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

Abstract

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 developmental disorders.

Description

Technology Field

[0001] The present invention relates to the use of an imidazopyrimidine or imidazotriazine compound of Formula 1 below, or a pharmaceutically acceptable salt, solvate, or hydrate thereof, for preventing, alleviating, or treating a developmental disorder:

[0002] [Chemical Formula 1]

[0003]

[0004] In the above chemical formula 1, X, Z, R1 and R2 are as defined in this specification. Background Technology

[0005] Developmental disorders include, for example, fragile X syndrome (FXS), Angelman syndrome, and Rett syndrome, and treatment for these developmental disorders is limited.

[0006] Fragile X syndrome is a genetic disorder that is the most common single-gene cause of autism and a genetic cause of intellectual disability, particularly among boys. Fragile X syndrome is caused by a mutation in the Fmr1 (Fragile X mental retardation 1) gene located on the X chromosome. The Fmr1 gene is the first identified autism-associated gene and codes for Fragile X mental retardation protein (FMRP), an RNA-binding protein that regulates translation. In other words, the Fmr1 gene produces the FMRP protein, which is necessary for normal brain development; however, in Fragile X syndrome, this protein is not produced in sufficient quantities (Source: Center for Disease Control and Prevention). This functional loss typically occurs when there is an expansion of the CGG trinucleotide repeat in the 5' non-translating region of the Fmr1 gene. This expansion appears as weak or “fragile-like” ends on the X chromosome.

[0007] Fragile X syndrome occurs in both men and women, but symptoms in women are relatively milder compared to men, and the incidence is higher in men. According to another report, this disease occurs at a rate of 1 in 4,600 men and 1 in 8,000 women (Source: Genetics Home Reference, National Library of Medicine).

[0008] Symptoms of Fragile X syndrome include developmental delays, learning disabilities, intellectual disabilities, socio-behavioral disorders (inability to make proper eye contact, anxiety, problems with attention, hand flapping, speaking or acting without thinking, excessive activity, and an easily excitable personality), and seizures. Men have moderate to severe intellectual disabilities, while some women have normal-range intelligence and others have intellectual disabilities. Autism spectrum disorder occurs frequently in people with Fragile X syndrome (Source: Center for Disease Control and Prevention). In addition, Fragile X syndrome carries a risk of seizures, and it is known that about 14% of men and 4% of women experience seizures (Berry-Kravis et al., 2010, "Seizures in Fragile X Syndrome: Characteristics and Comorbid Diagnoses". Am J Intellect Dev Disabil. 115 (6): 461-72). To diagnose Fragile X syndrome, abnormalities in the Fmr1 gene are diagnosed through DNA testing using blood.

[0009] Angelman syndrome is a disorder that occurs when a specific gene on chromosome 15 is not inherited genetically. Symptoms of Angelman syndrome include developmental delay, learning disabilities, intellectual disabilities, socio-behavioral disorders (inability to make proper eye contact, anxiety, problems with attention, hand flapping, speaking or acting without thinking, excessive activity, and an easily excitable personality), and seizures. Additionally, autism spectrum disorder frequently occurs in individuals with Angelman syndrome.

[0010] Rett syndrome is a disease caused by a genetic mutation in the MECP2 gene. Symptoms of Rett syndrome include developmental delay, learning disabilities, intellectual disabilities, socio-behavioral disorders (inability to make proper eye contact, anxiety, problems with attention, hand flapping, speaking or acting without thinking, excessive activity, and an easily excitable personality), and seizures. Additionally, individuals with Rett syndrome exhibit symptoms similar to those of autism spectrum disorder.

[0011] In addition, representative developmental disorders such as pervasive developmental disorder, autism, autistic spectrum disorder, Fragile X-associated tremor / ataxia syndrome (FXTAS), Asperger's syndrome, childhood disintegrative disorder, Landau-Kleffner syndrome, Prader-Willi syndrome, 22q11.2 deletion syndrome, tardive dyskinesia, seizure disorder, and Williams syndrome also exhibit symptoms common to the symptoms of the aforementioned Fragile X syndrome, Angelman syndrome, and Lett syndrome. In other words, developmental disorders including Fragile X syndrome, Angelman syndrome, and Lett syndrome commonly exhibit symptoms such as developmental delay, learning disabilities, intellectual disabilities, socio-behavioral disorders (inability to make proper eye contact, anxiety, problems with attention, hand flapping, speaking or acting without thinking, excessive activity, easily excitable personality), and seizures.

[0012] Currently, suitable treatments for such developmental disorders have not been developed. The problem to be solved

[0013] The present invention aims to provide a method for preventing, alleviating, or treating developmental disorders.

[0014] In addition, the present invention aims to provide a use for an imidazopyrimidine or imidazotriazine compound of the following formula 1, or a pharmaceutically acceptable salt, solvate, or hydrate thereof, for the prevention, alleviation, or treatment of developmental disorders:

[0015] [Chemical Formula 1]

[0016]

[0017] In the above chemical formula 1, X, Z, R1 and R2 are as defined in this specification. means of solving the problem

[0018] The present invention provides a drug for the prevention, alleviation, or treatment of developmental disorders comprising a therapeutically effective amount of an imidazopyrimidine or imidazotriazine compound of Formula 1 below, or a pharmaceutically acceptable salt, solvate, or hydrate thereof:

[0019] [Chemical Formula 1]

[0020]

[0021] In the above chemical formula 1,

[0022] X is CH or N;

[0023] Z is O or S;

[0024] R1 is substituted or unsubstituted with 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 to 12-membered unsaturated heterocyclil having 1 to 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;

[0025] R2 is a C6-C alkyl group substituted or unsubstituted with one or more substituents selected from halo, deuterium, hydroxyl, and C1-C5 alkyl groups. 12 It is a 5 to 12 unsaturated heterocyclile having 1 to 3 heteroatoms selected from N, O and S, substituted or unsubstituted with one or more substituents selected from aryl; or halo and C1-C5 alkyl.

[0026] In addition, the present invention provides a pharmaceutical composition for the alleviation or treatment of fragile X syndrome, comprising a therapeutically effective amount of an 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.

[0027] In addition, the present invention provides a method for alleviating or treating fragile X syndrome, comprising administering a therapeutically effective amount of the imidazopyrimidine or imidazotriazine compound of Formula 1, or a pharmaceutically acceptable salt, solvate, or hydrate thereof, to a subject for treatment.

[0028] In addition, the present invention provides a use for the imidazopyrimidine or imidazotriazine compound of Formula 1, or a pharmaceutically acceptable salt, solvate, or hydrate thereof, for the relief or treatment of fragile X syndrome.

[0029] According to one embodiment of the present invention, in the formula 1, R1 is substituted or unsubstituted with one to three 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 it is a 5 to 10-membered unsaturated heterocyclile having 1 to 3 heteroatoms selected from N, O and S, substituted or unsubstituted with 1 to 3 substituents selected from halo, hydroxy, C1-C5 alkyl, C1-C5 alkoxy and halo-C1-C5 alkyl.

[0030] According to another embodiment of the present invention, in Formula 1, R2 is a phenyl having 1 to 3 heteroatoms selected from N, O, and S, substituted or unsubstituted with 1 to 5 substituents selected from halo, deuterium, hydroxyl, and C1-C5 alkyl; or a 5 or 6-membered heteroaryl having 1 to 3 heteroatoms selected from halo and C1-C5 alkyl, substituted or unsubstituted with 1 to 3 substituents selected from halo and C1-C5 alkyl.

[0031] According to another embodiment of the present invention, in Formula 1,

[0032] X is CH or N;

[0033] Z is O and;

[0034] R1 is a 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 a 5 to 9-membered unsaturated heterocyclile having 1 or 2 heteroatoms selected from N, O, and S, which is 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;

[0035] R2 is a phenyl substituted or unsubstituted with 1 to 5 substituents selected from halo, deuterium, hydroxyl, and C1-C5 alkyl; or a hexavalent heteroaryl having 1 or 2 nitrogen atoms substituted or unsubstituted with 1 or 2 substituents selected from halo and C1-C5 alkyl.

