Use of imidazopyrimidine or imidazotriazine compounds for the prevention, alleviation or treatment of developmental disorders

Abstract

The present invention provides compounds for the prevention, alleviation or treatment of developmental disorders. The present invention relates to the use of an imidazopyrimidine or imidazotriazine compound of formula (1), or a pharmaceutically acceptable salt, solvate or hydrate thereof, for the prevention, alleviation or treatment of a developmental disorder.

Description

[Technical Field]

[0001] The present invention provides a compound represented by the following formula (1) for preventing, alleviating or treating developmental disorders: [ka] (1) wherein X, Z, R1 and R2 are as defined herein, or a pharmaceutically acceptable salt, solvate or hydrate thereof. [Background technology]

[0002] Developmental disorders include, for example, Fragile X Syndrome (FXS), Angelman Syndrome, and Rett Syndrome, and treatments for these developmental disorders are limited.

[0003] Fragile X syndrome (FRS) is a genetic disorder and the most common single genetic cause of autism and intellectual disability, particularly in boys. Fragile X syndrome is caused by mutations in the Fmr1 gene, located on the X chromosome. The Fmr1 gene was the first identified autism-related gene and encodes the fragile X mental retardation protein (FMRP), an RNA-binding protein that regulates translation. The protein produced by the Fmr1 gene, FMRP, is necessary for normal brain development, and its absence causes fragile X syndrome (Source: US Centers for Disease Control and Prevention). This loss of function typically occurs when there is an expansion of a CGG trinucleotide repeat in the 5' non-terminal region of the Fmr1 gene. This expansion manifests as a fragile or "fragile-like" end on the X chromosome.

[0004] Fragile X syndrome affects both men and women, but women tend to be less affected than men and it is more common in men. Another report estimates that the condition occurs in 1 in 4,600 men and 1 in 8,000 women (Source: Genetics Home Reference; National Library of Medicine).

[0005] Symptoms of fragile X syndrome include developmental delay, learning disabilities, intellectual disability, social behavioral disorders (inability to make appropriate eye contact, anxiety, attention and concentration problems, hand flapping tremors, speaking or acting without thinking, hyperactivity, and excitable personality), and seizures. The severity of fragile X syndrome varies, with males having severe intellectual disabilities, while some females have normal intelligence and others have intellectual disabilities. Autism spectrum disorders frequently occur in individuals with fragile X syndrome (Source: US Centers for Disease Control and Prevention). Individuals with fragile X syndrome are also at risk for seizures, with approximately 14% of males and 4% of females experiencing seizures (Non-Patent Document 1). To diagnose fragile X syndrome, abnormalities in the Fmr1 gene are identified using a blood DNA test.

[0006] Angelman syndrome is a condition that occurs when a specific gene on chromosome 15 is not inherited genetically. Symptoms of Angelman syndrome include developmental delay, learning disabilities, intellectual disability, social and behavioral disorders (inability to make appropriate eye contact, anxiety, attention and concentration problems, flapping tremors in the hands, speaking or acting without thinking, hyperactivity, and an excitable personality), and seizures. Autism spectrum disorders also frequently occur in individuals with Angelman syndrome.

[0007] Rett syndrome is a disorder caused by a genetic mutation in the MECP2 gene. Symptoms of Rett syndrome include developmental delay, learning disabilities, intellectual disability, social and behavioral disorders (inability to make appropriate eye contact, anxiety, attention and concentration problems, flapping tremors in the hands, speaking or acting without thinking, hyperactivity, and excitability), and seizures. Individuals with Rett syndrome also exhibit symptoms similar to those of autism spectrum disorder.

[0008] Furthermore, typical developmental disorders such as pervasive developmental disorders, autism, autism spectrum disorder, Fragile X-associated tremor / ataxia syndrome (FXTAS), Asperger's syndrome, childhood disintegrative disorder, Landau-Kleffner syndrome, Prader-Willi syndrome, chromosome 22q11.2 deletion syndrome, tardive dyskinesia, seizure disorders, and Williams syndrome also share symptoms with the Fragile X syndrome, Angelman syndrome, and Rett syndrome. That is, developmental disorders such as Fragile X syndrome, Angelman syndrome, and Rett syndrome generally exhibit symptoms such as developmental delay, learning disabilities, intellectual disability, social behavioral disorders (inability to make appropriate eye contact, anxiety, attention and concentration problems, hand flapping tremor, speaking or acting without thinking, hyperactivity, and excitable personality), and seizures. No therapeutic agent suitable for such developmental disorders has been developed to date. [Prior art documents] [Patent documents]

[0009] [Non-Patent Document 1] Berry-Kravis et al., 2010, "Seizures in Fragile X Syndrome: Characteristics and Comorbid Diagnoses". Am J Intellect Dev Disabil. 115 (6): 461-72 Summary of the Invention [Problem to be solved by the invention]

[0010] It is an object of the present invention to provide a method for preventing, alleviating or treating developmental disorders. Another object of the present invention is to provide a compound represented by the following formula (1) for preventing, alleviating or treating developmental disorders: [ka] (1) (wherein X, Z, R1 and R2 are as defined herein), or a pharmaceutically acceptable salt, solvate or hydrate thereof. [Means for solving the problem]

[0011] The present invention relates to a therapeutically effective amount of a compound represented by the following formula (1): [ka] (1) wherein X is CH or N; Z is O or S; R1 is a C6-C alkyl substituted or unsubstituted by one or more substituents selected from halo, C1-C5 alkyl, C1-C5 alkoxy, C1-C5 alkylthio, amino, di(C1-C5 alkyl)amino, cyano, formyl, halo-C1-C5 alkyl, hydroxy-C1-C5 alkyl, C1-C5 alkoxy-C1-C5 alkyl, carbamoyloxy-C1-C5 alkyl, C1-C5 alkyl-C(O)O-C1-C5 alkyl, 5- or 6-membered heterocycloalkyl-C1-C5 alkyl having 1-3 heteroatoms selected from N, O, and S, and di(C1-C5 alkyl)amino-C1-C5 alkyl. 12 aryl; or a 5-12-membered unsaturated heterocyclyl having 1-5 heteroatoms selected from N, O and S, substituted or unsubstituted with one or more substituents selected from halo, hydroxy, C1-C5 alkyl, C1-C5 alkoxy and halo-C1-C5 alkyl; R2 is a C6-C alkyl group substituted or unsubstituted with one or more substituents selected from halo, deuterium, hydroxy, and C1-C5 alkyl. 12 aryl; or a 5-12 membered unsaturated heterocyclyl having 1-3 heteroatoms selected from N, O and S, substituted or unsubstituted with one or more substituents selected from halo and C1-C5 alkyl. The present invention provides an agent for preventing, alleviating or treating developmental disorders, which comprises an imidazopyrimidine or imidazotriazine compound represented by the following formula (I): or a pharmaceutically acceptable salt, solvate or hydrate thereof.

[0012] The present invention also provides a pharmaceutical composition for preventing, alleviating, or treating a developmental disorder, comprising a therapeutically effective amount of the imidazopyrimidine or imidazotriazine compound of formula (1) or a pharmaceutically acceptable salt, solvate, or hydrate thereof, and further comprising one or more pharmaceutically acceptable carriers.

[0013] Furthermore, the present invention provides a method for preventing, alleviating, or treating a developmental disorder in a subject, comprising administering to the subject a therapeutically effective amount of an imidazopyrimidine or imidazotriazine compound of formula (1) or a pharmaceutically acceptable salt, solvate, or hydrate thereof.

[0014] The present invention also provides use of the imidazopyrimidine or imidazotriazine compound of formula (1) or a pharmaceutically acceptable salt, solvate or hydrate thereof for the prevention, alleviation or treatment of developmental disorders. [Effects of the Invention]

[0015] The medicaments and pharmaceutical compositions according to the present invention can effectively prevent, alleviate or treat developmental disorders. [Brief explanation of the drawings]

[0016] [Figure 1] 1 shows the effect of long-term administration (6 weeks) of the test compound (2 mg / kg, twice daily) on the reduction of fear conditioning in a contextual fear conditioning experiment performed using an Fmr1 gene knockout mouse model. [Figure 2] 1 shows the effect of long-term administration (6 weeks) of a test compound (2 mg / kg, twice a day) on an Fmr1 gene knockout mouse model in an open field test. [Figure 3]1 shows the effect of long-term administration (6 weeks) of a test compound (2 mg / kg, twice a day) on marble burying in an Fmr1 gene knockout mouse model. DETAILED DESCRIPTION OF THE INVENTION

[0017] According to one embodiment of the present invention, in the formula (1), R1 is phenyl substituted or unsubstituted by 1 to 3 substituents selected from halo, hydroxy, C1-C5 alkyl, C1-C5 alkoxy, C1-C5 alkylthio, amino, di(C1-C5 alkyl)amino, cyano, formyl, halo-C1-C5 alkyl, hydroxy-C1-C5 alkyl, C1-C5 alkoxy-C1-C5 alkyl, carbamoyloxy-C1-C5 alkyl, and C1-C5 alkyl-C(O)O-C1-C5 alkyl; or 5-10-membered unsaturated heterocyclyl having 1 to 3 heteroatoms selected from N, O, and S, substituted or unsubstituted by 1 to 3 substituents selected from halo, hydroxy, C1-C5 alkyl, C1-C5 alkoxy, and halo-C1-C5 alkyl.

