Novel imidazolone derivatives as protein kinase inhibitors, particularly DYRK1A, CLK1, and / or CLK4.

Abstract

The present invention relates to compounds of formula (I) below, or any one of its pharmaceutically acceptable salts: [Formula 1] JPEG2023523788000127.jpg41170 where R 1 is (C1-C6) alkyl group, spiro (C5-C 11 ) bicyclic rings, fused phenyl groups, substituted phenyl groups, R'-L- groups, where L is either a single bond or a (C1-C3) alkanediyl group, and R' is a (C3-C8) cycloalkyl group, a bridged (C6-C 10 ) cycloalkyl group, (C3-C8) heterocycloalkyl group, or (C3-C8) heteroaryl group, or R'-L- group, where L is a (C1-C3) alkanediyl group and R' is an optionally substituted phenyl group, and R 2 represents a hydrogen atom or a (C1-C3) alkyl group. The present invention further relates to compositions comprising the compound of formula (I), as well as methods for preparing the compound and synthetic intermediates thereof. The present invention also relates to the compound for use as a pharmaceutical, in particular for treating and / or preventing cognitive impairment associated with Down's syndrome; Alzheimer's disease; dementia; tauopathies; Parkinson's disease; CDKL5 deficiency disorders; Phelan-McDermid syndrome; autism; type 1 and type 2 diabetes; folate and methionine metabolism disorders; osteoarthritis; Duchenne muscular dystrophy; some cancers; neuroinflammation, anemia, and viral and unicellular infections, and for regulating body temperature.

Description

[Technical Field]

[0001] This invention relates to leucettinibs, a class of novel compounds useful as pharmaceuticals. These novel compounds are particularly useful as kinase inhibitors, and more particularly as inhibitors of DYRK1A and / or CLK1 and / or CLK4. They are efficient for treating and / or preventing cognitive impairment associated with Down syndrome; Alzheimer's disease and related disorders; dementia; tauopathies; Parkinson's disease; other neurodegenerative diseases; CDKL5 deficiency disorders; type 1 and type 2 diabetes; folic acid and methionine metabolic disorders; osteoarthritis; Duchenne muscular dystrophy; several cancers and leukemias; viral infections, and for regulating body temperature.

[0002] Some of these compounds are inhibitors of other kinases, namely other DYRKs (DYRK1B, 2, 3, 4) and closely related cdc2-like kinases (CLK) (CLK2, 3, 4). Furthermore, these compounds may be effective in treating and / or preventing Phelan-McDermid syndrome; autism; viral infections, cancer, neuroinflammation, anemia, and infections caused by single-celled parasites.

[0003] The present invention further relates to pharmaceutical compositions containing the novel compound and to chemical synthesis processes for obtaining them. [Background technology]

[0004] The DYRK and CLK kinase families belong to the CMGC group of kinases, which also includes mitogen-activated protein kinases (MAPKs), cyclin-dependent kinases (CDKs), and glycogen synthase kinase-3 (GSK-3). They phosphorylate many substrates involved in signaling pathways. DYRK and CLK play crucial roles in mRNA splicing, chromatin transcription, DNA damage repair, cell survival, cell cycle, differentiation, homocysteine / methionine / folate regulation, endocytosis, neuronal development and function, and synaptic plasticity.

[0005] DYRK1A and Down syndrome (DS)

[0006] The gene encoding DYRK1A is located on chromosome 21, specifically within the "Down syndrome critical region" (DSCR), and its triploidy is responsible for most defects associated with DS. There is considerable genetic and pharmacological evidence that even a 1.5-fold overexpression of DYRK1A is responsible for most cognitive impairments observed in DS patients, particularly memory and learning impairments (Rueda N et al., 2020. Translational validity and implications of pharmacotherapies in preclinical models of Downsyndrome. Prog Brain Res 251, 245). Pharmacological or genetic normalization of DYRK1A levels restores cognitive function (Nguyen TL et al., 2017. Dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A) inhibitors: a survey of recent patent literature. Expert Opin. Ther. Pat. 27, 1183-1199; Nguyen TL et al., 2018. Correction of cognitive deficits in mouse models of Down syndrome by pharmacological inhibitor of DYRK1A. Dis. Model Mech. 11, dmm035634).

[0007] DYRK1A and Alzheimer's disease (AD), tauopathy

[0008] Evidence is steadily emerging that DYRK1A is involved in the development of Alzheimer's disease (AD). DYRK1A phosphorylates the following key substrates involved in AD and dementia: tau, septin 4, amyloid precursor protein (APP), presenilin 1, neprilysin, Munc18-1, α-synuclein, RCAN1, and β-tubulin. Abnormal expression and post-translational modification of DYRK1A have been identified in AD. By regulating alternative splicing of exon 10, DYRK1A promotes the production of the 3R-tau splice isoform (characteristic of DS / AD / tauopathy) more than the normal 4R-tau isoform. Inhibition of DYRK1A promotes autophagy and may counteract the autophagy deficiency seen in AD.

[0009] DYRK1A, Parkinson's disease (PD), and Pick's disease

[0010] GWAS studies have revealed that DYRK1A is a risk factor for Parkinson's disease (Nalls MA et al., 2019. Identification of novel risk loci, causal insights, and heritable risk for Parkinson's disease: a meta-analysis of genome-wide association studies. Lancet Neurol 18, 1091). DYRK1A phosphorylates key factors for PD, such as parkin, septin 4, and α-synuclein. Upregulation of PD-specific microRNAs targets DYRK1A expression (Chiu CC et al., 2019. Upregulated expression of microRNA-204-5p leads to the death of dopaminergic cells by targeting DYRK1A-mediated apoptotic signaling cascade. Front Cell Neurosci 13, 399). Further evidence indicates increased DYRK1A expression in PD. DYRK1A is overexpressed in Pick's disease.

[0011] DYRK1A and other diseases (viral infections, type 1 and type 2 diabetes, cancer)

[0012] DYRK1A and DYRK1B are utilized during placental replication of HCMV. Inhibition of DYRK prevents replication of various viruses, including herpesviruses, cytomegaloviruses, and HIV-1. DYRK1A inhibitors stimulate the proliferation of insulin-producing β-cells in the pancreas, offering a promising approach to type 1 and type 2 diabetes (Ackeifi C et al., 2020. Pharmacologic and genetic approaches define human pancreatic β-cell mitogenic targets of DYRK1A inhibitors. JCI Insight 5, e132594; Kumar K et al., 2021. DYRK1A inhibitors as potential therapeutics for β-cell regeneration for diabetes. J Med Chem. 2021 Mar 8. doi:10.1021 / acs.jmedchem.0c02050. Epub ahead of print. PMID:33682417). There is a wealth of literature linking DYRK1A to cancer. The most prominent examples are megakaryocytic leukemia, acute lymphoblastic leukemia, pancreatic cancer, and brain tumors (glioblastoma).

[0013] Therefore, abnormalities in DYRK1A dosage are associated with cognitive impairment observed in Down syndrome and Alzheimer's disease. DYRK1A is a risk factor for Parkinson's disease. Inhibition of DYRK1A additionally triggers the proliferation of insulin-producing β-cells in the pancreas. Thus, DYRK1A inhibitors may find applications in the prevention and / or treatment of DS, AD and other tauopathies, dementia, PD, Niemann-Pick type C disease, CDKL5 deficiency disorder, type 1 and type 2 diabetes, viral infections, several cancers (leukemia, pancreatic cancer, glioblastoma), osteoarthritis, infections caused by single-celled parasites, and applications for regulating body temperature.

[0014] Other DYRKs and human diseases

[0015] DYRK1B is involved in the replication of various viruses, including, for example, hepatitis C virus, chikungunya virus, dengue virus, and SARS coronavirus, cytomegalovirus, and human papillomavirus. Similar to DYRK1A, inhibition of DYRK1B leads to the proliferation of pancreatic, insulin-producing β-cells. DYRK1B is also involved in neuroinflammation. Targeting DYRK1B provides a new rationale for the treatment of various cancers, such as liposarcoma or breast cancer.

[0016] DYRK2 works in conjunction with GSK-3β to regulate neuronal morphogenesis. DYRK2 is involved in various aspects of cancer development.

[0017] DYRK3 promotes hepatocellular carcinoma. DYRK3 links the condensation / decomposition of stress granules to mTORC1 signaling. DYRK3 regulates the phase transition of membrane-free organelles during mitosis. DYRK3 and DYRK4 are involved in regulating cytoskeletal structure and process extension in nerve cells.

[0018] DYRK1A reduces axonal growth, DYRK3 and DYRK4 increase dendritic branching, and DYRK2 reduces both axonal and dendritic growth and branching.

[0019] CLK and human diseases

[0020] Please note that CLK is a potentially confusing abbreviation because it has the following meanings: (a) monooxygenase CLK-1 (human homolog COQ7); (b) collection-K1 (CL-K1, or CL-11), a multifunctional Ca(2+)-dependent lectin; (c) the MAPK gene Clk1 of the maize pathogen Curvularia lunata; (d) mitochondrial membrane-binding enzyme Clock-1 (CLK-1); (e) colletotrichum lindemuthianum kinase 1 (clk1).

[0021] CLK plays a crucial role in alternative splicing. CLK acts as a body temperature sensor, globally regulating alternative splicing and gene expression. CLK activity is highly responsive to physiological temperature changes through structural rearrangement within the kinase activation segment (Haltenhof T et al., 2020. A conserved kinase-based body-temperature sensor globally controls alternative splicing and gene expression. Mol Cell 78, 57).

[0022] CLK1 and human diseases

[0023] CLK1 triggers periodic alternative splicing during the cell division cycle. CLK1 controls mRNA splicing in influenza A virus, and its inhibition prevents viral replication. CLK1 and CLK2 also regulate HIV-1 gene expression. CLK1 is an inducer of autophagy. CLK1 inhibition may prevent chemical resistance in gliomas, and CLK1 inhibition by TG693 enables the skipping of exon 31 of the dystrophin gene mutation in Duchenne muscular dystrophy.

[0024] Other CLK and human diseases

[0025] CLK2 inhibition has been proposed as a way to improve neurological function in Phelan-McDermid syndrome (PMDS) and as a method to combat intellectual disability and autism. Dual inhibition of CLK2 and DYRK1A with lorecivivint is a potential disease-modifying approach to osteoarthritis of the knee. CLK2 inhibition impairs MYC-driven breast cancer, triple-negative breast cancer, and glioblastoma. CLK2 inhibition improves autistic features in Phelan-McDermid syndrome (PMDS). Alternative splicing of tau exon 10 is controlled by CLK2 and other CLKs, leading to changes in the 3R / 4R isoform ratio and neurodegeneration in sporadic AD. Inhibition of CLK2, CLK3, and CLK4 inhibits HIV-1 production. By controlling alternative splicing, CLK modulates the balance between pro-apoptotic and anti-apoptotic regulators, and inhibition of CLK may have potential applications in the treatment of many cancers.

[0026] CLK3 contributes to hepatocellular carcinoma and prostate cancer.

[0027] Table 1 below summarizes the involvement of DYRK kinase and CLK kinase in various diseases.

[0028] [Table 1] JPEG0007842031000002.jpg80170

[0029] DYRK and CLK inhibitors

[0030] Several DYRK1A inhibitors have been reported in recent years. Most DYRK1A inhibitors also inhibit DYRK1B, 2, 3, and 4, as well as their close relatives CLK1, 2, 3, and 4, suggesting several possible inhibition profiles.

[0031] Several imidazolon derivatives, hereafter referred to as leucettines in this specification, are disclosed as kinase inhibitors, and more particularly as inhibitors of DYRK1A kinase. [Overview of the Initiative] [Problems that the invention aims to solve]

[0032] There remains a need to identify novel compounds to treat and / or prevent the diseases described above, particularly through the inhibition, especially selective inhibition, of DYRK1A, other DYRKs, and related CLK kinases. [Means for solving the problem]

[0033] It has now been found that the compound defined in formula (I) below in this specification is useful for the treatment and / or prevention of diseases selected from Down syndrome; Alzheimer's disease and related disorders; dementia; tauopathy; Parkinson's disease; other neurodegenerative diseases; CDKL5 deficiency disorder; Phelan-McDermid syndrome; autism; type 1 and type 2 diabetes; folic acid and methionine metabolic disorders; osteoarthritis; several cancers and leukemias; neuroinflammation, anemia, infections caused by single-celled parasites, and viral infections, as well as for regulating body temperature.

[0034] Therefore, the present invention relates to a compound of formula (I) as defined below.

[0035] The present invention further relates to a compound of formula (I) as defined below, for use as a pharmaceutical.

[0036] The present invention further relates to compounds of formula (I) as defined below for use in the treatment and / or prevention of diseases selected from several cancers and leukemias, neuroinflammation, anemia, unicellular parasitic infections, viral infections, and for use in thermoregulation.

[0037] The present invention further relates to a pharmaceutical composition containing the same and a method for producing the same.

[0038] The present invention ultimately relates to a synthetic intermediate of formula (II) as defined below.

[0039] definition

[0040] As used herein, the term “patient” means either an animal, for example, a valuable animal for breeding, mating or preservation purposes, or preferably a human or human child who is suffering from or is likely to suffer from one or more of the diseases and conditions described herein.

[0041] In particular, as used in this application, the term "patient" refers to mammals, such as rodents, cats, dogs, primates, or humans, and preferably the subject is humans, and also extends to birds.

[0042] Identifying patients who require treatment for the diseases and conditions described herein is within the scope of the skills and knowledge of those skilled in the art. Veterinarians or physicians skilled in the art can readily identify patients requiring such treatment by using clinical examinations, physical examinations, medical / family history, or biological and diagnostic tests.

[0043] In the context of the present invention, as used herein, the terms “treat” or “treat” mean to prevent, reverse, mitigate, suppress or inhibit the progression of diseases, more particularly those associated with the diseases described later in the “Pathology” section herein, and the cognitive, motor, or metabolic changes resulting from high expression and activity of DYRK1A kinase and / or CLK1, and optionally with abnormalities in other DYRKs (DYRK1B, 2, 3, 4) and closely related further cdc2-like kinases (CLK) (CLK2, 3, 4), and the cognitive, motor, or metabolic changes thereof.

[0044] Therefore, the term “to treat” or “treatment” encompasses within the framework of the present invention the improvement of the medical condition of patients suffering from diseases associated with high expression and activity of either DYRK1A or CLK1 kinase, and optionally with abnormalities in other DYRKs (DYRK 1B, 2, 3, 4) and closely related cdc2-like kinases (CLK) (CLK 2, 3, 4), as described later in the “Pathology” section of this specification.

[0045] As used herein, “effective amount” means the amount of the compound of the present invention that is effective in preventing, alleviating, eliminating, treating or controlling the symptoms of the diseases and conditions described herein.

[0046] The term “control” is intended to mean all processes that may slow, interrupt, stop, or halt the progression of the diseases and conditions described herein, but not necessarily indicate the complete elimination of the symptoms of all diseases and conditions, and is intended to include preventive measures.

[0047] The term "effective dose" includes both "preventive effective dose" and "treatment effective dose."

[0048] As used herein, the term “prevent” means reducing the risk of developing or delaying the onset of a disease caused by a particular phenomenon, namely, in the present invention, abnormal DYRK / CLK kinase activity, particularly abnormal DYRK1A kinase activity.

[0049] As used herein, “prevent” also includes “reduce the likelihood of occurrence” or “reduce the likelihood of recurrence.”

[0050] The term "preventive effective dose" means the concentration of the compound of the present invention that is effective in suppressing, preventing, or reducing any one of the disease possibilities described herein.

[0051] Similarly, the term “effective treatment dose” means, in this specification, a concentration of a compound that is effective in treating the diseases described above, such as DYRK1A and / or CLK1 kinase activity, and optionally, a concentration of the compound that results in an additional decrease or normalization of overall DYRK / CLK kinase activity following examination if administered after the onset of the disease.

[0052] As used herein, the term “pharmaceutically acceptable” means a compound, material, excipient, composition or dosage form that is suitable, within the bounds of sound medical judgment, for contact with human and animal tissues without undue toxicity, irritation, allergic reactions or complications of other problems commensurate with a reasonable benefit / risk ratio. [Modes for carrying out the invention]

[0053] To our surprise, the inventors have found that the compound of formula (I), disclosed later in this specification, inhibits DYRK1A, other DYRKs (DYRK1B, DYRK2, DYRK3, DYRK4), and CLKs (CLK1, CLK2, CLK3, CLK4). This claim is based on data such as those shown in the following examples and is further elaborated below in this specification.

[0054] According to the first aspect, the subject matter of the present invention relates to any one of the compounds of the following formula (I) or pharmaceutically acceptable salts thereof. [ka] Here, R 1 teeth, (i).-COOR a A (C1-C6) alkyl group substituted with one or two groups selected from a phenyl group, a hydroxyl group, a halogen atom, a (C1-C4) alkoxy group, and a benzyloxy group, wherein the benzyloxy group may be substituted with 1-3 halogen atoms on its phenyl group. (ii) Spiro (C5~C) 11 ) bicyclic ring, (iii) A condensed phenyl group selected from a phenyl group condensed with a (C5-C6) cycloalkyl or (C5-C6) heterocycloalkyl, where the (C5-C6) cycloalkyl and (C5-C6) heterocycloalkyl rings may include unsaturated rings, and also a (C1-C4) alkyl group, a hydroxyl group, a halogen atom, a (C1-C3) alkoxy group or -COR a It may be substituted by the group, (iv) A phenyl group substituted with one or two groups selected from (C1-C8) alkyl, (C1-C3) fluoroalkyl, fluoro(C1-C4) alkoxy groups, halogen atoms, and (C4-C7) heterocycloalkyl groups, wherein the (C4-C7) heterocycloalkyl group may itself be substituted with a (C1-C4) alkyl group, or (v) R'-L-base, where L is either a single bond or a (C1-C3)alkanediyl group, where the (C1-C3)alkanediyl group may be substituted with one group selected from a hydroxyl group and a (C1-C3)alkoxy group, and R' is (v.1) A (C3-C8) cycloalkyl group which may be substituted with one, two, or three groups selected from (C1-C4) alkyl groups, hydroxyl groups, halogen atoms, and (C1-C3) alkoxy groups. (v.2) (C1~C4) alkyl groups, (C1~C4) alkoxy groups, halogen atoms, hydroxyl groups, -OC(O)-R d group, -OC(O)-NHR d Base, -NH-C(O)-R d group, -SO2-Rd a group, -N(R e )2 group and -COOR a group, a crosslinked (C6 - C 10 ) cycloalkyl group, optionally substituted by 1 to 3 groups selected from the group consisting of: (v.3). -COOR a group, a hydroxy group, a halogen atom, a (C1 - C4) alkyl group, and a (C3 - C8) heterocycloalkyl group optionally substituted by 1 to 3 groups selected from the group consisting of an oxo group; (v.4). a (C3 - C8) heteroaryl group optionally substituted by 1 to 3 groups selected from the group consisting of a halogen atom, a (C1 - C4) alkyl group, a (C1 - C4) alkoxy group, and an N - methylpiperazinyl group, or (v.5). a crosslinked (C6 - C 10 ) heterocycloalkyl group represents, or, (vi). R f -L f -Base (In this specification, "R'-L-base" with respect to item (vi) is "R f -L f - These should be read as "base", and "L" and "R'" in item (vi) should be read as "L" f " and "R f (This should be interpreted as "...") , where, L f is a (C1 - C3) alkanediyl group optionally substituted by a group selected from the group consisting of an NR b R c group, a (C1 - C4) alkoxy group, a hydroxy group, -COOR a group, and a halogen atom, and R f is a phenyl group optionally substituted by 1 to 3 groups selected from the group consisting of a (C1 - C6) alkyl group, a fluoro (C1 - C4) alkyl group, a fluoro (C1 - C4) alkoxy group, a halogen atom, and a hydroxy group, where, R a represents a (C1 - C4) alkyl group or a hydrogen atom, R b and R c These independently represent (C1-C6) alkyl groups or hydrogen atoms. R d This represents a (C1-C4) alkyl group or a cyclopropyl group. R e This represents an (C1-C3) alkyl group. Represents, and R 2 However, this represents a hydrogen atom or a (C1-C3) alkyl group.

[0055] The inventors have surprisingly discovered that compounds having the following scaffolds of formulas (A) to (F) exhibit significantly reduced kinase inhibitory activity against DYRK1A and other related kinases compared to their benzothiazole congeners (compounds according to the present invention). 50 The values ​​decreased by a factor of 10 to 1000, and several compounds were completely inactive at the highest dose tested (10 μM). [ka]

[0056] These significantly reduced kinase inhibitory activities have been verified, for example, by individual comparisons of the compound of formula (I) and compounds having scaffolds of formulas (A) to (F), where R 2 is a hydrogen atom, and R 1 The compound is selected from the group consisting of cyclohexyl, cycloheptyl, cyclooctyl, and 2-methoxy-1-phenyl-ethyl.

[0057] According to a particular embodiment, the present invention relates to any one of the compounds of formula (I) as defined herein or a pharmaceutically acceptable salt thereof, wherein R 1 but, (i).-COOR aA (C2-C6) alkyl group substituted with one or two groups selected from a phenyl group, a hydroxyl group, a halogen atom, a (C1-C4) alkoxy group, and a benzyloxy group, wherein the benzyloxy group may be substituted with 1-3 halogen atoms on its phenyl group. (ii). Spiro (C7~C9) bicyclic ring, (iii) A condensed phenyl group selected from a phenyl group condensed with cyclopentyl or heterocyclopentyl, wherein the cyclopentyl and heterocyclopentyl groups may include unsaturated groups, and also includes (C1-C4) alkyl groups, hydroxyl groups, halogen atoms, (C1-C3) alkoxy groups or -COR a It may be substituted by the group, (iv) A phenyl group substituted with one or two groups selected from (C1-C8) alkyl, (C1-C3) fluoroalkyl, fluoro(C1-C4) alkoxy groups, halogen atoms, and (C4-C7) heterocycloalkyl groups, wherein the (C4-C7) heterocycloalkyl group may itself be substituted with a (C1-C4) alkyl group, or (v) R'-L-base, where L is either a single bond or a (C1-C3)alkanediyl group, where the (C1-C3)alkanediyl group may be substituted with one group selected from a hydroxyl group and a (C1-C3)alkoxy group, and R' is (v.1) A (C3-C8) cycloalkyl group which may be substituted with one, two, or three groups selected from (C1-C4) alkyl groups, hydroxyl groups, fluorine atoms, and (C1-C3) alkoxy groups. (v.2) (C1~C4) alkyl groups, (C1~C4) alkoxy groups, hydroxyl groups, halogen atoms, -OC(O)-R d group, -OC(O)-NHR d Base, -NH-C(O)-R d group, -SO2-R d group, -N(R e ) 2 units and -COOR aBridged (C7~C) which may be substituted by 1 to 3 groups selected from the group. 10 ) Cycloalkyl groups, (v.3).-COOR a (C4-C7) heterocycloalkyl groups may be substituted with 1 to 3 groups selected from a group, a hydroxyl group, a halogen atom, a (C1-C4) alkyl group, and an oxo group. (v.4) A heteroaryl group which may be substituted with 1 to 3 groups selected from a halogen atom, a (C1-C4) alkyl group, a (C1-C4) alkoxy group, or an N-methylpiperazinyl group, (v.5). Bridged (C6~C 10 ) Heterocycloalkyl groups Representing, Or, L is -NR b R c Group, (C1-C4) alkoxy group, hydroxyl group, -COOR a An alkanediyl group (C1-C3) which may be substituted with a group selected from the group and halogen atoms, R' is a phenyl group which may be substituted with 1 to 3 groups selected from the group consisting of (C1-C6) alkyl groups and fluoro(C1-C4) alkyl groups. Here, R a This represents a (C1-C4) alkyl group or a hydrogen atom. R b and R c These independently represent (C1-C6) alkyl groups or hydrogen atoms. R d This represents a (C1-C4) alkyl group or a cyclopropyl group. R e This represents an (C1-C3) alkyl group, It represents, and also, R 2 However, this represents a hydrogen atom or a (C1-C3) alkyl group.

[0058] According to other specific embodiments, the present invention relates to any one of the compounds of formula (I) as defined herein or a pharmaceutically acceptable salt thereof, wherein R 1 but, (i) A (C2-C6) alkyl group substituted with one or two groups selected from a -COOCH3 group, a hydroxyl group, a fluorine atom, a methoxy group, an ethoxy group, a tert-butoxy group, a cyclopropoxy group, and a benzyloxy group, wherein the benzyloxy group may be substituted with one fluorine atom on its phenyl group. (ii) Spiro(C7~C8) bicyclic rings, in particular spiro[3.3]heptyl, spiro[2.5]octanyl, or 7-azaspiro[3.5]nonyl, (iii) A condensed phenyl group selected from a phenyl group condensed with cyclopentyl or heterocyclopentyl, wherein the cyclopentyl group and heterocyclopentyl group may be unsaturated and may be substituted with methyl, hydroxyl, methoxy, and -COCH3 groups. (iv) A phenyl group substituted with one or two groups selected from methyl, hexyl, trifluoromethyl, difluoromethoxy, halogen atoms, in particular a fluorine atom, a morpholino group, and an N-methylpiperazinyl group, or (v) R'-L-base, where L is either a single bond or a (C1-C3)alkanediyl group, where the (C1-C3)alkanediyl group may be substituted with one group selected from a hydroxyl group and a (C1-C3)alkoxy group, and R' is (v.1) A (C3-C8) cycloalkyl group which may be substituted with one, two, or three groups selected from methyl, isopropyl, hydroxy, and methoxy groups, in particular chloropropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, or cyclooctyl, (v.2) A bridged (C7~C) group which may be substituted with 1 to 3 groups selected from methyl, methoxy, hydroxyl, fluorine atom, -OC(O)-CH3, -OC(O)-C(CH3)3, -OC(O)-NH-C(CH3)3, -NH-C(O)-CH3, -NH-C(O)-C3H4, -S(O)2-CH3, -S(O)2-C3H4, -N(CH3)2, and -C(O)-O-CH3 groups. 10 ) Cycloalkyl groups, particularly adamantyl or bicyclo[3.1.1]heptyl, (v.3).-COOR f A (C5-C8) heterocycloalkyl group which may be substituted with one, two, or three groups selected from a hydroxyl group, a methyl group, and an oxo group, in particular tetrahydropyranil, piperidinil, oxetanil, tetrahydrofuranil, oxepanil, tetrahydrothiopyranil, pyrrolidinil, dioxepanil, or piperidinil, where R f This represents either an ethyl group or an isopropyl group. (v.4) Heteroaryl groups which may be substituted with 1 to 3 groups selected from methyl, methoxy and N-methylpiperazinyl groups, in particular pyrimidinyl, pyridinyl, thiazolyl, imidazolyl, pyrazolyl, thiadiazolyl, pyridazinyl, pyrazinyl, furyl, or (v.5). Bridged (C7~C 10 ) Cycloalkyl groups, particularly quinuclidine-3-yl, or (vi) R'-L-base, where L is -NR b R c Group, (C1-C4) alkoxy group, hydroxyl group, -COOR a An alkanediyl group (C1-C3) which may be substituted with one group selected from the group consisting of a group and a halogen atom, particularly a fluorine atom, and, R' is a phenyl group which may be substituted with one or two groups selected from the group consisting of a methyl group, a trifluoromethyl group, and a trifluoromethoxy group. Here, R aThis represents an (C1-C3) alkyl group, R b and R c These independently represent a methyl group or a hydrogen atom. Selected from the group consisting of, R 2 However, this represents a hydrogen atom or a (C1-C3) alkyl group.