[0036] According to another embodiment of the present invention, in Formula 1,

[0037] R1 is a 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; 1,3-benzodioxolyl substituted or unsubstituted with 1 or 2 halos; or pyridyl or pyrimidinyl substituted or unsubstituted with 1 or 2 substituents selected from halo, hydroxy, C1-C5 alkyl, C1-C5 alkoxy and halo-C1-C5 alkyl, and

[0038] R2 is phenyl substituted or unsubstituted with 1 to 5 substituents selected from halo, deuterium, hydroxyl, and C1-C5 alkyl; or pyridyl substituted or unsubstituted with 1 or 2 substituents selected from halo and C1-C5 alkyl.

[0039] According to another embodiment of the present invention, in Formula 1,

[0040] X is CH and;

[0041] Z is O and;

[0042] R1 is a 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;

[0043] R2 is a pyridyl substituted or unsubstituted with one or two substituents selected from halo and C1-C5 alkyl.

[0044] Representative compounds of Formula 1 according to the present invention include the following:

[0045] 6-(2-fluorophenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;

[0046] 2-phenoxymethyl-6-phenylimidazo[1,2-a]pyrimidine;

[0047] 6-(2,4-difluorophenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;

[0048] 6-(2-methoxyphenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;

[0049] 6-(2-methylphenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;

[0050] 6-(4-fluoro-2-methylphenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;

[0051] 6-(2,3-difluorophenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;

[0052] 6-(4-fluorophenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;

[0053] 6-(3-aminophenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;

[0054] 6-(2-aminophenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;

[0055] 6-(3-amino-6-methylphenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;

[0056] 6-(3-amino-4-fluorophenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;

[0057] 6-(3-chloro-4-fluorophenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;

[0058] 6-(2-dimethylaminophenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;

[0059] 6-(2-chloro-4-fluorophenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;

[0060] 6-(2-hydroxyphenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;

[0061] 6-(3-hydroxyphenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;

[0062] 6-(4-fluoro-2-trifluoromethylphenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;

[0063] 6-(3,4-difluorophenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;

[0064] 6-(2-methoxy-4-fluorophenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;

[0065] 6-(4-fluoro-3-methoxyphenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;

[0066] 6-(4-chloro-2-methoxyphenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;

[0067] 6-(4-cyano-2-methoxyphenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;

[0068] 6-(7-fluorobenzo[1,3]dioxol-4-yl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;

[0069] 6-(4-fluoro-2-hydroxymethylphenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;

[0070] 6-(4-fluoro-2-methylthiophenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;

[0071] 6-(2-amino-4-fluorophenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;

[0072] 6-(2,4-difluoro-5-methoxyphenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;

[0073] 6-(2-fluoropyridine-3-yl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;

[0074] 6-(6-methoxypyridine-3-yl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;

[0075] 6-(6-fluoropyridine-3-yl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;

[0076] 6-(4-methylpyridine-3-yl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;

[0077] 6-(2,6-difluoropyridine-3-yl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;

[0078] 6-(6-chloropyridine-3-yl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;

[0079] 6-(2-fluoropyridine-4-yl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;

[0080] 6-(3-chloropyridine-4-yl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;

[0081] 6-(4-chlorophenyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;

[0082] 6-(6-fluoro-4-methyl-3-pyridyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;

[0083] 6-(6-fluoro-5-methyl-3-pyridyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;

[0084] 6-(5-fluoro-2-pyridyl)-2-phenoxymethylimidazo[1,2-a]pyrimidine;

[0085] 6-(2,4-difluorophenyl)-2-(3-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine;

[0086] 6-(4-fluoro-2-methoxyphenyl)-2-(3-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine;

[0087] 6-(4-fluoro-3-hydroxyphenyl)-2-(3-fluorophenoxymethyl)-imidazo[1,2-a]pyrimidine;

[0088] 6-(2-aminophenyl)-2-(3-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine;

[0089] 6-(3-chloropyridine-4-yl)-2-(3-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine;

[0090] 6-(4-methylpyridine-3-yl)-2-(3-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine;

[0091] 6-(2,4-difluorophenyl)-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine;

[0092] 6-(4-fluoro-2-methylphenyl)-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine;

[0093] 6-(3-chloropyridine-4-yl)-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine;

[0094] 6-(2,6-dimethylphenyl)-2-(4-fluorophenoxymethyl)imidazo[1,2-a]pyrimidine;

[0095] 2-[(4-fluorophenoxy)methyl]-6-(6-fluoro-3-pyridyl)imidazo[1,2-a]pyrimidine;

[0096] 4-[[6-(4-fluorophenyl)imidazo[1,2-a]pyrimidine-2-yl]methoxy]phenol;

[0097] 2-[(4-fluorophenoxy)methyl]-6-(4-fluorophenyl)imidazo[1,2-a]pyrimidine;

[0098] 2-[(3-fluorophenoxy)methyl]-6-(4-fluorophenyl)imidazo[1,2-a]pyrimidine;

[0099] 2-fluoro-5-[2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidine-6-yl]phenol;

[0100] 2-[(4-fluorophenoxy)methyl]-6-phenyl-imidazo[1,2-a]pyrimidine;

[0101] 5-fluoro-2-[2-[(3-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidine-6-yl]phenol;

[0102] 5-fluoro-2-[2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidine-6-yl]phenol;

[0103] 6-(4-fluorophenyl)-2-[(2,3,4,5,6-pentaduteriophenoxy)methyl]imidazo[1,2-a]pyrimidine;

[0104] 2-[(4-fluorophenoxy)methyl]6-(o-tolyl)imidazo[1,2-a]pyrimidine;

[0105] 6-(5-fluoro-2-methyl-phenyl)-2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidine;

[0106] 2-[(4-fluorophenoxy)methyl]-6-(2-fluoro-4-pyridyl)imidazo[1,2-a]pyrimidine;

[0107] 2-[2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidine-6-yl]phenol;

[0108] 6-(2-fluoro-4-methyl-phenyl)-2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidine;

[0109] 2-[(4-fluorophenoxy)methyl]-6-[6-(trifluoromethyl)-3-pyridyl]imidazo[1,2-a]pyrimidine;

[0110] 2-[2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidine-6-yl]aniline;

[0111] 6-(2-chloro-4-fluoro-phenyl)-2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidine;

[0112] 4-[2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidine-6-yl]-3-methoxy-benzonitrile;

[0113] 6-(4-chloro-2-methoxy-phenyl)-2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidine;

[0114] 2-fluoro-5-[2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidine-6-yl]aniline;

[0115] 6-(2,6-difluoro-3-pyridyl)-2-[(3-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidine;

[0116] 5-[2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidine-6-yl]-2-methyl-aniline;

[0117] 4,5-difluoro-2-[2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidine-6-yl]aniline;

[0118] 2-[2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidine-6-yl]-5-methyl-aniline;

[0119] 5-chloro-2-[2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidine-6-yl]aniline;

[0120] 2-[2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidine-6-yl]-4-methyl-aniline;

[0121] 5-fluoro-2-[2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidine-6-yl]aniline;

[0122] 2-[(4-fluorophenoxy)methyl]-6-(4-methyl-3-pyridyl)imidazo[1,2-a]pyrimidine;

[0123] 2-[(3-fluorophenoxy)methyl]-6-(2-fluoro-4-pyridyl)imidazo[1,2-a]pyrimidine;

[0124] 2-[(3-fluorophenoxy)methyl]-6-[6-(trifluoromethyl)-3-pyridyl)imidazo[1,2-a]pyrimidine;

[0125] 2-[(3-fluorophenoxy)methyl]-6-(6-fluoro-3-pyridyl)imidazo[1,2-a]pyrimidine;

[0126] 2-[(3-fluorophenoxy)methyl]-6-(2-fluoro-3-pyridyl)imidazo[1,2-a]pyrimidine;

[0127] 6-(5,6-difluoro-3-pyridyl)-2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidine;

[0128] 5-[2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidine-6-yl]-2-methoxy-aniline;

[0129] 2-[(4-fluorophenoxy)methyl]-6-(5-fluoro-2-pyridyl)imidazo[1,2-a]pyrimidine;

[0130] 2-[(4-fluorophenoxy)methyl]-6-(5-methoxy-2-pyridyl)imidazo[1,2-a]pyrimidine;

[0131] 6-(4-chloro-3-pyridyl)-2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidine;