[0018] According to another embodiment of the present invention, in the formula (1), R2 is phenyl substituted or unsubstituted with 1 to 5 substituents selected from halo, deuterium, hydroxy and C1-C5 alkyl; or 5- or 6-membered heteroaryl having 1 to 3 heteroatoms selected from N, O and S, substituted or unsubstituted with 1 to 3 substituents selected from halo and C1-C5 alkyl.

[0019] According to another embodiment of the present invention, in the formula (1), X is CH or N; Z is O; R1 is phenyl substituted or unsubstituted with 1 to 3 substituents selected from halo, hydroxy, C1-C5 alkyl, C1-C5 alkoxy, C1-C5 alkylthio, amino, di(C1-C5 alkyl)amino, cyano, formyl, halo-C1-C5 alkyl, hydroxy-C1-C5 alkyl, C1-C5 alkoxy-C1-C5 alkyl, carbamoyloxy-C1-C5 alkyl, and C1-C5 alkyl-C(O)O-C1-C5 alkyl; or 5-9 membered unsaturated heterocyclyl having 1 or 2 heteroatoms selected from N, O, and S, unsubstituted or substituted or unsubstituted with 1 or 2 substituents selected from halo, hydroxy, C1-C5 alkyl, C1-C5 alkoxy, and halo-C1-C5 alkyl; R2 is phenyl substituted or unsubstituted with 1 to 5 substituents selected from halo, deuterium, hydroxy, and C1-C5 alkyl; or a 6-membered heteroaryl having 1 or 2 nitrogen atoms substituted or unsubstituted with 1 or 2 substituents selected from halo and C1-C5 alkyl.

[0020] According to another embodiment of the present invention, in the formula (1), R1 is phenyl substituted or unsubstituted by 1 to 3 substituents selected from halo, hydroxy, C1-C5 alkyl, C1-C5 alkoxy, C1-C5 alkylthio, amino, di(C1-C5 alkyl)amino, cyano, formyl, halo-C1-C5 alkyl, hydroxy-C1-C5 alkyl, C1-C5 alkoxy-C1-C5 alkyl, carbamoyloxy-C1-C5 alkyl, and C1-C5 alkyl-C(O)O-C1-C5 alkyl; 1,3-benzodioxolyl substituted or unsubstituted by 1 or 2 halo; or pyridyl or pyrimidinyl substituted or unsubstituted by 1 or 2 substituents selected from halo, hydroxy, C1-C5 alkyl, C1-C5 alkoxy, and halo-C1-C5 alkyl; R2 is phenyl substituted or unsubstituted with 1 to 5 substituents selected from halo, deuterium, hydroxy, and C1-C5 alkyl; or pyridyl substituted or unsubstituted with 1 or 2 substituents selected from halo and C1-C5 alkyl.

[0021] According to another embodiment of the present invention, in the formula (1), X is CH; Z is O; R1 is phenyl substituted or unsubstituted with 1 to 3 substituents selected from halo, hydroxy, C1-C5 alkyl, C1-C5 alkoxy, C1-C5 alkylthio, amino, halo-C1-C5 alkyl, hydroxy-C1-C5 alkyl, and C1-C5 alkoxy-C1-C5 alkyl; R2 is pyridyl unsubstituted or substituted with one or two substituents selected from halo and C1-C5 alkyl.