[0059] According to other specific embodiments, the present invention relates to any one of the compounds of formula (I) as defined herein or a pharmaceutically acceptable salt thereof, wherein R 1 The R'-L- group is where L is -CH2-, -CH(CH3)-, -CH(CH2OH)-CH2-, -CH(CH2OH)-, -CH(CH2OCH3)-, -CH(OH)-CH2-, -CH2-CH(CH2OCH3)-, -CH(OCH3)-CH2-, -CH2-CH(COOCH3)-, -CH(CH2F)-, -CH(CH2NH2)-, The group is selected from the group consisting of -CH(CH2NHCH3)-, -CH(CH2N(CH3)2)-, -CH2-CH(CH2OH)-, -CH(OCH3)-CH2-, -CH2-CH(OCH3)-, -CH2-CH(OH)-CH2-, -CH2-CH(OCH3)-CH2-, -(CH2)3-, -(CH2)2-, and -CH(CH2OC(CH3)3).

[0060] According to other specific embodiments, the present invention relates to any one of the compounds of formula (I) as defined herein or a pharmaceutically acceptable salt thereof, wherein R 1 This is an R'-L- group, and here, (v.1) When R' is a (C3~C8) cycloalkyl group, L is selected from the group consisting of a single bond, a -CH2- group, a -CH(CH3)- group, a -CH(CH2OH)-CH2- group, a -CH(CH2OH)- group, a -CH(CH2OCH3)- group, and a -CH(OH)-CH2- group, and a -CH(OCH3)-CH2- group. (v.2) R' was bridged (C7~C 10)When it is a cycloalkyl group, L is a single bond, a -CH2- group, or a -CH(CH3)- group, (v.3) R' is a (C5-C8) heterocycloalkyl group containing a spiro(C3-C8) heterocycloalkyl group, and L is a single bond or a -CH2- group. (v.4) When R' is phenyl, L is selected from the group consisting of a single bond, -CH2- group, -CH2-CH(COOCH3)- group, -CH(CH2F)- group, -CH(CH2NH2)- group, -CH(CH2NHCH3)- group, CH(CH2N(CH3)2)- group, -CH2-CH(CH2OH)- group, -CH(CH2OH)- group, -CH(CH2OCH3)- group, -CH(OH)-CH2- group, -CH2-CH(CH2OCH3)- group, -CH2-CH(OH)-CH2- group, and -CH2-CH(OCH3)-CH2 group. (v.5) When R' is a heteroaryl group, L is selected from the group consisting of a single bond, a -CH2- group, a -(CH2)3- group, and a -(CH2)2- group.

[0061] According to other specific embodiments, the present invention relates to a compound of formula (I) as defined herein, wherein R 1 but, An adamantyl group which may be substituted with one to three groups selected from a methyl group, a methoxy group, a hydroxyl group, a fluorine atom, a -OC(O)-CH3 group, a -OC(O)-C(CH3)3 group, a -OC(O)-NH-C(CH3)3 group, a -NH-C(O)-CH3 group, a -NH-C(O)-C3H4 group, a -S(O)2-CH3 group, a -S(O)2-C3H4 group, a -N(CH3)2 group, and a -C(O)-O-CH3 group, particularly one group, where the adamantyl group is preferably unsubstituted; or, R”-O-CH2(R”')- group, where R'' is a (C1-C4) alkyl group, preferably a methyl or ethyl group, and R''' is a (C1-C4) alkyl group, particularly a (C3-C4) alkyl group, preferably an isopropylmethyl group, or R''' is a phenyl group which may be substituted with 1 to 3 groups selected from the group consisting of (C1-C6) alkyl groups, fluoro(C1-C4) alkyl groups, fluoro(C1-C4) alkoxy groups, halogen atoms, and hydroxyl groups, particularly 1 group, where the phenyl group is preferably unsubstituted. It represents.

[0062] According to other specific embodiments, the present invention relates to any one of the compounds of formula (I) as defined herein or a pharmaceutically acceptable salt thereof, wherein R 1 but, -COOR a A (C1-C6) alkyl group which may be substituted with one or two groups selected from a phenyl group, a hydroxyl group, a fluorine atom, a (C1-C4) alkoxy group, and a benzyloxy group, wherein the benzyloxy group may be substituted with 1-3 halogen atoms on its phenyl group. Spiro (C5~C 11 ) Biring ring, or R'-L- group, here, L is either a single bond or a (C1-C3)alkanediyl group, where the (C1-C3)alkanediyl group may be substituted with a group selected from a hydroxyl group and a (C1-C3)alkoxy group. It represents, and also, R' is (C3-C8) cycloalkyl groups which may be substituted with one, two, or three groups selected from halogen atoms, (C1-C4) alkyl groups, hydroxyl groups, and (C1-C3) alkoxy groups, (C1-C4) alkyl groups, (C1-C4) alkoxy groups, halogen atoms, hydroxyl groups, -OC(O)-R d group, -OC(O)-NHR d Base, -NH-C(O)-R d group, -SO2-R d group, -N(R e ) 2 units, and -COOR a Bridged (C6~C) which may be substituted by 1 to 3 groups selected from the group.10 ) Cycloalkyl groups, Here, R a represents an (C1-C4) alkyl group, R d represents a (C1-C4) alkyl group or a cyclopropyl group, and R e represents an alkyl group (C1-C3). Selected from the group consisting of, Here, R 2 However, this represents a hydrogen atom or a (C1-C3) alkyl group.

[0063] The above subgroups of these compounds are gathered under the "A1" type compounds in Table 1 below in this specification.

[0064] Further according to the above embodiment, R 1More specifically, cyclopropylmethyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexylmethyl, cyclohexyl, cycloheptylmethyl, cycloheptyl, cyclooctyl, 3-hydroxy-2,2-dimethylpropyl, 2-benzyloxyethyl, 2-methylcyclohexyl, 1-cyclohexylethyl, 1-adamantylmethyl, 1-(1-adamantyl)ethyl, 1-adamantyl, 2-adamantyl, 3,5-dimethyl-1-adamantyl, 5-hydroxy-2-adamantyl, 3-hydroxy-1-adamantyl Pentyl, 3-methoxy-1-adamantyl, 2,6,6-trimethylnorpinan-3-yl, 6,6-dimethylnorpinan-2-yl, spiro[2.5]octan-2-yl, spiro[3.3]heptan-2-yl, 1,7,7-trimethylnorboran-2-yl, norboran-2-yl, 2-isopropyl-5-methylcyclohexyl, 1-(cyclohexylmethyl)-2-hydroxyethyl, 1-(cyclopentylmethyl)-2-hydroxyethyl, 1-(cyclobutylmethyl)-2-hydroxyethyl, 1-(cyclopropyl Methyl)-2-hydroxy-ethyl, 1-(hydroxymethyl)-3-methyl-butyl, 1-(methoxymethyl)-3-methyl-butyl, 1-(hydroxymethyl)propyl, 1-(fluoromethyl)-3-methyl-butyl, 1-cyclohexyl-2-hydroxy-ethyl, 1-cyclohexyl-2-methoxy-ethyl, 2-cyclohexyl-2-hydroxy-ethyl, 2-cyclohexyl-2-methoxy-ethyl, 2-hydroxycyclopentyl, 2-methoxycyclopentyl, 2-hydroxycyclohexyl, 3-hydroxycyclohexyl Syl, 4-hydroxycyclohexyl, 2-methoxycyclohexyl, 4-methoxycyclohexyl, 2-hydroxycycloheptyl, 3-hydroxycycloheptyl, 2-methoxycycloheptyl, -CH(COOCH3)-CH(CH3)2, -CH(COOCH3)-CH3, -CH(COOCH3)-CH2-CH(CH3)2, -CH(COOCH3)-CHOH-CH3, 3,3-difluorocyclopentyl, 4,4-difluorocyclohexyl, 3,3-difluorocyclohexyl, 2,2-difluorocyclohexyl, 3,3-Difluorocycloheptyl, 3-Acetoxy-1-adamantyl, 3-Pivaloyloxy-1-adamantyl, 3-Methoxycyclohexyl, 4-Hydroxycycloheptyl, 3-Methoxycycloheptyl, 3-Methoxycycloheptyl, 4-Methoxycycloheptyl, 3-Noradamantyl, 3-Tert-Butylcarbamoyloxy-1-adamantyl, 3-Fluoro-1-adamantyl, 1-(Tert-Butoxymethyl)-3-Methyl-Butyl, 3-Acetamide-1-adamantyl, 3-(Cyclopropanecarbonylamino)-1-adamantyl This can represent 3-(methanesulfonamide)-1-adamantyl, 3-(cyclopropylsulfonylmino)-1-adamantyl, 3-(dimethylamino)-1-adamantyl, 2-methoxycarbonyl-2-adamantyl, 3,5-dihydroxy-1-adamantyl, 3,5,7-trifluoro-1-adamantyl, 1-(ethoxymethyl)-3-methyl-butyl, 1-(benzyloxymethyl)-3-methyl-butyl, 1-[(4-fluorophenyl)methoxymethyl]-3-methyl-butyl, or 1-(cyclopropoxymethyl)-3-methyl-butyl.

[0065] According to other specific embodiments, the present invention relates to any one of the compounds of formula (I) as defined herein or a pharmaceutically acceptable salt thereof, wherein R 1 but, A condensed phenyl group selected from a phenyl group condensed with a (C5-C6) cycloalkyl or (C5-C6) heterocycloalkyl ring, where the (C5-C6) cycloalkyl and (C5-C6) heterocycloalkyl rings may include unsaturated rings, as well as (C1-C4) alkyl groups, hydroxyl groups, halogen atoms, (C1-C3) alkoxy groups, and -COR a It may be substituted by the group, A phenyl group substituted by one or two groups selected from (C1-C8) alkyl, (C1-C3) fluoroalkyl, fluoro (C1-C4) alkoxy group, halogen atom and (C4-C7) heterocycloalkyl group, wherein the (C4-C7) heterocycloalkyl group may itself be substituted by a (C1-C4) alkyl group, or an R'-L-group, wherein L is a (C1-C4) alkane diyl group which may be substituted by a group selected from a hydroxy group, a (C1-C4) alkoxy group, -NR b R c group, -COOR a group, and a halogen atom, and R' is a phenyl group which may be substituted by 1 to 3 groups selected from a (C1-C6) alkyl group, a fluoro (C1-C4) alkyl group, and a fluoro (C1-C4) alkoxy group, a halogen atom and a hydroxy group, wherein R a is a (C1-C4) alkyl or a hydrogen atom, and R b and R c are independently selected from (C1-C6) alkyl and a hydrogen atom, represents, and R 2 represents a hydrogen atom or a (C1-C3) alkyl group.

[0066] The above subgroups of these compounds are grouped under the compounds of "A2" and "A5" in Table 1 below of this specification.

[0067] According to the above embodiment, R 1More particularly, it may represent benzyl, indan-2-yl, (3,4-dimethylphenyl)methyl, (2,4-dimethylphenyl)methyl, [2-(trifluoromethyl)phenyl]methyl, [2-(trifluoromethoxy)phenyl]methyl, 2-hydroxyindan-1-yl, 2-methoxyindan-1-yl, -CH(COOCH3)-CH2-Ph, -CH(CH2F)Ph, 2-amino-1-phenyl-ethyl, 2-(methylamino)-1-phenyl-ethyl, 2-(dimethylamino)-1-phenyl-ethyl, 1-benzyl-2-hydroxy-ethyl, 1-benzyl-2-methoxy-ethyl, 2-hydroxy-1-phenyl-ethyl, 2-methoxy-1-phenyl-ethyl, 2-hydroxy-2-phenyl-ethyl, 2-methoxy-2-phenyl-ethyl, 2-hydroxy-3-phenyl-propyl, 2-methoxy-3-phenyl-propyl, 3-fluoro-4-methyl-phenyl, 4-fluorophenyl, 4-n-hexylphenyl, 4-(4-methylpiperazin-1-yl)phenyl, 3-(difluoromethoxy)phenyl, 1-ethynylindolin-6-yl, 3-(trifluoromethyl)phenyl, indan-5-yl, 4-morpholinophenyl, 1-methylindazol-7-yl, or 2-tert-butoxy-1-phenyl-ethyl.

[0068] According to another specific embodiment, the present invention relates to a compound of formula (I) as defined above herein, where R 2 represents a hydrogen atom or a methyl group.

[0069] According to another specific embodiment, the present invention relates to any one of the compounds of formula (I) or a pharmaceutically acceptable salt thereof as defined above herein, where R 1 represents an R'-L-group, where R' is a (C3-C8) heteroaryl group optionally substituted by one to three groups selected from a halogen atom, a (C1-C4) alkyl group, a (C1-C4) alkoxy group, and an N-methylpiperazinyl group, and L is a (C1-C3) alkanediyl or a single bond, and Here, R 2 This represents a hydrogen atom.

[0070] The above subgroups of these compounds are gathered under the compounds labeled "A3" and "A6" in Table 1 below in this specification.

[0071] Further according to the above embodiment, R 1 More specifically, (5-methylpyrazine-2-yl)methyl, 2-pyridylmethyl, 3-pyridylmethyl, 4-pyridylmethyl, (5-methyl-2-furyl)methyl, (4-methylthiazole-2-yl)methyl, 3-imidazole-1-ylpropyl, 2-(2-pyridyl)ethyl, 1,3-benzothiazole-2-ylmethyl, 2-pyrimidinyl, 2-pyridyl, 1-methylpyrazole-3-yl, 2-methoxy-6-methyl-3-pyridyl, pyrimidine-5- It can represent yl, 3-pyridyl, 1,3,4-thiadiazole-2-yl, 5-(4-methylpiperazine-1-yl)-2-pyridyl, 6-(4-methylpiperazine-1-yl)-3-pyridyl, 2-(4-methylpiperazine-1-yl)pyrimidine-5-yl, 5-(4-methylpiperazine-1-yl)pyrimidine-2-yl, 5-(4-methylpiperazine-1-yl)pyrazine-2-yl, or 6-(4-methylpiperazine-1-yl)pyridazine-3-yl.

[0072] According to other specific embodiments, the present invention relates to any one of the compounds of formula (I) as defined herein or a pharmaceutically acceptable salt thereof, wherein R 1 This represents the R'-L- group, where, R' is a hydroxyl group, a (C1-C4) alkyl group, an oxo group, and -COOR a A (C3-C5) heterocycloalkyl group which may be substituted with 1 to 3 groups selected from the group, where R a This is as defined above in this specification, and L is methylene or a single bond, and Here, R 2 This represents a hydrogen atom.

[0073] The above subgroups of these compounds are gathered under compounds “A4” and “A7” in Table 1 below in this specification.

[0074] If we continue to follow the above embodiment, R 1 More specifically, (1-methyl-4-piperidyl)methyl, tetrahydropyran-4-yl-methyl, 1-tert-butyloxycarbonylpiperidine-4-yl-methyl, 7-methyl-7-azaspiro[3.5]nonan-2-yl, tetrahydropyran-4-yl, 1-tert-butyloxycarbonylpiperidine-4-yl, 1-ethyloxycarbonylpiperidine-4-yl, 1-methyl-4-piperidyl, 1-methyl-3-piperidyl, oxetan-3-yl, tetrahydrofuran-3-yl, tetrahydropyran-3-yl, 6,6-dimethyltetrahydropyran-3 This can represent -yl, 4-hydroxytetrahydropyran-3-yl, oxepan-3-yl, 2-oxo-piperidine-3-yl, 2-oxo-piperidine-5-yl, quinuclidin-3-yl, tetrahydrothiopyran-3-yl, 1,4-dioxepan-6-yl, 2-oxo-pyrrolidine-3-yl, 1-methyl-2-oxo-pyrrolidine-3-yl, 4,4-dimethyl-2-oxo-pyrrolidine-3-yl, 1-methyl-2-oxo-piperidine-3-yl, 3-methyl-2-oxo-pyrrolidine-3-yl, or 1,3-dimethyl-2-oxo-pyrrolidine-3-yl.

[0075] In the context of this invention, the following terms have the following meanings:

[0076] The term "halogen atom" is understood to mean a chlorine atom, fluorine atom, bromine atom, or iodine atom, and specifically refers to a chlorine atom, fluorine atom, or bromine atom.

[0077] When used herein, "(C1~C x )alkyl" refers to C1~C xThis refers to primary, secondary, or tertiary monovalent saturated hydrocarbon radicals, such as (C1-C6) alkyl groups. Examples include, but are not limited to, methyl, ethyl, propyl, n-propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, isopentyl, hexyl, and isohexyl groups.

[0078] As used herein, "(C1-C3) alkanediyl" means a branched or linear divalent saturated hydrocarbon radical containing 1 to 3 carbon atoms, more particularly methylene, ethylene, or propylene, for example, linear propylene or isopropylene, where the alkanediyl may be substituted as will be apparent from the following description.

[0079] As used herein, "(C3-C8) cycloalkyl" means a saturated or partially unsaturated, unsubstituted or substituted cyclic saturated hydrocarbon having 3 to 8 carbon atoms. Examples include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and cyclooctyl.

[0080] As used herein, “(C3-C8) heterocycloalkyl group” means a (C3-C8) cycloalkyl group in which one or two of the carbon atoms are substituted with a heteroatom, such as an oxygen atom, a nitrogen atom, or a sulfur atom, more particularly an oxygen atom or a nitrogen atom. Such heterocycloalkyl groups may be saturated or partially saturated, unsubstituted or substituted. Examples include, but are not limited to, morpholinyl, piperazinyl, piperidinyl, pyrrolidinyl, azilidinyl, oxanyl, oxetanyl, tetrahydropyranil, morpholinyl, tetrahydrofuranil, oxypanyl, diazepanyl, dioxanyl, and tetrahydrothiopyranil, more particularly piperidinyl and piperazinyl, and even more particularly piperazinyl.

[0081] When used herein, "(C1~Cx )alkoxy is -O-(C1~C x ) Alkyl moiety or -O-(C3-C x ) refers to the cycloalkyl portion, where alkyl and cycloalkyl are as defined above, for example, (C1-C6) alkoxy. Examples include, but are not limited to, methoxy, ethoxy, 1-propoxy, 2-propoxy, cyclopropoxy, butoxy, tert-butoxy, and pentoxy.

[0082] "Spiro (C5~C 11 A "bicyclic ring" refers to two rings connected by a single common atom. Such spiro-dicyclic alkyls are commonly called "spiro(C5~C)". 11 Refer to "bicyclic alkyl group" and include 5 to 11 carbon atoms. In certain embodiments, one or more carbon atoms of the ring are substituted with heteroatoms, such as oxygen, nitrogen, or sulfur atoms, and more particularly with nitrogen atoms, for example, a spiro (C5-C 11 ) forms a bicyclic heteroalkyl group. Such a spiro-dicyclic ring may be unsubstituted or substituted, and in particular may be substituted with at least one (C1-C3) alkyl group, such as methyl. Examples include, but are not limited to, spiro[3.3]heptanyl, spiro[2.5]octanyl, and 7-azaspiro[3.5]nonanyl.

[0083] As used herein, "crosslinked (C6~C 10 A "cycloalkyl" group refers to a dicyclic or tricyclic compound in which the cyclic structure is cycloalkyl, the ring shares three or more atoms, and the bridge contains at least one atom, for example, one, two, or three atoms. Such a bridged cycloalkyl group may be substituted with one or more C1-C3 alkyl groups. Examples include, but are not limited to, adamantyl, 2,6,6-trimethylbicyclo[3.1.1]heptyl, 6,6-dimethylbicyclo[3.1.1]heptyl, bicyclo[3.1.1]heptyl, and 1,6,6-trimethylbicyclo[3.1.1]heptyl.

[0084] As used herein, "crosslinked (C6~C 10 A heterocycloalkyl group is defined as a bridged (C6~C) group in which one or more carbon atoms of the ring are substituted by one or more heteroatoms, such as oxygen, nitrogen, or sulfur atoms, more particularly, for example, nitrogen atoms. 10 This refers to cycloalkyl compounds. An example is quinuclidine-3-yl, but it is not limited to these.

[0085] A "condensed phenyl group" refers to a bicyclic radical that includes and may be substituted with a phenyl moiety. The condensed phenyl group may be condensed with a cycloalkyl or heterocycloalkyl group and bonded to the rest of the molecule by the phenyl moiety or by the cycloalkyl or heterocycloalkyl group. Examples include, but are not limited to, indanyl, acetylindolinyl, methylindazolyl, hydroxyindanyl, benzothiazolyl, indolyl, indazolyl, and methoxyindanyl.

[0086] When used herein, "(C5~C 11 A "heteroaryl group" refers to a monocyclic or bicyclic aromatic group, wherein at least one of the rings of the bicyclic aromatic group is aromatic and 1 to 3 ring carbon atoms are substituted with heteroatoms, such as nitrogen, oxygen, or sulfur atoms. Examples of heteroaryl groups include, but are not limited to, oxazole, isoxazole, pyridine, pyrimidine, pyridazine, triazine, pyrazine, oxadiazole, furan, pyrazole, thiazole, isothiazole, thiadiazole, imidazole, and triazole. In the framework of the present invention, the heteroaryl is preferably pyridine, imidazole, pyrazine, furan, thiazole, pyrazole, thiadiazole, pyridazine, and pyrimidine.

[0087] According to Hückel's law, an aromatic ring is a molecule that has 4n+2 π electrons.

[0088] When used in this specification, (C1~C x )Fluoroalkyl groups are defined herein as (C1~C) in which one or more fluorine atoms are substituted by hydrogen atoms. x ) refers to alkyl. In one embodiment, all hydrogen atoms are substituted with fluorine atoms to form a perfluoroalkyl group, such as trifluoromethyl.

[0089] When used in this specification, (C1~C x )Fluoroalkoxys are defined herein as (C1-C) in which one or more fluorine atoms are substituted for hydrogen atoms. x ) refers to an alkoxy group, such as trifluoromethoxy. In one embodiment, all hydrogen atoms are substituted with fluorine atoms to form a perfluoroalkoxy group, such as trifluoromethoxy.

[0090] In the context of this invention, the terms "aromatic ring" and "heteroaryl" encompass all positional isomers.

[0091] The nomenclature rules for the following compounds (1)–(216) were created using Accelrys Draw 4.1 SP1, in accordance with the principles of the International Union of Pure and Applied Chemistry. To avoid confusion, the symbols "(±)" were added to indicate racemic mixtures, and the prefixes "cis" and "trans" were also used to assign the relative stereochemistry of two adjacent chiral centers.