[0132] 6-(5-chloro-3-pyridyl)-2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidine;

[0133] 2-[(4-fluorophenoxy)methyl]-6-(5-methoxy-3-pyridyl)imidazo[1,2-a]pyrimidine;

[0134] 5-[2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidine-6-yl]pyridine-2-ol;

[0135] 6-(6-fluoro-5-methyl-3-pyridyl)-2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidine;

[0136] 2-[(4-fluorophenoxy)methyl]-6-(6-methyl-3-pyridyl)imidazo[1,2-a]pyrimidine;

[0137] 2-[(3-fluorophenoxy)methyl]-6-(5-fluoro-2-pyridyl)imidazo[1,2-a]pyrimidine;

[0138] 2-[(3-fluorophenoxy)methyl]-6-[4-fluoro-2-(trifluoromethyl)phenyl]imidazo[1,2-a]pyrimidine;

[0139] 4-[2-[(3-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidine-6-yl]-3-methoxy-benzonitrile;

[0140] [5-fluoro-2-[2-[(3-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidine-6-yl]phenyl]methanol;

[0141] [5-fluoro-2-[2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidine-6-yl]phenyl]methanol;

[0142] 6-(4-fluoro-2-methylsulfanyl-phenyl)-2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidine;

[0143] 2-[(4-fluorophenoxy)methyl]-6-(2-methoxy-4-pyridyl)imidazo[1,2-a]pyrimidine;

[0144] 2-[2-[(3-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidine-6-yl]-4-methyl-aniline;

[0145] 5-fluoro-2-[2-[(3-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidine-6-yl]aniline;

[0146] 6-(4-fluorophenyl)-2-(pyridine-2-yloxymethyl)imidazo[1,2-a]pyrimidine;

[0147] 6-(2-methylphenyl)-2-(pyridine-2-yloxymethyl)imidazo[1,2-a]pyrimidine;

[0148] 6-(4-fluoro-2-methoxyphenyl)-2-(pyridine-2-yloxymethyl)imidazo[1,2-a]pyrimidine;

[0149] 6-(2,4-difluorophenyl)-2-(pyridine-2-iloxymethyl)imidazo[1,2-a]pyrimidine;

[0150] 6-(4-fluoro-2-methylphenyl)-2-(pyridine-2-iloxymethyl)imidazo[1,2-a]pyrimidine;

[0151] 6-(2,3-difluorophenyl)-2-(pyridine-2-iloxymethyl)imidazo[1,2-a]pyrimidine;

[0152] 6-(5-fluoro-2-methylphenyl)-2-(pyridine-2-yloxymethyl)imidazo[1,2-a]pyrimidine;

[0153] 6-(3-fluoro-2-methylphenyl)-2-(pyridine-2-iloxymethyl)imidazo[1,2-a]pyrimidine;

[0154] 6-(7-fluoro-2H-benzo[1,3]dioxol-4-yl)-2-(pyridine-2-yloxymethyl)imidazo[1,2-a]pyrimidine;

[0155] 6-(4-chloro-2-methoxyphenyl)-2-(pyridine-2-iloxymethyl)imidazo[1,2-a]pyrimidine;

[0156] 6-(3-fluoro-2-methoxy-phenyl)-2-(2-pyridyloxymethyl)imidazo[1,2-a]pyrimidine;

[0157] 6-[4-fluoro-2-(trifluoromethyl)phenyl]-2-(2-pyridyloxymethyl)imidazo[1,2-a]pyrimidine;

[0158] 6-(4-fluoro-2-methyl-phenyl)-2-[(5-fluoro-2-pyridyl)oxymethyl)imidazo[1,2-a]pyrimidine;

[0159] 6-(2-ethylphenyl)-2-(2-pyridyloxymethyl)imidazo[1,2-a]pyrimidine;

[0160] 6-(4-fluoro-2-methyl-phenyl)-2-[(4-fluoro-2-pyridyl)oxymethyl)imidazo[1,2-a]pyrimidine;

[0161] 6-(2-fluoro-4-methyl-phenyl)-2-(2-pyridyloxymethyl)imidazo[1,2-a]pyrimidine;

[0162] 6-(4-fluoro-2-methoxy-phenyl)-2-[(4-fluoro-2-pyridyl)oxymethyl)imidazo[1,2-a]pyrimidine;

[0163] 2-[(5-fluoro-2-pyridyl)oxymethyl]-6-[4-fluoro-2-(trifluoromethyl)phenyl]imidazo[1,2-a]pyrimidine;

[0164] 6-(2,4-difluorophenyl)-2-[(4-fluoro-2-pyridyl)oxymethyl)imidazo[1,2-a]pyrimidine;

[0165] 6-(3-fluoro-2-methoxy-phenyl)-2-[(4-fluoro-2-pyridyl)oxymethyl)imidazo[1,2-a]pyrimidine;

[0166] 6-(2,3-difluorophenyl)-2-[(4-fluoro-2-pyridyl)oxymethyl)imidazo[1,2-a]pyrimidine;

[0167] 6-(4-fluorophenyl)-2-[(4-fluoro-2-pyridyl)oxymethyl)imidazo[1,2-a]pyrimidine;

[0168] 6-(3-fluoro-2-methyl-phenyl)-2-[(5-fluoro-2-pyridyl)oxymethyl)imidazo[1,2-a]pyrimidine;

[0169] 2-[(4-fluoro-2-pyridyl)oxymethyl]-6-[4-fluoro-2-(trifluoromethyl)phenyl]imidazo[1,2-a]pyrimidine;

[0170] 2-[(5-fluoro-2-pyridyl)oxymethyl]-6-(o-tolyl)imidazo[1,2-a]pyrimidine;

[0171] 6-(4-chloro-2-methyl-phenyl)-2-[(5-fluoro-2-pyridyl)oxymethyl)imidazo[1,2-a]pyrimidine;

[0172] 6-(2,4-dimethylphenyl)-2-[(5-fluoro-2-pyridyl)oxymethyl)imidazo[1,2-a]pyrimidine;

[0173] 6-(4-fluorophenyl)-2-[(5-fluoro-2-pyridyl)oxymethyl)imidazo[1,2-a]pyrimidine;

[0174] 2-(2-pyridyloxymethyl)-6-[6-(trifluoromethyl)-3-pyridyl]imidazo[1,2-a]pyrimidine;

[0175] 2-[(5-fluoro-2-pyridyl)oxymethyl]-6-[6-(trifluoromethyl)-3-pyridyl]imidazo[1,2-a]pyrimidine;

[0176] 6-(5-fluoro-2-pyridyl)-2-(2-pyridyloxymethyl)imidazo[1,2-a]pyrimidine;

[0177] 2-fluoro-5-[2-[(5-fluoro-2-pyridyl)oxymethyl]imidazo[1,2-a]pyrimidine-6-yl]aniline;

[0178] 2-fluoro-5-[2-(2-pyridyloxymethyl)imidazo[1,2-a]pyrimidine-6-yl]aniline;

[0179] [5-fluoro-2-[2-(2-pyridyloxymethyl)imidazo[1,2-a]pyrimidine-6-yl]phenyl]methanol;

[0180] 3-methoxy-4-[2-(2-pyridyloxymethyl)imidazo[1,2-a]pyrimidine-6-yl]benzonitrile;

[0181] 4-[2-[(5-fluoro-2-pyridyl)oxymethyl]imidazo[1,2-a]pyrimidine-6-yl]-3-methoxy-benzonitrile;

[0182] 6-(4-fluoro-2-methylsulfanyl-phenyl)-2-(2-pyridyloxymethyl)imidazo[1,2-a]pyrimidine;

[0183] [5-fluoro-2-[2-[(5-fluoro-2-pyridyl)oxymethyl]imidazo[1,2-a]pyrimidine-6-yl]phenyl]methanol;

[0184] 4-[2-(2-pyridyloxymethyl)imidazo[1,2-a]pyrimidine-6-yl]benzonitrile;

[0185] 6-[4-fluoro-2-(methoxymethyl)phenyl]-2-(2-pyridyloxymethyl)imidazo[1,2-a]pyrimidine;

[0186] [2-[2-(2-pyridyloxymethyl)imidazo[1,2-a]pyrimidine-6-yl]-5-(trifluoromethyl)phenyl]methanol;