[0022] Representative compounds of formula (1) according to the present invention include: 6-(2-fluorophenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine; 2-phenoxymethyl-6-phenylimidazo[1,2-a]pyrimidine; 6-(2,4-difluorophenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine; 6-(2-Methoxyphenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine; 6-(2-methylphenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine; 6-(4-fluoro-2-methylphenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine; 6-(2,3-difluorophenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine; 6-(4-fluorophenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine; 6-(3-aminophenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine; 6-(2-aminophenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine; 6-(3-amino-6-methylphenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine; 6-(3-amino-4-fluorophenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine; 6-(3-chloro-4-fluorophenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine; 6-(2-dimethylaminophenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine; 6-(2-chloro-4-fluorophenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine; 6-(2-hydroxyphenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine; 6-(3-hydroxyphenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine; 6-(4-fluoro-2-trifluoromethylphenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine; 6-(3,4-difluorophenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine; 6-(2-Methoxy-4-fluorophenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine; 6-(4-fluoro-3-methoxyphenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine; 6-(4-chloro-2-methoxyphenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine; 6-(4-cyano-2-methoxyphenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine; 6-(7-fluorobenzo[1,3]dioxol-4-yl)-2-phenoxymethylimidazo[1,2-a]pyrimidine; 6-(4-fluoro-2-hydroxymethylphenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine; 6-(4-fluoro-2-methylthiophenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine; 6-(2-amino-4-fluorophenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine; 6-(2,4-difluoro-5-methoxyphenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine; 6-(2-fluoropyridin-3-yl)-2-phenoxymethylimidazo[1,2-a]pyrimidine; 6-(6-Methoxypyridin-3-yl)-2-phenoxymethylimidazo[1,2-a]pyrimidine; 6-(6-fluoropyridin-3-yl)-2-phenoxymethylimidazo[1,2-a]pyrimidine; 6-(4-methylpyridin-3-yl)-2-phenoxymethylimidazo[1,2-a]pyrimidine; 6-(2,6-difluoropyridin-3-yl)-2-phenoxymethylimidazo[1,2-a]pyrimidine; 6-(6-chloropyridin-3-yl)-2-phenoxymethylimidazo[1,2-a]pyrimidine; 6-(2-fluoropyridin-4-yl)-2-phenoxymethylimidazo[1,2-a]pyrimidine; 6-(3-chloropyridin-4-yl)-2-phenoxymethylimidazo[1,2-a]pyrimidine; 6-(4-chlorophenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine; 6-(6-fluoro-4-methyl-3-pyridyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine; 6-(6-fluoro-5-methyl-3-pyridyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine; 6-(5-Fluoro-2-pyridyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine; 6-(2,4-difluorophenyl)-2-(3-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine; 6-(4-fluoro-2-methoxyphenyl)-2-(3-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine; 6-(4-fluoro-3-hydroxyphenyl)-2-(3-fluorophenoxymethyl)-imidazo[1,2-a]pyrimidine; 6-(2-aminophenyl)-2-(3-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine; 6-(3-chloropyridin-4-yl)-2-(3-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine; 6-(4-methylpyridin-3-yl)-2-(3-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine; 6-(2,4-difluorophenyl)-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine; 6-(4-fluoro-2-methylphenyl)-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine; 6-(3-chloropyridin-4-yl)-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine; 6-(2,6-dimethylphenyl)-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine; 2-[(4-fluorophenoxy)methyl]-6-(6-fluoro-3-pyridyl)imidazo[1,2-a]pyrimidine; 4-[[6-(4-fluorophenyl)imidazo[1,2-a]pyrimidin-2-yl]methoxy]phenol; 2-[(4-fluorophenoxy)methyl]-6-(4-fluorophenyl)imidazo[1,2-a]pyrimidine; 2-[(3-fluorophenoxy)methyl]-6-(4-fluorophenyl)imidazo[1,2-a]pyrimidine; 2-Fluoro-5-[2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]phenol; 2-[(4-fluorophenoxy)methyl]-6-phenyl-imidazo[1,2-a]pyrimidine; 5-Fluoro-2-[2-[(3-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]phenol; 5-fluoro-2-[2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]phenol; 6-(4-fluorophenyl)-2-[(2,3,4,5,6-pentadeuteriophenoxy)methyl]imidazo[1,2-a]pyrimidine; 2-[(4-fluorophenoxy)methyl]6-(o-tolyl)imidazo[1,2-a]pyrimidine; 6-(5-fluoro-2-methyl-phenyl)-2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidine; 2-[(4-fluorophenoxy)methyl]-6-(2-fluoro-4-pyridyl)imidazo[1,2-a]pyrimidine; 2-[2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]phenol; 6-(2-fluoro-4-methyl-phenyl)-2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidine; 2-[(4-fluorophenoxy)methyl]-6-[6-(trifluoromethyl)-3-pyridyl]imidazo[1,2-a]pyrimidine; 2-[2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]aniline; 6-(2-chloro-4-fluoro-phenyl)-2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidine; 4-[2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]-3-methoxy-benzonitrile; 6-(4-chloro-2-methoxy-phenyl)-2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidine; 2-Fluoro-5-[2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]aniline; 6-(2,6-difluoro-3-pyridyl)-2-[(3-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidine; 5-[2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]-2-methyl-aniline; 4,5-Difluoro-2-[2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]aniline; 2-[2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]-5-methyl-aniline; 5-chloro-2-[2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]aniline; 2-[2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]-4-methyl-aniline; 5-Fluoro-2-[2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]aniline; 2-[(4-fluorophenoxy)methyl]-6-(4-methyl-3-pyridyl)imidazo[1,2-a]pyrimidine; 2-[(3-fluorophenoxy)methyl]-6-(2-fluoro-4-pyridyl)imidazo[1,2-a]pyrimidine; 2-[(3-fluorophenoxy)methyl]-6-[6-(trifluoromethyl)-3-pyridyl)imidazo[1,2-a]pyrimidine; 2-[(3-fluorophenoxy)methyl]-6-(6-fluoro-3-pyridyl)imidazo[1,2-a]pyrimidine; 2-[(3-fluorophenoxy)methyl]-6-(2-fluoro-3-pyridyl)imidazo[1,2-a]pyrimidine; 6-(5,6-difluoro-3-pyridyl)-2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidine; 5-[2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]-2-methoxy-aniline; 2-[(4-fluorophenoxy)methyl]-6-(5-fluoro-2-pyridyl)imidazo[1,2-a]pyrimidine; 2-[(4-fluorophenoxy)methyl]-6-(5-methoxy-2-pyridyl)imidazo[1,2-a]pyrimidine; 6-(4-chloro-3-pyridyl)-2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidine; 6-(5-chloro-3-pyridyl)-2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidine; 2-[(4-fluorophenoxy)methyl]-6-(5-methoxy-3-pyridyl)imidazo[1,2-a]pyrimidine; 5-[2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]pyridin-2-ol; 6-(6-fluoro-5-methyl-3-pyridyl)-2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidine; 2-[(4-fluorophenoxy)methyl]-6-(6-methyl-3-pyridyl)imidazo[1,2-a]pyrimidine; 2-[(3-fluorophenoxy)methyl]-6-(5-fluoro-2-pyridyl)imidazo[1,2-a]pyrimidine; 2-[(3-fluorophenoxy)methyl]-6-[4-fluoro-2-(trifluoromethyl)phenyl]imidazo[1,2-a]pyrimidine; 4-[2-[(3-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]-3-methoxy-benzonitrile; [5-fluoro-2-[2-[(3-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]phenyl]methanol; [5-fluoro-2-[2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]phenyl]methanol; 6-(4-fluoro-2-methylsulfanyl-phenyl)-2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidine; 2-[(4-fluorophenoxy)methyl]-6-(2-methoxy-4-pyridyl)imidazo[1,2-a]pyrimidine; 2-[2-[(3-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]-4-methyl-aniline; 5-Fluoro-2-[2-[(3-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]aniline; 6-(4-fluorophenyl)-2-(pyridin-2-yloxymethyl)imidazo[1,2-a]pyrimidine; 