[0092] According to a preferred embodiment of the present invention, one of the following compounds of formula (I) or pharmaceutically acceptable salts thereof is selected: (1) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-(cyclopropylmethylamino)-1H-imidazole-5-one, (2) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-(cyclopropylamino)-1H-imidazole-5-one, (3) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-(cyclobutylamino)-1H-imidazole-5-one, (4) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-(cyclopentylamino)-1H-imidazole-5-one, (5) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-(cyclohexylmethylamino)-1H-imidazole-5-one, (6) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-(cyclohexylamino)-1H-imidazole-5-one, (7) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-(cycloheptylmethylamino)-1H-imidazole-5-one, (8) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-(cycloheptylamino)-1H-imidazole-5-one, (9) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-(cyclooctylamino)-1H-imidazole-5-one, (10) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[(3-hydroxy-2,2-dimethylpropyl)amino]-1H-imidazole-5-one, (11) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-(2-benzyloxyethylamino)-1H-imidazole-5-one, (12) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[cis-2-methylcyclohexyl]amino]-1H-imidazole-5-one, (13) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(1R)-1-cyclohexylethyl]amino]-1H-imidazole-5-one, (14) (4Z)-2-(1-adamantylmethylamino)-4-(1,3-benzothiazole-6-ylmethylene)-1H-imidazole-5-one, (15) (±)-(4Z)-2-[1-(1-adamantyl)ethylamino]-4-(1,3-benzothiazole-6-ylmethylene)-1H-imidazole-5-one, (16) (4Z)-2-(1-adamantylamino)-4-(1,3-benzothiazole-6-ylmethylene)-1H-imidazole-5-one, (17) (4Z)-2-(2-adamantylamino)-4-(1,3-benzothiazole-6-ylmethylene)-1H-imidazole-5-one, (18) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[3,5-dimethyl-1-adamantyl]amino]-1H-imidazole-5-one, (19) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[(trans-5-hydroxy-2-adamantyl)amino]-1H-imidazole-5-one, (20) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[(3-hydroxy-1-adamantyl)amino]-1H-imidazole-5-one, (21) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[(3-methoxy-1-adamantyl)amino]-1H-imidazole-5-one, (22) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(1R,2R,3R,5S)-2,6,6-trimethylnorpinan-3-yl]amino]-1H-imidazole-5-one, (23) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(1S,2S,3S,5R)-2,6,6-trimethylnorpinan-3-yl]amino]-1H-imidazole-5-one, (24) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(1R,2R,5R)-6,6-dimethylnorpinan-2-yl]methylamino]-1H-imidazole-5-one, (25) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-(spiro[2.5]octane-2-ylamino)-1H-imidazole-5-one, (26) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-(spiro[3.3]heptan-2-ylamino)-1H-imidazole-5-one, (27) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(2R)-1,7,7-trimethylnorboran-2-yl]amino]-1H-imidazole-5-one, (28) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-(norborane-2-ylamino)-1H-imidazole-5-one, (29) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(1R,2S,5R)-2-isopropyl-5-methylcyclohexyl]amino]-1H-imidazole-5-one, (30) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(1R)-1-(cyclohexylmethyl)-2-hydroxy-ethyl]amino]-1H-imidazole-5-one, (31) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(1R)-1-(cyclopentylmethyl)-2-hydroxy-ethyl]amino]-1H-imidazole-5-one, (32) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(1R)-1-(cyclobutylmethyl)-2-hydroxy-ethyl]amino]-1H-imidazole-5-one, (33) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(1R)-1-(cyclopropylmethyl)-2-hydroxy-ethyl]amino]-1H-imidazole-5-one, (34) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(1R)-1-(hydroxymethyl)-3-methyl-butyl]amino]-1H-imidazole-5-one, (35) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(1R)-1-(methoxymethyl)-3-methyl-butyl]amino]-1H-imidazole-5-one, (36) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(1S)-1-(hydroxymethyl)-3-methyl-butyl]amino]-1H-imidazole-5-one, (37) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(1S)-1-(methoxymethyl)-3-methyl-butyl]amino]-1H-imidazole-5-one, (38) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(1R)-1-(hydroxymethyl)propyl]amino]-1H-imidazole-5-one, (39) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(1S)-1-(hydroxymethyl)propyl]amino]-1H-imidazole-5-one, (40) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[1-(fluoromethyl)-3-methyl-butyl]amino]-1H-imidazole-5-one, (41) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[(1-cyclohexyl-2-hydroxyethyl)amino]-1H-imidazole-5-one, (42) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[(1-cyclohexyl-2-methoxyethyl)amino]-1H-imidazole-5-one, (43) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[(2-cyclohexyl-2-hydroxyethyl)amino]-1H-imidazole-5-one, (44) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[(2-cyclohexyl-2-methoxyethyl)amino]-1H-imidazole-5-one, (45) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[cis-2-hydroxycyclopentyl]amino]-1H-imidazole-5-one, (46) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[trans-2-hydroxycyclopentyl]amino]-1H-imidazole-5-one, (47) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[cis-2-methoxycyclopentyl]amino]-1H-imidazole-5-one, (48) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[trans-2-methoxycyclopentyl]amino]-1H-imidazole-5-one, (49) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[cis-2-hydroxycyclohexyl]amino]-1H-imidazole-5-one, (50) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[trans-2-hydroxycyclohexyl]amino]-1H-imidazole-5-one, (51) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(1R,2S)-2-hydroxycyclohexyl]amino]-1H-imidazole-5-one, (52) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(1S,2R)-2-hydroxycyclohexyl]amino]-1H-imidazole-5-one, (53) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(1R,2R)-2-hydroxycyclohexyl]amino]-1H-imidazole-5-one, (54) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(1S,2S)-2-hydroxycyclohexyl]amino]-1H-imidazole-5-one, (55) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[cis-3-hydroxycyclohexyl]amino]-1H-imidazole-5-one, (56) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[trans-3-hydroxycyclohexyl]amino]-1H-imidazole-5-one, (57) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[(trans-4-hydroxycyclohexyl)amino]-1H-imidazole-5-one, (58) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[cis-2-methoxycyclohexyl]amino]-1H-imidazole-5-one, (59) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[trans-2-methoxycyclohexyl]amino]-1H-imidazole-5-one, (60) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[(trans-4-methoxycyclohexyl)amino]-1H-imidazole-5-one, (61) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[cis-2-hydroxycycloheptyl]amino]-1H-imidazole-5-one, (62) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[trans-2-hydroxycycloheptyl]amino]-1H-imidazole-5-one, (63) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(1R,2R)-2-hydroxycycloheptyl]amino]-1H-imidazole-5-one, (64) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(1S,2S)-2-hydroxycycloheptyl]amino]-1H-imidazole-5-one, (65) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[cis-3-hydroxycycloheptyl]amino]-1H-imidazole-5-one, (66) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[trans-3-hydroxycycloheptyl]amino]-1H-imidazole-5-one, (67) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[cis-2-methoxycycloheptyl]amino]-1H-imidazole-5-one, (68) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[trans-2-methoxycycloheptyl]amino]-1H-imidazole-5-one, (69) (2S)-2-[[(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-5-oxo-1H-imidazole-2-yl]amino]-3-methylbutanoate methyl (70) (2S)-2-[[(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-5-oxo-1H-imidazole-2-yl]amino]methyl propanoate (71) (2S)-2-[[(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-5-oxo-1H-imidazole-2-yl]amino]-4-methylpentanoate methyl, (72) (2R)-2-[[(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-5-oxo-1H-imidazole-2-yl]amino]-4-methylpentanoate methyl, (73) (2S)-2-[[(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-5-oxo-1H-imidazole-2-yl]amino]-3-hydroxybutanoate methyl, (74) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-(benzylamino)-1H-imidazole-5-one, (75) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-(indan-2-ylamino)-1H-imidazole-5-one, (76) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[(3,4-dimethylphenyl)methylamino]-1H-imidazole-5-one, (77) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[(2,4-dimethylphenyl)methylamino]-1H-imidazole-5-one, (78) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[2-(trifluoromethyl)phenyl]methylamino]-1H-imidazole-5-one, (79) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[2-(trifluoromethoxy)phenyl]methylamino]-1H-imidazole-5-one, (80) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[cis-2-hydroxyindan-1-yl]amino]-1H-imidazole-5-one, (81) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[trans-2-hydroxyindan-1-yl]amino]-1H-imidazole-5-one, (82) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(1R,2R)-2-hydroxyindan-1-yl]amino]-1H-imidazole-5-one, (83) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(1S,2S)-2-hydroxyindan-1-yl]amino]-1H-imidazole-5-one, (84) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[cis-2-methoxyindan-1-yl]amino]-1H-imidazole-5-one, (85) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[trans-2-methoxyindan-1-yl]amino]-1H-imidazole-5-one, (86) (2S)-2-[[(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-5-oxo-1H-imidazole-2-yl]amino]-3-phenyl-propanoate methyl (87) (2R)-2-[[(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-5-oxo-1H-imidazole-2-yl]amino]-3-phenyl-propanoate methyl (88) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[(2-fluoro-1-phenyl-ethyl)amino]-1H-imidazole-5-one, (89) (±)-(4Z)-2-[(2-amino-1-phenyl-ethyl)amino]-4-(1,3-benzothiazole-6-ylmethylene)-1H-imidazole-5-one dihydrochloride, (90) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[2-(methylamino)-1-phenylethyl]amino]-1H-imidazole-5-one dihydrochloride, (91) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[2-(dimethylamino)-1-phenyl-ethyl]amino]-1H-imidazole-5-one, (92) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[(1-benzyl-2-hydroxyethyl)amino]-1H-imidazole-5-one, (93) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(1R)-1-benzyl-2-hydroxyethyl]amino]-1H-imidazole-5-one, (94) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[(1-benzyl-2-methoxyethyl)amino]-1H-imidazole-5-one, (95) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[(2-hydroxy-1-phenylethyl)amino]-1H-imidazole-5-one, (96) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(1R)-2-hydroxy-1-phenylethyl]amino]-1H-imidazole-5-one, (97) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(1S)-2-hydroxy-1-phenylethyl]amino]-1H-imidazole-5-one, (98) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[(2-methoxy-1-phenylethyl)amino]-1H-imidazole-5-one, (99) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[(2-hydroxy-2-phenylethyl)amino]-1H-imidazole-5-one, (100) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[(2-methoxy-2-phenylethyl)amino]-1H-imidazole-5-one, (101) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[(2-hydroxy-3-phenylpropyl)amino]-1H-imidazole-5-one, (102) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[(2-methoxy-3-phenylpropyl)amino]-1H-imidazole-5-one, (103) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[(5-methylpyrazine-2-yl)methylamino]-1H-imidazole-5-one, (104) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-(2-pyridylmethylamino)-1H-imidazole-5-one, (105) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-(3-pyridylmethylamino)-1H-imidazole-5-one, (106) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-(4-pyridylmethylamino)-1H-imidazole-5-one, (107) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[(5-methyl-2-furyl)methylamino]-1H-imidazole-5-one, (108) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[(4-methylthiazole-2-yl)methylamino]-1H-imidazole-5-one, (109) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-(3-imidazole-1-ylpropylamino)-1H-imidazole-5-one, (110) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[2-(2-pyridyl)ethylamino]-1H-imidazole-5-one, (111) (4Z)-2-(1,3-benzothiazole-2-ylmethylamino)-4-(1,3-benzothiazole-6-ylmethylene)-1H-imidazole-5-one, (112) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[(1-methyl-4-piperidyl)methylamino]-1H-imidazole-5-one, (113) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-(tetrahydropyran-4-ylmethylamino)-1H-imidazole-5-one, (114) 4-[[[(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-5-oxo-1H-imidazole-2-yl]amino]methyl]piperidine-1-carboxylate Tert-butyl, (115) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[(7-methyl-7-azaspiro[3.5]nonan-2-yl)amino]-1H-imidazole-5-one, (116) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-(3-fluoro-4-methyl-anilino)-1H-imidazole-5-one, (117) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-(4-fluoroanilino)-1H-imidazole-5-one, (118) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-(4-hexylanilino)-1H-imidazole-5-one, (119) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[4-(4-methylpiperazine-1-yl)anilino]-1H-imidazole-5-one, (120) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[3-(difluoromethoxy)anilino]-1H-imidazole-5-one, (121) (4Z)-2-[(1-acetyldindrin-6-yl)amino]-4-(1,3-benzothiazole-6-ylmethylene)-1H-imidazole-5-one, (122) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[3-(trifluoromethyl)anilino]-1H-imidazole-5-one, (123) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-(indan-5-ylamino)-1H-imidazole-5-one, (124) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-(4-morpholinoanilino)-1H-imidazole-5-one, (125) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[(1-methylindazole-7-yl)amino]-1H-imidazole-5-one, (126) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-(pyrimidine-2-ylamino)-1H-imidazole-5-one, (127) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-(2-pyridylamino)-1H-imidazole-5-one, (128) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[(1-methylpyrazole-3-yl)amino]-1H-imidazole-5-one, (129) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[(2-methoxy-6-methyl-3-pyridyl)amino]-1H-imidazole-5-one, (130) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-(pyrimidine-5-ylamino)-1H-imidazole-5-one, (131) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-(3-pyridylamino)-1H-imidazole-5-one, (132) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-(1,3,4-thiadiazole-2-ylamino)-1H-imidazole-5-one, (133) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[5-(4-methylpiperazine-1-yl)-2-pyridyl]amino]-1H-imidazole-5-one, (134) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[6-(4-methylpiperazine-1-yl)-3-pyridyl]amino]-1H-imidazole-5-one, (135) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[2-(4-methylpiperazine-1-yl)pyrimidine-5-yl]amino]-1H-imidazole-5-one, (136) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[5-(4-methylpiperazine-1-yl)pyrimidine-2-yl]amino]-1H-imidazole-5-one, (137) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[5-(4-methylpiperazine-1-yl)pyrazine-2-yl]amino]-1H-imidazole-5-one, (138) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[6-(4-methylpiperazine-1-yl)pyridazin-3-yl]amino]-1H-imidazole-5-one, (139) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-(tetrahydropyran-4-ylamino)-1H-imidazole-5-one, (140) 4-[[(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-5-oxo-1H-imidazole-2-yl]amino]piperidine-1-carboxylate Tert-butyl, (141) 4-[[(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-5-oxo-1H-imidazole-2-yl]amino]piperidine-1-carboxylate ethyl, (142) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[(1-methyl-4-piperidyl)amino]-1H-imidazole-5-one, (143) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[(1-methyl-3-piperidyl)amino]-1H-imidazole-5-one, (144) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-(oxetane-3-ylamino)-1H-imidazole-5-one, (145) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(3R)-tetrahydrofuran-3-yl]amino]-1H-imidazole-5-one, (146) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(3S)-tetrahydrofuran-3-yl]amino]-1H-imidazole-5-one, (147) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(3R)-tetrahydropyran-3-yl]amino]-1H-imidazole-5-one, (148) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(3S)-tetrahydropyran-3-yl]amino]-1H-imidazole-5-one, (149) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[(6,6-dimethyltetrahydropyran-3-yl)amino]-1H-imidazole-5-one, (149A) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(3R) / (3S)-6,6-dimethyltetrahydropyran-3-yl]amino]-1H-imidazole-5-one, (149B) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(3R) / (3S)-6,6-dimethyltetrahydropyran-3-yl]amino]-1H-imidazole-5-one, (150) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(3R,4R)-4-hydroxytetrahydropyran-3-yl]amino]-1H-imidazole-5-one, (151) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-(oxepan-3-ylamino)-1H-imidazole-5-one, (152) (±)-3-[[(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-5-oxo-1H-imidazole-2-yl]amino]piperidine-2-one, (153) (3S)-3-[[(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-5-oxo-1H-imidazole-2-yl]amino]piperidine-2-one, (154) (5S)-5-[[(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-5-oxo-1H-imidazole-2-yl]amino]piperidine-2-one, (155) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[(3,3-difluorocyclopentyl)amino]-1H-imidazole-5-one, (156) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[(4,4-difluorocyclohexyl)amino]-1H-imidazole-5-one, (157) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[(3,3-difluorocyclohexyl)amino]-1H-imidazole-5-one, (158) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[(2,2-difluorocyclohexyl)amino]-1H-imidazole-5-one, (159) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[(3,3-difluorocycloheptyl)amino]-1H-imidazole-5-one, (160) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(1R)-1-(fluoromethyl)-3-methyl-butyl]amino]-1H-imidazole-5-one, (161) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(1S)-1-(fluoromethyl)-3-methyl-butyl]amino]-1H-imidazole-5-one, (162) [3-[[(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-5-oxo-1H-imidazole-2-yl]amino]-1-adamantyl]acetate, (163) [3-[[(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-5-oxo-1H-imidazole-2-yl]amino]-1-adamantyl]2,2-dimethylpropanoate, (164) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(1R,2R)-2-methoxycyclopentyl]amino]-1H-imidazole-5-one, (165) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(1S,2S)-2-methoxycyclopentyl]amino]-1H-imidazole-5-one, (166) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(1R,2R)-2-methoxycyclohexyl]amino]-1H-imidazole-5-one, (167) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(1S,2S)-2-methoxycyclohexyl]amino]-1H-imidazole-5-one, (168) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[cis-3-methoxycyclohexyl]amino]-1H-imidazole-5-one, (169) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[trans-3-methoxycyclohexyl]amino]-1H-imidazole-5-one, (169A) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(1R,3R) / (1S,3S)-3-methoxycyclohexyl]amino]-1H-imidazole-5-one, (169B) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(1R,3R) / (1S,3S)-3-methoxycyclohexyl]amino]-1H-imidazole-5-one, (170) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[cis-4-hydroxycycloheptyl]amino]-1H-imidazole-5-one, (171) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[trans-4-hydroxycycloheptyl]amino]-1H-imidazole-5-one, (171A) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(1R,4R) / (1S,4S)-4-hydroxycycloheptyl]amino]-1H-imidazole-5-one, (171B) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(1R,4R) / (1S,4S)-4-hydroxycycloheptyl]amino]-1H-imidazole-5-one, (172) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[cis-3-methoxycycloheptyl]amino]-1H-imidazole-5-one, (173) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[trans-3-methoxycycloheptyl]amino]-1H-imidazole-5-one, (174) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[cis-4-methoxycycloheptyl]amino]-1H-imidazole-5-one, (175) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[trans-4-methoxycycloheptyl]amino]-1H-imidazole-5-one, (176) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(1R)-2-methoxy-1-phenylethyl]amino]-1H-imidazole-5-one, (177) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(1S)-2-methoxy-1-phenylethyl]amino]-1H-imidazole-5-one, (178) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(2R)-2-hydroxy-2-phenylethyl]amino]-1H-imidazole-5-one, (179) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(2S)-2-hydroxy-2-phenylethyl]amino]-1H-imidazole-5-one, (180) (4Z)-2-[[(1R)-2-amino-1-phenylethyl]amino]-4-(1,3-benzothiazole-6-ylmethylene)-1H-imidazole-5-one dihydrochloride, (181) (4Z)-2-[[(1S)-2-Amino-1-phenyl-ethyl]amino]-4-(1,3-benzothiazol-6-ylmethylene)-1H-imidazol-5-one dihydrochloride, (182) (4Z)-4-(1,3-Benzothiazol-6-ylmethylene)-2-[[(3R)-quinucidin-3-yl]amino]-1H-imidazol-5-one, (183) (4Z)-4-(1,3-Benzothiazol-6-ylmethylene)-2-[[(3S)-quinucidin-3-yl]amino]-1H-imidazol-5-one, (184) (±)-(4Z)-4-(1,3-Benzothiazol-6-ylmethylene)-2-(tetrahydrothiopyran-3-ylamino)-1H-imidazol-5-one, (185) (±)-(4Z)-4-(1,3-Benzothiazol-6-ylmethylene)-2-(1,4-dioxepan-6-ylamino)-1H-imidazol-5-one, (186) (±)-(4Z)-4-(1,3-Benzothiazol-6-ylmethylene)-2-[(2-oxopyrrolidin-3-yl)amino]-1H-imidazol-5-one, (187) (±)-(4Z)-4-(1,3-Benzothiazol-6-ylmethylene)-2-[(1-methyl-2-oxo-pyrrolidin-3-yl)amino]-1H-imidazol-5-one, (188) (±)-(4Z)-4-(1,3-Benzothiazol-6-ylmethylene)-2-[(4,4-dimethyl-2-oxo-pyrrolidin-3-yl)amino]-1H-imidazol-5-one, (189) (3R)-3-[[(4Z)-4-(1,3-Benzothiazol-6-ylmethylene)-5-oxo-1H-imidazol-2-yl]amino]piperidin-2-one, (190) (±)-3-[[(4Z)-4-(1,3-Benzothiazol-6-ylmethylene)-5-oxo-1H-imidazol-2-yl]amino]-1-methyl-piperidin-2-one, (191) (±)-(4Z)-4-(1,3-Benzothiazol-6-ylmethylene)-2-[(3-methyl-2-oxo-pyrrolidin-3-yl)amino]-1H-imidazol-5-one, (192) (±)-(4Z)-4-(1,3-Benzothiazol-6-ylmethylene)-2-[(1,3-dimethyl-2-oxo-pyrrolidin-3-yl)amino]-1H-imidazol-5-one, (192A) (4Z)-4-(1,3-Benzothiazol-6-ylmethylene)-2-[[(3R) / (3S)-1,3-dimethyl-2-oxo-pyrrolidin-3-yl]amino]-1H-imidazol-5-one, (192B) (4Z)-4-(1,3-Benzothiazol-6-ylmethylene)-2-[[(3R) / (3S)-1,3-dimethyl-2-oxo-pyrrolidin-3-yl]amino]-1H-imidazol-5-one, (193) (4Z)-4-(1,3-Benzothiazol-6-ylmethylene)-2-[[(3S,4S)-4-hydroxytetrahydropyran-3-yl]amino]-1H-imidazol-5-one, (194) (4Z)-2-(3-Noradamantylamino)-4-(1,3-benzothiazol-6-ylmethylene)-1H-imidazol-5-one, (195) [3-[[(4Z)-4-(1,3-Benzothiazol-6-ylmethylene)-5-oxo-1H-imidazol-2-yl]amino]-1-adamantyl] N-tert-butylcarbamate, (196) (4Z)-4-(1,3-Benzothiazol-6-ylmethylene)-2-[(3-fluoro-1-adamantyl)amino]-1H-imidazol-5-one, (197) (4Z)-4-(1,3-Benzothiazol-6-ylmethylene)-2-[[(1R)-1-(tert-butoxymethyl)-3-methyl-butyl]amino]-1H-imidazol-5-one, (198) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(1R)-2-tert-butoxy-1-phenylethyl]amino]-1H-imidazole-5-one, (199) N-[3-[[(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-5-oxo-1H-imidazole-2-yl]amino]-1-adamantyl]acetamide, (200) N-[3-[[(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-5-oxo-1H-imidazole-2-yl]amino]-1-adamantyl]cyclopropanecarboxamide, (201) N-[3-[[(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-5-oxo-1H-imidazole-2-yl]amino]-1-adamantyl]methanesulfonamide, (202) N-[3-[[(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-5-oxo-1H-imidazole-2-yl]amino]-1-adamantyl]cyclopropanesulfonamide, (203) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[3-(dimethylamino)-1-adamantyl]amino]-1H-imidazole-5-one, (204) 2-[[(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-5-oxo-1H-imidazole-2-yl]amino]adamantane-2-carboxylate methyl, (205) (4Z)-2-(cyclohexylamino)-4-[(2-methyl-1,3-benzothiazole-6-yl)methylene]-1H-imidazole-5-one, (206) (4Z)-2-(cycloheptylamino)-4-[(2-methyl-1,3-benzothiazole-6-yl)methylene]-1H-imidazole-5-one, (207) (4Z)-2-[[(1R)-1-(methoxymethyl)-3-methyl-butyl]amino]-4-[(2-methyl-1,3-benzothiazole-6-yl)methylene]-1H-imidazole-5-one, (208) (4Z)-2-[[(1R)-2-methoxy-1-phenylethyl]amino]-4-[(2-methyl-1,3-benzothiazole-6-yl)methylene]-1H-imidazole-5-one, (209) (4Z)-2-(1-adamantylamino)-4-[(2-methyl-1,3-benzothiazole-6-yl)methylene]-1H-imidazole-5-one, and (210) (4Z)-2-[(3-hydroxy-1-adamantyl)amino]-4-[(2-methyl-1,3-benzothiazole-6-yl)methylene]-1H-imidazole-5-one, (211) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[(3,5-dihydroxy-1-adamantyl)amino]-1H-imidazole-5-one, (212) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[(3,5,7-trifluoro-1-adamantyl)amino]-1H-imidazole-5-one, (213) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(1R)-1-(ethoxymethyl)-3-methyl-butyl]amino]-1H-imidazole-5-one, (214) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(1R)-1-(benzyloxymethyl)-3-methyl-butyl]amino]-1H-imidazole-5-one, (215) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(1R)-1-[(4-fluorophenyl)methoxymethyl]-3-methyl-butyl]amino]-1H-imidazole-5-one, (216) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(1R)-1-(cyclopropoxymethyl)-3-methyl-butyl]amino]-1H-imidazole-5-one.

[0093] According to a more preferred embodiment of the present invention, the compound of formula (I) is compound (4), (5), (6), (7), (8), (9), (12), (13), (14), (16), (17), (18), (19), (20), (21), (22), (23), (24), (25), (27), (28), (30), (31), (32), (34), (35), (36), (38), (40), (41), (42), (43), (44), (46), (48), ( 49), (50), (51), (53), (55), (56), (57), (59), (60), (61), (62), (63), (64), (65), (66), (67), (68), (69), (70), (71), (72), (73), (74), (77), (78), (80), (81), (83), (85), (86), (89), (90), (92), (93), (94), (95), (96), (97), (98), (99), (104), ( 106), (108), (117), (119), (125), (127), (128), (135), (146), (147), (148), (149), (149A), (149B), (150), (151), (154), (155), (157), (158), (159), (160), (161), (162), (164), (165), (167), (168), (169), (169A), (169B), (170), (171), (171A Selected from the group consisting of (171B), (172), (173), (174), (175), (176), (178), (179), (180), (181), (182), (184), (185), (191), (192), (192A), (194), (195), (196), (197), (198), (199), (200), (201), (203), (204), (208), (209), (210) and pharmaceutically acceptable salts thereof.

[0094] According to a more preferred embodiment of the present invention, the compound of formula (I) is compound (6), (7), (8), (9), (12), (14), (16), (17), (19), (20), (21), (22), (24), (25), (27), (28), (31), (32), (34), (35), (36), (38), (40), (41), (43), (44), (46), (48), ( 49), (51), (53), (55), (56), (57), (59), (61), (62), (63), (64), (65), (66), (67), (68), (69), (74), (77), (78), (81), (83), (85), (86), (89), (90), (92), (93), (95), (96), (97), (98), (99), (108), (119), (1 25), (146), (148), (149), (149A), (149B), (150), (151), (155), (157), (158), (159), (160), (161), (1 62), (164), (165), (167), (168), (169), (169A), (169B), (170), (171), (171A), (171B), (172), (173), Selected from the group consisting of (174), (175), (176), (178), (179), (180), (181), (182), (184), (185), (191), (192), (192A), (194), (195), (196), (197), (198), (199), (200), (201), (203), (204), (208) and pharmaceutically acceptable salts thereof.

[0095] According to a more preferred embodiment of the present invention, the compound of formula (I) is compound (9), (16), (17), (19), (20), (21), (22), (25), (27), (34), (35), (40), (48), (61), (65), (66), (78), (81), (83), (89), (95), (96), (97), (99), (158), (159), (160), (162), (169), (172), (173), (175), (176), (184), (194), (195), (196), (199), (200), (201), (203), (210) Selected from the group consisting of and pharmaceutically acceptable salts thereof.

[0096] According to an alternative embodiment of the present invention, the compound of formula (I) is compound (1), (3), (4), (5), (6), (7), (8), (9), (10), (12), (13), (14), (16), (17), (19), (20), (21), (22), (23), (24), (25), (26), (27), (28), (30), (31), (32), (33), (34), (35), (36), (37), (38), (39), (40), (41), (42), (43), (44), (45), (46), (47), (48), (49), (50), ( 51), (53), (55), (56), (57), (58), (59), (60), (61), (62), (63), (64), (65), (66), (67), (68), (69), (70), (71), (72), (73), (74), (75), (76), (77), ( 78), (79), (80), (81), (82), (83), (85), (86), (88), (89), (90), (92), (93), (94), (95), (96), (97), (98), (99), (100), (101), (102), (103), (104), ( 105), (106), (107), (108), (109), (110), (111), (113), (117), (119), (120), (121), (126), (127), (128), (129), (130), (131), (132), (135), (137) , (139), (141), (144), (145), (146), (147), (148), (149), (149A), (149B) , (150), (151), (154), (155), (156), (157), (158), (159), (160), (161), (1 62), (163), (164), (165), (166), (167), (168), (169), (169A), (169B), (1 70), (171), (171A), (171B), (172), (173), (174), (175), (176), (178), (17 9), (180), (181), (182), (183), (184), (185), (191), (192), (192A), (192 B), (194), (195), (196), (197), (198), (199), (200), (201), (203), (208),Selected from the group consisting of (209) and (210) and their pharmaceutically acceptable salts.

[0097] According to a preferred embodiment of the present invention, the compound of formula (I) is compound (1), (4), (5), (6), (7), (8), (9), (10), (12), (13), (14), (16), (17), (19), (20), (21), (22), (23), (24), (25), (26), (27), (28), (30), (31), (32), (33), (34), (35), (36), (38), (40), (41), (43), (44), (46), (48), (49), (51), (53 ), (55), (56), (57), (59), (61), (62), (63), (64), (65), (66), (67), (68), (69), (70), (71), (73), (74), (76), (77), (78), (79), (80), (81), (82), (83), (85), (86), (88), (89), (90), (92), (93), (94), (95), (96), (97), (98), (99), (100), (101), (102), (104), (105), (106), (108), (109), (113), (117), (119), (127), (128), (130), (131), (135), (139), (141), (146), (147), (148), (149), (149A), (1 49B), (150), (151), (155), (156), (157), (158), (159), (160), (161), (162), (163), (164), (165), (166), (167), (168), (169), (169) Selected from the group consisting of A), (169B), (170), (171), (171A), (171B), (172), (173), (174), (175), (176), (178), (179), (180), (181), (182), (183), (184), (185), (191), (192), (192A), (192B), (194), (195), (196), (198), (199), (200), (201), (203), (210) and pharmaceutically acceptable salts thereof.

[0098] According to a more preferred embodiment of the present invention, the compound of formula (I) is selected from the group consisting of compounds (9), (16), (19), (20), (21), (35), (48), (61), (73), (78), (81), (95), (96), (155), (159), (160), (161), (169), (169A), (171A), (176), (184), (196), (199), (200), (201), (203), (210) and pharmaceutically acceptable salts thereof.

[0099] According to further embodiments of the present invention, the compound of formula (I) is compound (7), (8), (9), (10), (12), (16), (17), (19), (20), (21), (23), (25), (26), (28), (32), (33), (34), (35), (40), (41), (43), (44), (46), (48), (55), (56 ), (57), (59), (61), (62), (63), (65), (66), (67), (68), (69), (70), (73), (77), (78), (81), (83), (88), (89), (90), (95), (96), (97), (98), (99), (100), (101), (102), (104), (105), (106 ), (117), (119), (127), (131), (139), (148), (149), (149B), (151), (155), (156), (157), (1 58), (159, (160), (161), (164), (165), (167), (169), (169A), (169B), (170), (171), (171A), Selected from the group consisting of (171B), (172), (173), (176), (178), (179), (180), (181), (184), (185), (191), (192), (192A), (194), (196), (198), (199), (200), (201), (203), (210) and pharmaceutically acceptable salts thereof.