[0187] 6-(2-isopropylphenyl)-2-(2-pyridyloxymethyl)imidazo[1,2-a]pyrimidine;

[0188] 4-[2-(2-pyridyloxymethyl)imidazo[1,2-a]pyrimidine-6-yl]-3-(trifluoromethyl)benzaldehyde;

[0189] 6-[4-chloro-2-(trifluoromethyl)phenyl]-2-(2-pyridyloxymethyl)imidazo[1,2-a]pyrimidine;

[0190] 6-(4-fluorophenyl)-2-(pyridine-3-yloxymethyl)imidazo[1,2-a]pyrimidine;

[0191] 6-(4-fluoro-2-methoxyphenyl)-2-(pyridine-3-yloxymethyl)imidazo[1,2-a]pyrimidine;

[0192] 6-(2,4-difluorophenyl)-2-(pyridine-3-yloxymethyl)imidazo[1,2-a]pyrimidine;

[0193] 6-(4-fluoro-2-methylphenyl)-2-(pyridine-3-yloxymethyl)imidazo[1,2-a]pyrimidine;

[0194] 6-(4-fluoro-2-hydroxyphenyl)-2-(pyridine-3-yloxymethyl)imidazo[1,2-a]pyrimidine;

[0195] 6-(4-fluoro-2-methoxyphenyl)-2-(pyridine-4-yloxymethyl)imidazo[1,2-a]pyrimidine;

[0196] 6-(2,4-difluorophenyl)-2-(pyridine-4-iloxymethyl)imidazo[1,2-a]pyrimidine;

[0197] 6-(2-methylphenyl)-2-(5-fluoro-pyridine-3-yloxymethyl)imidazo[1,2-a]pyrimidine;

[0198] 6-(4-fluoro-2-methylphenyl)-2-(5-fluoro-pyridine-3-yloxymethyl)imidazo[1,2-a]pyrimidine;

[0199] 6-(4-fluoro-2-methoxyphenyl)-2-(5-fluoropyridine-3-yloxymethyl)imidazo[1,2-a]pyrimidine;

[0200] 6-(4-fluoro-2-hydroxyphenyl)-2-(5-fluoropyridine-3-yloxymethyl)imidazo[1,2-a]pyrimidine;

[0201] 6-(2,4-difluorophenyl)-2-(6-fluoropyridine-3-yloxymethyl)imidazo[1,2-a]pyrimidine;

[0202] 6-(4-fluoro-2-methylphenyl)-2-(6-fluoropyridine-3-yloxymethyl)imidazo[1,2-a]pyrimidine;

[0203] 6-(4-fluoro-2-methylphenyl)-2-(2-fluoropyridine-3-yloxymethyl)imidazo[1,2-a]pyrimidine;

[0204] 6-(4-fluoro-2-methylphenyl)-2-(5-chloropyridine-3-yloxymethyl)imidazo[1,2-a]pyrimidine;

[0205] 6-(2,4-difluorophenyl)-2-(2-fluoropyridine-4-iloxymethyl)imidazo[1,2-a]pyrimidine;

[0206] 6-(4-fluoro-2-methylphenyl)-2-(2-fluoropyridine-4-yloxymethyl)imidazo[1,2-a]pyrimidine;

[0207] 6-(4-fluoro-2-methoxyphenyl)-2-(2-fluoropyridine-4-yloxymethyl)imidazo[1,2-a]pyrimidine;

[0208] 6-(4-fluorophenyl)-2-(2-fluoropyridine-4-yloxymethyl)imidazo[1,2-a]pyrimidine;

[0209] 6-(2,3-difluorophenyl)-2-(2-fluoropyridine-4-iloxymethyl)imidazo[1,2-a]pyrimidine;

[0210] 6-(2-fluorophenyl)-2-(2-fluoropyridine-4-yloxymethyl)imidazo[1,2-a]pyrimidine;

[0211] 6-(4-fluoro-2-hydroxyphenyl)-2-(2-fluoropyridine-4-yloxymethyl)imidazo[1,2-a]pyrimidine;

[0212] 6-(2-methylphenyl)-2-(2-fluoropyridine-4-yloxymethyl)imidazo[1,2-a]pyrimidine;

[0213] 6-(2-hydroxyphenyl)-2-(2-fluoropyridine-4-yloxymethyl)imidazo[1,2-a]pyrimidine;

[0214] 6-(4-fluoro-2-hydroxymethylphenyl)-2-(2-fluoropyridine-4-yloxymethyl)imidazo[1,2-a]pyrimidine;

[0215] 6-(4-fluorophenyl)-2-[(5-fluoro-3-pyridyl)oxymethyl)imidazo[1,2-a]pyrimidine;

[0216] 2-[(2-chloro-4-pyridyl)oxymethyl]-6-(4-fluorophenyl)imidazo[1,2-a]pyrimidine;

[0217] 2-[(5-fluoro-3-pyridyl)oxymethyl]-6-[4-fluoro-2-(trifluoromethyl)phenyl]imidazo[1,2-a]pyrimidine;

[0218] 2-[(2-fluoro-4-pyridyl)oxymethyl]-6-[4-fluoro-2-(trifluoromethyl)phenyl]imidazo[1,2-a]pyrimidine;

[0219] 5-fluoro-2-[2-[(5-fluoro-3-pyridyl)oxymethyl]imidazo[1,2-a]pyrimidine-6-yl]aniline;

[0220] 5-fluoro-2-[2-[(2-fluoro-4-pyridyl)oxymethyl]imidazo[1,2-a]pyrimidine-6-yl]aniline;

[0221] [5-fluoro-2-[2-[(5-fluoro-3-pyridyl)oxymethyl]imidazo[1,2-a]pyrimidine-6-yl]phenyl]methanol;

[0222] 2-(2,4-difluorophenyl)-6-(phenoxymethyl)imidazo[1,2-b][1,2,4]triazine;

[0223] 2-(2,4-difluorophenyl)-6-((pyridine-4-yloxy)methyl)imidazo[1,2-b][1,2,4]triazine;

[0224] 2-(2,4-difluorophenyl)-6-((pyridine-2-yloxy)methyl)imidazo[1,2-b][1,2,4]triazine;

[0225] 2-(4-fluorophenyl)-6-((pyridine-4-yloxy)methyl)imidazo[1,2-b][1,2,4]triazine;

[0226] 2-(2-methylphenyl)-6-((pyridine-4-yloxy)methyl)imidazo[1,2-b][1,2,4]triazine;

[0227] 2-(2,4-difluorophenyl)-6-((2-fluoropyridine-4-yloxy)methyl)imidazo[1,2-b][1,2,4]triazine;

[0228] 2-(4-fluoro-2-methylphenyl)-6-((2-fluoropyridine-4-yloxy)methyl)imidazo[1,2-b][1,2,4]triazine;

[0229] 2-(2-methylphenyl)-6-((2-fluoropyridine-4-yloxy)methyl)imidazo[1,2-b][1,2,4]triazine;

[0230] 2-[4-fluoro-2-(trifluoromethyl)phenyl]-6-(2-pyridyloxymethyl)imidazo[1,2-b][1,2,4]triazine;

[0231] 2-(3-fluoro-2-methyl-phenyl)-6-(2-pyridyloxymethyl)imidazo[1,2-b][1,2,4]triazine;

[0232] 2-(4-fluoro-2-methyl-phenyl)-6-(2-pyridyloxymethyl)imidazo[1,2-b][1,2,4]triazine;

[0233] 2-[4-chloro-2-(trifluoromethyl)phenyl]-6-(2-pyridyloxymethyl)imidazo[1,2-b][1,2,4]triazine;

[0234] 2-(4-chloro-2-methyl-phenyl)-6-(2-pyridyloxymethyl)imidazo[1,2-b][1,2,4]triazine;

[0235] 2-(4-fluoro-2-methyl-phenyl)-6-(2-pyridyloxymethyl)imidazo[1,2-b][1,2,4]triazine;

[0236] 2-(4-fluoro-2-methyl-phenyl)-6-[(5-fluoro-2-pyridyl)oxymethyl]imidazo[1,2-b][1,2,4]triazine;

[0237] [5-fluoro-2-[2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidine-6-yl]phenyl]methyl carbamate;

[0238] [5-fluoro-2-[2-(phenoxymethyl)imidazo[1,2-a]pyrimidine-6-yl]phenyl]methyl carbamate;

[0239] [5-fluoro-2-[2-(2-pyridyloxymethyl)imidazo[1,2-a]pyrimidine-6-yl]phenyl]methyl carbamate;

[0240] [5-fluoro-2-[2-(2-pyridyloxymethyl)imidazo[1,2-a]pyrimidine-6-yl]phenyl]methyl acetate;

[0241] 6-[2-(chloromethyl)-4-fluoro-phenyl]-2-[(4-fluorophenoxy)methyl)imidazo[1,2-a]pyrimidine;

[0242] 6-[4-fluoro-2-(fluoromethyl)phenyl]-2-(2-pyridyloxymethyl)imidazo[1,2-a]pyrimidine; and

[0243] 6-[4-fluoro-2-(fluoromethyl)phenyl]-2-[(4-fluorophenoxy)methyl]imidazo[1,2-a]pyrimidine.