6-(2-methylphenyl)-2-(pyridin-2-yloxymethyl)imidazo[1,2-a]pyrimidine; 6-(4-fluoro-2-methoxyphenyl)-2-(pyridin-2-yloxymethyl)imidazo[1,2-a]pyrimidine; 6-(2,4-difluorophenyl)-2-(pyridin-2-yloxymethyl)imidazo[1,2-a]pyrimidine; 6-(4-fluoro-2-methylphenyl)-2-(pyridin-2-yloxymethyl)imidazo[1,2-a]pyrimidine; 6-(2,3-difluorophenyl)-2-(pyridin-2-yloxymethyl)imidazo[1,2-a]pyrimidine; 6-(5-fluoro-2-methylphenyl)-2-(pyridin-2-yloxymethyl)imidazo[1,2-a]pyrimidine; 6-(3-fluoro-2-methylphenyl)-2-(pyridin-2-yloxymethyl)imidazo[1,2-a]pyrimidine; 6-(7-fluoro-2H-benzo[1,3]dioxol-4-yl)-2-(pyridin-2-yloxymethyl)imidazo[1,2-a]pyrimidine; 6-(4-chloro-2-methoxyphenyl)-2-(pyridin-2-yloxymethyl)imidazo[1,2-a]pyrimidine; 6-(3-fluoro-2-methoxy-phenyl)-2-(2-pyridyloxymethyl)imidazo[1,2-a]pyrimidine; 6-[4-fluoro-2-(trifluoromethyl)phenyl]-2-(2-pyridyloxymethyl)imidazo[1,2-a]pyrimidine; 6-(4-fluoro-2-methyl-phenyl)-2-[(5-fluoro-2-pyridyl)oxymethyl)imidazo[1,2-a]pyrimidine; 6-(2-ethylphenyl)-2-(2-pyridyloxymethyl)imidazo[1,2-a]pyrimidine; 6-(4-fluoro-2-methyl-phenyl)-2-[(4-fluoro-2-pyridyl)oxymethyl)imidazo[1,2-a]pyrimidine; 6-(2-fluoro-4-methyl-phenyl)-2-(2-pyridyloxymethyl)imidazo[1,2-a]pyrimidine; 6-(4-fluoro-2-methoxy-phenyl)-2-[(4-fluoro-2-pyridyl)oxymethyl)imidazo[1,2-a]pyrimidine; 2-[(5-fluoro-2-pyridyl)oxymethyl]-6-[4-fluoro-2-(trifluoromethyl)phenyl]imidazo[1,2-a]pyrimidine; 6-(2,4-difluorophenyl)-2-[(4-fluoro-2-pyridyl)oxymethyl)imidazo[1,2-a]pyrimidine; 6-(3-fluoro-2-methoxy-phenyl)-2-[(4-fluoro-2-pyridyl)oxymethyl)imidazo[1,2-a]pyrimidine; 6-(2,3-difluorophenyl)-2-[(4-fluoro-2-pyridyl)oxymethyl)imidazo[1,2-a]pyrimidine; 6-(4-fluorophenyl)-2-[(4-fluoro-2-pyridyl)oxymethyl)imidazo[1,2-a]pyrimidine; 6-(3-fluoro-2-methyl-phenyl)-2-[(5-fluoro-2-pyridyl)oxymethyl)imidazo[1,2-a]pyrimidine; 2-[(4-fluoro-2-pyridyl)oxymethyl]-6-[4-fluoro-2-(trifluoromethyl)phenyl]imidazo[1,2-a]pyrimidine; 2-[(5-fluoro-2-pyridyl)oxymethyl]-6-(o-tolyl)imidazo[1,2-a]pyrimidine; 6-(4-chloro-2-methyl-phenyl)-2-[(5-fluoro-2-pyridyl)oxymethyl)imidazo[1,2-a]pyrimidine; 6-(2,4-dimethylphenyl)-2-[(5-fluoro-2-pyridyl)oxymethyl)imidazo[1,2-a]pyrimidine; 6-(4-fluorophenyl)-2-[(5-fluoro-2-pyridyl)oxymethyl)imidazo[1,2-a]pyrimidine; 2-(2-pyridyloxymethyl)-6-[6-(trifluoromethyl)-3-pyridyl]imidazo[1,2-a]pyrimidine; 2-[(5-fluoro-2-pyridyl)oxymethyl]-6-[6-(trifluoromethyl)-3-pyridyl]imidazo[1,2-a]pyrimidine; 6-(5-Fluoro-2-pyridyl)-2-(2-pyridyloxymethyl)imidazo[1,2-a]pyrimidine; 2-Fluoro-5-[2-[(5-fluoro-2-pyridyl)oxymethyl]imidazo[1,2-a]pyrimidin-6-yl]aniline; 2-Fluoro-5-[2-(2-pyridyloxymethyl)imidazo[1,2-a]pyrimidin-6-yl]aniline; [5-fluoro-2-[2-(2-pyridyloxymethyl)imidazo[1,2-a]pyrimidin-6-yl]phenyl]methanol; 3-Methoxy-4-[2-(2-pyridyloxymethyl)imidazo[1,2-a]pyrimidin-6-yl]benzonitrile; 4-[2-[(5-fluoro-2-pyridyl)oxymethyl]imidazo[1,2-a]pyrimidin-6-yl]-3-methoxy-benzonitrile; 6-(4-Fluoro-2-methylsulfanyl-phenyl)-2-(2-pyridyloxymethyl)imidazo[1,2-a]pyrimidine; [5-fluoro-2-[2-[(5-fluoro-2-pyridyl)oxymethyl]imidazo[1,2-a]pyrimidin-6-yl]phenyl]methanol; 4-[2-(2-pyridyloxymethyl)imidazo[1,2-a]pyrimidin-6-yl]benzonitrile; 6-[4-fluoro-2-(methoxymethyl)phenyl]-2-(2-pyridyloxymethyl)imidazo[1,2-a]pyrimidine; [2-[2-(2-pyridyloxymethyl)imidazo[1,2-a]pyrimidin-6-yl]-5-(trifluoromethyl)phenyl]methanol; 6-(2-isopropylphenyl)-2-(2-pyridyloxymethyl)imidazo[1,2-a]pyrimidine; 4-[2-(2-pyridyloxymethyl)imidazo[1,2-a]pyrimidin-6-yl]-3-(trifluoromethyl)benzaldehyde; 6-[4-chloro-2-(trifluoromethyl)phenyl]-2-(2-pyridyloxymethyl)imidazo[1,2-a]pyrimidine; 6-(4-fluorophenyl)-2-(pyridin-3-yloxymethyl)imidazo[1,2-a]pyrimidine; 6-(4-fluoro-2-methoxyphenyl)-2-(pyridin-3-yloxymethyl)imidazo[1,2-a]pyrimidine; 6-(2,4-difluorophenyl)-2-(pyridin-3-yloxymethyl)imidazo[1,2-a]pyrimidine; 6-(4-fluoro-2-methylphenyl)-2-(pyridin-3-yloxymethyl)imidazo[1,2-a]pyrimidine; 6-(4-fluoro-2-hydroxyphenyl)-2-(pyridin-3-yloxymethyl)imidazo[1,2-a]pyrimidine; 6-(4-fluoro-2-methoxyphenyl)-2-(pyridin-4-yloxymethyl)imidazo[1,2-a]pyrimidine; 6-(2,4-difluorophenyl)-2-(pyridin-4-yloxymethyl)imidazo[1,2-a]pyrimidine; 6-(2-methylphenyl)-2-(5-fluoro-pyridin-3-yloxymethyl)imidazo[1,2-a]pyrimidine; 6-(4-fluoro-2-methylphenyl)-2-(5-fluoro-pyridin-3-yloxymethyl)imidazo[1,2-a]pyrimidine; 6-(4-fluoro-2-methoxyphenyl)-2-(5-fluoropyridin-3-yloxymethyl)imidazo[1,2-a]pyrimidine; 6-(4-fluoro-2-hydroxyphenyl)-2-(5-fluoropyridin-3-yloxymethyl)imidazo[1,2-a]pyrimidine; 6-(2,4-difluorophenyl)-2-(6-fluoropyridin-3-yloxymethyl)imidazo[1,2-a]pyrimidine; 6-(4-fluoro-2-methylphenyl)-2-(6-fluoropyridin-3-yloxymethyl)imidazo[1,2-a]pyrimidine; 6-(4-fluoro-2-methylphenyl)-2-(2-fluoropyridin-3-yloxymethyl)imidazo[1,2-a]pyrimidine; 6-(4-fluoro-2-methylphenyl)-2-(5-chloropyridin-3-yloxymethyl)imidazo[1,2-a]pyrimidine; 6-(2,4-difluorophenyl)-2-(2-fluoropyridin-4-yloxymethyl)imidazo[1,2-a]pyrimidine; 6-(4-fluoro-2-methylphenyl)-2-(2-fluoropyridin-4-yloxymethyl)imidazo[1,2-a]pyrimidine; 6-(4-fluoro-2-methoxyphenyl)-2-(2-fluoropyridin-4-yloxymethyl)imidazo[1,2-a]pyrimidine; 6-(4-fluorophenyl)-2-(2-fluoropyridin-4-yloxymethyl)imidazo[1,2-a]pyrimidine; 6-(2,3-difluorophenyl)-2-(2-fluoropyridin-4-yloxymethyl)imidazo[1,2-a]pyrimidine; 6-(2-fluorophenyl)-2-(2-fluoropyridin-4-yloxymethyl)imidazo[1,2-a]pyrimidine; 6-(4-fluoro-2-hydroxyphenyl)-2-(2-fluoropyridin-4-yloxymethyl)imidazo[1,2-a]pyrimidine; 6-(2-methylphenyl)-2-(2-fluoropyridin-4-yloxymethyl)imidazo[1,2-a]pyrimidine; 6-(2-hydroxyphenyl)-2-(2-fluoropyridin-4-yloxymethyl)imidazo[1,2-a]pyrimidine; 6-(4-fluoro-2-hydroxymethylphenyl)-2-(2-fluoropyridin-4-yloxymethyl)imidazo[1,2-a]pyrimidine; 6-(4-fluorophenyl)-2-[(5-fluoro-3-pyridyl)oxymethyl)imidazo[1,2-a]pyrimidine; 2-[(2-chloro-4-pyridyl)oxymethyl]-6-(4-fluorophenyl)imidazo[1,2-a]pyrimidine; 2-[(5-fluoro-3-pyridyl)oxymethyl]-6-[4-fluoro-2-(trifluoromethyl)phenyl]imidazo[1,2-a]pyrimidine; 2-[(2-fluoro-4-pyridyl)oxymethyl]-6-[4-fluoro-2-(trifluoromethyl)phenyl]imidazo[1,2-a]pyrimidine; 5-Fluoro-2-[2-[(5-fluoro-3-pyridyl)oxymethyl]imidazo[1,2-a]pyrimidin-6-yl]aniline; 5-Fluoro-2-[2-[(2-fluoro-4-pyridyl)oxymethyl]imidazo[1,2-a]pyrimidin-6-yl]aniline; [5-fluoro-2-[2-[(5-fluoro-3-pyridyl)oxymethyl]imidazo[1,2-a]pyrimidin-6-yl]phenyl]methanol; 2-(2,4-difluorophenyl)-6-(phenoxymethyl)imidazo[1,2-b][1,2,4]triazine; 2-(2,4-difluorophenyl)-6-((pyridin-4-yloxy)methyl)imidazo[1,2-b][1,2,4]triazine; 2-(2,4-difluorophenyl)-6-((pyridin-2-yloxy)methyl)imidazo[1,2-b][1,2,4]triazine; 2-(4-fluorophenyl)-6-((pyridin-4-yloxy)methyl)imidazo[1,2-b][1,2,4]triazine; 2-(2-methylphenyl)-6-((pyridin-4-yloxy)methyl)imidazo[1,2-b][1,2,4]triazine; 2-(2,4-difluorophenyl)-6-((2-fluoropyridin-4-yloxy)methyl)imidazo[1,2-b][1,2,4]triazine; 2-(4-fluoro-2-methylphenyl)-6-((2-fluoropyridin-4-yloxy)methyl)imidazo[1,2-b][1,2,4]triazine; 2-(2-methylphenyl)-6-((2-fluoropyridin-4-yloxy)methyl)imidazo[1,2-b][1,2,4]triazine; 2-[4-fluoro-2-(trifluoromethyl)phenyl]-6-(2-pyridyloxymethyl)imidazo[1,2-b][1,2,4]triazine; 2-(3-fluoro-2-methyl-phenyl)-6-(2-pyridyloxymethyl)imidazo[1,2-b][1,2,4]triazine; 2-(4-Fluoro-2-methyl-phenyl)-6-(2-pyridyloxymethyl)imidazo[1,2-b][1,2,4]triazine; 2-[4-chloro-2-(trifluoromethyl)phenyl]-6-(2-pyridyloxymethyl)imidazo[1,2-b][1,2,4]triazine; 2-(4-chloro-2-methyl-phenyl)-6-(2-pyridyloxymethyl)imidazo[1,2-b][1,2,4]triazine; 2-(4-Fluoro-2-methyl-phenyl)-6-(2-pyridyloxymethyl)imidazo[1,2-b][1,2,4]triazine; 2-(4-fluoro-2-methyl-phenyl)-6-[(5-fluoro-2-pyridyl)oxymethyl]imidazo[1,2-b][1,2,4]triazine; Methyl [5-fluoro-2-[2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidin-6-yl]phenyl]carbamate; Methyl [5-fluoro-2-[2-(phenoxymethyl)imidazo[1,2-a]pyrimidin-6-yl]phenyl]carbamate; Methyl [5-fluoro-2-[2-(2-pyridyloxymethyl)imidazo[1,2-a]pyrimidin-6-yl]phenyl]carbamate; Methyl [5-fluoro-2-[2-(2-pyridyloxymethyl)imidazo[1,2-a]pyrimidin-6-yl]phenyl]acetate; 6-[2-(chloromethyl)-4-fluoro-phenyl]-2-[(4-fluorophenoxy)methyl)imidazo[1,2-a]pyrimidine; 6-[4-fluoro-2-(fluoromethyl)phenyl]-2-(2-pyridyloxymethyl)imidazo[1,2-a]pyrimidine; and 6-[4-Fluoro-2-(fluoromethyl)phenyl]-2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidine.