[0100] The group of compounds defined by the list of compounds identified through Tables 4A to 4F in Example 4 below, and specifically identified as the most potent kinase inhibitors and multi-target kinase inhibitors, also forms part of the present invention.

[0101] In other words, the subject matter of the present invention relates to any one of the compounds of formula (I) defined above or any pharmaceutically acceptable salt thereof, or to any one of the compounds (1) to (216) or any pharmaceutically acceptable salt thereof, for use as a pharmaceutical.

[0102] "The pharmaceutically acceptable salt" refers to a salt formed with an acid, such as an acid addition salt formed with an inorganic acid, such as hydrochloric acid or hydrobromic acid, and an acid addition salt formed with an organic acid, such as acetic acid, tartaric acid, or succinic acid.

[0103] Suitable physiologically acceptable acid addition salts of the compound of formula (I) include hydrobromide, tartrate, hydrochloride, succinate, and acetate.

[0104] The compound of formula (I), and any of compounds (1) to (216), or any pharmaceutically acceptable salt thereof, may form solvates or hydrates, and the present invention encompasses all such solvates and hydrates.

[0105] The terms "hydrate" and "solvate" simply mean that compound (I) according to the present invention can be in the form of a hydrate or solvate, i.e., it is bound to or associated with one or more water or solvent molecules. This is merely a chemical characteristic of such a compound and can be applied to all organic compounds of this kind.

[0106] The compounds of formula (I) can contain one or more asymmetric carbon atoms. Therefore, the compounds of formula (I) can exist in the form of enantiomers or diastereoisomers. These enantiomers, diastereoisomers and their mixtures (including racemic mixtures) are included within the scope of the present invention.

[0107] The compounds of the present invention can be prepared by conventional methods of organic synthesis carried out by those skilled in the art. The general reaction sequences outlined below represent general methods useful for preparing the compounds of the present invention and are not meant to limit their scope or utility.

[0108]

Table 1-1

[0109] The compounds of general formula (I) can be prepared according to Scheme 1 below.

Chemical formula

[0110] The synthesis of the compounds according to the present invention is based on the functionalization of the compounds of formula (II) with an amine of formula R 1 NH2 (where R 1 is as defined above), according to the general protocol 3 (GP3: general protocol 3) described hereinafter in this specification.

[0111] According to GP3, the compounds of formula (II) may be placed in an aprotic solvent, such as THF or dioxane or a mixture of both. The formula R 1An NH2 amine may be added, for example, in a molar ratio of 2 to 6, particularly 4, relative to the compound of formula (II). The reaction mixture may be placed in a sealed tube and receive energy, for example, from a heating block or microwave. After the reaction is complete, the mixture may be returned to room temperature.

[0112] In one embodiment designated GP3-A, the reaction mixture may be stirred at a temperature of -10°C to 10°C, for example at 0°C, for 30 minutes to 2 hours, for example, 1 hour. Depending on the state of the obtained product (solid, precipitate), purification methods well known to those skilled in the art, such as filtration, washing, grinding, vacuum drying, flash chromatography, precipitation, and reflux, may be performed.

[0113] In one embodiment, named GP3-B, in which no product precipitated, the reaction mixture may be concentrated, particularly under vacuum, and purified, particularly by flash chromatography. The second purification step may be carried out by a purification method selected particularly from reprecipitation, grinding, and recrystallization.

[0114] In another embodiment, named GP3-C, in which no product precipitates, the reaction mixture may be concentrated, particularly under vacuum, and the resulting crude product may be purified by grinding in a protic polar solvent, such as ethanol. This grinding may be carried out at a temperature of 20–100°C, particularly at room temperature. The second purification step may be carried out by a purification method selected particularly from reprecipitation, grinding, and recrystallization.

[0115] The compound of formula (II) defined above can be obtained by the S-alkylation of the compound of formula (III) shown below. Here, R 2 As defined above, Alk is (C1-C5) alkyl.

[0116] According to the general protocol GP2, the compound of formula (III) can be placed in a polar aprotic solvent, such as dimethylformamide (DMF). Then, an alkyl halide of formula Alk-Hal (where Hal is a halide, such as iodine or bromine) can be added dropwise in the presence of an inorganic base, such as K2CO3, in a molar ratio of, for example, 0.75 to 1.50, especially 1.05, with respect to the compound of formula (III), and in a molar ratio of, for example, 0.7 to 1.5, especially 1, with respect to the compound of formula (III). The reaction mixture may be stirred while the alkyl halide is added.

[0117] In certain embodiments, the resulting mixture may then be stirred at room temperature for, for example, 8 to 16 hours, particularly 12 hours.

[0118] In other embodiments, the resulting mixture may be stirred for, for example, 2 to 8 hours, particularly 6 hours, at a temperature of -10°C to 10°C, particularly at 0°C.

[0119] R 2 From the compound of formula (IV) as defined above, the compound of formula (III) as defined above can be obtained according to the general protocol GP1.

[0120] According to GP1, the compound of formula (IV) may be placed in a protic solvent, such as ethanol, in the presence of 2-thiohydantoin in a molar ratio of, for example, 0.85 to 1.15, particularly 1, relative to the compound of formula (IV); in the presence of an organic base, such as piperidine, in a molar ratio of, for example, 0.85 to 1.15, particularly 1, relative to the compound of formula (II); or in the presence of an organic acid, such as acetic acid, in a molar ratio of, for example, 0.85 to 1.15, particularly 1, relative to the compound of formula (IV). The reaction mixture may be placed in a sealed tube, stirred, and heated, for example, at a temperature of 60°C to 130°C, particularly 80°C, for 10 to 100 minutes, particularly 15 to 90 minutes. The reaction mixture may be irradiated, for example, with microwaves.

[0121] Accordingly, the present invention further relates to a synthesis method for producing a novel compound of formula (I) as defined above, comprising at least the step of substituting a compound of formula (II) with a primary amine. The present invention relates to a synthesis method for producing any of the compounds of formula (I) as defined above or a pharmaceutically acceptable salt thereof, or any of the compounds (1) to (216) as defined above or a pharmaceutically acceptable salt thereof, wherein the compound of formula (II) below is substituted with formula R 1 NH2(here, R 1 and R 2 The present invention relates to the synthesis method comprising at least a step of coupling with an amine (as defined above). [ka]

[0122] The present invention further relates to a synthetic intermediate of the following formula (II). [ka] Here, Alk is an (C1-C5) alkyl group, and in particular Alk is selected from the group consisting of ethyl and methyl, and R 2 This is as defined above.

[0123] The chemical structures, analytical data, and spectroscopic data of several compounds of formula (I) of the present invention are shown in Tables 2 and 3 below, respectively.

[0124] The reactions were carried out under an inert argon atmosphere using oven-dried glassware. Unless otherwise noted, all reagent-grade chemicals and solvents were obtained from commercial suppliers and used as received. The reactions were monitored by thin-layer chromatography using silica gel 60 F254 pre-coated aluminum plates (0.25 mm). Visualization was performed under UV light and at 254 nm or 312 nm, or with appropriate TLC staining, including but not limited to the above TLC stainings, such as phosphomolybdic acid, KMnO4, ninhydrin, CAM, vanillin, and p-anisaldehyde.

[0125] Microwave experiment, Anton Paar Monowave 400 登録商標 The experiment was conducted in a microwave reactor. The experiment took place in a monomode cavity with an output range of 0–850 W, allowing the pressurized reaction (0–30 bar) to be carried out in a sealed glass vial (4–30 mL) equipped with a snap cap and silicon septum. The temperature (0–300 °C) was monitored by a non-contact infrared sensor and calibrated with a ruby ​​thermometer. Temperature, pressure, and output profiles were edited and monitored via a touchscreen control panel. The times indicated in various protocols are measured when the mixture reached the programmed temperature after a 3-minute ramp period.

[0126] Chromatographic purification of the compound was performed using an automated instrument, an Interchim Puriflash XS420, equipped with a 30 μm spherical silica-packed prepacked column as the stationary phase.

[0127] Some of the compounds of the present invention are described in Table 2 below, along with their structures, but these are merely examples and do not limit the scope of the present invention.

[0128] [Table 2] JPEG0007842031000011.jpg231170JPEG0007842031000012.jpg228170JPEG0007842 031000013.jpg241170JPEG0007842031000014.jpg239170JPEG0007842031000015.j pg239170JPEG0007842031000016.jpg227170JPEG0007842031000017.jpg235170JPE G0007842031000018.jpg233170JPEG0007842031000019.jpg238170JPEG0007842031 000020.jpg235170JPEG0007842031000021.jpg241170JPEG0007842031000022.jpg2 28170JPEG0007842031000023.jpg234170JPEG0007842031000024.jpg238170JPEG00 07842031000025.jpg227170JPEG0007842031000026.jpg237170JPEG0007842031000 027.jpg239170JPEG0007842031000028.jpg241170JPEG0007842031000029.jpg79170

[0129] Table 3 below lists the analytical and spectral data for the compounds introduced in Table 2.

[0130] 1 1H NMR analysis (400 or 500 MHz) and 13 ¹³C NMR spectra (10¹ MHz) were recorded using a Bruker ULTRASHIELD 500 or 400 spectrometer. Spectrum processing and analysis were performed using MestReNova. The data are presented in the following order: chemical shift, multiplicity, proton number, and coupling constant J in ppm relative to the internal solvent signal.

[0131] Reverse-phase HPLC / MS analysis was performed on a Waters Alliance 2795 HPLC equipped with an autosampler, in-line membrane degasser, column oven (T=45°C), UV detector, and ZQ quadrupole mass detector operating in ionization electrospray mode. The compound (0.1–0.3 mg) was dissolved in a minimum amount of DMSO and acetonitrile (V 合計 (=1 mL) was added. Standard analytical parameters: Flow rate: 1 mL / min, V 注入量 = 5 μL. Acidic conditions: Waters Select CSH 18 column (3.5 μm, 2.1 x 50 mm). Gradient: (H2O + 0.04% v / v HCOOH (10 mM)) / ACN from 95 / 5 to 0 / 100 over 18.5 minutes. Alkaline conditions: Waters Xbridge C18 column (3.5 μm, 2.1 x 50 mm). Gradient: (H2O + 0.06% v / v NH4) 3(水性) (10mM)) / ACN 95 / 5 to 0 / 100 in 18.5 minutes.

[0132] Enantiomers of the racemic products (149), (169), (171), and (192) were separated by preparative chiral SFC by Reach Separations (Bio City, Pennyfoot St., Nottingham, NG1 1GF, UK. www.reachseparations.com). Briefly, the racemic products were solubilized in MeOH and purified by preparative SFC (conditions in Table 3). The combined fraction containing the first eluted enantiomer was evaporated to near dryness using a rotary evaporator, the removed DCM was transferred to a final container in Biotage V10 at 35°C, and then stored to a constant weight in a vacuum oven at 35°C and 5 mbar to give the pure enantiomer. The fraction containing the second eluted enantiomer was combined, concentrated, and re-purified as described above. The optical purity of each enantiomer was controlled with respect to the racemic product by analytical chiral SFC (conditions in Table 3). The chemical purity of each enantiomer was determined using Acquity BEH C18 (1.7 μm, 50 x 2.1 mm) (60°C, 1 mL / min, injection volume = 1 μL), with a gradient of (H2O + 0.1% v / v TFA) / CAN 98 / 2 to 0 / 100 over 2.02 minutes.

[0133] [Table 3] JPEG0007842031000031.jpg255148JPEG0007842031000032.jpg255144JPEG0007842031000033.jpg255131JPEG0007842031000034.jpg255138JPEG0007842031000035.jpg255122JPEG0007842031000036.jpg255129JPEG0007842031000037.jpg255134JPEG0007842031000038.jpg255130JPEG0007842031000039.jpg255130JPEG0007842031000040.jpg255133JPEG0007842031000041.jpg255138JPEG0007842031000042.jpg255137JPEG0007842031000043.jpg255135JPEG0007842031000044.jpg255134JPEG0007842031000045.jpg255157JPEG0007842031000046.jpg255137JPEG0007842031000047.jpg255137JPEG0007842031000048.jpg255137JPEG0007842031000049.jpg255124JPEG0007842031000050.jpg255131JPEG0007842031000051.jpg255136JPEG0007842031000052.jpg255146JPEG0007842031000053.jpg255141JPEG0007842031000054.jpg255133JPEG0007842031000055.jpg255140JPEG0007842031000056.jpg255143JPEG0007842031000057.jpg255128JPEG0007842031000058.jpg255131JPEG0007842031000059.jpg255127JPEG0007842031000060.jpg255126JPEG0007842031000061.jpg255151JPEG0007842031000062.jpg255128JPEG0007842031000063.jpg255150JPEG0007842031000064.jpg255150JPEG0007842031000065.jpg255151JPEG0007842031000066.jpg255147JPEG0007842031000067.jpg255146JPEG0007842031000068.jpg255132JPEG0007842031000069.jpg255147JPEG0007842031000070.jpg255130JPEG0007842031000071.jpg255134JPEG0007842031000072.jpg255129JPEG0007842031000073.jpg255149JPEG0007842031000074.jpg255126JPEG0007842031000075.jpg255146JPEG0007842031000076.jpg255148JPEG0007842031000077.jpg255145JPEG0007842031000078.jpg255131JPEG0007842031000079.jpg255131JPEG0007842031000080.jpg255122JPEG0007842031000081.jpg255128JPEG0007842031000082.jpg255115JPEG0007842031000083.jpg255124JPEG0007842031000084.jpg255141JPEG0007842031000085.jpg255137JPEG0007842031000086.jpg255136JPEG0007842031000087.jpg255135JPEG0007842031000088.jpg255136JPEG0007842031000089.jpg255136JPEG0007842031000090.jpg255119JPEG0007842031000091.jpg255127JPEG0007842031000092.jpg255144JPEG0007842031000093.jpg255135JPEG0007842031000094.jpg255131JPEG0007842031000095.jpg255133JPEG0007842031000096.jpg255125JPEG0007842031000097.jpg255137JPEG0007842031000098.jpg255152JPEG0007842031000099.jpg255128.

[0134] Pathological characteristics

[0135] The compound of formula (I) is associated with cognitive impairments associated with Down syndrome (trisomy 21); Alzheimer's disease and related illnesses; dementia; tauopathy; and other neurodegenerative diseases (Parkinson's disease; Pick's disease, e.g., Niemann-Pick type C). The above-mentioned diseases (including Pick's disease); CDKL5 deficiency; McDermid syndrome; autism; type 1 and type 2 diabetes; folic acid and methionine metabolic disorders; osteoarthritis, especially osteoarthritis of the knee; Duchenne muscular dystrophy; several cancers, such as brain tumors, such as glioblastoma; leukemia, such as megakaryoblastic leukemia and acute lymphoblastic leukemia; squamous cell carcinoma of the head and neck; pancreatic cancer, such as pancreatic ductal adenocarcinoma; prostate cancer; gastrointestinal cancer; and breast cancer, such as triple-negative breast cancer (TNBC); tissue cancer, such as liposarcoma and Hedgehog / GLI-dependent cancer; liver cancer. It may be useful in the treatment and / or prevention of diseases selected from, for example, liver cancer including hepatocellular carcinoma; viral infections, such as human immunodeficiency virus type 1 (HIV-1), human cytomegalovirus (HCMV), influenza A, herpesvirus, rhesus macaque cytomegalovirus, varicella-zoster virus, herpes simplex virus (HSV), hepatitis C virus, chikungunya virus, dengue virus, influenza virus and severe acute respiratory syndrome (SARS) coronavirus, cytomegalovirus and human papillomavirus; neuroinflammation; anemia; infections caused by single-cell parasites, such as malaria, leishmaniasis, Chagas disease, sleeping sickness (Trypanosoma sp.), and diseases of livestock caused by single-cell parasites; and for regulating body temperature.

[0136] According to a specific embodiment, the compound of formula (I) of the present invention is used for cognitive impairment associated with Down syndrome (trisomy 21); Alzheimer's disease and related diseases; dementia; tauopathy; other neurodegenerative diseases (Parkinson's disease; Pick's disease, including Niemann-Pick disease type C); CDKL5 deficiency; type 1 and type 2 diabetes; folic acid and methionine metabolic disorders; osteoarthritis, especially osteoarthritis of the knee; Duchenne muscular dystrophy; several cancers, including brain tumors, including glioblastoma; leukemia, including megakaryoblastic leukemia and acute lymphoblastic leukemia. It may be useful in the treatment and / or prevention of diseases selected from the above-mentioned leukemia, head and neck squamous cell carcinoma, pancreatic cancer, including pancreatic ductal adenocarcinoma, prostate cancer, gastrointestinal cancer, and breast cancer, including triple-negative breast cancer (TNBC), as well as viral infections, including human immunodeficiency virus type 1 (HIV-1), human cytomegalovirus (HCMV), influenza A, herpesvirus, rhesus monkey cytomegalovirus, varicella-zoster virus, and herpes simplex virus (HSV), and for regulating body temperature. The above-mentioned diseases are more specifically associated with abnormalities in the dosage of DYRK1A and / or CLK1.

[0137] Further according to this particular embodiment, compounds of formula (I) of the present invention may be useful in the treatment and / or prevention of Down syndrome, Alzheimer's disease, dementia, tauopathy, Parkinson's disease, Niemann-Pick disease type C, CDKL5 deficiency disorder, and Phelan McDermid syndrome, and diseases selected from the cognitive and motor conditions associated therewith, more particularly diseases resulting from high expression and activity of DYRK1A.

[0138] Further according to this particular embodiment, compounds of formula (I) of the present invention may be useful in treating and / or preventing Down syndrome, Alzheimer's disease, related tauopathies, Parkinson's disease, associated cognitive / motor impairments, or diseases selected from one or more symptoms of such diseases. Typical symptoms of such diseases include declines in learning and memory and social interaction.

[0139] Further according to this particular embodiment, the compounds of formula (I) of the present invention may be useful in combating cognitive decline associated with Down syndrome (trisomy 21), cognitive decline associated with learning and memory, and in particular cognitive decline associated with the aforementioned cognitive or neurodegenerative disorders.

[0140] Further according to this particular embodiment, the compounds of formula (I) of the present invention may be useful for the treatment and / or prevention of type 1 diabetes and type 2 diabetes.

[0141] The compound of formula (I) of the present invention may be useful in the treatment and / or prevention of type 1 and type 2 diabetes by directly treating diabetic patients or by treating pancreatic islets or β-cells before transplantation into diabetic patients.

[0142] Further according to this particular embodiment, compounds of formula (I) of the present invention may be useful in the treatment and / or prevention of viral infections, particularly those caused by human immunodeficiency virus type 1 (HIV-1), human cytomegalovirus (HCMV), influenza A, herpesvirus, rhesus cytomegalovirus, varicella-zoster virus and herpes simplex virus (HSV), and especially herpes, coronavirus, cytomegalovirus and influenza virus. These infections may be associated with high expression and activity of DYRK1A and / or CLK1, and optionally with dual inhibitors of CLK / DYRKS.

[0143] Acute respiratory illnesses have recently been caused by the novel coronavirus (SARS-CoV-2, formerly known as 2019-nCoV), which belongs to the Coronaviridae family and is known as coronavirus 2019 (COVID-19). Compounds of formula (I) according to the present invention can also treat the above-mentioned infections caused by the SARS-CoV-2 virus.

[0144] Further according to this particular embodiment, compounds of formula (I) of the present invention may be useful in the treatment and / or prevention of cancers, such as brain tumors, including glioblastoma, leukemias, including megakaryocytic leukemia and acute lymphoblastic leukemia, squamous cell carcinoma of the head and neck, pancreatic cancers, including pancreatic ductal adenocarcinoma, prostate cancer, gastrointestinal cancer, and breast cancers, including triple-negative breast cancer (TNBC). These cancers may be associated with high expression and activity of DYRK1A and / or CLK1, and optionally with CLK / DYRKS dual inhibitors.

[0145] Further according to this particular embodiment, the compounds of formula (I) of the present invention may be useful in the treatment and / or prevention of osteoarthritis. Osteoarthritis may be associated with high expression and activity of DYRK1A and / or CLK2.

[0146] Further according to this particular embodiment, the compounds of formula (I) of the present invention may be useful in the treatment and / or prevention of single-cell parasitic infections, such as malaria, leishmaniasis, Chagas disease, sleeping sickness (Trypanosoma sp.), and single-cell parasitic diseases of livestock. The above parasitic infections may be associated with the expression and activity of DYRK / CLK.

[0147] Further according to this particular embodiment, the compound of formula (I) of the present invention may be useful in regulating body temperature. This thermoregulation may be associated with the expression and activity of CLK.

[0148] According to other specific embodiments, compounds of formula (I) of the present invention may be useful in the treatment and / or prevention of diseases selected from Phelan McDermid syndrome; autism; further viral infections, e.g., the above viral infections including hepatitis C virus, chikungunya virus, dengue virus, influenza virus and severe acute respiratory syndrome (SARS) coronavirus, cytomegalovirus and human papillomavirus; further cancers, e.g., the above tissue cancers including liposarcoma and hedgehog / GLI-dependent cancers; liver cancers, e.g., hepatocellular carcinoma; neuroinflammation, anemia, infections caused by single-celled parasites, e.g., malaria, leishmaniasis, Chagas disease and sleeping sickness (Trypanosoma species); and diseases of livestock caused by single-celled parasites. The above diseases are particularly associated with abnormalities in other DYRKs (DYR1B, 2, 3, 4) and closely related further cdc2-like kinases (CLK) (CLK2, 3, 4).

[0149] The following embodiments are provided for illustrative purposes only and are not intended to limit the scope of this invention.

[0150] The following examples illustrate in detail the preparation of several compounds according to the present invention. The structures of the obtained products have been confirmed by NMR analysis and mass spectrometry.

[0151] Example 1 : General protocol 1: Synthesis of (5Z)-5-heteroaryl-2-thioxoimidazolidined-4-one [ka]

[0152] In the above scheme, R 2 represents a hydrogen atom or a (C1-C3) alkyl group, and in particular R 2 represents a hydrogen atom or a methyl group.

[0153] A stirred solution of 2-thiohydantoin (1 eq), a suitable heteroaryl carboxylase (1 equivalent), piperidine (1 equivalent), and AcOH (1 equivalent) in GP1:EtOH (c=0.3M) was heated in a sealed tube in a microwave oven (Anton Paar) at the indicated temperature for the appropriate time. After completion (followed by consumption of the aldehyde on TLC), the reaction medium was cooled and then added dropwise to water. The precipitated solid was stirred for 30 minutes, filtered through a fritted glass funnel, thoroughly dried, and can be used in the next step without further purification. If necessary, trace impurities may be removed by final grinding with EtOH without significantly reducing the yield.

[0154] Example 1.1: Synthesis of (5Z)-5-(1,3-benzothiazole-6-ylmethylene)-2-thioxoimidazolidined-4-one (1.1) [ka]

[0155] Compound (1.1) was synthesized according to GP1: the reaction was carried out on a 4.2 mmol scale with 2-thiohydantoin, benzothiazole-6-carbaldehyde, AcOH, and piperidine. Reaction temperature: 110°C, time: 90 minutes. After filtration, the yellow solid was ground in EtOH. Yellow solid, 89% (978 mg). 1 1H NMR (400MHz, DMSO-d6) δ H 12.44 (br s, 1H, NH, D2O replaced), 12.25 (br s, 1H, NH, D2O replaced), 9.47 (s, 1H), 8.61 (d, J=1.8Hz, 1H), 8.09 (d, J=8.5Hz, 1H), 7.84 (dd, J=8.6, 1.8Hz, 1H), 6.64 (s, 1H). 13 ¹³C NMR (101 MHz, DMSO-d6) δ C 179.3,165.7,158.0,153.1,134.4,129.8,128.9,128.1,123.7,123.1,110.9. MS(ESI + ):[M+H]+ 262.1.

[0156] Example 1.2: Synthesis of (5Z)-5-[(2-methyl-1,3-benzothiazole-6-yl)methylene]-2-thioxoimidazolidined-4-one (1.2) [ka]

[0157] Compound (1.2) was synthesized according to GP1: the reaction was carried out on a 7.34 mmol scale with 2-thiohydantoin, 2-methyl-1,3-benzothiazole-6-carbaldehyde, AcOH, and piperidine. Reaction temperature: 110°C, time: 90 minutes. After filtration, the yellow solid was ground in EtOH. Yellow solid, 94% (1.898 g). 1 1H NMR (400MHz, DMSO-d6) δ H 12.42 (br s, 1H, NH, D2O replaced), 12.21 (br s, 1H, NH, D2O replaced), 8.48 (s, 1H), 7.91 (d, J=8.4Hz, 1H), 7.77 (d, J=8.5Hz, 1H), 6.60 (s, 1H), 2.82 (s, 3H). 13 ¹³C NMR (101 MHz, DMSO-d6) δ C 179.2,169.1,165.7,153.1,136.0,129.0,128.8,127.7,123.0,122.0,111.1,20.0. MS(ESI + ):[M+H] + 275.9.

[0158] Example 2: General Protocol 2 - S-alkylation of (5Z)-5-heteroaryl-2-thioxoimidazolidined-4-one [ka]

[0159] In the above scheme, Hal represents a halogen atom, particularly selected from iodine and bromine atoms, Alk represents an (C1-C5) alkyl group, and R 2 is a hydrogen atom or a (C1-C3) alkyl group, especially R 2 represents a hydrogen atom or a methyl group.

[0160] GP2: A suitable alkyl iodide (1.05 equivalent) was added dropwise at a suitable temperature to a stirred solution of DMF (c=0.3M), (5Z)-5-heteroaryl-2-thioxoimidazolidined-4-one (1 equivalent), and K2CO3 (1 equivalent). The resulting mixture was stirred at the indicated temperature for the appropriate time. After completion (TLC), the mixture was poured into water. The precipitated solid was stirred for 30 minutes, filtered through a fritted glass funnel, thoroughly dried, and can be used in the next step without further purification. Trace impurities resulting from double alkylation may be removed by FC: elution: cyclohexane / AcOEt 7 / 3~3 / 7 or grinding.

[0161] Example 2.1: Synthesis of (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-ethylsulfanyl-1H-imidazole-5-one (2.1) [ka]

[0162] Compound (2.1) was synthesized according to GP2: the reaction was carried out at room temperature for 12 hours using (5Z)-5-(1,3-benzothiazole-6-ylmethylene)-2-thioxo-imidazolidined-4-one (7.69 mmol) and EtI. Yellow solid, 89% (978 mg). 1 1H NMR (400MHz, DMSO-d6) δ H 11.85 (br s, 1H, NH, D2O replaced), 9.46 (s, 1H), 8.90 (s, 1H), 8.45 (d, J=8.6Hz, 1H), 8.12 (d, J=8.6Hz, 1H), 6.88 (s, 1H), 3.70-3.17 (m, 2H), 1.44 (t, J=7.3Hz, 3H).13 ¹³C NMR (101 MHz, DMSO-d6) δ C 170.5,165.0,157.8,153.2,139.5,134.1,132.0,129.2,125.4,123.0,119.9,24.4,14.5. MS(ESI + ):[M+H] + 289.9.