[0244] More specifically, representative compounds of Formula 1 according to the present invention include the following:

[0245] 6-(4-fluorophenyl)-2-(pyridine-2-yloxymethyl)imidazo[1,2-a]pyrimidine;

[0246] 6-[4-fluoro-2-(trifluoromethyl)phenyl]-2-(2-pyridyloxymethyl)imidazo[1,2-a]pyrimidine;

[0247] 6-(4-fluoro-2-methyl-phenyl)-2-[(5-fluoro-2-pyridyl)oxymethyl)imidazo[1,2-a]pyrimidine;

[0248] 6-(4-fluorophenyl)-2-[(5-fluoro-2-pyridyl)oxymethyl)imidazo[1,2-a]pyrimidine;

[0249] [5-fluoro-2-[2-(2-pyridyloxymethyl)imidazo[1,2-a]pyrimidine-6-yl]phenyl]methanol; and

[0250] 6-[4-fluoro-2-(fluoromethyl)phenyl]-2-(2-pyridyloxymethyl)imidazo[1,2-a]pyrimidine.

[0251] The imidazopyrimidine or imidazotriazine compound of Formula 1 above can be prepared by using known compounds or compounds that can be easily prepared from them, provided that there is ordinary knowledge of compound synthesis in the art. In particular, the method for preparing the compound of Formula 1 above is described in detail in International Patent Publication WO 2016 / 137260 A1, and said document is incorporated herein by reference. Although the compound of Formula 1 can be chemically synthesized by the method described in said document, this is merely an exemplary method and the order of unit operations, etc., may be selectively changed as necessary, and is not intended to limit the scope of the invention.

[0252] The imidazopyrimidine or imidazotriazine compound of Chemical Formula 1 above can be used for the prevention, alleviation, or treatment of developmental disorders.

[0253] The imidazopyrimidine or imidazotriazine compounds of Chemical Formula 1 above can also be applied to the prevention, alleviation, or treatment of symptoms of developmental disorders.

[0254] In one embodiment, the developmental disorder is a pervasive developmental disorder, autism, autistic spectrum disorder, Fragile X syndrome, a developmental disorder caused by Fragile X syndrome, a developmental disorder exhibiting symptoms similar to Fragile X syndrome, Angelman syndrome, a developmental disorder caused by Angelman syndrome, a developmental disorder exhibiting symptoms similar to Angelman syndrome, Rett syndrome, a developmental disorder caused by Rett syndrome, a developmental disorder exhibiting symptoms similar to Rett syndrome, Fragile X-associated tremor / ataxia syndrome (FXTAS), Asperger's syndrome, a developmental disorder caused by Asperger's syndrome, a developmental disorder exhibiting symptoms similar to Asperger syndrome, childhood disintegrative disorder, a developmental disorder caused by childhood disintegrative disorder, a developmental disorder exhibiting symptoms similar to childhood disintegrative disorder, Landau-Kleffner syndrome Syndrome), developmental disorder caused by Lando-Krepner syndrome, developmental disorder exhibiting symptoms similar to Lando-Krepner syndrome, Prader-Willi Syndrome, developmental disorder caused by Prader-Willi syndrome, developmental disorder exhibiting symptoms similar to Prader-Willi syndrome, 22q11.2 deletion syndrome, developmental disorder caused by 22q11.2 deletion syndrome, 22q11.2 deletion syndrome.It is selected from a group consisting of developmental disorders showing symptoms similar to 2nd position deficit syndrome, tardive dyskinesia, developmental disorders caused by tardive dyskinesia, developmental disorders showing symptoms similar to tardive dyskinesia, seizure disorders, developmental disorders caused by seizure disorders, developmental disorders showing symptoms similar to seizure disorders, Williams syndrome, developmental disorders caused by Williams syndrome, and developmental disorders showing symptoms similar to Williams syndrome.

[0255] 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 showing symptoms similar to Fragile X syndrome, Angelman syndrome, a developmental disorder caused by Angelman syndrome, a developmental disorder showing symptoms similar to Angelman syndrome, Rett syndrome, a developmental disorder caused by Rett syndrome, and a developmental disorder showing symptoms similar to Rett syndrome.

[0256] In one embodiment, the developmental disorder is selected from a group consisting of fragile X syndrome, a developmental disorder caused by fragile X syndrome, and a developmental disorder exhibiting symptoms similar to fragile X syndrome.

[0257] In one specific example, developmental disorders exhibiting symptoms similar to Fragile X syndrome, developmental disorders exhibiting symptoms similar to Angelman syndrome, developmental disorders exhibiting symptoms similar to Rett syndrome, developmental disorders exhibiting symptoms similar to Asperger syndrome, developmental disorders exhibiting symptoms similar to childhood disintegrative disorder, developmental disorders exhibiting symptoms similar to Lando-Krepner syndrome, developmental disorders exhibiting symptoms similar to Prader-Willi syndrome, developmental disorders exhibiting symptoms similar to deletion at position 11.2 of chromosome 22, developmental disorders exhibiting symptoms similar to tardive dyskinesia, developmental disorders exhibiting symptoms similar to seizure disorders, and developmental disorders exhibiting symptoms similar to Williams syndrome may refer to disorders exhibiting symptoms including developmental delay, learning disabilities, intellectual disabilities, socio-behavioral disorders (inability to make proper eye contact, anxiety, problems with attention, hand flapping, speaking or acting without thinking, excessive activity, easily excitable personality), seizures, etc.

[0258] In one embodiment, the imidazopyrimidine or imidazotriazine compound of Formula 1 may be used for the prevention, alleviation, or treatment of fragile X syndrome.

[0259] In one embodiment, the imidazopyrimidine or imidazotriazine compound of Formula 1 may also be applied to the prevention, alleviation, or treatment of symptoms of fragile X syndrome.

[0260] Accordingly, a drug or pharmaceutical composition according to one embodiment of the present invention may be used to prevent, alleviate, or treat symptoms of fragile X syndrome, said symptoms including, but not limited to, developmental delay, learning disability, socio-behavioral disorder and seizures.

[0261] In addition, a pharmaceutical or pharmaceutical composition according to one embodiment of the present invention may be used to prevent, alleviate, or treat autism spectrum disorder caused by fragile X syndrome, or autism spectrum disorder exhibiting symptoms similar to fragile X syndrome.

[0262] The efficacy of the compound of Formula 1 above against Fragile X syndrome can be verified using known models. For example, the Fmr1 gene deletion mouse model exhibits various clinical symptoms observed in Fragile X syndrome and is used as a means to study the mechanism of the disease and verify drug efficacy 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). The typical phenotype of this mouse model includes audiogenic seizures, locomotor activity, cognitive deficits including visual memory, spatial memory, and fear memory, and attention deficits (Reinhard et al., Neurobiol Learn Mem. 2019 Oct;164:107042).

[0263] The dosage of the imidazopyrimidine or imidazotriazine compound of Formula 1 for the alleviation or treatment of the above-mentioned disease will typically vary depending on the severity of the disease, the body weight, and the metabolic status of the subject being treated. The "therapeutically effective amount" for an individual patient refers to an amount sufficient to achieve the aforementioned pharmacological effect, i.e., therapeutic effect. When administered to mammals, including humans, the therapeutically effective amount of the compound of Formula 1 is, The above pharmaceutical composition may be included in an amount of 0.1 to 500 mg / kg (body weight) per day, preferably 0.5 to 100 mg / kg (body weight), and the above pharmaceutical composition may be administered once a day or divided into two or more doses.