[0023] More specifically, representative compounds of formula (1) according to the present invention include: 6-(4-fluorophenyl)-2-(pyridin-2-yloxymethyl)imidazo[1,2-a]pyrimidine; 6-[4-fluoro-2-(trifluoromethyl)phenyl]-2-(2-pyridyloxymethyl)imidazo[1,2-a]pyrimidine; 6-(4-fluoro-2-methyl-phenyl)-2-[(5-fluoro-2-pyridyl)oxymethyl)imidazo[1,2-a]pyrimidine; 6-(4-fluorophenyl)-2-[(5-fluoro-2-pyridyl)oxymethyl)imidazo[1,2-a]pyrimidine; [5-fluoro-2-[2-(2-pyridyloxymethyl)imidazo[1,2-a]pyrimidin-6-yl]phenyl]methanol; and 6-[4-Fluoro-2-(fluoromethyl)phenyl]-2-(2-pyridyloxymethyl)imidazo[1,2-a]pyrimidine.

[0024] The imidazopyrimidine or imidazotriazine compound of formula (1) can be prepared using known compounds or compounds that can be easily prepared by those skilled in the art of compound synthesis. In particular, the preparation method of the compound of formula (1) is described in detail in International Publication WO2016 / 137260A1, which is incorporated herein by reference. The compound of formula (1) can be chemically synthesized by the method described in the document, but this is merely an exemplary method, and the order of unit operations can be selectively changed as necessary, so it is not intended to limit the scope of the present invention.

[0025] The imidazopyrimidine or imidazotriazine compounds of the formula (1) can be used for the prevention, alleviation or treatment of developmental disorders. The imidazopyrimidine or imidazotriazine compounds of formula (1) may also be applied to the prevention, alleviation or treatment of symptoms of developmental disorders.

[0026] In one embodiment, the developmental disorder is pervasive developmental disorder, autism, autism spectrum disorder, fragile X syndrome, developmental disorder caused by fragile X syndrome, developmental disorder with the same symptoms as fragile X syndrome, Angelman syndrome, developmental disorder caused by Angelman syndrome, developmental disorder with the same symptoms as Angelman syndrome, Rett syndrome, developmental disorder caused by Rett syndrome, developmental disorder with the same symptoms as Rett syndrome, Fragile X-associated tremor / ataxia syndrome (FXTAS), Asperger syndrome, developmental disorder caused by Asperger syndrome, developmental disorder with the same symptoms as Asperger syndrome, childhood disintegrative disorder, developmental disorder caused by childhood disintegrative disorder, developmental disorder with the same symptoms as childhood disintegrative disorder, Landau-Kleffner syndrome, Landau-Kleffner syndrome. The developmental disorder is selected from the group consisting of developmental disorders caused by Prader-Willi syndrome, developmental disorders presenting the same symptoms as Landau-Kleffner syndrome, Prader-Willi syndrome, developmental disorders caused by Prader-Willi syndrome, developmental disorders presenting the same symptoms as Prader-Willi syndrome, chromosome 22q11.2 deletion syndrome, developmental disorders caused by chromosome 22q11.2 deletion syndrome, developmental disorders presenting the same symptoms as chromosome 22q11.2 deletion syndrome, tardive dyskinesia, developmental disorders caused by tardive dyskinesia, developmental disorders presenting the same symptoms as tardive dyskinesia, seizure disorders, developmental disorders caused by seizure disorders, developmental disorders presenting the same symptoms as seizure disorders, Williams syndrome, developmental disorders caused by Williams syndrome, and developmental disorders presenting the same symptoms as Williams syndrome.

[0027] In one embodiment, the developmental disorder is selected from the group consisting of fragile X syndrome, a developmental disorder caused by fragile X syndrome, a developmental disorder that presents the same symptoms as fragile X syndrome, Angelman syndrome, a developmental disorder caused by Angelman syndrome, a developmental disorder that presents the same symptoms as Angelman syndrome, Rett syndrome, a developmental disorder caused by Rett syndrome, and a developmental disorder that presents the same symptoms as Rett syndrome.

[0028] In one embodiment, the developmental disorder is selected from the group consisting of fragile X syndrome, a developmental disorder caused by fragile X syndrome, and a developmental disorder that exhibits the same symptoms as fragile X syndrome.

[0029] In one embodiment, developmental disorders identical to Fragile X Syndrome, developmental disorders identical to Angelman Syndrome, developmental disorders identical to Rett Syndrome, developmental disorders identical to Asperger Syndrome, developmental disorders identical to Childhood Disintegrative Disorder, developmental disorders identical to Landau-Kleffner Syndrome, developmental disorders identical to Prader-Willi Syndrome, developmental disorders identical to chromosome 22q11.2 deletion syndrome, developmental disorders identical to tardive dyskinesia, developmental disorders identical to seizure disorders, and developmental disorders identical to Williams Syndrome may refer to disorders whose symptoms include developmental delay, learning disabilities, intellectual disabilities, social behavioral disorders (such as inability to make appropriate eye contact, anxiety, attention and concentration problems, flapping tremor of the hands, speaking or acting without thinking, hyperactivity, excitable personality), seizures, etc.

[0030] In one embodiment, the imidazopyrimidine or imidazotriazine compounds of formula (1) can be used to prevent, alleviate or treat fragile X syndrome.

[0031] In one embodiment, the imidazopyrimidine or imidazotriazine compounds of formula (1) may also be applied in the prevention, alleviation or treatment of symptoms of fragile X syndrome. Thus, a medicament or pharmaceutical composition according to one embodiment of the present invention can be used to prevent, alleviate or treat symptoms of Fragile X Syndrome, including, but not limited to, developmental delay, learning disabilities, social behavioral disorders and seizures.

[0032] Furthermore, the medicament or pharmaceutical composition according to one embodiment of the present invention can be used to prevent, alleviate, or treat an autism spectrum disorder caused by fragile X syndrome or an autism spectrum disorder that presents the same symptoms as fragile X syndrome.

[0033] The efficacy of the compound of formula (1) for fragile X syndrome can be verified using known models. For example, the Fmr1 gene knockout mouse model exhibits several clinical symptoms observed in fragile X syndrome and has been used as a means of investigating the mechanism of the disease and verifying the efficacy of drugs for the development of therapeutic agents (Bakker et al., 1994, "Fmr1 knockout mice: A model to study fragile X mental retardation", Cell, 15;78(1):23-33). Typical phenotypes of this mouse model include audiogenic seizures, locomotor activity, cognitive dysfunction such as time memory, spatial memory, and fear memory, and impaired concentration (Reinhard et al., Neurobiol Learn Mem. 2019 Oct;164:107042).

[0034] The dosage of the imidazopyrimidine or imidazotriazine compound of Formula (1) for the alleviation or treatment of the above-mentioned diseases will generally vary depending on the severity of the disease, the body weight, and the metabolic state of the subject. A "therapeutically effective amount" for an individual patient means an amount sufficient to achieve the aforementioned pharmacological effect, i.e., therapeutic effect. The therapeutically effective amount of the compound of Formula (1) may be contained in the pharmaceutical composition in an amount of 0.1 to 500 mg / kg (body weight), preferably 0.5 to 100 mg / kg (body weight), per day when administered to mammals, including humans. Such pharmaceutical compositions can be administered once a day or in two or more divided doses.

[0035] The compounds of the present invention can be administered by any method used for administering therapeutic agents, including oral, parenteral, intravenous, intramuscular, subcutaneous, or rectal administration.

[0036] A medicament or pharmaceutical composition according to one embodiment of the present invention can comprise a therapeutically effective amount of a compound selected from the group consisting of an imidazopyrimidine or imidazotriazine compound of the present invention, its pharmaceutically acceptable salt, solvate, hydrate, and combinations thereof.

[0037] The pharmaceutically acceptable salts include both acid or base addition salts and their stereochemically isomeric forms. The salts include, but are not limited to, any salt that maintains the activity of the parent compound in the subject to which it is administered and does not induce undesired effects. Such salts include inorganic salts and organic salts, such as acetic acid, nitric acid, aspartic acid, sulfonic acid, sulfuric acid, maleic acid, glutamic acid, formic acid, succinic acid, phosphoric acid, phthalic acid, tannic acid, tartaric acid, hydrobromic acid, propionic acid, benzenesulfonic acid, benzoic acid, stearic acid, esylic acid, lactic acid, bicarbonate, bisulfate, bitartaric acid, oxalic acid, butyric acid, calcium edetate, camsylic acid, carbonic acid, chlorobenzoic acid, citric acid, edetic acid, toluenesulfonic acid, edisylic acid, esylic acid, fumaric acid, and gluceptic acid. The basic salt may be pamoic acid, gluconic acid, glycolylarsanilic acid, methyl nitrate, polygalacturonic acid, hexylresorcylic acid, malonic acid, hydrobamic acid, hydrochloric acid, hydroiodic acid, hydroxynaphthoic acid, isethionic acid, lactobionic acid, mandelic acid, estronic acid, mucic acid, napsylic acid, muconic acid, p-nitromethanesulfonic acid, hexamic acid, pantothenic acid, monohydrogen phosphate, dihydrogen phosphate, salicylic acid, sulfamic acid, sulfanilic acid, methanesulfonic acid, or theoclic acid. The basic salt may also be alkali and alkaline earth metal salts such as ammonium salt, lithium salt, sodium salt, potassium salt, magnesium salt, and calcium salt; salts with organic bases such as benzathine, N-methyl-D-glucamine, and hydrabamine salt; and salts with amino acids such as arginine and lysine. The salt forms can also be converted into the free forms by treatment with an appropriate base or acid. The term "addition salts" includes solvates that the compounds of formula (1) and their salts can form. Such solvates are, for example, hydrates and alcoholates.