[0163] Example 2.2: Synthesis of (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-methylsulfanyl-1H-imidazole-5-one (2.2) [ka]

[0164] Compound (2.2) was synthesized according to GP2: the reaction was carried out at 0°C for 6 hours using (5Z)-5-(1,3-benzothiazole-6-ylmethylene)-2-thioxoimidazolidined-4-one (3.83 mmol) and MeI. After filtration, the yellow solid was ground with DCM. Yellow solid, 83% (879 mg). 1 1H NMR (400MHz, DMSO-d6) δ H 11.89 (br s, 1H, NH, D2O replaced), 9.46 (s, 1H), 8.92 (d, J=1.6Hz, 1H), 8.45 (d, J=8.6Hz, 1H), 8.12 (d, J=8.6Hz, 1H), 6.88 (s, 1H), 2.72 (s, 3H). 13 C NMR (101MHz, DMSO-d6) δ 171.1,166.1,158.3,153.7,140.0,134.6,132.4,129.8,125.9,123.5,120.4,12.8. MS(ESI + ):[M+H] + 275.9.

[0165] Example 2.3: Synthesis of (4Z)-2-ethylsulfanyl-4-[(2-methyl-1,3-benzothiazole-6-yl)methylene]-1H-imidazole-5-one (2.3) [ka]

[0166] Compound (2.3) was synthesized according to GP2: The reaction was carried out at room temperature for 12 hours using (5Z)-5-[(2-methyl-1,3-benzothiazole-6-yl)methylene]-2-thioxo-imidazolidined-4-one (1.45 mmol) and EtI. Yellow solid, 84% (368 mg). 1 1H NMR (400MHz, DMSO-d6) δ H 11.82 (br s, 1H, NH, D2O replaced), 8.75 (s, 1H), 8.39 (d, J=8.5Hz, 1H), 7.94 (d, J=8.6Hz, 1H), 6.85 (s, 1H), 3.43-3.21 (m, 2H), 2.82 (s, 3H), 1.44 (t, J=7.3Hz, 3H). 13 ¹³C NMR (101 MHz, DMSO-d6) δ C 170.5,169.0,164.6,153.3,139.2,135.7,131.2,129.1,124.8,122.0,120.1,24.3,19.9,14.5. MS(ESI + ):[M+H] + 303.9.

[0167] Example 2.4: Synthesis of (4Z)-4-[(2-methyl-1,3-benzothiazole-6-yl)methylene]-2-methylsulfanyl-1H-imidazole-5-one (2.4) [ka]

[0168] Compound (2.4) was synthesized according to GP2: the reaction was carried out at room temperature for 6 hours using (5Z)-5-[(2-methyl-1,3-benzothiazole-6-yl)methylene]-2-thioxo-imidazolidined-4-one (3.63 mmol) and MeI. After filtration, the yellow solid was ground with DCM. Yellow solid, 92% (962 mg). 1 1H NMR (400MHz, DMSO-d6) δ H11.86 (br s, 1H, NH, D2O replaced), 8.77 (s, 1H), 8.39 (d, J=8.6Hz, 1H), 7.94 (d, J=8.6Hz, 1H), 6.85 (s, 1H), 2.82 (s, 3H), 2.71 (s, 3H). 13 ¹³C NMR (101 MHz, DMSO-d6) δ C 170.6,169.0,165.3,153.3,139.2,135.7,131.2,129.3,124.9,121.9,120.2,19.9,12.3. MS(ESI + ):[M+H] + 290.1.

[0169] Example 3: General Protocol 3 - Addition reaction of aliphatic and aromatic amines with (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-alkylsulfanyl-1H-imidazole-5-one [ka]

[0170] In the above scheme, Alk is ((C1~C5) alkyl, and R 2 represents a hydrogen atom or a (C1-C3) alkyl group, and in particular R 2 represents a hydrogen atom or a methyl group.

[0171] appropriate amines (a) (x equivalents) in a suitable solvent mixture (c=0.3M) in a sealed tube (heating block or μw), (4Z)-4-heteroaryl-2-alkylsulfanyl-1H-imidazole-5-one (b) It was added to (1 equivalent) of a stirred suspension. This mixture was thoroughly purged in a vacuum / argon cycle and then heated (μw or in a heating block) at a suitable temperature for the indicated time. After completion (followed by consumption of isothiourea on TLC), the mixture was returned to room temperature.

[0172] GP3-A: Direct precipitation of the desired product: The reaction medium was stirred at 0°C for 1 hour. The precipitated solid was filtered through a frit-lined glass funnel. After filtration, higher purity may be achieved by washing, reprecipitation, grinding, or recrystallization.

[0173] GP3-B: No product precipitated: The reaction mixture was concentrated in vacuum, adsorbed onto silica, and purified by FC. After filtration, further purification may be achieved by washing, reprecipitation, grinding, or recrystallization.

[0174] GP3-C: Product precipitation failed: The reaction mixture was concentrated under vacuum. The resulting crude product was ground with EtOH (at room temperature or under reflux) and filtered over a frit glass funnel. After filtration, higher purity may be achieved by washing, reprecipitation, grinding, or recrystallization. (a) When amine hydrochloride was used, the solution was quenched in situ with TEA or DIPEA. (b) Depending on the amine, activation with AcOH may be required.

[0175] Selected examples from subgroup A1:

[0176] Example 3.1: Synthesis of (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-(cyclohexylamino)-1H-imidazole-5-one (6) The reaction was carried out according to GP3-A, using 4 equivalents of cyclohexylamine in 0.3 M THF with a scale of 2.73 mmol of compound (2.1) at 110°C (sealed tube, heating block) for 12 hours. The product precipitated directly in the reaction medium; it was isolated after filtration, washing with cold THF, then pentane. Yield of isolated product: 34%.

[0177] Example 3.2: Synthesis of (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-(cycloheptylmethylamino)-1H-imidazole-5-one (7) The reaction was carried out according to GP3-B, using 4 equivalents of cycloheptylmethylamine in THF (0.3M) at a scale of 1.01 mmol of compound (2.1). The reaction was performed at 110°C (sealed tube, heating block) for 12 hours. Purification by FC (elution: DCM / MeOH: 99 / 1~93 / 7). The final product required reprecipitation from DCM / pentane at 0°C. Yield of isolation: 23%.

[0178] Example 3.3: Synthesis of (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-(cycloheptylamino)-1H-imidazole-5-one (8) The reaction was carried out according to GP3-A, using 4 equivalents of cycloheptylamine in 0.3 M THF with a scale of 4.84 mmol of compound (2.1), at 110°C (sealed tube, heating block) for 12 hours. The product precipitated directly in the reaction medium; it was isolated after filtration, washed with cold THF, then pentane. Yield of isolated product: 49%.

[0179] Example 3.4: Synthesis of (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-(cyclooctylamino)-1H-imidazole-5-one (9) The reaction was carried out according to GP3-A, using 4 equivalents of cyclooctylamine in 0.3 M THF with a scale of 2.73 mmol of compound (2.1), at 110°C (sealed tube, heating block) for 12 hours. The product precipitated directly in the reaction medium; it was isolated after filtration, washing with cold THF, then pentane. Yield of isolation: 58%.

[0180] Example 3.5: Synthesis of (4Z)-2-(1-adamantylamino)-4-(1,3-benzothiazole-6-ylmethylene)-1H-imidazole-5-one (16) The reaction was carried out according to GP3-B, with a scale of 2.54 mmol of compound (2.2) in THF (0.3M), using 3 equivalents of 1-adamantylamine and 15 equivalents of AcOH, at 160°C (sealed tube, heating block) for 24 hours. Purification by FC (elution: DCM / MeOH: 99 / 1~93 / 7). The final product required two consecutive grindings in reflux EtOH. Yield of isolation: 61%.

[0181] Example 3.6: Synthesis of (4Z)-2-(2-adamantylamino)-4-(1,3-benzothiazole-6-ylmethylene)-1H-imidazole-5-one (17) The reaction was carried out according to GP3-B, with a scale of 746 micromoles of compound (2.2), using 4 equivalents of 2-adamantylamine and 15 equivalents of AcOH, at 170°C (sealed tube, heating block) for 12 hours. Purification by FC (elution: DCM / MeOH: 99 / 1~93 / 7). The final product required grinding in EtOH at 0°C. Yield of isolation: 44%.

[0182] Example 3.7: Synthesis of (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[(trans-5-hydroxy-2-adamantyl)amino]-1H-imidazole-5-one (19) The reaction was carried out according to GP3-B, with a scale of 746 micromoles of compound (2.2) in THF (0.3M), using 4 equivalents of trans-4-aminoadamantan-1-ol and 15 equivalents of AcOH, at 170°C (sealed tube, heating block) for 12 hours. Purification by FC (elution: DCM / MeOH: 99 / 1~93 / 7). The final product required grinding in EtOH at 0°C. Yield of isolation: 27%.

[0183] Example 3.8: Synthesis of (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[(3-hydroxy-1-adamantyl)amino]-1H-imidazole-5-one (20) The reaction was carried out according to GP3-B, with a scale of 746 micromoles of compound (2.2) in THF (0.3M), using 4 equivalents of 3-amino-1-adamantanol and 15 equivalents of AcOH, at 160°C (sealed tube, heating block) for 12 hours. Purification by FC (elution: DCM / MeOH: 99 / 1~93 / 7). The final product required grinding in EtOH at 0°C. Yield of isolation: 59%.

[0184] Example 3.9: Synthesis of (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(1R,2R,3R,5S)-2,6,6-trimethylnorpinan-3-yl]amino]-1H-imidazole-5-one (22) The reaction was carried out according to GP3-B, using 4 equivalents of (1R,2R,3R,5S)-3-pinanamine in THF (0.3M) at a scale of 746 micromoles of compound (2.1), at 120°C (sealed tube, heating block) for 12 hours. Purification by FC (elution: DCM / MeOH: 99 / 1~93 / 7). The final product required reprecipitation from DCM / pentane at 0°C. Yield of isolation: 60%.

[0185] Example 3.10: Synthesis of (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-(spiro[2.5]octan-2-ylamino)-1H-imidazole-5-one (25) The reaction was carried out according to GP3-B, with a scale of 773 micromoles of compound (2.1) in THF (0.3M), using two equivalents of (±)-spiro[2.5]octane-2-amine hydrochloride and two equivalents of TEA, at 110°C (sealed tube, heating block) for 12 hours. Purification by FC (elution: DCM / MeOH: 99 / 1~93 / 7). The final product required reprecipitation from DCM / pentane at 0°C. Yield of isolation: 61%.

[0186] Example 3.11: Synthesis of (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(2R)-1,7,7-trimethylnorboran-2-yl]amino]-1H-imidazole-5-one (27) The reaction was carried out according to GP3-B, using 3 equivalents of (R)-(+)-bornylamine in THF (0.3M) at a scale of 746 micromoles of compound (2.1). The reaction was carried out at 150°C (sealed tube, heating block) for 8 hours. Purification by FC (elution: DCM / MeOH: 99 / 1~93 / 7). The final product required reprecipitation from DCM / pentane at 0°C. Yield of isolation: 34%.

[0187] Example 3.12: Synthesis of (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(1R)-1-(hydroxymethyl)-3-methyl-butyl]amino]-1H-imidazole-5-one (34) The reaction was carried out according to GP3-B, using 4 equivalents of D-leucinol in THF (0.3M) at a scale of 746 micromoles of compound (2.1). The reaction was performed at 110°C (sealed tube, heating block) for 12 hours. Purification by FC (elution: DCM / MeOH: 99 / 1~93 / 7). The final product required reprecipitation from DCM / pentane at 0°C. Yield of isolation: 39%.

[0188] Example 3.13: Synthesis of (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(1R)-1-(methoxymethyl)-3-methyl-butyl]amino]-1H-imidazole-5-one (35) The reaction was carried out according to GP3-B, using 2.91 mmol of compound (2.2) in THF (0.3 M) with 2.5 equivalents of (2R)-1-methoxy-4-methylpentane-2-amine at 120°C (sealed tube, heating block) for 12 hours. Purification by FC (elution: DCM / MeOH: 99 / 1~93 / 7). The final product required reprecipitation from DCM / pentane at 0°C. Yield of isolation: 74%.

[0189] Example 3.14: Synthesis of (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(1S)-1-(hydroxymethyl)-3-methyl-butyl]amino]-1H-imidazole-5-one (36) The reaction was carried out according to GP3-B, using 4 equivalents of L-leucinol in THF (0.3M) at a scale of 746 micromoles of compound (2.1). The reaction was performed at 110°C (sealed tube, heating block) for 12 hours. Purification by FC (elution: DCM / MeOH: 99 / 1~93 / 7). The final product required reprecipitation from DCM / pentane at 0°C. Yield of isolation: 39%.

[0190] Example 3.15: Synthesis of (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[1-(fluoromethyl)-3-methyl-butyl]amino]-1H-imidazole-5-one (40) The reaction was carried out according to GP3-B, with 908 micromoles of compound (2.2) in THF (0.3M) using 1.2 equivalents of (±)-1-fluoro-4-methylpentane-2-amine, at 150°C (sealed tube, heating block) for 96 hours. Purification was performed by FC (elution: DCM / MeOH: 99 / 1~93 / 7), followed by PTLC. Yield of isolated compound: 8%.

[0191] Example 3.16: Synthesis of (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[trans-2-methoxycyclopentyl]amino]-1H-imidazole-5-one (48) The reaction was carried out according to GP3-B, using 3 equivalents of (±)-trans-2-methoxycyclopentanamine hydrochloride and 4 equivalents of DIPEA in THF (0.3M) at a scale of 272 micromoles of compound (2.2) at 120°C (sealed tube, heating block) for 7 hours. Purification by FC (elution: DCM / MeOH: 99 / 1~93 / 7). The final product required grinding in refluxed EtOH. Yield of isolation: 81%.

[0192] Example 3.17: Synthesis of (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[cis-3-hydroxycyclohexyl]amino]-1H-imidazole-5-one (55) The reaction was carried out according to GP3-B, with a scale of 272 micromoles of compound (2.2) in THF (0.3M), using 3 equivalents of (±)-cis-3-aminocyclohexanol hydrochloride and 4 equivalents of DIPEA, at 120°C (sealed tube, heating block) for 24 hours. Purification by FC (elution: DCM / MeOH: 99 / 1~93 / 7). Yield of isolated compound: 82%.

[0193] Example 3.18: Synthesis of (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[trans-3-hydroxycyclohexyl]amino]-1H-imidazole-5-one (56) The reaction was carried out according to GP3-B, with a scale of 272 micromoles of compound (2.2) in THF (0.3M), using 3 equivalents of (±)-trans-3-aminocyclohexanol hydrochloride and 4 equivalents of DIPEA, at 120°C (sealed tube, heating block) for 24 hours. Purification was performed by FC (elution: DCM / MeOH: 99 / 1~93 / 7), followed by PTLC. Yield of isolated compound: 82%.

[0194] Example 3.19: Synthesis of (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[trans-2-methoxycyclohexyl]amino]-1H-imidazole-5-one (59) The reaction was carried out according to GP3-B, with a scale of 272 micromoles of compound (2.2) in THF (0.3M), using 3 equivalents of (±)-trans-2-methoxycyclohexanamine hydrochloride and 4 equivalents of DIPEA, at 120°C (sealed tube, heating block) for 28 hours. Purification by FC (elution: DCM / MeOH: 99 / 1~93 / 7). Yield of isolated compound: 82%.

[0195] Example 3.20: Synthesis of (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[cis-2-hydroxycycloheptyl]amino]-1H-imidazole-5-one (61) The reaction was carried out according to GP3-B, with a scale of 272 micromoles of compound (2.2) in THF (0.3M), using 3 equivalents of (±)-cis-2-aminocycloheptanol hydrochloride and 4 equivalents of DIPEA, at 120°C (sealed tube, heating block) for 28 hours. Purification by FC (elution: DCM / MeOH: 99 / 1~93 / 7). The final product required grinding in refluxed EtOH. Yield of isolation: 56%.

[0196] Example 3.21: Synthesis of (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[trans-2-hydroxycycloheptyl]amino]-1H-imidazole-5-one (62) The reaction was carried out according to GP3-B, with 272 micromoles of compound (2.2) in THF (0.3M) using 3 equivalents of (±)-trans-2-aminocycloheptanol, at 120°C (sealed tube, heating block) for 6 hours. Purification by FC (elution: DCM / MeOH: 99 / 1~93 / 7). The final product required grinding in refluxed EtOH. Yield of isolation: 31%.

[0197] Example 3.22: Synthesis of (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(1R,2R)-2-hydroxycycloheptyl]amino]-1H-imidazole-5-one (63) The reaction was carried out according to GP3-B, with a scale of 746 micromoles of compound (2.1) in THF (0.3M) using 3 equivalents of (1R,2R)-2-aminocycloheptanol, at 110°C (sealed tube, heating block) for 12 hours. Purification by FC (elution: DCM / MeOH: 99 / 1~93 / 7). The final product required reprecipitation from DCM / pentane at 0°C. Yield of isolation: 49%.

[0198] Example 3.23: Synthesis of (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[cis-3-hydroxycycloheptyl]amino]-1H-imidazole-5-one (65) The reaction was carried out according to GP3-B, with a scale of 218 micromoles of compound (2.2) in THF (0.3M), using 3 equivalents of (±)-cis-3-aminocycloheptanol hydrochloride and 4 equivalents of DIPEA, at 150°C (sealed tube, μw) for 6 hours. Purification by FC (elution: DCM / MeOH: 99 / 1~93 / 7). Yield of isolated compound: 46%.

[0199] Example 3.24: Synthesis of (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[trans-3-hydroxycycloheptyl]amino]-1H-imidazole-5-one (66) The reaction was carried out according to GP3-B, with a scale of 272 micromoles of compound (2.2) in THF (0.3M), using 3 equivalents of (±)-trans-3-aminocycloheptanol hydrochloride and 4 equivalents of DIPEA, at 120°C (sealed tube, heating block) for 31 hours. Purification and isolation yield: 67% by FC (elution: DCM / MeOH: 99 / 1~93 / 7), followed by PTLC.

[0200] Example 3.25: Synthesis of (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[trans-2-methoxycycloheptyl]amino]-1H-imidazole-5-one (68) The reaction was carried out according to GP3-B, with a scale of 272 micromoles of compound (2.2) in THF (0.3M) using 3 equivalents of (±)-trans-2-methoxycycloheptanamine, at 120°C (sealed tube, heating block) for 24 hours. Purification by FC (elution: DCM / MeOH: 99 / 1~93 / 7). Yield of isolation: 79%.

[0201] Selected examples from subgroup A2:

[0202] Example 3.26: Synthesis of (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-(benzylamino)-1H-imidazole-5-one (74) The reaction was carried out according to GP3-A, using 4 equivalents of benzylamine in 0.3M THF with a scale of 1.38 mmol of compound (2.1). The reaction was carried out at 110°C (sealed tube, heating block) for 12 hours. The product precipitated directly in the reaction medium; it was isolated after filtration, washed with cold THF, and then pentane. Yield of isolation: 80%.

[0203] Example 3.27: Synthesis of (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[2-(trifluoromethyl)phenyl]methylamino]-1H-imidazole-5-one (78) The reaction was carried out according to GP3-A, using 3 equivalents of [2-(trifluoromethyl)phenyl]methanamine in THF (0.3M) at a scale of 272 micromoles of compound (2.2) for 24 hours at 120°C (sealed tube, heating block). The product precipitated directly in the reaction medium: it was isolated after filtration, washing with cold THF, then pentane. The final product required grinding in refluxed EtOH. Yield of isolation: 72%.

[0204] Example 3.28: Synthesis of (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[trans-2-hydroxyindan-1-yl]amino]-1H-imidazole-5-one (81) The reaction was carried out according to GP3-A, with 272 micromoles of compound (2.2) in THF (0.3M) using 3 equivalents of (±)-trans-1-aminoindan-2-ol at 120°C (sealed tube, heating block) for 30 hours. The product precipitated directly in the reaction medium: it was isolated after filtration, washing with cold THF, then pentane. The final product required grinding in EtOH at room temperature. Yield of isolation: 56%.

[0205] Example 3.29: Synthesis of (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(1S,2S)-2-hydroxyindan-1-yl]amino]-1H-imidazole-5-one (83) The reaction was carried out according to GP3-A, with 272 micromoles of compound (2.2) in THF (0.3M) using 3 equivalents of (1S,2S)-1-aminoindan-2-ol, at 120°C (sealed tube, heating block) for 40 hours. The product precipitated directly in the reaction medium: it was isolated after filtration, washing with cold THF, then pentane. The final product required grinding in EtOH at room temperature. Yield of isolation: 62%.

[0206] Example 3.30: Synthesis of (±)-(4Z)-2-[(2-amino-1-phenylethyl)amino]-4-(1,3-benzothiazole-6-ylmethylene)-1H-imidazole-5-one dihydrochloride (89) The reaction was carried out according to GP3-B, with a scale of 363 micromoles of compound (2.2) in THF (0.3M) using 3 equivalents of N-(2-amino-2-phenyl-ethyl)carbamate (±)-tert-butyl, at 120°C (sealed tube, heating block) for 48 hours. Purification by FC (elution: DCM / MeOH: 99 / 1~93 / 7), followed by deprotection with HCl (in dioxane, 4M). Yield of isolated compound: 63%.

[0207] Example 3.31: Synthesis of (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[(2-hydroxy-1-phenylethyl)amino]-1H-imidazole-5-one (95) The reaction was carried out according to GP3-B, with a scale of 272 micromoles of compound (2.2) in THF (0.3M) using 3 equivalents of (±)-2-phenylglycinol, at 150°C (sealed tube, heating block) for 8 hours. Purification by FC (elution: DCM / MeOH: 99 / 1~93 / 7). The final product required grinding in refluxed EtOH. Yield of isolation: 37%.

[0208] Example 3.32: Synthesis of (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[(2-methoxy-1-phenylethyl)amino]-1H-imidazole-5-one (98) The reaction was carried out according to GP3-B, using 3 equivalents of (±)-2-methoxy-1-phenyl-ethanamine in THF (0.3M) at a scale of 272 micromoles of compound (2.2) for 48 hours at 120°C (sealed tube, heating block). Purification by FC (elution: DCM / MeOH: 99 / 1~93 / 7). The final product required grinding in refluxed EtOH. Yield of isolation: 41%.

[0209] Example 3.33: Synthesis of (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[(2-hydroxy-1-phenylethyl)amino]-1H-imidazole-5-one (99) The reaction was carried out according to GP3-B, with a scale of 272 micromoles of compound (2.2) in THF (0.3M), using 3 equivalents of (±)-2-amino-1-phenyl-ethanol hydrochloride and 4 equivalents of DIPEA, at 120°C (sealed tube, heating block) for 2.5 hours. Purification by FC (elution: DCM / MeOH: 99 / 1~93 / 7). The final product required grinding in refluxed EtOH. Yield of isolation: 41%.

[0210] Example 3.34: Synthesis of (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(1R)-2-methoxy-1-phenylethyl]amino]-1H-imidazole-5-one (176) The reaction was carried out according to GP3-A, using 3 equivalents of (1R)-2-methoxy-1-phenyl-ethanamine in THF (0.3M) at a scale of 12.71 mmol of compound (2.2) for 24 hours at 140°C (sealed tube, heating block). The product precipitated directly in the reaction medium: it was isolated after filtration, washing with cold THF, then pentane. The final product required grinding in refluxed EtOH. Yield of isolation: 51%.

[0211] Selected examples from subgroup A3:

[0212] Example 3.35: Synthesis of (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[(5-methylpyrazine-2-yl)methylamino]-1H-imidazole-5-one (103) The reaction was carried out according to GP3-B, using 3 equivalents of (5-methylpyrazine-2-yl)methanamine in THF (0.3M) at a scale of 182 micromoles of compound (2.2). The reaction was carried out at 80°C (sealed tube, heating block) for 16 hours. Purification by FC (elution: DCM / MeOH: 99 / 1~93 / 7). Yield of isolated compound: 47%.

[0213] Example 3.36: Synthesis of (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[(4-methylthiazole-2-yl)methylamino]-1H-imidazole-5-one (108) The reaction was carried out according to GP3-B, using 3 equivalents of (4-methylthiazole-2-yl)methanamine in THF (0.3M) at a scale of 182 micromoles of compound (2.2), at 120°C (sealed tube, heating block) for 24 hours. Purification by FC (elution: DCM / MeOH: 99 / 1~93 / 7). The final product required grinding in refluxed EtOH. Yield of isolation: 40%.

[0214] Selected examples from subgroup A4:

[0215] Example 3.37: Synthesis of (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-(tetrahydropyran-4-ylmethylamino)-1H-imidazole-5-one (113) The reaction was carried out according to GP3-B, using 3 equivalents of tetrahydropyran-4-ylmetanamine in THF (0.3M) at a scale of 182 micromoles of compound (2.2). The reaction was carried out at 120°C (sealed tube, heating block) for 2 hours. Purification by FC (elution: DCM / MeOH: 99 / 1~93 / 7). Yield of isolated compound: 51%.

[0216] Selected examples from subgroup A5:

[0217] Example 3.38: Synthesis of (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[4-(4-methylpiperazine-1-yl)anilino]-1H-imidazole-5-one (119) The reaction was carried out according to GP3-A, using 5 equivalents of 4-(4-methylpiperazin-1-yl)aniline in THF (0.3M) at a scale of 182 micromoles of compound (2.1), at 150°C (sealed tube, μw) for 3 hours. The product precipitated directly in the reaction medium; it was isolated after filtration. The final product required two consecutive grindings in refluxed EtOH. Yield of isolation: 65%.

[0218] Example 3.39: Synthesis of (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[(1-methylindazole-7-yl)amino]-1H-imidazole-5-one (125) The reaction was carried out according to GP3-A, with a scale of 182 micromoles of compound (2.2) in THF (0.3M), using 5 equivalents of 1-methylindazole-7-amine and 15 equivalents of AcOH, at 130°C (sealed tube, heating block) for 5 hours. The product precipitated directly in the reaction medium; it was isolated after filtration. The final product required grinding in EtOH at room temperature. Yield of isolation: 52%.

[0219] Selected examples from subgroup A6:

[0220] Example 3.40: Synthesis of (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-(2-pyridylamino)-1H-imidazole-5-one (127) The reaction was carried out according to GP3-A, using 5 equivalents of pyridine-2-amine and 15 equivalents of AcOH in THF (0.3 M) at a scale of 1.05 mmol of compound (2.2), at 150°C (sealed tube, μw) for 2 hours. The product precipitated directly in the reaction medium; it was isolated after filtration. The final product required grinding in refluxed EtOH. Yield of isolation: 41%.

[0221] Example 3.41: Synthesis of (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[(1-methylpyrazole-3-yl)amino]-1H-imidazole-5-one (128) The reaction was carried out according to GP3-A, using 5 equivalents of 1-methylpyrazole-3-amine in THF (0.3M) at a scale of 182 micromoles of compound (2.2). The reaction was performed at 150°C (sealed tube, μw) for 3 hours. The product precipitated directly in the reaction medium; it was isolated after filtration. The final product required grinding in EtOH at room temperature. Yield of isolation: 71%.