[0264] The compounds of the present invention may be administered by conventional methods used for the administration of therapeutic agents, such as oral, parenteral, intravenous, intramuscular, subcutaneous, or rectal administration.

[0265] A pharmaceutical 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 imidazopyrimidine or imidazotriazine compound of the present invention, pharmaceutically acceptable salts, solvates, hydrates, and combinations thereof.

[0266] The above pharmaceutically acceptable salts include both addition salts of acids or bases and their stereochemical isomer forms. The salts include any salt that maintains the activity of the parent compound in the subject of administration and does not cause undesirable effects, and are not particularly limited. Such salts include inorganic and organic salts, for example, 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, ecyl acid, lactic acid, non-carboxylic acid, non-sulfuric acid, non-tartaric acid, oxalic acid, butyric acid, calcium idetic acid, camsylic acid, carbonic acid, chlorobenzoic acid, citric acid, idetic acid, toluenesulfonic acid, edicillic acid, ecylic acid, fumaric acid, gluteptic acid, pamoic acid, gluconic acid, glycolylarsanilic acid, methylnitric acid, polygalatroxonic acid, hexyl lysorcinonic acid, malonic acid, It may be hydrabamic acid, hydrochloric acid, hydroiodoic acid, hydroxynaphtholic acid, isethionic acid, lactobionic acid, mandelic acid, estolinic acid, mucinous acid, napsylic acid, muconic acid, p-nitromethanesulfonic acid, hexamic acid, pantothenic acid, monohydrogenated phosphate, dihydrogenated phosphate, salicylic acid, sulfamic acid, sulfanilic acid, methanesulfonic acid, or teoclic acid. In addition, the form of the basic salt includes, for example, alkali and alkaline earth metal salts such as ammonium salts, lithium salts, sodium salts, potassium salts, magnesium salts, and calcium salts; salts having organic bases such as benzathine, N-methyl-D-glucarmine, and hydrabamin salts; and salts having amino acids such as arginine and lysine. Furthermore, the salt form may be converted into a free form by treatment with a suitable base or acid. The term "additional salt" includes compounds of Formula 1 and solvent compounds that can be formed by the salt thereof. Such solvent compounds are, for example, hydrates and alcohols.

[0267] A drug or pharmaceutical composition according to one embodiment of the present invention may be for oral or parenteral administration, preferably for oral administration. In the case of parenteral administration, it may be for intravenous infusion, subcutaneous infusion, intramuscular infusion, intraperitoneal infusion, endodermal administration, topical administration, intranasal administration, vaginal administration, intrapulmonary administration, or rectal administration. In the case of oral administration, the drug or pharmaceutical composition of the present invention may be formulated in the form of powder, granules, tablets, pills, coated tablets, capsules, liquids, gels, syrups, suspensions, wafers, etc., according to methods known in the art. A pharmaceutical composition according to one embodiment may be formulated as a bare tablet, or the active drug may be coated or protected from degradation in the stomach. Additionally, the composition may be administered by any device capable of delivering the active substance to target cells. The route of administration may vary depending on the general condition and age of the subject being treated, the nature of the treatment conditions, and the selected active ingredient.

[0268] A suitable dosage of a drug or pharmaceutical composition according to one embodiment of the present invention varies depending on factors such as the method of formulation, the mode of administration, the patient's age, body weight, sex, pathological condition, food, time of administration, route of administration, excretion rate, and response sensitivity, and a physician of ordinary skill can easily determine and prescribe a dosage effective for the desired treatment or prevention. The pharmaceutical composition according to one embodiment may be administered in a single or multiple doses, for example, divided into 1 to 4 doses per day. The pharmaceutical composition according to one embodiment may contain a compound of Formula 1 in an amount of 0.1 to 500 mg / kg (body weight), preferably 0.5 to 100 mg / kg (body weight).

[0269] A pharmaceutical or pharmaceutical composition according to one embodiment of the present invention may be prepared in a unit dose form or contained in a multi-dose container by formulation using a pharmaceutically acceptable carrier and / or excipient, according to a method that can be easily carried out by a person skilled in the art to which the invention pertains. In this case, the formulation may be in the form of a solution, suspension, or emulsion in an oil or aqueous medium, or in the form of an extract, powder, granule, tablet, or capsule, and may additionally include a dispersant or a stabilizer. Furthermore, the pharmaceutical composition may be administered in the form of a suppository, spray, ointment, cream, gel, inhalant, or skin patch. Additionally, the pharmaceutical composition may be prepared for administration to mammals, more preferably for administration to humans.

[0270] Pharmaceutically acceptable carriers may be solid or liquid and may be one or more selected from excipients, antioxidants, buffers, bacteriostatic agents, dispersants, adsorbents, surfactants, binders, preservatives, disintegrants, sweeteners, flavorings, lubricants, release regulators, wetting agents, stabilizers, suspending agents, and lubricants. Additionally, pharmaceutically acceptable carriers may be selected from saline solution, sterile water, Ringer's solution, buffered saline solution, dextrose solution, maltodextrin solution, glycerol, ethanol, and mixtures thereof.

[0271] In one embodiment, suitable fillers may include, but are not limited to, sugars (e.g., dextrose, sucrose, maltose and lactose), starch (e.g., corn starch), sugar-alcohols (e.g., mannitol, sorbitol, maltitol, erythritol and xylitol), starch hydrolysates (e.g., dextrin and maltodextrin), cellulose or cellulose derivatives (e.g., microcrystalline cellulose).

[0272] In one embodiment, suitable binders may include, but are not limited to, magnesium aluminum silicate, povidone, copovidone, methylcellulose, hydroxymethylcellulose, hydroxypropylmethylcellulose, hydroxypropylcellulose, hydroxyethylcellulose, gelatin, gums, sucrose, starch paste, or mixtures thereof.

[0273] In one embodiment, suitable preservatives may include, but are not limited to, benzoic acid, sodium benzoate, benzyl alcohol, butylated hydroxyanisole, butylated hydroxytoluene, chlorbutol, gallate, hydroxybenzoate, EDTA, or mixtures thereof.

[0274] In one embodiment, suitable disintegrant may be sodium starch glycolate, cross-linked polyvinylpyrrolidone, cross-linked carboxymethylcellulose, starch, microcrystalline cellulose, or a mixture thereof, but is not limited thereto.

[0275] In one embodiment, suitable sweeteners may 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.

[0276] In one embodiment, suitable glidant may be silica, colloidal silicon dioxide, talc, etc., but is not limited thereto.

[0277] In one embodiment, suitable lubricants may include long-chain fatty acids and their salts, such as magnesium stearate and stearic acid, talc, glyceride wax, or mixtures thereof, but are not limited thereto.

[0278] The imidazopyrimidine or imidazotriazine compound of Chemical Formula 1 above may be used in combination with additional drugs for the alleviation or treatment of developmental disorders.

[0279] Accordingly, the pharmaceutical or pharmaceutical composition of the present invention may be a combination preparation comprising, as a therapeutically effective amount of active ingredient, an imidazopyrimidine or imidazotriazine compound of Formula 1 and such additional drug.

[0280] Such additional drugs 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.), anticonvulsants (e.g., cenobamate, carbamazepine, levetiracetam, lamotrigine), Examples include phenytoin, valproate, topiramate, phenobarbital, gabapentin, vigabatrin, etc.), and anti-anxiety drugs (e.g., chlordiazepoxide, diazepam, oxazepam, clonazepam, alprazolam, lorazepam, temazepam, flurazepam, triazolam, clorazepate, pregabalin, buspirone, etc.).

[0281] In one embodiment, when the pharmaceutical or pharmaceutical composition of the present invention is the above-described compound formulation, the mixing weight ratio (a:b) of the imidazopyrimidine or imidazotriazine compound of Formula 1 [component (a)] and the additional drug [component (b)] in the compound formulation may be, for example, within the range of 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, but is not limited thereto.

[0282] Accordingly, a 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, anticonvulsants, and anti-anxiety agents.