[0038] The medicament or pharmaceutical composition according to one embodiment of the present invention may be for oral or parenteral administration, preferably for oral administration. For parenteral administration, the medicament or pharmaceutical composition may be for parenteral administration, such as intravenous, subcutaneous, intramuscular, intraperitoneal, intradermal, topical, intranasal, intravaginal, pulmonary, or rectal administration. For oral administration, the medicament or pharmaceutical composition of the present invention may be formulated into powder, granules, tablets, pills, dragees, capsules, liquids, gels, syrups, suspensions, wafers, and the like, by methods known in the art. The pharmaceutical composition according to one embodiment may be uncoated, coated with an active agent, or formulated to protect against digestion in the stomach. The composition may be administered by any device capable of delivering the active agent to target cells. The route of administration will vary depending on the general condition and age of the subject, the nature of the condition being treated, and the active ingredient selected.

[0039] The appropriate dosage of a drug or pharmaceutical composition according to one embodiment of the present invention varies depending on factors such as the formulation method, mode of administration, the patient's age, weight, sex, pathological condition, diet, administration time, administration route, excretion rate, and reaction sensitivity. A skilled physician can easily determine and prescribe an effective dosage for the desired treatment or prevention. The pharmaceutical composition according to one embodiment can be administered in one or several doses, for example, in divided doses from one to four times daily. The pharmaceutical composition according to one embodiment may contain 0.1 to 500 mg / kg (body weight), preferably 0.5 to 100 mg / kg (body weight), of the compound of Formula (1).

[0040] A medicament or pharmaceutical composition according to one embodiment of the present invention can be formulated using pharmaceutically acceptable carriers and / or excipients according to a method readily understood by those skilled in the art, and thereby produced in unit dosage form or contained in a multi-dose container. The formulation may be in the form of a solution, suspension, or emulsion in an oily or aqueous medium, an extract, powder, granules, tablets, or capsules, and may further contain a dispersing agent or stabilizer. Furthermore, the pharmaceutical composition can be administered in the form of a suppository, spray, ointment, cream, gel, inhalant, or skin patch. The pharmaceutical composition can also be prepared for administration to mammals, more preferably to humans.

[0041] The pharmaceutically acceptable carrier may be solid or liquid and may be one or more selected from excipients, antioxidants, buffers, bacteriostats, dispersing agents, adsorbents, surfactants, binders, preservatives, disintegrants, sweeteners, flavoring agents, glidants, release-modifying agents, wetting agents, stabilizers, suspending agents, and lubricants. The pharmaceutically acceptable carrier may also be selected from saline, sterile water, Ringer's solution, buffered saline, dextrose solution, maltodextrin solution, glycerol, ethanol, and mixtures thereof.

[0042] The pharmaceutically acceptable carrier may be solid or liquid and may be one or more selected from excipients, antioxidants, buffers, bacteriostats, dispersants, adsorbents, surfactants, binders, preservatives, disintegrants, sweeteners, flavorings, glidants, release-modifying agents, wetting agents, stabilizers, suspending agents, and lubricants. The pharmaceutically acceptable carrier may also be selected from physiological saline, sterile water, Ringer's solution, buffered saline, dextrose solution, maltodextrin solution, glycerol, ethanol, and mixtures thereof.

[0043] In one embodiment, suitable fillers include, but are not limited to, sugars (e.g., dextrose, 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.

[0044] In one embodiment, suitable binders include, but are not limited to, magnesium aluminum silicate, povidone, copovidone, methylcellulose, hydroxymethylcellulose, hydroxypropylmethylcellulose, hydroxypropylcellulose, hydroxyethylcellulose, gelatin, gums, sucrose, starch paste, or mixtures thereof.

[0045] In one embodiment, suitable preservatives include, but are not limited to, benzoic acid, sodium benzoate, benzyl alcohol, butylated hydroxyanisole, butylated hydroxytoluene, chlorbutol, gallate, hydroxybenzoate, EDTA, or mixtures thereof.

[0046] In one embodiment, suitable disintegrants include, but are not limited to, sodium starch glycolate, cross-linked polyvinylpyrrolidone, cross-linked carboxymethylcellulose, starch, microcrystalline cellulose, or mixtures thereof.

[0047] In one embodiment, suitable sweetening agents include, but are not limited to, sucralose, saccharin, sodium or potassium or calcium saccharin, acesulfame potassium or sodium cyclamate, mannitol, fructose, sucrose, maltose, or mixtures thereof.

[0048] In one embodiment, suitable glidants include, but are not limited to, silica, colloidal silicone dioxide, talc, and the like.

[0049] In one embodiment, suitable lubricants include, but are not limited to, long chain fatty acids and their salts, such as magnesium stearate and stearic acid, talc, glyceride waxes, or mixtures thereof.

[0050] The imidazopyrimidine or imidazotriazine compounds of formula (1) can be used in conjunction with additional drugs for the alleviation or treatment of developmental disorders. Therefore, the medicament or pharmaceutical composition of the present invention may be a combination preparation containing, as active ingredients, therapeutically effective amounts of the imidazopyrimidine or imidazotriazine compound of formula (1) and such an additional drug.

[0051] Such additional medications include, for example, stimulants (e.g., methylphenidate, guanfacine, amphetamine, lisdexamfetamine, etc.) and antidepressants (e.g., fluoxetine, venlafaxine, sertraline, paroxetine, duloxetine, escitalopram, etc.), and / or antipsychotics (e.g., risperidone, quetiapine, aripiprazole, olanzapine, etc.), antiepileptics (e.g., cenobacillo, cefotaxime, etc.), and / or antipsychotics (e.g., cefotaxime ... antidepressants (e.g., benzodiazepine, carbamazepine, levetiracetam, lamotrigine, phenytoin, valproate, topiramate, phenobarbital, gabapentin, vigabatrin, etc.), antianxiety agents (e.g., chlorodiazepoxide, diazepam, oxazepam, clonazepam, alprazolam, lorazepam, temazepam, flurazepam, triazolam, clorazepate, pregabalin, buspirone, etc.).

[0052] In one embodiment, when the medicament or pharmaceutical composition of the present invention is the above-mentioned combined preparation, the weight ratio (A:b) of the imidazopyrimidine or imidazotriazine compound of formula (1) [component (a)] and the additional drug [component (b)] in the combined preparation is, for example, within the range of, but not limited to, 1,000:1 to 1:1,000, or 500:1 to 1:500, or 100:1 to 1:100, or 50:1 to 1:50, or 10:1 to 1:10. Therefore, the drug or pharmaceutical composition according to one embodiment of the present invention may further comprise one or more drugs selected from the group consisting of stimulants, antidepressants, antipsychotics, antiepileptics, and antianxiety drugs.

[0053] More specifically, the stimulant may be one or more selected from the group consisting of methylphenidate, guanfacine, amphetamine, and lisdexamfetamine.

[0054] More specifically, the antidepressant may be one or more selected from the group consisting of fluoxetine, venlafaxine, sertraline, paroxetine, duloxetine, and escitalopram.

[0055] More specifically, the antipsychotic drug may be one or more selected from the group consisting of risperidone, quetiapine, aripiprazole, and olanzapine.

[0056] More specifically, the antiepileptic drug may be one or more selected from the group consisting of cenobamate, carbamazepine, levetiracetam, lamotrigine, phenytoin, valproate, topiramate, phenobarbital, gabapentin, and vigabatrin.

[0057] More specifically, the anti-anxiety agent may be one or more selected from the group consisting of chlorodiazepoxide, diazepam, oxazepam, clonazepam, alprazolam, lorazepam, temazepam, flurazepam, triazolam, clorazepate, pregabalin, and buspirone.

[0058] As used herein, the terms "prevent," "preventing," and "prevention" refer to reducing or eliminating the chance of disease.

[0059] As used herein, the terms "alleviate," "alleviating," and "alleviation" refer to the complete or partial relief of a disease and / or its associated symptoms.

[0060] As used herein, the terms "treat," "treating," and "treatment" refer to the total or partial elimination of a disease and / or its attendant symptoms.

[0061] As used herein, the term "subject" means an animal, preferably a mammal (e.g., primates (e.g., humans)), cows, sheep, goats, horses, dogs, cats, rabbits, rats, mice, etc.), who has been the object of treatment, observation, or experiment, most preferably a human.

[0062] As used herein, the term "therapeutically effective amount" means the amount of an active compound or pharmaceutical preparation that elicits the biological or medical response in a system, animal or human, that is desired by a researcher, veterinarian, pharmacist, or other clinician, including alleviation of the symptoms of the disease or disorder being treated. As used herein, the term "composition" includes a product containing specified ingredients in specified amounts, and any product produced directly or indirectly from the production of specified ingredients in specified amounts. [Example]

[0063] The present invention will be described in more detail below with reference to examples. However, these examples are merely for illustrative purposes of one or more embodiments, and the scope of the present invention is not limited thereto.

[0064] Manufacturing Example: Preparation of Test Compounds 6-[4-Fluoro-2-(trifluoromethyl)phenyl]-2-(2-pyridyloxymethyl)imidazo[1,2-a]pyrimidine (test compound) was prepared by the method described in Example 113 of International Publication No. WO2016 / 137260.