[0222] Selected examples from subgroup A7:

[0223] Example 3.42: Synthesis of (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(3S)-tetrahydrofuran-3-yl]amino]-1H-imidazole-5-one (146) The reaction was carried out according to GP3-B, using 3 equivalents of (3S)-tetrahydrofuran-3-amine in THF (0.3M) at a scale of 746 micromoles of compound (2.2). The reaction was carried out at 120°C (sealed tube, heating block) for 12 hours. The product precipitated directly in the reaction medium; it was isolated after filtration. Purification by FC (elution: DCM / MeOH: 99 / 1~93 / 7). The final product required reprecipitation from DCM / pentane at 0°C. Yield of isolation: 51%.

[0224] Example 3.43: Synthesis of (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(3R)-tetrahydropyran-3-yl]amino]-1H-imidazole-5-one (147) The reaction was carried out according to GP3-B, using 4 equivalents of (3R)-tetrahydropyran-3-amine hydrochloride and 6 equivalents of TEA in THF (0.3M) at a scale of 1.04 mmol of compound (2.1), at 110°C (sealed tube, heating block) for 12 hours. Purification by FC (elution: DCM / MeOH: 99 / 1~93 / 7). The final product required reprecipitation from DCM / pentane at 0°C. Yield of isolation: 60%.

[0225] Example 3.44: Synthesis of (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(3S)-tetrahydropyran-3-yl]amino]-1H-imidazole-5-one (148) The reaction was carried out according to GP3-B, with a scale of 746 micromoles of compound (2.2) in THF (0.3M), using 3 equivalents of (3S)-tetrahydropyran-3-amine hydrochloride and 4 equivalents of DIPEA, at 130°C (sealed tube, heating block) for 12 hours. Purification by FC (elution: DCM / MeOH: 99 / 1~93 / 7). The final product required reprecipitation from DCM / pentane at 0°C. Yield of isolation: 62%.

[0226] Example 3.45: Synthesis of (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(3R,4R)-4-hydroxytetrahydropyran-3-yl]amino]-1H-imidazole-5-one (150) The reaction was carried out according to GP3-B, using 3 equivalents of (3R,4R)-3-aminotetrahydropyran-4-ol in THF (0.3M) at a scale of 746 micromoles of compound (2.2) and at 130°C (sealed tube, heating block) for 12 hours. Purification by FC (elution: DCM / MeOH: 99 / 1~93 / 7). The final product required reprecipitation from DCM / pentane at 0°C. Yield of isolation: 35%.

[0227] Example 3.46: Synthesis of (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-(oxepan-3-ylamino)-1H-imidazole-5-one (151) The reaction was carried out according to GP3-B, with 272 micromoles of compound (2.2) in THF (0.3M) using 1.2 equivalents of (±)-oxepane-3-amine, at 130°C (sealed tube, heating block) for 12 hours. Purification by FC (elution: DCM / MeOH: 99 / 1~93 / 7). Yield of isolated compound: 33%.

[0228] Example 4: biological activity

[0229] Materials and methods Protein kinase assay

[0230] 1. Overview The assay was performed by ProQinase GmbH (Engesserstr.4, D-79108 Freiburg, Germany, www.proqinase.com) (Now Reaction Biology; https: / / www.reactionbiology.com / ). IC for all compounds. 50Profiles were determined using 12 protein kinases (CDK5 / p25, CK1ε, CLK1,2,3,4, DYRK1A,1B,2,3,4, GSK3β). 50 The values ​​were measured by performing single tests at 10 different concentrations (10 μM to 30 nM) for each compound.

[0231] 2. Test Compounds

[0232] The compound was provided as a 1 μM stock solution in 100% DMSO. Prior to testing, the 1 μM stock solution was subjected to sequential semi-logarithmic dilution using 100% DMSO as the solvent. This resulted in a dilution endpoint of 3 x 10 nM / 100% DMSO, yielding 10 individual concentrations with 100% DMSO as the control. During this process, 90 μL of H2O was added to each well of each compound dilution plate. To minimize the possibility of precipitation, H2O was added to each plate a few minutes before transferring the compound solution to the assay plate. The plates were shaken thoroughly to obtain compound dilution plates / 10% DMSO as a result.

[0233] For the assay (see below), 5 μL of solution was transferred from each well of the compound dilution plate / 10% DMSO to the assay plate. The final volume of the assay was 50 μL. All compounds were tested at 10 assay final concentrations ranging from 10 μM to 30 nM. The final DMSO concentration in the reaction cocktail was 1% in all cases.

[0234] 3. Recombinant protein kinase

[0235] All protein kinases provided by ProQinase were expressed in Sf9 insect cells or E. coli as recombinant GST fusion proteins or His-tagged proteins, either as full-length or enzymatically active fragments. All kinases were constructed from human cDNA and purified by either GSH-affinity chromatography or immobilized metal. Affinity tags were removed from many kinases during purification. The purity of the protein kinases was tested by SDS-PAGE / Coomassie staining, and identity was confirmed by mass spectrometry.

[0236] 4. Protein kinase assay

[0237] Synchrotron radiation protein kinase assay (33PanQinase (登録商標) Activity assays were used to measure the kinase activity of 12 protein kinases. All kinase assays were performed in 96-well FlashPlates (trademark) from PerkinElmer (Boston, MA, USA) at a reaction volume of 50 μL. The reaction cocktail was pipetted in four steps in the following order. • 25 μL assay buffer (standard buffer / [γ- 33 P]-ATP), • 10 μL of ATP solution (in H2O), • 5 μL of test compound (in 10% DMSO), • 10 μL of enzyme / substrate mixture.

[0238] The assay for all protein kinases consists of 70 mM HEPES-NaOH pH 7.5, 3 mM MgCl2, 3 mM MnCl2, 3 μM sodium orthovanadate, 1.2 mM DTT, 50 μg / ml PEG20000, ATP (variable concentration, corresponding to the apparent ATP-Km of individual kinases), and [γ- 33The reaction cocktail contained P]-ATP (6.5 x 10⁻⁵ cpm / well), protein kinase (variable amount), and substrate (variable amount). The reaction cocktail was incubated at 30°C for 60 minutes. The reaction was stopped with 50 μL of 2% H₃PO₄, the plate was aspirated, and washed twice with 200 μL of 0.9% (w / v) NaCl. 33 Pi uptake was determined using a microplate scintillation counter (Microbeta, Wallac). IC for all compounds. 50 The values ​​were calculated from the dose-response curve.

[0239] 5.Quality control

[0240] As parameters for assay quality, low-control and high-control Z'-factor values ​​were used for each assay plate (n=8) (Zhang et al., J. Biomol.Screen.2:67-73, 1999). The criterion for ProQinase in assay plate repeats was a Z'-factor value of less than 0.4 (Iversen et al., J. Biomol.Screen.3:247-252, 2006).

[0241] Their activities were classified according to two criteria: kinase inhibitory efficacy and kinase selectivity.

[0242] The classification of kinase inhibitory activity is as follows: 50 It was done according to the range of values: Some compounds exhibit ICs that fluctuate above 0.050 μM. 50 They are active. These compounds correspond to the Class E reported above. Some compounds exhibit varying IC50 at 0.025–0.050 μM. 50 They are active. These compounds correspond to the Class D compounds reported above. Some of the compounds of the present invention have ICs that vary in the range of 0.010 to 0.025 μM. 50 They are active. These compounds correspond to the Class C compounds reported above. Furthermore, some specific compounds exhibit IC50 activity varying from 0.005 to 0.010 μM. 50They are active. These compounds correspond to the Class B compounds reported above. IC50 is less than 0.005 μM. 50 Compounds of the present invention that exhibit activity are preferred. These compounds correspond to the Class A reported above. This classification was applied to CLK1 and DYRK1A. The letters A-E above are used to refer to the activity / efficacy of the compounds of the present invention in Tables 4, 4A, and 4B below.

[0243] Kinase selectivity classification is based on IC of DYRK1A 50 This was done by comparing the value with the value of CLK1 or the value of DYRK1B. The classification was performed according to the following range of values: I: IC on CLK1 or DYRK1B 50 IC for DYRK1A 50 The ratio of 1 to 10 is greater than (most selective compounds of DYRK1A); II: ratio of 2 to 10; III: ratio of 0.5 to 2; IV: ratio of 0.1 to 0.5; V: ratio greater than 0.1 (most selective compounds of CLK1- or DYRK1B). The above numbers I to V are used in the table below to refer to the relative selectivity of the compounds of the present invention.

[0244] [Table 4] JPEG0007842031000110.jpg108170JPEG0007842031000111.jpg107170JPEG0007842031000112.jpg108170JPEG0007842031000113.jpg85170

[0245] [Table 4A]

[0246] I C 50The most potent CLK2 inhibitors with a CLK2 level of 10 nM or less are compounds (9), (16), (20), (21), (22), (24), (25), (81), (83), (89), (95), (96), (159), (181), (194), (196), (199), (200), (201), (202), and (203).

[0247] I C 50 The most potent CLK3 inhibitors with a CLK-500 nM level are compounds (48), (89), (90), (159), (164), (165), (169), (169B), (178), and (181).

[0248] I C 50 The most potent CLK4 inhibitors with a CLK4 level of 10 nM or less are compounds (7), (8), (9), (10), (12), (16), (17), (19), (20), (21), (23), (25), (26), (28), (32), (33), (34), (35), (40), (41), (43), (44), (46), (48), (51), (5 5), (56), (57), (59), (61), (62), (63), (65), (66), (67), (68), (69), (70), (73), (77), (78), (81), (83), (88), (89), (90), (95), (96), (97), (98), (99), (100), (101), (102), (104), (105), (106), (117), (119), (127), (131), (139), (148), (149), (149B), (151), (155), (15 6), (157), (158), (159), (160), (161), (164), (165), (167), (169), (169A), (169B), (170) These are (171), (171A), (171B), (172), (173), (176), (178), (179), (180), (181), (184), (185), (191), (192), (192A), (194), (196), (198), (199), (200), (201), (202), (203), and (210).

[0249] [Table 4B] JPEG0007842031000116.jpg138170

[0250] I C 50 The most potent DYRK1B inhibitors with a DYRK1B level of 10 nM or less are compounds (20), (16), (83), (81), (34), (95), (21), (22), (27), (35), (61), (9), (96), (159), (160), (162), (176), (194), (196), (199), (200), (201), (202), (203), and (210).

[0251] I C 50 The most potent DYRK2 inhibitors with a DYRK2 level of 100 nM or less are compounds (16), (20), (21), (48), (89), (90), (99), (119), (158), (159), (169), (179), (194), (196), (199), (200), (201), (203), and (210).

[0252] I C 50 The most potent DYRK3 inhibitors with a DYRK3 level of 100 nM or less are compounds (16), (20), (21), (89), (90), (119), (162), (159), (181), (194), (196), (199), (200), (201), and (203).

[0253] I C 50 The most potent DYRK4 inhibitors with a DYRK4 level of 100 nM or less are compounds (20), (48), (164), (194), and (196).

[0254] [Table 4C]

[0255] [Table 4D]

[0256] [Table 4E] JPEG0007842031000120.jpg249170JPEG0007842031000121.jpg89170

[0257] [Table 4F]

[0258] result

[0259] Most of the compounds of the present invention exhibit an IC50 of less than 2 μM relative to CLK or DYRK. All compounds were inhibitors of DYRK1A and CLK1 (Table 4).

[0260] The compound preferably showed inhibitory activity at CLK1 (Table 4A), CLK4, DYRK1A (Table 4B), and DYRK1B.

[0261] Some compounds are most selective for DYRK1A vs. CLK1 (Table 4C), DYRK1A vs. DYRK1B (Table 4E), DYRK1B vs. DYRK1A (Table 4F), or CLK1 vs. DYRK1A (Table 4D). Several compounds show better selectivity for DYRK1A compared to CLK1 or DYRK1B. These compounds correspond to Class I (more than 10x selectivity) or Class II (2 to 10x selectivity) as described above. Several compounds are equivalent. These compounds correspond to Class III (0.5 to 2x selectivity) as described above. Several compounds show better selectivity for CLK1 or DYRK1B compared to DYRK1A. These compounds correspond to Class IV (2 to 10x selectivity) or Class V (more than 10x selectivity) as reported above.

[0262] conclusion

[0263] Based on previous results, the compound of formula (I) is associated with cognitive impairments associated with Down syndrome (trisomy 21); Alzheimer's disease and related diseases; dementia; tauopathy; other neurodegenerative diseases (Parkinson's disease; Pick's disease, including Niemann-Pick disease type C); CDKL5 deficiency; type 1 and type 2 diabetes; folic acid and methionine metabolic disorders; osteoarthritis, especially osteoarthritis of the knee; Duchenne muscular dystrophy; several cancers, including brain tumors, including glioblastic brain cancer; leukemia, including megakaryoblastic leukemia and acute lymphoblastic leukemia; squamous cell carcinoma of the head and neck; pancreatic cancer, including pancreatic ductal adenocarcinoma; prostate cancer; gastrointestinal cancer; breast cancer, including triple-negative breast cancer (TNBC); malaria; leishmaniasis; Chagas disease; sleeping sickness (Trypanosoma species) It can be concluded that this is a chemical compound suitable for the prevention and / or treatment of the above-mentioned viral infections, including diseases of livestock caused by single-celled parasites, viral infections, such as human immunodeficiency virus type 1 (HIV-1), human cytomegalovirus (HCMV), influenza A, herpesvirus, rhesusca cytomegalovirus, varicella-zoster virus, and herpes simplex virus (HSV), as well as for the regulation of body temperature.

[0264] It can be concluded that some compounds of formula (I) are more suitable for treating and / or preventing Phelan McDermid syndrome; autism; further viral infections, including hepatitis C virus, chikungunya virus, dengue virus, influenza virus and severe acute respiratory syndrome (SARS) coronavirus, cytomegalovirus and human papillomavirus; further cancers, including tissue cancers such as liposarcoma and hedgehog / GLI-dependent cancers; liver cancers such as hepatocellular carcinoma; neuroinflammation, anemia, infections caused by single-celled parasites, including malaria, leishmaniasis, Chagas disease and sleeping sickness (Trypanosoma species); and diseases of livestock caused by single-celled parasites.

[0265] Leusetinib exhibits significantly enhanced efficacy compared to the reference compound (sub-micromolar and single-digit micromolar IC50). 50 They show values ​​up to a certain range. They also exhibit a wide range of selectivity for DYRK1A or CLK1. Furthermore, some products equivalent to CLK and DYRK may find applications as bispecific inhibitors.

[0266] The present invention further relates to a pharmaceutical composition comprising at least one compound of formula (I) as defined above or any pharmaceutically acceptable salt thereof, or at least one compound (1) to (216) as defined above or any pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable additive.

[0267] The pharmaceutical compositions of the present invention may contain one or more compounds of the present invention in any form described herein.

[0268] A further object of the present invention is cognitive impairment associated with Down syndrome (trisomy 21); Alzheimer's disease and related diseases; dementia; tauopathy; and other neurodegenerative diseases (Parkinson's disease; Pick's disease, including Niemann-Pick disease type C); CDKL5 deficiency; McDermid syndrome; autism; type 1 and type 2 diabetes; regulation of folic acid and methionine metabolism; osteoarthritis, especially osteoarthritis of the knee; Duchenne muscular dystrophy; several cancers, including brain tumors, including glioblastoma; leukemia, including megakaryoblastic leukemia; squamous cell carcinoma of the head and neck; pancreatic cancer, including pancreatic ductal adenocarcinoma; prostate cancer; gastrointestinal cancer; and breast cancer, including triple-negative breast cancer (TNBC). Tissue cancers, such as liposarcoma and hedgehog / GLI-dependent cancers, liver cancers, such as hepatocellular carcinoma, and viral infections, such as human immunodeficiency virus type 1 (HIV-1), human cytomegalovirus (HCMV), influenza A, herpesvirus, rhesus cytomegalovirus, varicella-zoster virus, herpes simplex virus (HSV), hepatitis C virus, chikungunya virus, dengue virus, influenza virus and severe acute respiratory syndrome (SARS) coronavirus, cytomegalovirus and human papillomavirus; neuroinflammation; anemia; single-cell parasites, such as malaria, leishmaniasis, Chagas disease and sleeping sickness (Trypanosoma species) The invention comprises using at least one of the compounds of formula (I) defined above and compounds (1) to (216) defined above, or one of their pharmaceutically acceptable salts, for the prevention and / or treatment of diseases selected from infectious diseases caused by sp.)), and diseases of livestock caused by single-celled parasites, and for the regulation of body temperature.

[0269] Further objects of the present invention include cognitive impairment associated with Down syndrome (trisomy 21); Alzheimer's disease and related diseases; dementia; tauopathy; other neurodegenerative diseases (Parkinson's disease; Pick's disease, including Niemann-Pick disease type C); CDKL5 deficiency; type 1 and type 2 diabetes; regulation of folic acid and methionine metabolism; osteoarthritis, especially osteoarthritis of the knee; Duchenne muscular dystrophy; several cancers, including brain tumors, including glioblastoma; leukemia, including megakaryoblastic leukemia; squamous cell carcinoma of the head and neck; pancreatic cancer, including pancreatic ductal adenocarcinoma; prostate cancer; gastrointestinal cancer; and breast cancer, including triple-negative breast cancer (TNBC); infections caused by single-celled parasites, such as malaria, leishmaniasis, Chagas disease, and sleeping sickness (Trypanosoma species). The invention comprises the use of a compound of formula (I) as defined in accordance with the present invention and at least one of the compounds (1) to (216) defined above, or one of their pharmaceutically acceptable salts, for preparing a drug for preventing and / or treating diseases selected from diseases of livestock caused by single-celled parasites, such as viral infections, including, for example, human immunodeficiency virus type 1 (HIV-1), human cytomegalovirus (HCMV), influenza A, herpesvirus, rhesusa cytomegalovirus, varicella-zoster virus, and herpes simplex virus (HSV), and for regulating body temperature.

[0270] Further objects of the present invention include the use of at least one of the compounds of formula (I) defined above and compounds (1) to (216) defined above, or one of their pharmaceutically acceptable salts, according to the present invention, for preparing agents to combat diseases selected from type 1 and type 2 diabetes, viral infections, particularly the viral infections described above, osteoarthritis, cancer, particularly the cancers described above, infections caused by single-celled parasites, such as malaria, leishmaniasis, Chagas disease, sleeping sickness (Trypanosoma species), and diseases of livestock caused by single-celled parasites, and for regulating body temperature.

[0271] According to a particular embodiment, the procedure may be continuous or non-continuous.

[0272] "Continuous treatment" refers to long-term treatment that can be implemented at various administration frequencies, for example, once daily, once every three days, once a week, once every two weeks, once a month, or via transdermal patch administration.

[0273] According to one embodiment, any one of the compounds of formula (I) or a pharmaceutically acceptable salt thereof is administered in doses varying from 0.1 to 1000 mg, particularly in doses varying from 1 to 500 mg, or, for example, in doses varying from 5 to 100 mg.

[0274] Other objects of the present invention include cognitive impairment associated with Down syndrome (trisomy 21); Alzheimer's disease and related diseases; dementia; tauopathy; and other neurodegenerative diseases (Parkinson's disease; Pick's disease, including Niemann-Pick disease type C); CDKL5 deficiency; McDermid syndrome; autism; type 1 and type 2 diabetes; regulation of folic acid and methionine metabolism; osteoarthritis, especially osteoarthritis of the knee; Duchenne muscular dystrophy; several cancers, including brain tumors, including glioblastoma; leukemia, including megakaryoblastic leukemia; squamous cell carcinoma of the head and neck; pancreatic cancer, including pancreatic ductal adenocarcinoma; prostate cancer; gastrointestinal cancer; and breast cancer, including triple-negative breast cancer (TNBC). Cancer, including the above-mentioned tissue cancers such as liposarcoma and hedgehog / GLI-dependent cancer; liver cancer, including the above-mentioned liver cancers such as hepatocellular carcinoma; viral infections, including the above-mentioned viral infections such as human immunodeficiency virus type 1 (HIV-1), human cytomegalovirus (HCMV), influenza A, herpesvirus, rhesusa cytomegalovirus, varicella-zoster virus, herpes simplex virus (HSV), hepatitis C virus, chikungunya virus, dengue virus, influenza virus and severe acute respiratory syndrome (SARS) coronavirus, cytomegalovirus and human papillomavirus; neuroinflammation; anemia; single-cell parasites, including malaria, leishmaniasis, Chagas disease and sleeping sickness (Trypanosoma species) A method for treating and / or preventing diseases selected from infectious diseases caused by sp.)) and diseases of livestock caused by single-celled parasites, in a patient in need thereof, the method comprising at least the step of administering a therapeutically effective amount of one of the compounds of formula (I) as defined above, or compounds (1) to (216), or acceptable salts thereof.

[0275] In certain embodiments, the present invention provides the use of a compound of formula (I) or a pharmaceutically acceptable salt thereof or a pharmaceutically active derivative thereof, or a method of the present invention in which a compound of formula (I) is to be administered in combination with a co-agent useful for any one of the diseases described above.

[0276] The compound can be administered, for example, by any mode of administration, such as intramuscular, intravenous, intranasal, or oral routes, or via a transdermal patch.

[0277] The composition of the present invention may further contain one or more additives, such as diluents, excipients, stabilizers, and preservatives. Such additives are well known to those skilled in the art, in particular to “Ullmann's Encyclopedia of Industrial Chemistry, 6 th It is described in “Ed.” (various editors, 1989-1998, Marcel Dekker) and “Pharmaceutical Dosage Forms and Drug Delivery Systems” (ANSEL et al, 1994, WILLIAMS & WILKINS).

[0278] The excipients described above are selected according to the dosage form and desired administration method.

[0279] The compositions of the present invention may be administered by any method, including but not limited to oral, parenteral, sublingual, transdermal, vaginal, rectal, transmucosal, topical, nasal, cheek, or intranasal administration via inhalation, or a combination thereof. Parenteral administration includes, but is not limited to, intravenous, intra-arterial, intraperitoneal, subcutaneous, intramuscular, intracranial, and intra-articular administration. The compositions of the present invention may also be administered in the form of implants, which allow for sustained release of the compositions and slow, controlled intravenous (IV) infusion.

[0280] For example, the compound of formula (I), in association with a suitable excipient, may exist in any pharmaceutical form suitable for enteral or parenteral administration, such as plain tablets or coated tablets, hard gelatin, soft-shelled capsules and other capsules, suppositories, or in oral form, such as suspensions, syrups or injectable solutions or suspensions.

[0281] In certain embodiments, the compound of formula (I) according to the present invention is administered orally.