[0283] More specifically, the stimulant may be one or more selected from the group consisting of methylphenidate, guanfacine, amphetamine, and lisdexamphetamine.

[0284] More specifically, the antidepressant may be one or more selected from the group consisting of fluoxetine, venlafaxine, sertraline, paroxetine, duloxetine, and esquitalopram.

[0285] More specifically, the above antipsychotic agent may be one or more selected from the group consisting of risperidone, quetiapine, aripiprazole, and olanzapine.

[0286] More specifically, the above anticonvulsant may be one or more selected from the group consisting of cenobamate, carbamazepine, levetiracetam, lamotrigine, phenytoin, valproate, topiramate, phenobarbital, gabapentin, and vigabatrin.

[0287] More specifically, the anxiolytic agent may be one or more selected from the group consisting of chlordiazepoxide, diazepam, oxazepam, clonazepam, alprazolam, lorazepam, temazepam, flurazepam, triazolam, clorazepate, pregabalin, and buspirone.

[0288] As used herein, the terms “prevent,” “preventing,” and “prevention” refer to reducing or eliminating the possibility of contracting a disease.

[0289] As used herein, the terms "alleviate," "alleviating," and "alleviation" refer to alleviating a disease and / or its accompanying symptoms, in whole or in part.

[0290] As used herein, the terms "treat," "treating," and "treatment" refer to the removal of a disease and / or its accompanying symptoms, in whole or in part.

[0291] As used herein, the term “object” means an animal that is the object of treatment, observation, or experiment, preferably a mammal (e.g., primates (e.g., human), cattle, sheep, goats, horses, dogs, cats, rabbits, rats, mice, etc.), most preferably a human.

[0292] As used herein, the term “therapeutic effective dose” means an amount of an active compound or pharmaceutical preparation sought by a researcher, veterinarian, physician, or other clinician that induces a biological or medical response in a tissue system, animal, or human, including alleviating signs of a disease or disorder to be treated.

[0293] As used herein, the term "composition" includes a product containing a specific component in a specific amount and any product produced directly or indirectly from a mixture of a specific amount of a specific component. Effects of the invention

[0294] The pharmaceutical and pharmaceutical composition according to the present invention can efficiently prevent, alleviate, or treat developmental disorders. Brief explanation of the drawing

[0295] Figure 1 shows the results of a contextual fear conditioning experiment performed using an Fmr1 gene-deficient mouse model, showing the effect of long-term administration (6 weeks) of the test compound (2 mg / kg, twice a day) on reduced fear conditioning. Figure 2 shows the results of long-term administration (6 weeks) of the test compound (2 mg / kg, twice a day) on the open field test in an Fmr1 gene deletion mouse model. Figure 3 shows the results of long-term administration (6 weeks) of the test compound (2 mg / kg, twice a day) on the marble burying test in an Fmr1 gene deletion mouse model. Specific details for implementing the invention

[0296] The present invention will be explained in more detail below through examples. However, these examples are merely illustrative of one or more specific embodiments and do not limit the scope of the invention.

[0297] Preparation Example: Preparation of Test Compound

[0298] 6-[4-fluoro-2-(trifluoromethyl)phenyl]-2-(2-pyridyloxymethyl)imidazo[1,2-a]pyrimidine (test compound) was prepared according to the method described in Example 113 of International Publication No. WO 2016 / 137260.

[0299] Example 1: Anticonvulsant efficacy test against audiogenic seizures in an Fmr1 gene-deficient mouse model, contextual fear conditioning test, open field test, and marble burying test

[0300] An Fmr1 knockout mouse model was used as an animal model of fragile X syndrome, in which the FMRP protein is deficient due to the disruption of the Fmr1 gene. The typical phenotype of this mouse model includes audiogenic seizures, locomotor activity, cognitive deficit, and attention deficit.

[0301] Experimental animals

[0302] Male Fmr1 C57BL / 6J knockout mice derived from an early herd from Jackson Laboratories were used in the experiments. The animals were housed in a light-controlled environment (12 hours of light / 12 hours of non-light) and maintained at a temperature of 21±2°C and a relative humidity of approximately 55±5%. Food and water were provided at the discretion of the animals. Anticonvulsant efficacy tests on audiogenic seizures in the Fmr1 knockout mouse model, contextual fear conditioning, open field tests, and marble burying tests were conducted under the Fragile X Syndrome Drug Validation Initiative (FRAXA-DVI). Mice were randomly divided into groups, and the tests were performed under light.

[0303] drugs

[0304] The test compound was dissolved in 10% DMSO (dimethylsulfoxide) + 30% PEG 300 in DW (distilled water), and a dose of 2 mg / kg was administered intraperitoneally twice a day for 6 weeks. As a control, a vehicle (10% DMSO (dimethylsulfoxide) + 30% PEG 300 in DW (distilled water)) was administered.

[0305] Test group

[0306] 1. Wild-type mouse - Vehicle administration

[0307] 2. Fmr1 gene deletion mouse - Vehicle administration

[0308] 3. Wild-type mice - Administration of test compound 2 mg / kg

[0309] 4. Fmr1 gene-deficient mice - administration of test compound 2 mg / kg

[0310] Ten mice were used per group.

[0311] Auditory seizure test

[0312] After administering the vehicle or test compound intraperitoneally at a dose of 2 mg / kg twice daily for 6 weeks, mice were placed in a chamber and exposed to a horn sound. During the experiment, the response of the mice was quantified and evaluated according to the intensity of the seizures based on the following criteria, and survival rates were also observed.

[0313] 0: No response

[0314] 1: Wild running and jumping

[0315] 2: Clonic seizures

[0316] 3: Clonic-tonic seizures

[0317] 4: Tonic seizures

[0318] 5: Respiratory arrest

[0319] Environmental fear conditioning experiment

[0320] Training and efficacy studies were performed, respectively, after administering the vehicle or test compound intraperitoneally at a dose of 2 mg / kg twice daily for 6 weeks. The chambers were cleaned with 70% ethanol after each mouse replacement. Mice were placed in the conditioning chamber and subjected to an electric shock (unconditioned stimulus). To perform the efficacy study on contextual memory, mice were placed in the same chamber and left for 5 minutes without shock or other disturbances, and freezing behavior, defined as the complete loss of movement except breathing, was observed.

[0321] Open field inspection

[0322] After administering the vehicle or test compound intraperitoneally at a dose of 2 mg / kg twice daily for 6 weeks, an open-field test was performed to observe the pharmacological behavior of mice fearlessly entering the center of the open field. Prior to the test, mice were acclimatized to the laboratory and placed in the center of the open field to measure their activity. The number of times the mouse crossed the center of the open field was measured based on the disruption of the horizontal light caused by the mouse's movement. The test area was cleaned after each mouse replacement.

[0323] Marble burial test

[0324] A hippocampal function-dependent bead burial test was performed after administering the vehicle or test compound intraperitoneally at a dose of 2 mg / kg twice daily for 6 weeks. Sixteen clear beads were placed in a 4 x 4 array inside a mouse cage, submerging 2 / 3 of the bedding. Mice were placed in the cage and left for 30 minutes, after which the number of beads buried by the mice was checked.

[0325] Statistical analysis

[0326] The data were analyzed by ANOVA, and an effect was defined as p < 0.05. All results were expressed as mean ± SEM.

[0327] test

[0328] Table 1 summarizes the results of the anticonvulsant efficacy test of the test compound for auditory seizures.

[0329] [Table 1]

[0330] Results of the anticonvulsant efficacy test of the test compound for auditory seizures

[0331]

[0332] In wild-type mice, no mice in the vehicle administration group or the test compound administration group showed signs of auditory seizures. In the vehicle administration group of Fmr1 gene-deficient mice, 9 mice ran wildly, and among them, 8 mice exhibited seizures of 3 points or higher; all of them died after respiratory arrest. Auditory seizure vulnerability is the proportion of mice running wildly, and therefore, the auditory seizure vulnerability in the vehicle administration group of Fmr1 gene-deficient mice was 90%. In the test compound administration group of Fmr1 gene-deficient mice, 6 mice ran wildly, and among them, 5 mice exhibited seizures of 3 points or higher; all of them died after respiratory arrest. Therefore, the auditory seizure vulnerability was 60%. From this, it was shown that in Fmr1 gene-deficient mice, the auditory seizure vulnerability in the test compound administration group decreased from 90% to 60% compared to the vehicle administration group.