[0065] Example 1: Anticonvulsant efficacy experiment against audiogenic seizures in Fmr1 gene knockout mouse model, contextual fear conditioning experiment, open field test, and marble burying test The Fmr1 gene knockout mouse model has been used as an animal model of fragile X syndrome. This model lacks the FMRP protein due to disruption of the Fmr1 gene. Typical phenotypes of this mouse model include audiogenic seizures, hyperactivity, cognitive impairment, and impaired concentration.

[0066] experimental animals Experiments were performed using male Fmr1 C57BL / 6J knockout mice derived from an early colony imported from the Jackson Laboratory. Experimental animals were housed in a light-controlled environment (12 hours light / 12 hours dark) maintained at a temperature of 21 ± 2°C and a relative humidity of approximately 55 ± 5%. Food and water were provided ad libitum. Anticonvulsant efficacy experiments against audiogenic seizures in the Fmr1 gene knockout mouse model, contextual fear conditioning experiments, open field tests, and marble burying tests were performed by the Fragile X Syndrome Drug Validation Initiative (FRAXA-DVI). Mice were randomly assigned to groups, and tests were performed under light.

[0067] drugs Test compounds were dissolved in 30% PEG300 in 10% DMSO (dimethyl sulfoxide) + DW (distilled water) and administered intraperitoneally at a dose of 2 mg / kg twice daily for 6 weeks. A control group received the vehicle (30% PEG300 in 10% DMSO (dimethyl sulfoxide) + DW (distilled water)).

[0068] Test group 1. Wild-type mice - vehicle administration 2. Fmr1 gene knockout mice - vehicle administration 3. Wild-type mice - 2 mg / kg test compound 4. Fmr1 gene knockout mice - test compound administered at 2 mg / kg Ten mice were used per group.

[0069] Audiogenic Seizure Test After intraperitoneal administration of vehicle or test compound at a dose of 2 mg / kg twice daily for 6 weeks, mice were placed in the chamber and exposed to the alarm. The mice's response during the test was numerically evaluated according to the intensity of the seizures using the following criteria, and the survival rate was also observed. 0: No response 1. Wild running and jumping 2: Clonic seizures 3: Tonic-clonic seizures 4: Tonic seizures 5: Stop breathing

[0070] Contextual fear conditioning experiments Vehicle or test compound was intraperitoneally administered at a dose of 2 mg / kg twice daily for 6 weeks, followed by training and a drug efficacy test. Each time mice were replaced, the chamber was washed with 70% ethanol. Mice were placed in the conditioning chamber and given an electrical shock (non-conditioned stimulus). To test drug efficacy on contextual memory, mice were placed in the same chamber and left for 5 minutes without shock or other distractions. Freezing behavior, defined as a complete loss of movement except for breathing, was observed.

[0071] Open field test After intraperitoneal administration of vehicle or test compound at a dose of 2 mg / kg twice daily for 6 weeks, an open field test was conducted to observe the behavioral effects of the drug on mice that boldly stepped into the center of the open field. Before the test, mice were adapted to the test chamber and then placed in the center of the open field to measure their activity. The number of times a mouse crossed the center of the open field was measured by the breakage of a horizontal beam caused by the mouse's movement. The test chamber was cleaned every time a mouse was replaced.

[0072] Marble burying test After intraperitoneal administration of vehicle or test compound at a dose of 2 mg / kg twice daily for 6 weeks, a hippocampal function-dependent marble-burying test was performed. Sixteen transparent glass marbles were arranged in a 4x4 array in a mouse cage, and placed in a bedding so that two-thirds of them were submerged. After placing the mouse in the cage and leaving it for 30 minutes, the number of marbles buried by the mouse was counted.

[0073] statistical analysis After data analysis by ANOVA, effects were defined as significant when p<0.05. All results were expressed as mean±SEM.

[0074] Test results The results of the anticonvulsant effect test on audiogenic seizures using the test compounds are summarized in Table 1. Results of anticonvulsant efficacy studies of test compounds against audiogenic seizures [Table 1]

[0075] In wild-type mice, none of the vehicle- or test compound-treated groups exhibited audiogenic seizures. In the vehicle-treated Fmr1 knockout mice, nine mice exhibited wild running behavior, of which three or more seizures were observed, and eight died of respiratory arrest. Vulnerability to audiogenic seizures is the proportion of mice exhibiting wild running behavior. Therefore, the vulnerability to audiogenic seizures in the vehicle-treated Fmr1 knockout mice was 90%. In the test compound-treated Fmr1 knockout mice, six mice exhibited wild running behavior, of which three or more seizures were observed, and all five died of respiratory arrest. Therefore, the vulnerability to audiogenic seizures was 60%. These results indicate that the vulnerability to audiogenic seizures in the test compound-treated Fmr1 knockout mice was reduced from 90% to 60% compared to the vehicle-treated group.

[0076] The rate of behavioral freezing during the contextual fear conditioning test is shown in Figure 1. ANOVA analysis showed that vehicle-administered Fmr1 gene knockout mice showed significantly reduced behavioral freezing compared to wild-type mice. In Fmr1 gene knockout mice, the test compound-administered group showed significantly increased behavioral freezing compared to the vehicle-administered group, and showed behavioral freezing similar to that of vehicle-administered wild-type mice. In other words, these results indicate that the fear learning ability of Fmr1 gene knockout mice is improved.

[0077] The results of the open field test, including the number of times the mice crossed the center, are shown in Figure 2. Both the vehicle-administered Fmr1 gene knockout mice and the test compound-administered Fmr1 gene knockout mice showed a significant increase in movement compared to wild-type mice, with a P value of 0.0001 or less.

[0078] The results of the marble burying test, measured by the number of buried marbles, are shown in Figure 3. Vehicle-treated Fmr1 gene knockout mice buried more marbles than wild-type mice. The test compound-treated Fmr1 gene knockout mice also showed a statistically significant difference compared to wild-type mice, but the number of buried marbles in the test compound-treated Fmr1 gene knockout mice was increased compared to the vehicle-treated Fmr1 gene knockout mice.

Claims

1. A therapeutically effective amount of the following formula (1) 【Chemistry 1】 （１） wherein X is CH or N; Z is O; R 1 is halo, hydroxy, C 1 -C 5 Alkyl, C 1 -C 5 Alkoxy, C 1 -C 5 Alkylthio, amino, di(C 1 -C 5 alkyl)amino, cyano, formyl, halo-C 1 -C 5 Alkyl, hydroxy-C 1 -C 5 Alkyl, C 1 -C 5 Alkoxy-C 1 -C 5 Alkyl, carbamoyloxy-C 1 -C 5 Alkyl, and C 1 -C 5 Alkyl-C(O)O-C 1 -C 5 phenyl substituted or unsubstituted with 1 to 3 substituents selected from alkyl, halo, hydroxy, C 1 -C 5 Alkyl, C 1 -C 5 Alkoxy and halo-C 1 -C 5 a 5- to 9-membered unsaturated heterocyclyl having 1 or 2 heteroatoms selected from N, O and S, substituted or unsubstituted with 1 or 2 substituents selected from alkyl; R 2 is halo, deuterium, hydroxy and C 1 -C 5 phenyl substituted or unsubstituted with 1 to 5 substituents selected from alkyl; or halo and C 1 -C 5 and a 6-membered heteroaryl having 1 or 2 nitrogen atoms, substituted or unsubstituted with 1 or 2 substituents selected from alkyl. A pharmaceutical composition for preventing, alleviating or treating a developmental disorder, comprising an imidazopyrimidine or imidazotriazine compound represented by the following formula (I): or a pharmaceutically acceptable salt, solvate or hydrate thereof, and further comprising one or more pharmaceutically acceptable carriers.

2. The R 1 But halo, hydroxy, C 1 -C 5 Alkyl, C 1 -C 5 Alkoxy, C 1 -C 5 Alkylthio, amino, di(C 1 -C 5 alkyl)amino, cyano, formyl, halo-C 1 -C 5 Alkyl, hydroxy-C 1 -C 5 Alkyl, C 1 -C 5 Alkoxy-C 1 -C 5 Alkyl, carbamoyloxy-C 1 -C 5 Alkyl and C 1 -C 5 Alkyl-C(O)O-C 1 -C 5 phenyl substituted or unsubstituted by 1 to 3 substituents selected from alkyl; 1,3-benzodioxolyl substituted or unsubstituted by 1 or 2 halo; or halo, hydroxy, C 1 -C 5 Alkyl, C 1 -C 5 Alkoxy and halo-C 1 -C 5 pyridyl or pyrimidinyl substituted or unsubstituted by 1 or 2 substituents selected from alkyl; The R 2 halo, deuterium, hydroxy and C 1 -C 5 phenyl substituted or unsubstituted with 1 to 5 substituents selected from alkyl; or halo and C 1 -C 5 2. The pharmaceutical composition according to claim 1, which is pyridyl substituted or unsubstituted with one or two substituents selected from alkyl.

3. X is CH; Z is O; The R 1 But halo, hydroxy, C 1 -C 5 Alkyl, C 1 -C 5 Alkoxy, C 1 -C 5 Alkylthio, amino, halo-C 1 -C 5 Alkyl, hydroxy-C 1 -C 5 Alkyl and C 1 -C 5 Alkoxy-C 1 -C 5 phenyl substituted or unsubstituted with 1 to 3 substituents selected from alkyl; The R 2 But halo and C 1 -C 5 2. The pharmaceutical composition according to claim 1, which is pyridyl substituted or unsubstituted with one or two substituents selected from alkyl.