[0282] Oral administration is particularly preferred from the viewpoint of prevention or treatment of the present invention. The present invention may be configured as follows. [Section 1] Any one of the compounds of formula (I) below, or any pharmaceutically acceptable salt thereof. [ka] Here, R 1 teeth, (i).-COOR a group, hydroxyl group, halogen atom, (C 1 ~C 4 ) Substituted with one or two groups selected from alkoxy groups and benzyloxy groups (C 1 ~C 6 ) an alkyl group, where the benzyloxy may be substituted with 1 to 3 halogen atoms on its phenyl group, (ii) Spiro(C 5 ~C 11 ) bicyclic ring, (iii).(C 5 ~C 6 )Cycloalkyl or (C 5 ~C 6 ) A condensed phenyl group selected from a phenyl group condensed with a heterocycloalkyl group, where (C 5 ~C 6 )cycloalkyl and (C 5 ~C 6 The heterocycloalkyl ring may contain unsaturation, and also (C 1 ~C 4 ) Alkyl group, hydroxyl group, halogen atom, (C 1 ~C 3 ) Alkoxy group or -COR a It may be substituted by the group, (iv).(C 1 ~C 8 ) alkyl, (C 1 ~C 3 ) Fluoroalkyl, Fluoro(C 1 ~C 4 )alkoxy group, halogen atom and (C 4 ~C 7 A phenyl group substituted with one or two groups selected from heterocycloalkyl groups, wherein the (C 4 ~C 7 ) Heterocycloalkyl groups are themselves (C 1 ~C 4 ) may be substituted with an alkyl group, or (v) R'-L-base, where L is a single bond or (C 1 ~C 3 ) is any of the alkanediyl groups, where (C 1 ~C 3 ) The alkanediyl group is a hydroxyl group and (C 1 ~C 3 ) may be substituted with one group selected from alkoxy groups, R' is (v.1).(C 1 ~C 4 )alkyl groups, hydroxyl groups, halogen atoms and (C 1 ~C 3 ) may be substituted with one, two, or three groups selected from alkoxy groups (C 3 ~C 8 ) Cycloalkyl groups, (v.2).(C 1 ~C 4 ) alkyl group, (C 1 ~C 4 ) Alkoxy group, halogen atom, hydroxyl group, -OC(O)-R d group, -OC(O)-NHR d Base, -NH-C(O)-R d Base, -SO 2 -R d group, -N(R e ) 2 Base and -COOR a A cross-linked (C) which may be substituted by 1 to 3 groups selected from the group. 6 ~C 10 ) Cycloalkyl groups, (v.3).-COOR a group, hydroxyl group, halogen atom, (C 1 ~C 4 )May be substituted with 1 to 3 groups selected from alkyl groups and oxo groups (C 3 ~C 8 ) Heterocycloalkyl groups, (v.4) Halogen atom, (C 1 ~C 4 ) alkyl group, (C 1 ~C 4 ) It may be substituted with 1 to 3 groups selected from alkoxy groups and N-methylpiperazinyl groups (C 3 ~C 8 ) Heteroaryl group, or, (v.5). Bridged (C 6 ~C 10 ) Heterocycloalkyl groups Representing, Or, (vi) R'-L-base, where L is NR b R c Group, (C 1 ~C 4 ) Alkoxy group, hydroxyl group, -COOR a It may be substituted with a group selected from the group and halogen atoms (C 1 ~C 3 ) is an alkanediyl group, and also, R' is (C 1 ~C 6 ) alkyl groups, fluoro(C 1 ~C 4 ) Alkyl and fluoro(C 1 ~C 4 A phenyl group which may be substituted with 1 to 3 groups selected from the group consisting of alkoxy groups, halogen atoms, and hydroxyl groups. Here, R a is, (C 1 ~C 4 ) Represents an alkyl group or a hydrogen atom, R b and R c (C 1 ~C 6 ) Represents an alkyl group or a hydrogen atom, R d is, (C 1 ~C 4 ) Represents an alkyl group or a cyclopropyl group, R e is, (C 1 ~C 3 ) Represents an alkyl group, Represents, and R 2 However, hydrogen atoms or (C 1 ~C 3 ) Represents an alkyl group. [Section 2] Here, R 1 but, (i).-COOR a group, hydroxyl group, halogen atom, (C 1 ~C 4 ) Substituted with one or two groups selected from alkoxy groups and benzyloxy groups (C 2 ~C 6 ) an alkyl group, where the benzyloxy may be substituted with 1 to 3 halogen atoms on its phenyl group, (ii) Spiro(C 7 ~C 9 ) bicyclic ring, (iii) A condensed phenyl group selected from a phenyl group condensed with cyclopentyl or heterocyclopentyl, wherein the cyclopentyl group and heterocyclopentyl group may be unsaturated, and (C 1~C 4 ) Alkyl group, hydroxyl group, halogen atom, (C 1 ~C 3 ) Alkoxy group or -COR a It may be substituted by the group, (iv).(C 1 ~C 8 ) alkyl, (C 1 ~C 3 ) Fluoroalkyl, Fluoro(C 1 ~C 4 )alkoxy group, halogen atom and (C 4 ~C 7 A phenyl group substituted with one or two groups selected from heterocycloalkyl groups, wherein the (C 4 ~C 7 ) Heterocycloalkyl groups are themselves (C 1 ~C 4 ) may be substituted with an alkyl group, or (v) R'-L-base, where L is a single bond or (C 1 ~C 3 ) is any of the alkanediyl groups, where (C 1 ~C 3 ) The alkanediyl group is a hydroxyl group and (C 1 ~C 3 ) may be substituted with one group selected from alkoxy groups, R' is (v.1).(C 1 ~C 4 )alkyl groups, hydroxyl groups, fluorine atoms and (C 1 ~C 3 ) It may be substituted with one, two, or three groups selected from alkoxy groups (C 3 ~C 8 ) Cycloalkyl groups, (v.2).(C 1 ~C 4 ) alkyl group, (C 1 ~C 4 ) Alkoxy group, hydroxyl group, halogen atom, -OC(O)-R d group, -OC(O)-NHR d Base, -NH-C(O)-R d Base, -SO 2 -R d group, -N(R e ) 2 Base and -COOR a A cross-linked (C) which may be substituted by 1 to 3 groups selected from the group. 7 ~C 10 ) Cycloalkyl groups, (v.3).-COOR a group, hydroxyl group, halogen atom, (C 1 ~C 4 )May be substituted with 1 to 3 groups selected from alkyl groups and oxo groups (C 4 ~C 7 ) Heterocycloalkyl groups, (v.4) Halogen atom, (C 1 ~C 4 ) alkyl group, (C 1 ~C 4 ) A heteroaryl group which may be substituted with 1 to 3 groups selected from alkoxy groups and N-methylpiperazinyl groups, (v.5). Bridged (C 6 ~C 10 ) Heterocycloalkyl groups Representing, Or, (vi) R'-L-base, where L is -NR b R c Group, (C 1 ~C 4 ) Alkoxy group, hydroxyl group, -COOR a It may be substituted with a group selected from the group and halogen atoms (C 1 ~C 3 ) is an alkanediyl group, and also, R' is (C 1 ~C 6 ) alkyl groups, fluoro(C 1 ~C 4 A phenyl group which may be substituted with 1 to 3 groups selected from the group consisting of alkyl groups, Here, R a is, (C 1 ~C 4 ) Represents an alkyl group or a hydrogen atom, R b and R c (C 1 ~C 6 ) Represents an alkyl group or a hydrogen atom, R d is, (C 1 ~C 4 ) Represents an alkyl group or a cyclopropyl group, R e is, (C 1 ~C 3 ) Represents an alkyl group, It represents, and also, R 2 However, hydrogen atoms or (C 1 ~C 3 ) Represents an alkyl group, Any one of the compounds of formula (I) described in item 1 or any pharmaceutically acceptable salt thereof. [Section 3] Here, R 1 but, (i)-COOCH 3 Substituted with one or two groups selected from the following: a hydroxyl group, a fluorine atom, a methoxy group, an ethoxy group, a tert-butoxy group, a cyclopropoxy group, and a benzyloxy group (C 2 ~C 6 ) an alkyl group, where the benzyloxy may be substituted with one fluorine atom on its phenyl group, (ii) Spiro(C 7 ~C 8 ) Bicyclic rings, in particular spiro[3.3]heptyl, spiro[2.5]octanyl, or 7-azaspiro[3.5]nonyl, (iii) A condensed phenyl group selected from a phenyl group condensed with cyclopentyl or heterocyclopentyl, wherein the cyclopentyl group and heterocyclopentyl group may include unsaturated groups, as well as methyl, hydroxyl, methoxy and -COCH 3 It may be substituted by the group, (iv) A phenyl group substituted with one or two groups selected from methyl, hexyl, trifluoromethyl, difluoromethoxy, halogen atoms, in particular a fluorine atom, a morpholino group, and an N-methylpiperazinyl group, or (v) R'-L-base, where L is a single bond or (C 1 ~C 3 ) is any of the alkanediyl groups, where (C 1 ~C 3 The alkanediyl group may be substituted with one group selected from a hydroxyl group and a (C1-C3) alkoxy group, and R' is (v.1) It may be substituted with one, two or three groups selected from methyl, isopropyl, hydroxyl, and methoxy groups (C 3 ~C 8 ) Cycloalkyl groups, particularly cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, or cyclooctyl, (v.2) Methyl group, methoxy group, hydroxyl group, fluorine atom, -OC(O)-CH 3 group, -OC(O)-C(CH 3 ) 3 group, -OC(O)-NH-C(CH 3 ) 3 group, -NH-C(O)-CH 3 group, -NH-C(O)-C 3 H 4基 , -S(O) 2 -CH 3 group, -S(O) 2 -C 3 H 4 group, -N(CH 3 ) 2 The group and -C(O)-O-CH 3 A cross-linked (C) which may be substituted by 1 to 3 groups selected from the group. 7 ~C 10 ) Cycloalkyl groups, particularly adamantyl or bicyclo[3.1.1]heptyl, (v.3).-COOR f It may be substituted with one, two, or three groups selected from the group, hydroxyl group, methyl group, and oxo group (C 5 ~C 8 ) Heterocycloalkyl groups, particularly tetrahydropyranil, piperidinil, oxetanil, tetrahydrofuranil, oxepanil, tetrahydrothiopyranil, pyrrolidinil, dioxepanil, or piperidinil, where Rf represents either an ethyl group or an isopropyl group. (v.4) Heteroaryl groups which may be substituted with 1 to 3 groups selected from methyl, methoxy and N-methylpiperazinyl groups, in particular pyrimidinyl, pyridinyl, thiazolyl, imidazolyl, pyrazolyl, thiadiazolyl, pyridazinyl, pyrazinyl, furyl, or (v.5) Crosslinked (C7-C10) cycloalkyl groups, particularly quinuclidine-3-yl, (vi) R'-L-base, where L is -NR b R c Group, (C 1 ~C 4 ) Alkoxy group, hydroxyl group, -COOR a It may be substituted with one group selected from the group consisting of a group and a halogen atom, particularly a fluorine atom (C 1 ~C 3 ) is an alkanediyl group, and also, R' is a phenyl group which may be substituted with one or two groups selected from the group consisting of a methyl group, a trifluoromethyl group, and a trifluoromethoxy group. Here, R a is, (C 1 ~C 3 ) Represents an alkyl group, R b and R c These independently represent a methyl group or a hydrogen atom. Selected from the group consisting of, R 2 However, hydrogen atoms or (C 1 ~C 3 ) Represents an alkyl group, Any one of the compounds of formula (I) described in item 1 or 2, or any pharmaceutically acceptable salt thereof. [Section 4] L is a CH2- group, -CH(CH 3 )-base, -CH(CH 2 OH)-CH 2 -base, -CH(CH 2 OH)- group, -CH(CH 2 OCH 3 )-base, -CH(OH)-CH 2 -group, -CH 2 -CH(CH 2 OCH 3 )-base, -CH(OCH 3 )-CH 2 -group, -CH 2 -CH(COOCH 3 )-base, -CH(CH 2 F)-group, -CH(CH 2 NH 2 )-base, -CH(CH 2 NHCH 3 )-base, -CH(CH 2 N(CH 3 ) 2 )-group, -CH 2 -CH(CH 2 OH)- group, -CH(OCH 3 )-CH 2 -group, -CH 2 -CH(OCH 3 )-group, -CH 2 -CH(OH)-CH 2 -group, -CH 2 -CH(OCH 3 )-CH 2 group, -(CH 2 ) 3 - group, -(CH 2 ) 2 - group and -CH(CH 2 OC(CH 3 ) 3 One of the compounds of formula (I) described in any one of items 1 to 3, or a pharmaceutically acceptable salt thereof, selected from the group consisting of ) groups. [Section 5] (v.1) R' is (C 3 ~C 8 )When it is a cycloalkyl group, L is a single bond, -CH 2 -base, -CH(CH 3 )-base, -CH(CH 2 OH)-CH 2 -base, -CH(CH 2 OH)- group, -CH(CH 2 OCH 3 )-group, and -CH(OH)-CH 2 - group and -CH(OCH 3 )-CH 2 - Selected from a group consisting of members, (v.2) R' is bridged (C 7 ~C 10 )When it is a cycloalkyl group, L is a single bond, -CH 2 - group or -CH(CH 3 )-Based, (v.3) R' is spiro(C 3 ~C 8 ) containing heterocycloalkyl (C 5 ~C 8 ) is a heterocycloalkyl group, where L is a single bond or -CH 2 - is a base, (v.4) When R' is phenyl, L is a single bond, -CH 2 -group, -CH 2 -CH(COOCH 3 )-base, -CH(CH 2 F)-group, -CH(CH 2 NH 2 )-base, -CH(CH 2 NHCH 3 )-base, CH(CH 2 N(CH 3 ) 2 )-group, -CH 2 -CH(CH 2 OH)- group, -CH(CH 2 OH)- group, -CH(CH 2 OCH 3 )-base, -CH(OH)-CH 2 -group, -CH 2 -CH(CH 2 OCH 3 )-group, -CH 2 -CH(OH)-CH 2 - group and -CH 2 -CH(OCH 3 )-CH 2 Selected from a group consisting of elements, (v.5) When R' is a heteroaryl group, L is a single bond, -CH 2 - group, -(CH 2 ) 3 -Base and -(CH 2 ) 2 - Selected from a group consisting of members, (v.6) R is bridged (C 7 ~C 10 ) When it is a heterocycloalkyl group, L is a single bond. One of the compounds of formula (I) described in any one of items 1 to 4, or any pharmaceutically acceptable salt thereof. [Section 6] Here, R 1 but, Methyl group, methoxy group, hydroxyl group, fluorine atom, -OC(O)-CH 3 group, -OC(O)-C(CH 3 ) 3 group, -OC(O)-NH-C(CH 3 ) 3 group, -NH-C(O)-CH 3 group, -NH-C(O)-C 3 H 4 group, -S(O) 2 -CH 3 group, -S(O) 2 -C 3 H 4 group, -N(CH 3 ) 2 The group and -C(O)-O-CH 3 One to three groups selected from the group, particularly an adamantyl group which may be substituted by one group, where the adamantyl group is preferably unsubstituted; or, R"-O-CH 2 (R"')-base, here, R" is (C 1 ~C 4 ) an alkyl group, preferably a methyl or ethyl group, and R"' is (C 1 ~C 4 ) Alkyl groups, especially (C 3 ~C 4 ) an alkyl group, preferably an isopropylmethyl group, or, R"' is (C 1 ~C 6 ) alkyl groups, fluoro(C 1 ~C 4 ) alkyl groups, fluoro(C 1 ~C 4 A phenyl group which may be substituted with 1 to 3 groups selected from the group consisting of alkoxy groups, halogen atoms, and hydroxyl groups, particularly 1 group, where the phenyl group is preferably unsubstituted. One of the compounds of formula (I) described in any one of items 1 to 5, or a pharmaceutically acceptable salt thereof, that represents [the specified formula]. [Section 7] Here, R 1 but, -COOR a It may be substituted with one or two groups selected from a group, a hydroxyl group, a fluorine atom, a (C1-C4) alkoxy group and a benzyloxy group (C 1 ~C 6 ) an alkyl group, where the benzyloxy may be substituted with 1 to 3 halogen atoms on its phenyl group, Spiro (C 5 ~C 11 ) Biring ring, or R'-L- group, here, L is a single bond or (C 1 ~C 3 ) is any of the alkanediyl groups, where (C 1 ~C 3 ) The alkanediyl group is a hydroxyl group and (C 1 ~C 3 ) may be substituted with a group selected from alkoxy groups, It represents, and also, R' is Halogen atom, (C 1 ~C 4 )alkyl groups, hydroxyl groups and (C 1~C 3 ) It may be substituted with one, two, or three groups selected from alkoxy groups (C 3 ~C 8 ) Cycloalkyl groups, and, (C 1 ~C 4 ) alkyl group, (C 1 ~C 4 ) Alkoxy group, halogen atom, hydroxyl group, -OC(O)-R d group, -OC(O)-NHR d Base, -NH-C(O)-R d Base, -SO 2 -R d group, -N(R e ) 2 Base, and -COOR a A cross-linked (C) which may be substituted by 1 to 3 groups selected from the group. 6 ~C 10 ) Cycloalkyl groups, Here, R a is (C 1 ~C 4 ) Represents an alkyl group, R d is, (C 1 ~C 4 ) Represents an alkyl group or a cyclopropyl group, and R e is (C 1 ~C 3 ) Represents an alkyl group Selected from the group consisting of, Here, R 2 However, hydrogen atoms or (C 1 ~C 3 ) Represents an alkyl group, Any one of the compounds of formula (I) described in item 1 or any pharmaceutically acceptable salt thereof. [Section 8] Here, R 1 but, (C 5 ~C 6 )Cycloalkyl or (C 5 ~C 6 A condensed phenyl group selected from a heterocycloalkyl group and a phenyl group, where the (C5-C6) cycloalkyl and (C 5 ~C 6 The heterocycloalkyl ring may contain unsaturation, and also (C 1 ~C 4 ) Alkyl group, hydroxyl group, halogen atom, (C 1 ~C 3 ) Alkoxy groups, and -COR a It may be substituted by the group, (C 1 ~C 8 ) alkyl, (C1 ~C 3 ) Fluoroalkyl, Fluoro(C 1 ~C 4 )alkoxy group, halogen atom and (C 4 ~C 7 A phenyl group substituted with one or two groups selected from heterocycloalkyl groups, wherein the (C 4 ~C 7 ) Heterocycloalkyl groups are themselves (C 1 ~C 4 ) may be substituted with an alkyl group, or R'-L- group, here, L is a hydroxyl group, (C 1 ~C 4 ) Alkoxy group, -NR b R c group, -COOR a It may be substituted with a group selected from the group and halogen atoms (C 1 ~C 3 ) is an alkanediyl group, and also, R' is (C 1 ~C 6 ) alkyl groups, fluoro(C 1 ~C 4 ) alkyl groups, and fluoro(C 1 ~C 4 ) A phenyl group which may be substituted with 1 to 3 groups selected from alkoxy groups, halogen atoms, and hydroxyl groups, Here, R a is, (C 1 ~C 4 ) an alkyl or hydrogen atom, and R b and R c (C 1 ~C 6 ) Selected from alkyl and hydrogen atoms, It represents, and also, R2 is a hydrogen atom or (C 1 ~C 3 ) Represents an alkyl group, Any one of the compounds of formula (I) described in item 1 or any pharmaceutically acceptable salt thereof. [Section 9] R 2 A compound of formula (I) as described in any one of items 1 to 8, wherein the compound represents either a hydrogen atom or a methyl group. [Section 10] R 1 This represents the R'-L- group, where, R' is a halogen atom, (C 1 ~C 4 ) alkyl group, (C 1 ~C 4 ) It may be substituted with 1 to 3 groups selected from alkoxy groups and N-methylpiperazinyl groups (C 3 ~C 8 ) is a heteroaryl group, and, L, (C 1~C 3 ) Alkanediyl or single bond, and Here, R 2 This represents a hydrogen atom. Any one of the compounds of formula (I) described in item 1 or any pharmaceutically acceptable salt thereof. [Section 11] Here, R 1 This represents the R'-L- group, where, R' is a hydroxyl group, (C 1 ~C 4 ) alkyl groups, oxo groups and -COOR a It may be substituted by 1 to 3 groups selected from the group (C 3 ~C 5 ) is a heterocycloalkyl group, where R a This is as defined in Section 1, and L is methylene or a single bond, and Here, R2 represents a hydrogen atom. Any one of the compounds of formula (I) described in item 1 or any pharmaceutically acceptable salt thereof. [Section 12] (1) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-(cyclopropylmethylamino)-1H-imidazole-5-one, (2) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-(cyclopropylamino)-1H-imidazole-5-one, (3) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-(cyclobutylamino)-1H-imidazole-5-one, (4) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-(cyclopentylamino)-1H-imidazole-5-one, (5) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-(cyclohexylmethylamino)-1H-imidazole-5-one, (6) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-(cyclohexylamino)-1H-imidazole-5-one, (7) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-(cycloheptylmethylamino)-1H-imidazole-5-one, (8) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-(cycloheptylamino)-1H-imidazole-5-one, (9) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-(cyclooctylamino)-1H-imidazole-5-one, (10) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[(3-hydroxy-2,2-dimethylpropyl)amino]-1H-imidazole-5-one, (11) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-(2-benzyloxyethylamino)-1H-imidazole-5-one, (12) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[cis-2-methylcyclohexyl]amino]-1H-imidazole-5-one, (13) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(1R)-1-cyclohexylethyl]amino]-1H-imidazole-5-one, (14) (4Z)-2-(1-adamantylmethylamino)-4-(1,3-benzothiazole-6-ylmethylene)-1H-imidazole-5-one, (15) (±)-(4Z)-2-[1-(1-adamantyl)ethylamino]-4-(1,3-benzothiazole-6-ylmethylene)-1H-imidazole-5-one, (16) (4Z)-2-(1-adamantylamino)-4-(1,3-benzothiazole-6-ylmethylene)-1H-imidazole-5-one, (17) (4Z)-2-(2-adamantylamino)-4-(1,3-benzothiazole-6-ylmethylene)-1H-imidazole-5-one, (18) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[3,5-dimethyl-1-adamantyl]amino]-1H-imidazole-5-one, (19) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[(trans-5-hydroxy-2-adamantyl)amino]-1H-imidazole-5-one, (20) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[(3-hydroxy-1-adamantyl)amino]-1H-imidazole-5-one, (21) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[(3-methoxy-1-adamantyl)amino]-1H-imidazole-5-one, (22) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(1R,2R,3R,5S)-2,6,6-trimethylnorpinan-3-yl]amino]-1H-imidazole-5-one, (23) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(1S,2S,3S,5R)-2,6,6-trimethylnorpinan-3-yl]amino]-1H-imidazole-5-one, (24) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(1R,2R,5R)-6,6-dimethylnorpinan-2-yl]methylamino]-1H-imidazole-5-one, (25) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-(spiro[2.5]octane-2-ylamino)-1H-imidazole-5-one, (26) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-(spiro[3.3]heptan-2-ylamino)-1H-imidazole-5-one, (27) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(2R)-1,7,7-trimethylnorboran-2-yl]amino]-1H-imidazole-5-one, (28) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-(norborane-2-ylamino)-1H-imidazole-5-one, (29) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(1R,2S,5R)-2-isopropyl-5-methylcyclohexyl]amino]-1H-imidazole-5-one, (30) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(1R)-1-(cyclohexylmethyl)-2-hydroxy-ethyl]amino]-1H-imidazole-5-one, (31) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(1R)-1-(cyclopentylmethyl)-2-hydroxy-ethyl]amino]-1H-imidazole-5-one, (32) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(1R)-1-(cyclobutylmethyl)-2-hydroxy-ethyl]amino]-1H-imidazole-5-one, (33) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(1R)-1-(cyclopropylmethyl)-2-hydroxy-ethyl]amino]-1H-imidazole-5-one, (34) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(1R)-1-(hydroxymethyl)-3-methyl-butyl]amino]-1H-imidazole-5-one, (35) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(1R)-1-(methoxymethyl)-3-methyl-butyl]amino]-1H-imidazole-5-one, (36) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(1S)-1-(hydroxymethyl)-3-methyl-butyl]amino]-1H-imidazole-5-one, (37) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(1S)-1-(methoxymethyl)-3-methyl-butyl]amino]-1H-imidazole-5-one, (38) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(1R)-1-(hydroxymethyl)propyl]amino]-1H-imidazole-5-one, (39) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(1S)-1-(hydroxymethyl)propyl]amino]-1H-imidazole-5-one, (40) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[1-(fluoromethyl)-3-methyl-butyl]amino]-1H-imidazole-5-one, (41) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[(1-cyclohexyl-2-hydroxyethyl)amino]-1H-imidazole-5-one, (42) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[(1-cyclohexyl-2-methoxyethyl)amino]-1H-imidazole-5-one, (43) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[(2-cyclohexyl-2-hydroxyethyl)amino]-1H-imidazole-5-one, (44) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[(2-cyclohexyl-2-methoxyethyl)amino]-1H-imidazole-5-one, (45) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[cis-2-hydroxycyclopentyl]amino]-1H-imidazole-5-one, (46) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[trans-2-hydroxycyclopentyl]amino]-1H-imidazole-5-one, (47) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[cis-2-methoxycyclopentyl]amino]-1H-imidazole-5-one, (48) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[trans-2-methoxycyclopentyl]amino]-1H-imidazole-5-one, (49) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[cis-2-hydroxycyclohexyl]amino]-1H-imidazole-5-one, (50) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[trans-2-hydroxycyclohexyl]amino]-1H-imidazole-5-one, (51) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(1R,2S)-2-hydroxycyclohexyl]amino]-1H-imidazole-5-one, (52) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(1S,2R)-2-hydroxycyclohexyl]amino]-1H-imidazole-5-one, (53) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(1R,2R)-2-hydroxycyclohexyl]amino]-1H-imidazole-5-one, (54) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(1S,2S)-2-hydroxycyclohexyl]amino]-1H-imidazole-5-one, (55) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[cis-3-hydroxycyclohexyl]amino]-1H-imidazole-5-one, (56) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[trans-3-hydroxycyclohexyl]amino]-1H-imidazole-5-one, (57) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[(trans-4-hydroxycyclohexyl)amino]-1H-imidazole-5-one, (58) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[cis-2-methoxycyclohexyl]amino]-1H-imidazole-5-one, (59) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[trans-2-methoxycyclohexyl]amino]-1H-imidazole-5-one, (60) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[(trans-4-methoxycyclohexyl)amino]-1H-imidazole-5-one, (61) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[cis-2-hydroxycycloheptyl]amino]-1H-imidazole-5-one, (62) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[trans-2-hydroxycycloheptyl]amino]-1H-imidazole-5-one, (63) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(1R,2R)-2-hydroxycycloheptyl]amino]-1H-imidazole-5-one, (64) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(1S,2S)-2-hydroxycycloheptyl]amino]-1H-imidazole-5-one, (65) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[cis-3-hydroxycycloheptyl]amino]-1H-imidazole-5-one, (66) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[trans-3-hydroxycycloheptyl]amino]-1H-imidazole-5-one, (67) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[cis-2-methoxycycloheptyl]amino]-1H-imidazole-5-one, (68) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[trans-2-methoxycycloheptyl]amino]-1H-imidazole-5-one, (69) (2S)-2-[[(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-5-oxo-1H-imidazole-2-yl]amino]-3-methylbutanoate methyl, (70) (2S)-2-[[(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-5-oxo-1H-imidazole-2-yl]amino]methyl propanoate, (71) (2S)-2-[[(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-5-oxo-1H-imidazole-2-yl]amino]-4-methylpentanoate methyl, (72) (2R)-2-[[(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-5-oxo-1H-imidazole-2-yl]amino]-4-methylpentanoate methyl, (73) (2S)-2-[[(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-5-oxo-1H-imidazole-2-yl]amino]-3-hydroxybutanoate methyl (74) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-(benzylamino)-1H-imidazole-5-one, (75) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-(indan-2-ylamino)-1H-imidazole-5-one, (76) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[(3,4-dimethylphenyl)methylamino]-1H-imidazole-5-one, (77) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[(2,4-dimethylphenyl)methylamino]-1H-imidazole-5-one, (78) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[2-(trifluoromethyl)phenyl]methylamino]-1H-imidazole-5-one, (79) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[2-(trifluoromethoxy)phenyl]methylamino]-1H-imidazole-5-one, (80) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[cis-2-hydroxyindan-1-yl]amino]-1H-imidazole-5-one, (81) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[trans-2-hydroxyindan-1-yl]amino]-1H-imidazole-5-one, (82) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(1R,2R)-2-hydroxyindan-1-yl]amino]-1H-imidazole-5-one, (83) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(1S,2S)-2-hydroxyindan-1-yl]amino]-1H-imidazole-5-one, (84) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[cis-2-methoxyindan-1-yl]amino]-1H-imidazole-5-one, (85) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[trans-2-methoxyindan-1-yl]amino]-1H-imidazole-5-one, (86) (2S)-2-[[(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-5-oxo-1H-imidazole-2-yl]amino]-3-phenyl-propanoate methyl, (87) (2R)-2-[[(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-5-oxo-1H-imidazole-2-yl]amino]-3-phenyl-propanoate methyl, (88) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[(2-fluoro-1-phenyl-ethyl)amino]-1H-imidazole-5-one, (89) (±)-(4Z)-2-[(2-amino-1-phenyl-ethyl)amino]-4-(1,3-benzothiazole-6-ylmethylene)-1H-imidazole-5-one dihydrochloride, (90) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[2-(methylamino)-1-phenylethyl]amino]-1H-imidazole-5-one dihydrochloride, (91) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[2-(dimethylamino)-1-phenyl-ethyl]amino]-1H-imidazole-5-one, (92) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[(1-benzyl-2-hydroxyethyl)amino]-1H-imidazole-5-one, (93) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(1R)-1-benzyl-2-hydroxyethyl]amino]-1H-imidazole-5-one, (94) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[(1-benzyl-2-methoxyethyl)amino]-1H-imidazole-5-one, (95) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[(2-hydroxy-1-phenylethyl)amino]-1H-imidazole-5-one, (96) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(1R)-2-hydroxy-1-phenylethyl]amino]-1H-imidazole-5-one, (97) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(1S)-2-hydroxy-1-phenylethyl]amino]-1H-imidazole-5-one, (98) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[(2-methoxy-1-phenylethyl)amino]-1H-imidazole-5-one, (99) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[(2-hydroxy-2-phenylethyl)amino]-1H-imidazole-5-one, (100) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[(2-methoxy-2-phenylethyl)amino]-1H-imidazole-5-one, (101) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[(2-hydroxy-3-phenylpropyl)amino]-1H-imidazole-5-one, (102) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[(2-methoxy-3-phenylpropyl)amino]-1H-imidazole-5-one, (103) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[(5-methylpyrazine-2-yl)methylamino]-1H-imidazole-5-one, (104) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-(2-pyridylmethylamino)-1H-imidazole-5-one, (105) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-(3-pyridylmethylamino)-1H-imidazole-5-one, (106) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-(4-pyridylmethylamino)-1H-imidazole-5-one, (107) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[(5-methyl-2-furyl)methylamino]-1H-imidazole-5-one, (108) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[(4-methylthiazole-2-yl)methylamino]-1H-imidazole-5-one, (109) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-(3-imidazole-1-ylpropylamino)-1H-imidazole-5-one, (110) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[2-(2-pyridyl)ethylamino]-1H-imidazole-5-one, (111) (4Z)-2-(1,3-benzothiazole-2-ylmethylamino)-4-(1,3-benzothiazole-6-ylmethylene)-1H-imidazole-5-one, (112) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[(1-methyl-4-piperidyl)methylamino]-1H-imidazole-5-one, (113) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-(tetrahydropyran-4-ylmethylamino)-1H-imidazole-5-one, (114) 4-[[[(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-5-oxo-1H-imidazole-2-yl]amino]methyl]piperidine-1-carboxylate Tert-butyl, (115) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[(7-methyl-7-azaspiro[3.5]nonan-2-yl)amino]-1H-imidazole-5-one, (116) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-(3-fluoro-4-methyl-anilino)-1H-imidazole-5-one, (117) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-(4-fluoroanilino)-1H-imidazole-5-one, (118) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-(4-hexylanilino)-1H-imidazole-5-one, (119) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[4-(4-methylpiperazine-1-yl)anilino]-1H-imidazole-5-one, (120) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[3-(difluoromethoxy)anilino]-1H-imidazole-5-one, (121) (4Z)-2-[(1-acetyldindrin-6-yl)amino]-4-(1,3-benzothiazole-6-ylmethylene)-1H-imidazole-5-one, (122) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[3-(trifluoromethyl)anilino]-1H-imidazole-5-one, (123) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-(indan-5-ylamino)-1H-imidazole-5-one, (124) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-(4-morpholinoanilino)-1H-imidazole-5-one, (125) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[(1-methylindazole-7-yl)amino]-1H-imidazole-5-one, (126) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-(pyrimidine-2-ylamino)-1H-imidazole-5-one, (127) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-(2-pyridylamino)-1H-imidazole-5-one, (128) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[(1-methylpyrazole-3-yl)amino]-1H-imidazole-5-one, (129) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[(2-methoxy-6-methyl-3-pyridyl)amino]-1H-imidazole-5-one, (130) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-(pyrimidine-5-ylamino)-1H-imidazole-5-one, (131) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-(3-pyridylamino)-1H-imidazole-5-one, (132) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-(1,3,4-thiadiazole-2-ylamino)-1H-imidazole-5-one, (133) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[5-(4-methylpiperazine-1-yl)-2-pyridyl]amino]-1H-imidazole-5-one, (134) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[6-(4-methylpiperazine-1-yl)-3-pyridyl]amino]-1H-imidazole-5-one, (135) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[2-(4-methylpiperazine-1-yl)pyrimidine-5-yl]amino]-1H-imidazole-5-one, (136) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[5-(4-methylpiperazine-1-yl)pyrimidine-2-yl]amino]-1H-imidazole-5-one, (137) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[5-(4-methylpiperazine-1-yl)pyrazine-2-yl]amino]-1H-imidazole-5-one, (138) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[6-(4-methylpiperazine-1-yl)pyridazin-3-yl]amino]-1H-imidazole-5-one, (139) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-(tetrahydropyran-4-ylamino)-1H-imidazole-5-one, (140) 4-[[(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-5-oxo-1H-imidazole-2-yl]amino]piperidine-1-carboxylate Tert-butyl, (141) 4-[[(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-5-oxo-1H-imidazole-2-yl]amino]piperidine-1-carboxylate ethyl, (142) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[(1-methyl-4-piperidyl)amino]-1H-imidazole-5-one, (143) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[(1-methyl-3-piperidyl)amino]-1H-imidazole-5-one, (144) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-(oxetane-3-ylamino)-1H-imidazole-5-one, (145) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(3R)-tetrahydrofuran-3-yl]amino]-1H-imidazole-5-one, (146) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(3S)-tetrahydrofuran-3-yl]amino]-1H-imidazole-5-one, (147) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(3R)-tetrahydropyran-3-yl]amino]-1H-imidazole-5-one, (148) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(3S)-tetrahydropyran-3-yl]amino]-1H-imidazole-5-one, (149) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[(6,6-dimethyltetrahydropyran-3-yl)amino]-1H-imidazole-5-one, (149A) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(3R) / (3S)-6,6-dimethyltetrahydropyran-3-yl]amino]-1H-imidazole-5-one, (149B) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(3R) / (3S)-6,6-dimethyltetrahydropyran-3-yl]amino]-1H-imidazole-5-one, (150) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(3R,4R)-4-hydroxytetrahydropyran-3-yl]amino]-1H-imidazole-5-one, (151) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-(oxepan-3-ylamino)-1H-imidazole-5-one, (152) (±)-3-[[(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-5-oxo-1H-imidazole-2-yl]amino]piperidine-2-one, (153) (3S)-3-[[(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-5-oxo-1H-imidazole-2-yl]amino]piperidine-2-one, (154) (5S)-5-[[(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-5-oxo-1H-imidazole-2-yl]amino]piperidine-2-one, (155) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[(3,3-difluorocyclopentyl)amino]-1H-imidazole-5-one, (156) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[(4,4-difluorocyclohexyl)amino]-1H-imidazole-5-one, (157) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[(3,3-difluorocyclohexyl)amino]-1H-imidazole-5-one, (158) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[(2,2-difluorocyclohexyl)amino]-1H-imidazole-5-one, (159) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[(3,3-difluorocycloheptyl)amino]-1H-imidazole-5-one, (160) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(1R)-1-(fluoromethyl)-3-methyl-butyl]amino]-1H-imidazole-5-one, (161) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(1S)-1-(fluoromethyl)-3-methyl-butyl]amino]-1H-imidazole-5-one, (162) [3-[[(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-5-oxo-1H-imidazole-2-yl]amino]-1-adamantyl]acetate, (163) [3-[[(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-5-oxo-1H-imidazole-2-yl]amino]-1-adamantyl]2,2-dimethylpropanoate, (164) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(1R,2R)-2-methoxycyclopentyl]amino]-1H-imidazole-5-one, (165) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(1S,2S)-2-methoxycyclopentyl]amino]-1H-imidazole-5-one, (166) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(1R,2R)-2-methoxycyclohexyl]amino]-1H-imidazole-5-one, (167) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(1S,2S)-2-methoxycyclohexyl]amino]-1H-imidazole-5-one, (168) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[cis-3-methoxycyclohexyl]amino]-1H-imidazole-5-one, (169) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[trans-3-methoxycyclohexyl]amino]-1H-imidazole-5-one, (169A) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(1R,3R) / (1S,3S)-3-methoxycyclohexyl]amino]-1H-imidazole-5-one, (169B) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(1R,3R) / (1S,3S)-3-methoxycyclohexyl]amino]-1H-imidazole-5-one, (170) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[cis-4-hydroxycycloheptyl]amino]-1H-imidazole-5-one, (171) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[trans-4-hydroxycycloheptyl]amino]-1H-imidazole-5-one, (171A) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(1R,4R) / (1S,4S)-4-hydroxycycloheptyl]amino]-1H-imidazole-5-one, (171B) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(1R,4R) / (1S,4S)-4-hydroxycycloheptyl]amino]-1H-imidazole-5-one, (172) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[cis-3-methoxycycloheptyl]amino]-1H-imidazole-5-one, (173) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[trans-3-methoxycycloheptyl]amino]-1H-imidazole-5-one, (174) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[cis-4-methoxycycloheptyl]amino]-1H-imidazole-5-one, (175) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[trans-4-methoxycycloheptyl]amino]-1H-imidazole-5-one, (176) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(1R)-2-methoxy-1-phenylethyl]amino]-1H-imidazole-5-one, (177) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(1S)-2-methoxy-1-phenylethyl]amino]-1H-imidazole-5-one, (178) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(2R)-2-hydroxy-2-phenylethyl]amino]-1H-imidazole-5-one, (179) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(2S)-2-hydroxy-2-phenylethyl]amino]-1H-imidazole-5-one, (180) (4Z)-2-[[(1R)-2-amino-1-phenylethyl]amino]-4-(1,3-benzothiazole-6-ylmethylene)-1H-imidazole-5-one dihydrochloride, (181) (4Z)-2-[[(1S)-2-amino-1-phenylethyl]amino]-4-(1,3-benzothiazole-6-ylmethylene)-1H-imidazole-5-one dihydrochloride, (182) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(3R)-quinuclidin-3-yl]amino]-1H-imidazole-5-one, (183) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(3S)-quinuclidin-3-yl]amino]-1H-imidazole-5-one, (184) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-(tetrahydrothiopyran-3-ylamino)-1H-imidazole-5-one, (185) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-(1,4-dioxepan-6-ylamino)-1H-imidazole-5-one, (186) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[(2-oxopyrrolidine-3-yl)amino]-1H-imidazole-5-one, (187) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[(1-methyl-2-oxo-pyrrolidine-3-yl)amino]-1H-imidazole-5-one, (188) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[(4,4-dimethyl-2-oxo-pyrrolidine-3-yl)amino]-1H-imidazole-5-one, (189) (3R)-3-[[(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-5-oxo-1H-imidazole-2-yl]amino]piperidine-2-one, (190) (±)-3-[[(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-5-oxo-1H-imidazole-2-yl]amino]-1-methyl-piperidine-2-one, (191) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[(3-methyl-2-oxo-pyrrolidine-3-yl)amino]-1H-imidazole-5-one, (192) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[(1,3-dimethyl-2-oxo-pyrrolidine-3-yl)amino]-1H-imidazole-5-one, (192A) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(3R) / (3S)-1,3-dimethyl-2-oxo-pyrrolidine-3-yl]amino]-1H-imidazole-5-one, (192B) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(3R) / (3S)-1,3-dimethyl-2-oxo-pyrrolidine-3-yl]amino]-1H-imidazole-5-one, (193) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(3S,4S)-4-hydroxytetrahydropyran-3-yl]amino]-1H-imidazole-5-one, (194) (4Z)-2-(3-noadamantylamino)-4-(1,3-benzothiazole-6-ylmethylene)-1H-imidazole-5-one, (195) 3-[[(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-5-oxo-1H-imidazole-2-yl]amino]-1-adamantyl]N-tert-butylcarbamate, (196) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[(3-fluoro-1-adamantyl)amino]-1H-imidazole-5-one, (197) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(1R)-1-(tert-butoxymethyl)-3-methyl-butyl]amino]-1H-imidazole-5-one, (198) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(1R)-2-tert-butoxy-1-phenylethyl]amino]-1H-imidazole-5-one, (199) N-[3-[[(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-5-oxo-1H-imidazole-2-yl]amino]-1-adamantyl]acetamide, (200) N-[3-[[(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-5-oxo-1H-imidazole-2-yl]amino]-1-adamantyl]cyclopropanecarboxamide, (201) N-[3-[[(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-5-oxo-1H-imidazole-2-yl]amino]-1-adamantyl]methanesulfonamide, (202) N-[3-[[(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-5-oxo-1H-imidazole-2-yl]amino]-1-adamantyl]cyclopropanesulfonamide, (203) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[3-(dimethylamino)-1-adamantyl]amino]-1H-imidazole-5-one, (204) 2-[[(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-5-oxo-1H-imidazole-2-yl]amino]adamantane-2-carboxylate methyl, (205) (4Z)-2-(cyclohexylamino)-4-[(2-methyl-1,3-benzothiazole-6-yl)methylene]-1H-imidazole-5-one, (206) (4Z)-2-(cycloheptylamino)-4-[(2-methyl-1,3-benzothiazole-6-yl)methylene]-1H-imidazole-5-one, (207) (4Z)-2-[[(1R)-1-(methoxymethyl)-3-methyl-butyl]amino]-4-[(2-methyl-1,3-benzothiazole-6-yl)methylene]-1H-imidazole-5-one, (208) (4Z)-2-[[(1R)-2-methoxy-1-phenylethyl]amino]-4-[(2-methyl-1,3-benzothiazole-6-yl)methylene]-1H-imidazole-5-one, (209) (4Z)-2-(1-adamantylamino)-4-[(2-methyl-1,3-benzothiazole-6-yl)methylene]-1H-imidazole-5-one, and (210) (4Z)-2-[(3-hydroxy-1-adamantyl)amino]-4-[(2-methyl-1,3-benzothiazole-6-yl)methylene]-1H-imidazole-5-one, (211) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[(3,5-dihydroxy-1-adamantyl)amino]-1H-imidazole-5-one, (212) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[(3,5,7-trifluoro-1-adamantyl)amino]-1H-imidazole-5-one, (213) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(1R)-1-(ethoxymethyl)-3-methyl-butyl]amino]-1H-imidazole-5-one, (214) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(1R)-1-(benzyloxymethyl)-3-methyl-butyl]amino]-1H-imidazole-5-one, (215) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(1R)-1-[(4-fluorophenyl)methoxymethyl]-3-methyl-butyl]amino]-1H-imidazole-5-one, (216) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(1R)-1-(cyclopropoxymethyl)-3-methyl-butyl]amino]-1H-imidazole-5-one, One of the compounds of formula (I) described in any one of items 1 to 5, or any pharmaceutically acceptable salt thereof, selected from the above. [Section 13] A pharmaceutical composition comprising at least one compound or pharmaceutically acceptable salt thereof as described in any one of items 1 to 11, or a compound or salt described in item 12. [Section 14] A method for synthesizing at least one compound or pharmaceutically acceptable salt thereof as described in any one of items 1 to 11, or a compound or salt described in item 12, wherein the compound of formula (II) below is R 1 NH 2 The process includes at least the step of coupling with an amine, 1 and R 2 The method, wherein is as defined in any one of items 1 to 11.