[0333] Figure 1 shows the percentage of freezing during the environmental fear conditioning experiment. ANOVA analysis revealed that Fmr1 gene-deficient mice administered the vehicle showed significantly reduced freezing compared to wild-type mice, while the test compound administration group showed significantly increased freezing compared to the vehicle administration group, and exhibited a degree of freezing similar to that of wild-type mice administered the vehicle. In other words, the results showed that the test compound improved the impaired fear learning ability in Fmr1 gene-deficient mice.

[0334] The number of times the center was crossed as a result of the open-field test is shown in Figure 2. Both Fmr1 gene-deficient mice administered with the vehicle and Fmr1 gene-deficient mice administered with the test compound showed a significant increase in movement compared to wild-type mice, with a P-value of 0.0001 or less.

[0335] The number of buried beads resulting from the bead burial test is shown in Figure 3. Fmr1 gene-deficient mice administered the vehicle buried more beads compared to wild-type mice. The group of Fmr1 gene-deficient mice administered the test compound also showed a statistical difference compared to wild-type mice, but the number of buried beads increased compared to the group of Fmr1 gene-deficient mice administered the vehicle.

Claims

Claim 1 A drug for the prevention, alleviation, or treatment of a developmental disorder comprising a therapeutically effective amount of an imidazopyrimidine compound of Formula 1 below, or a pharmaceutically acceptable salt, solvate, or hydrate thereof: [Formula 1] In the above Chemical Formula 1, X is CH; Z is O; R1 is a 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 a pyridyl substituted or unsubstituted with 1 or 2 substituents selected from halo and C1-C5 alkyl, and the developmental disorder is pervasive developmental disorder, autism, autistic spectrum disorder, Fragile X syndrome, developmental disorder caused by Fragile X syndrome, Angelman syndrome, developmental disorder caused by Angelman syndrome, Rett syndrome, developmental disorder caused by Rett syndrome, Fragile X-associated tremor ataxia. tremor / ataxia syndrome (FXTAS), Asperger's syndrome, developmental disorder caused by Asperger's syndrome, childhood disintegrative disorder, developmental disorder caused by childhood disintegrative disorder, Landau-Kleffner Syndrome, developmental disorder caused by Landau-Kleffner syndrome, Prader-Willi Syndrome, developmental disorder caused by Prader-Willi syndrome, 22q11.2 deletion syndrome, 22q11.2 deletion syndrome.It is selected from the group consisting of developmental disorders caused by 2-position deficit syndrome, tardive dyskinesia, developmental disorders caused by tardive dyskinesia, seizure disorders, developmental disorders caused by seizure disorders, Williams syndrome, and developmental disorders caused by Williams syndrome. Claim 2 delete Claim 3 delete Claim 4 delete Claim 5 delete Claim 6 delete Claim 7 The agent according to claim 1, characterized in that the imidazopyrimidine 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]pyrimidine-6-yl]phenyl]methanol; and 6-[4-fluoro-2-(fluoromethyl)phenyl]-2-(2-pyridyloxymethyl)imidazo[1,2-a]pyrimidine. Claim 8 delete Claim 9 A drug selected from the group consisting of developmental disorders of Fragile X syndrome, developmental disorders caused by Fragile X syndrome, Angelman syndrome, developmental disorders caused by Angelman syndrome, Rett syndrome, and developmental disorders caused by Rett syndrome. Claim 10 In paragraph 1, a pharmaceutical product for a developmental disability caused by Fragile X syndrome or Fragile X syndrome. Claim 11 In paragraph 1, a drug used for the prevention, alleviation, or treatment of symptoms of developmental disorders. Claim 12 In paragraph 11, a drug in which the symptoms of a developmental disorder are developmental delay, learning disability, intellectual disability, socio-behavioral disorder, or seizures. Claim 13 In paragraph 1, a drug manufactured for administration to mammals. Claim 14 A drug according to claim 1 comprising an imidazopyrimidine or imidazotriazine compound of Formula 1 in an amount of 0.1 to 500 mg / kg (body weight). Claim 15 A drug according to 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, endodermal administration, local administration, nasal administration, vaginal administration, pulmonary administration, and rectal administration. Claim 16 A drug according to claim 1, further comprising one or more drugs selected from the group consisting of stimulants, antidepressants, antipsychotics, anticonvulsants, and anti-anxiety drugs. Claim 17 A pharmaceutical composition for the prevention, alleviation, or treatment of a developmental disorder comprising a therapeutically effective amount of an imidazopyrimidine compound of Formula 1 below, or a pharmaceutically acceptable salt, solvate, or hydrate thereof, and further comprising one or more pharmaceutically acceptable carriers: [Formula 1] In the above Chemical Formula 1, X is CH; Z is O; R1 is a 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 a pyridyl substituted or unsubstituted with 1 or 2 substituents selected from halo and C1-C5 alkyl, and the developmental disorder is pervasive developmental disorder, autism, autistic spectrum disorder, Fragile X syndrome, developmental disorder caused by Fragile X syndrome, Angelman syndrome, developmental disorder caused by Angelman syndrome, Rett syndrome, developmental disorder caused by Rett syndrome, Fragile X-associated tremor ataxia. tremor / ataxia syndrome (FXTAS), Asperger's syndrome, developmental disorder caused by Asperger's syndrome, childhood disintegrative disorder, developmental disorder caused by childhood disintegrative disorder, Landau-Kleffner Syndrome, developmental disorder caused by Landau-Kleffner syndrome, Prader-Willi Syndrome, developmental disorder caused by Prader-Willi syndrome, 22q11.2 deletion syndrome, 22q11.2 deletion syndrome.It is selected from the group consisting of developmental disorders caused by 2-position deficit syndrome, tardive dyskinesia, developmental disorders caused by tardive dyskinesia, seizure disorders, developmental disorders caused by seizure disorders, Williams syndrome, and developmental disorders caused by Williams syndrome. Claim 18 delete Claim 19 A pharmaceutical composition according to claim 17, selected from the group consisting of developmental disorders of Fragile X syndrome, developmental disorders caused by Fragile X syndrome, Angelman syndrome, developmental disorders caused by Angelman syndrome, Rett syndrome, and developmental disorders caused by Rett syndrome. Claim 20 In claim 17, a pharmaceutical composition for a developmental disorder caused by Fragile X syndrome or Fragile X syndrome. Claim 21 A pharmaceutical composition used for the prevention, alleviation, or treatment of symptoms of developmental disorders in paragraph 17. Claim 22 A pharmaceutical composition according to claim 21, wherein the symptoms of a developmental disorder are developmental delay, learning disability, intellectual disability, socio-behavioral disorder, or seizures. Claim 23 In paragraph 17, a pharmaceutical composition manufactured for administration to mammals. Claim 24 A pharmaceutical composition according to claim 17, comprising 0.1 to 500 mg / kg (body weight) of an imidazopyrimidine or imidazotriazine compound of Formula 1. Claim 25 A pharmaceutical composition according to claim 17, which is for oral administration or for parenteral administration selected from the group consisting of intravenous injection, subcutaneous injection, intramuscular injection, intraperitoneal injection, endodermal administration, local administration, nasal administration, vaginal administration, pulmonary administration and rectal administration. Claim 26 A pharmaceutical composition according to claim 17, wherein the pharmaceutically acceptable carrier is one or more selected from excipients, antioxidants, buffers, bacteriostatic agents, dispersants, adsorbents, surfactants, binders, preservatives, disintegrants, sweeteners, flavorings, lubricants, release regulators, wetting agents, stabilizers, suspending agents, and lubricants. Claim 27 A pharmaceutical composition according to claim 17, further comprising one or more drugs selected from the group consisting of stimulants, antidepressants, antipsychotics, anticonvulsants, and anti-anxiety agents. Claim 28 delete Claim 29 delete Claim 30 delete Claim 31 delete Claim 32 delete Claim 33 delete Claim 34 delete Claim 35 delete Claim 36 delete Claim 37 delete Claim 38 delete Claim 39 delete Claim 40 delete Claim 41 delete Claim 42 delete Claim 43 delete Claim 44 delete Claim 45 delete

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