encompasses a product comprising the specified amounts of the specified ingredients and any product which results, directly or indirectly, from combination of the specified amounts of the specified ingredients.

[ Effect of the invention ]

The medicaments and pharmaceutical compositions according to the invention may be effective in the alleviation and treatment of developmental disorders such as fragile X syndrome, Angelman syndrome or Rett syndrome.

Drawings

FIG. 1 shows the results of the inhibitory effect of the test compound (10mg/kg, 20mg/kg) and a positive control group (MPEP, 2-methyl-6- (phenylethynyl) pyridine) on the onset of seizures in an audiogenic seizures test conducted using a mouse model with Fmr1 gene deletion.

FIG. 2 shows the results of the preventive effect of the test compound (10mg/kg, 20mg/kg) and the positive control group (MPEP) on the apnea due to seizures in the audiogenic seizure test using the Fmr1 gene-deleted mouse model.

FIG. 3 shows the results of the effect of test compounds (10mg/kg, 20mg/kg) and positive control group (MPEP) on the modulation of seizure scores in an audiogenic seizure test using the Fmr1 gene-deleted mouse model.

FIG. 4 shows the results of the effect of test compounds (10mg/kg, 20mg/kg) and positive control group (MPEP) on mouse survival in an audiogenic seizure test using a mouse model with Fmr1 gene deletion.

Fig. 5 shows the results of the effect of test compound (10mg/kg, 20mg/kg) and positive control group (MPEP) on the percent of episodes in the audiogenic episode test using the Fmr1 gene-deleted mouse model.

Fig. 6 shows the results of testing the effect of compounds (10mg/kg, 20mg/kg) on voluntary action in the Fmr1 gene-deleted mouse model.

Fig. 7 shows the results of testing the effect of compounds (10mg/kg, 20mg/kg) on increased upright activity (exercising activity) in the Fmr1 gene-deleted mouse model.

Fig. 8 shows the results of testing the effect of compounds (10mg/kg, 20mg/kg) on reduced fear conditions in a contextual fear conditioning test (contextual fear conditioning test) using the Fmr1 gene-deleted mouse model.

Fig. 9 shows the results of testing the effect of compounds (10mg/kg, 20mg/kg) on reduced fear conditions in the implied fear conditioning test by stimulation signal (cut fear conditioning test) using the Fmr1 gene-deleted mouse model.

Detailed Description

Hereinafter, the present invention will be explained in more detail by working examples. However, the following working examples are intended only to illustrate one or more embodiments and are not intended to limit the scope of the invention.

Preparation examples: synthesis of (R) -1- (2-chlorophenyl) -2-tetrazol-2-yl-ethyl carbamate

(R) -1- (2-chlorophenyl) -2-tetrazol-2-yl-ethyl carbamate (test compound) was prepared according to the method described in preparation example 50 of International publication No. WO 2010/150946.