4. 2. The pharmaceutical composition according to claim 1, wherein the imidazopyrimidine or imidazotriazine compound of formula (1) is selected from the following compounds: 6-(4-fluorophenyl)-2-(pyridin-2-yloxymethyl)imidazo[1,2-a]pyrimidine; 6-[4-fluoro-2-(trifluoromethyl)phenyl]-2-(2-pyridyloxymethyl)imidazo[1,2-a]pyrimidine; 6-(4-fluoro-2-methyl-phenyl)-2-[(5-fluoro-2-pyridyl)oxymethyl)imidazo[1,2-a]pyrimidine; 6-(4-fluorophenyl)-2-[(5-fluoro-2-pyridyl)oxymethyl)imidazo[1,2-a]pyrimidine; [5-fluoro-2-[2-(2-pyridyloxymethyl)imidazo[1,2-a]pyrimidin-6-yl]phenyl]methanol; and 6-[4-Fluoro-2-(fluoromethyl)phenyl]-2-(2-pyridyloxymethyl)imidazo[1,2-a]pyrimidine.

5. Developmental disorders include pervasive developmental disorder, autism, autism spectrum disorder, fragile X syndrome, developmental disorders caused by fragile X syndrome, developmental disorders with the same symptoms as fragile X syndrome, Angelman syndrome, developmental disorders caused by Angelman syndrome, developmental disorders with the same symptoms as Angelman syndrome, Rett syndrome, developmental disorders caused by Rett syndrome, developmental disorders with the same symptoms as Rett syndrome, Fragile X-associated tremor / ataxia syndrome (FXTAS), Asperger syndrome, developmental disorders caused by Asperger syndrome, developmental disorders with the same symptoms as Asperger syndrome, childhood disintegrative disorder, developmental disorders caused by childhood disintegrative disorder, developmental disorders with the same symptoms as childhood disintegrative disorder, Landau-Kleffner syndrome, developmental disorders caused by Landau-Kleffner syndrome 2. The pharmaceutical composition of claim 1, wherein the patient is selected from the group consisting of disorders, developmental disorders presenting the same symptoms as Landau-Kleffner syndrome, Prader-Willi syndrome, developmental disorders caused by Prader-Willi syndrome, developmental disorders presenting the same symptoms as Prader-Willi syndrome, chromosome 22q11.2 deletion syndrome, developmental disorders caused by chromosome 22q11.2 deletion syndrome, developmental disorders presenting the same symptoms as chromosome 22q11.2 deletion syndrome, tardive dyskinesia, developmental disorders caused by tardive dyskinesia, developmental disorders presenting the same symptoms as tardive dyskinesia, seizure disorders, developmental disorders caused by seizure disorders, developmental disorders presenting the same symptoms as seizure disorders, Williams syndrome, developmental disorders caused by Williams syndrome, and developmental disorders presenting the same symptoms as Williams syndrome.

6. 2. The pharmaceutical composition according to claim 1, wherein the developmental disorder is selected from the group consisting of fragile X syndrome, a developmental disorder caused by fragile X syndrome, a developmental disorder presenting the same symptoms as fragile X syndrome, Angelman syndrome, a developmental disorder caused by Angelman syndrome, a developmental disorder presenting the same symptoms as Angelman syndrome, Rett syndrome, a developmental disorder caused by Rett syndrome, and a developmental disorder presenting the same symptoms as Rett syndrome.

7. 2. The pharmaceutical composition according to claim 1, wherein the developmental disorder is selected from the group consisting of fragile X syndrome, a developmental disorder caused by fragile X syndrome, and a developmental disorder exhibiting the same symptoms as fragile X syndrome.

8. The pharmaceutical composition according to claim 1, which is used to prevent, alleviate or treat symptoms of a developmental disorder.

9. 9. The pharmaceutical composition of claim 8, wherein the symptoms of the developmental disorder are developmental delay, learning disability, intellectual disability, social behavioral disorder, or seizures.

10. 10. The pharmaceutical composition of claim 1, prepared for administration to a mammal.

11. 2. The pharmaceutical composition of claim 1, comprising 0.1 to 500 mg / kg body weight of the imidazopyrimidine or imidazotriazine compound of formula (1).

12. 2. The pharmaceutical composition of claim 1, which is for oral administration or for parenteral administration selected from the group consisting of intravenous injection, subcutaneous injection, intramuscular injection, intraperitoneal injection, intradermal administration, topical administration, intranasal administration, intravaginal administration, intrapulmonary administration, and intrarectal administration.

13. 10. The pharmaceutical composition of claim 1, further comprising one or more drugs selected from the group consisting of stimulants, antidepressants, antipsychotics, antiepileptics, and antianxiety agents.

14. 2. The pharmaceutical composition of claim 1, wherein the pharmaceutically acceptable carrier is one or more selected from the group consisting of excipients, antioxidants, buffers, bacteriostats, dispersants, adsorbents, surfactants, binders, preservatives, disintegrants, sweeteners, flavoring agents, glidants, release-modifying agents, wetting agents, stabilizers, suspending agents, and lubricants.

15. The following formula (1) 【Chemistry 2】 （１） wherein X is CH or N; Z is O; R 1 is halo, hydroxy, C 1 -C 5 Alkyl, C 1 -C 5 Alkoxy, C 1 -C 5 Alkylthio, amino, di(C 1 -C 5 alkyl)amino, cyano, formyl, halo-C 1 -C 5 Alkyl, hydroxy-C 1 -C 5 Alkyl, C 1 -C 5 Alkoxy-C 1 -C 5 Alkyl, carbamoyloxy-C 1 -C 5 Alkyl, and C 1 -C 5 Alkyl-C(O)O-C 1 -C 5 phenyl substituted or unsubstituted with 1 to 3 substituents selected from alkyl, halo, hydroxy, C 1 -C 5 Alkyl, C 1 -C 5 Alkoxy and halo-C 1 -C 5 a 5- to 9-membered unsaturated heterocyclyl having 1 or 2 heteroatoms selected from N, O and S, substituted or unsubstituted with 1 or 2 substituents selected from alkyl; R 2 is halo, deuterium, hydroxy and C 1 -C 5 phenyl substituted or unsubstituted with 1 to 5 substituents selected from alkyl; or halo and C 1 -C 5 and a 6-membered heteroaryl having 1 or 2 nitrogen atoms, substituted or unsubstituted with 1 or 2 substituents selected from alkyl.

1. Use of an imidazopyrimidine or imidazotriazine compound represented by the formula: or a pharmaceutically acceptable salt, solvate or hydrate thereof in the manufacture of a medicament for the prevention, alleviation or treatment of developmental disorders.

16. 16. The use according to claim 15, wherein 0.1 to 500 mg / kg (body weight) of the imidazopyrimidine or imidazotriazine compound of formula (1) is used.

17. 16. The use of claim 15, wherein the medicament further comprises one or more drugs selected from the group consisting of stimulants, antidepressants, antipsychotics, antiepileptics, and anti-anxiety agents.

18. The following formula (1) 【Transformation 3】 （１） wherein X is CH or N; Z is O; R 1 is halo, hydroxy, C 1 -C 5 Alkyl, C 1 -C 5 Alkoxy, C 1 -C 5 Alkylthio, amino, di(C 1 -C 5 alkyl)amino, cyano, formyl, halo-C 1 -C 5 Alkyl, hydroxy-C 1 -C 5 Alkyl, C 1 -C 5 Alkoxy-C 1 -C 5 Alkyl, carbamoyloxy-C 1 -C 5 Alkyl, and C 1 -C 5 Alkyl-C(O)O-C 1 -C 5 phenyl substituted or unsubstituted with 1 to 3 substituents selected from alkyl, halo, hydroxy, C 1 -C 5 Alkyl, C 1 -C 5 Alkoxy and halo-C 1 -C 5 a 5- to 9-membered unsaturated heterocyclyl having 1 to 2 heteroatoms selected from N, O, and S, substituted or unsubstituted with 1 or 2 substituents selected from alkyl; R 2 is halo, deuterium, hydroxy and C 1 -C 5 phenyl substituted or unsubstituted with 1 to 5 substituents selected from alkyl; or halo and C 1 -C 5 and a 6-membered heteroaryl having 1 or 2 nitrogen atoms, substituted or unsubstituted with 1 or 2 substituents selected from alkyl. or a pharmaceutically acceptable salt, solvate or hydrate thereof, and one or more drugs selected from the group consisting of stimulants, antidepressants, antipsychotics, antiepileptics, and antianxiety drugs; A drug for preventing, alleviating or treating developmental disorders, comprising a combination of:

19. 19. The method of claim 18, wherein the imidazopyrimidine or imidazotriazine compound of formula (1), or a pharmaceutically acceptable salt, solvate, or hydrate thereof, is administered before, after, or simultaneously with one or more of the drugs.

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