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Claims

1. Any one of the compounds of formula (I) below, or any pharmaceutically acceptable salt thereof. 【Chemistry 1】 Here, R 1 teeth, (i) -COOR a Substituted with one or two groups selected from the following: (C) group, hydroxyl group, halogen atom, -O-(C1-C4) alkyl group, -O-(C3-C4) cycloalkyl group, and benzyloxy group. 1 ~C 6 ) an alkyl group, where the benzyloxy may be substituted with 1 to 3 halogen atoms on its phenyl group, (ii) Spiro(C 5 ~C 11 ) bicyclic ring, (iii). (C 5 - C 6 ) cycloalkyl or a phenyl group fused with (C 5 - C 6 ) heterocycloalkyl, wherein the (C 5 - C 6 ) cycloalkyl and (C 5 - C 6 ) heterocycloalkyl rings may contain unsaturation, and may be substituted by a (C 1 - C 4 ) alkyl group, a hydroxy group, a halogen atom, an -O-(C1 - C3) alkyl group or a -COR a group, (iv) (C 1 ~C 8 ) alkyl, (C 1 ~C 3 ) fluoroalkyl, -O-fluorosubstituted (C1-C4) alkyl, halogen atom and (C 4 ~C 7 A phenyl group substituted with one or two groups selected from heterocycloalkyl groups, wherein the (C 4 ~C 7 ) Heterocycloalkyl groups are themselves (C 1 ~C 4 ) may be substituted with an alkyl group, or (v) R'-L- group, where, L is a single bond or (C 1 ~C 3 ) is any of the alkanediyl groups, where (C 1 ~C 3 The alkanediyl group may be substituted with one group selected from a hydroxyl group and an -O-(C1-C3) alkyl group, R' is (v.1). (C 1 ~C 4 ) may be substituted with one, two, or three groups selected from alkyl groups, hydroxyl groups, halogen atoms, and -O-(C1-C3) alkyl groups (C 3 ~C 8 ) Cycloalkyl groups, (v.2). (C 1 ~C 4 )alkyl group, -O-(C1-C4)alkyl group, halogen atom, hydroxyl group, -OC(O)-R d group, -OC(O)-NHR d Base, -NH-C(O)-R d Base, -SO 2 -R d group, -N(R e ) 2 Base and -COOR a A cross-linked (C) which may be substituted by 1 to 3 groups selected from the group. 6 ~C 10 ) Cycloalkyl groups, (v.3) -COOR a group, hydroxyl group, halogen atom, (C 1 ~C 4 )May be substituted with 1 to 3 groups selected from alkyl groups and oxo groups (C 3 ~C 8 ) Heterocycloalkyl groups, (v.4) Halogen atom, (C 1 ~C 4 ) may be substituted with 1 to 3 groups selected from alkyl groups, -O-(C1-C4) alkyl groups and N-methylpiperazinyl groups (C 5 ~C 11 ) Heteroaryl group, or, (v.5) Bridged (C 6 ~C 10 ) Heterocycloalkyl Representing, Or, (vi) R f -L f -Base, here, L f , NR b R c Group, -O-(C1-C4)alkyl group, hydroxyl group, -COOR a It may be substituted with a group selected from the group and halogen atoms (C 1 ~C 3 ) is an alkanediyl group, and also, R f is, (C 1 ~C 6 ) alkyl groups, fluoro(C 1 ~C 4 A phenyl group which may be substituted with 1 to 3 groups selected from the group consisting of alkyl groups and -O-fluorosubstituted (C1-C4) alkyl groups, halogen atoms and hydroxyl groups. Here, R a is, (C 1 ~C 4 ) Represents an alkyl group or a hydrogen atom, R b and R c (C 1 ~C 6 ) Represents an alkyl group or a hydrogen atom, R d is, (C 1 ~C 4 ) Represents an alkyl group or a cyclopropyl group, R e is, (C 1 ~C 3 ) Represents an alkyl group, Represents, and R 2 However, hydrogen atoms or (C 1 ~C 3 ) Represents an alkyl group, However, excluding the following compounds 【Chemistry 4】 。

2. Here, R 1 but, (i). -COOR a A (C 2 ~C 6 )alkyl group substituted by one or two groups selected from a group consisting of a -COOR group, a hydroxy group, a halogen atom, an -O-(C1-C4)alkyl group, an -O-(C3-C4)cycloalkyl group, and a benzyloxy group, wherein the benzyloxy may be substituted by 1 to 3 halogen atoms on its phenyl group, (ii) Spiro(C 7 ~C 9 ) bicyclic ring, (iii) A condensed phenyl group selected from a phenyl group condensed with cyclopentyl or heterocyclopentyl, wherein the cyclopentyl group and heterocyclopentyl group may be unsaturated, and (C 1 ~C 4 ) Alkyl group, hydroxyl group, halogen atom, -O-(C1-C3) alkyl group or -COR a It may be substituted by the group, (iv). (C 1 ~C 8 ) alkyl, (C 1 ~C 3 ) fluoroalkyl, -O-fluoro-substituted (C1-C4) alkyl group, halogen atom, and a phenyl group substituted by one or two groups selected from (C 4 ~C 7 ) heterocycloalkyl group, wherein the (C 4 ~C 7 ) heterocycloalkyl group may itself be substituted by a (C 1 ~C 4 ) alkyl group, or (v) R'-L- group, where, L is a single bond or (C 1 ~C 3 ) is any of the alkanediyl groups, where (C 1 ~C 3 The alkanediyl group may be substituted with one group selected from a hydroxyl group and an -O-(C1-C3) alkyl group, R' is (v.1). (C 1 ~C 4 ) may be substituted with one, two, or three groups selected from alkyl groups, hydroxyl groups, fluorine atoms, and -O-(C1-C3) alkyl groups (C 3 ~C 8 ) Cycloalkyl groups, (v.2). (C 1 ~C 4 )alkyl group, -O-(C1-C4)alkyl group, hydroxyl group, halogen atom, -OC(O)-R d group, -OC(O)-NHR d Base, -NH-C(O)-R d Base, -SO 2 -R d group, -N(R e ) 2 Base and -COOR a A cross-linked (C) which may be substituted by 1 to 3 groups selected from the group. 7 ~C 10 ) Cycloalkyl groups, (v.3) -COOR a group, hydroxyl group, halogen atom, (C 1 ~C 4 )May be substituted with 1 to 3 groups selected from alkyl groups and oxo groups (C 3 ~C 8 ) Heterocycloalkyl groups, (v.4) Halogen atom, (C 1 ~C 4 ) may be substituted with 1 to 3 groups selected from alkyl groups, -O-(C1-C4) alkyl groups, and N-methylpiperazinyl groups (C 5 ~C 11 ) Heteroaryl group, or, (v.5) Bridged (C 6 ~C 10 ) Heterocycloalkyl Representing, Or, (vi) R f -L f -Base, here, L f -NR b R c Group, -O-(C1-C4) alkyl group, hydroxyl group, -COOR a It may be substituted with a group selected from the group and halogen atoms (C 1 ~C 3 ) is an alkanediyl group, and also, R f is, (C 1 ~C 6 ) alkyl groups, fluoro(C 1 ~C 4 A phenyl group which may be substituted with 1 to 3 groups selected from the group consisting of alkyl groups and -O-fluorosubstituted (C1-C4) alkyl groups, hydroxyl groups and halogen atoms. Here, R a is, (C 1 ~C 4 ) Represents an alkyl group or a hydrogen atom, R b and R c (C 1 ~C 6 ) Represents an alkyl group or a hydrogen atom, R d is, (C 1 ~C 4 ) Represents an alkyl group or a cyclopropyl group, R e is, (C 1 ~C 3 ) Represents an alkyl group, It represents, and also, R 2 However, hydrogen atoms or (C 1 ~C 3 ) Represents an alkyl group, Any one of the compounds of formula (I) described in claim 1 or a pharmaceutically acceptable salt thereof.

3. Here, R 1 but, (i) -COOCH 3 Substituted with one or two groups selected from the following: a hydroxyl group, a fluorine atom, a methoxy group, an ethoxy group, a tert-butoxy group, a cyclopropoxy group, and a benzyloxy group (C 2 ~C 6 ) an alkyl group, where the benzyloxy may be substituted with one fluorine atom on its phenyl group, (ii) Spiro(C 7 ~C 8 ) bicyclic ring, (iii) A condensed phenyl group selected from a phenyl group condensed with cyclopentyl or heterocyclopentyl, wherein the cyclopentyl group and heterocyclopentyl group may include unsaturated groups, as well as methyl, hydroxyl, methoxy and -COCH 3 It may be substituted by the group, (iv) A phenyl group substituted with one or two groups selected from methyl, hexyl, trifluoromethyl, difluoromethoxy, halogen atom, morpholino group and N-methylpiperazinyl group, (v) R'-L- group, where, L is a single bond or (C 1 ~C 3 ) is any of the alkanediyl groups, where (C 1 ~C 3 The alkanediyl group may be substituted with one group selected from a hydroxyl group and an -O-(C1-C3) alkyl group, R' is (v.1) It may be substituted with one, two, or three groups selected from methyl, isopropyl, hydroxy, and methoxy groups (C 3 ~C 8 ) Cycloalkyl groups, (v.2) Methyl group, methoxy group, hydroxyl group, fluorine atom, -OC(O)-CH 3 group, -OC(O)-C(CH 3 ) 3 group, -OC(O)-NH-C(CH 3 ) 3 group, -NH-C(O)-CH 3 group, -NH-C(O)-C 3 H 5 group, -S(O) 2 -CH 3 group, -S(O) 2 -C 3 H 5 group, -N(CH 3 ) 2 The group and -C(O)-O-CH 3 A cross-linked (C) which may be substituted by 1 to 3 groups selected from the group. 7 ~C 10 ) Cycloalkyl groups, (v.3) -COOR a It may be substituted with one, two, or three groups selected from the group, hydroxyl group, methyl group, and oxo group (C 5 ~C 8 ) Heterocycloalkyl group, where R a This represents either an ethyl group or an isopropyl group. (v.4) It may be substituted with 1 to 3 groups selected from a methyl group, a methoxy group and an N-methylpiperazinyl group (C 5 ~C 11 ) Heteroaryl group, or, (v.5) Bridged (C 7 ~C 10 ) Heterocycloalkyl groups, or (vi) R f -L f -Base, here, L f -NR b R c Group, -O-(C1-C4) alkyl group, hydroxyl group, -COOR a It may be substituted with one group selected from the group consisting of a group and a halogen atom (C 1 ~C 3 ) is an alkanediyl group, R a is, (C 1 -C 3 ) represents an alkyl group, and also, R f This is a phenyl group which may be substituted with one or two groups selected from the group consisting of a methyl group, a trifluoromethyl group, and a trifluoromethoxy group. R b and R c These independently represent a methyl group or a hydrogen atom. Selected from the group consisting of, R 2 However, hydrogen atoms or (C 1 ~C 3 ) Represents an alkyl group, Any one of the compounds of formula (I) described in claim 1 or 2, or a pharmaceutically acceptable salt thereof.

4. L is -CH 2 -base, -CH(CH 3 )-base, -CH(CH 2 OH)-CH 2 -base, -CH(CH 2 OH)- group, -CH(CH 2 OCH 3 )-base, -CH(OH)-CH 2 -group, -CH 2 -CH(CH 2 OCH 3 )-base, -CH(OCH 3 )-CH 2 -group, -CH 2 -CH(CH 2 OH)- group, -CH(OCH 3 )-CH 2 -group, -CH 2 -CH(OCH 3 )-group, -CH 2 -CH(OH)-CH 2 -group, -CH 2 -CH(OCH 3 )-CH 2 group, -(CH 2 ) 3 -Base and -(CH 2 ) 2 - Selected from a group consisting of groups, and / or L f However, -CH 2 -base, -CH(CH 3 )-base, -CH(CH 2 OH)-CH 2 -base, -CH(CH 2 OH)- group, -CH(CH 2 OCH 3 )-base, -CH(OH)-CH 2 -group, -CH 2 -CH(CH 2 OCH 3 )-base, -CH(OCH 3 )-CH 2 -group, -CH 2 -CH(COOCH 3 )-base, -CH(CH 2 F)-group, -CH(CH 2 NH 2 )-base, -CH(CH 2 NHCH 3 )-base, -CH(CH 2 N(CH 3 ) 2 )-group, -CH 2 -CH(CH 2 OH)- group, -CH(OCH 3 )-CH 2 -group, -CH 2 -CH(OCH 3 )-group, -CH 2 -CH(OH)-CH 2 -group, -CH 2 -CH(OCH 3 )-CH 2 group, -(CH 2 ) 3 - group, -(CH 2 ) 2 - group and -CH(CH 2 OC(CH 3 ) 3 A compound of formula (I) according to any one of claims 1 to 3, or a pharmaceutically acceptable salt thereof, selected from the group consisting of ) groups.

5. (v.1) R' is (C 3 ~C 8 )When it is a cycloalkyl group, L is a single bond, -CH 2 -base, -CH(CH 3 )-base, -CH(CH 2 OH)-CH 2 -base, -CH(CH 2 OH)- group, -CH(CH 2 OCH 3 )-group, and -CH(OH)-CH 2 - group and -CH(OCH 3 )-CH 2 - Selected from a group consisting of members, (v.2) R' is bridged (C 7 ~C 10 )When it is a cycloalkyl group, L is a single bond, -CH 2 - group or -CH(CH 3 )-Based, (v.3) R' is spiro(C 3 ~C 8 ) containing heterocycloalkyl (C 5 ~C 8 ) When it is a heterocycloalkyl group, L is a single bond or -CH 2 - is a base, (v.4) R f When L is phenyl, f is, -CH 2 -group, -CH 2 -CH(COOCH 3 )-base, -CH(CH 2 F)-group, -CH(CH 2 NH 2 )-base, -CH(CH 2 NHCH 3 )-base, CH(CH 2 N(CH 3 ) 2 )-group, -CH 2 -CH(CH 2 OH)- group, -CH(CH 2 OH)- group, -CH(CH 2 OCH 3 )-base, -CH(OH)-CH 2 -group, -CH 2 -CH(CH 2 OCH 3 )-group, -CH 2 -CH(OH)-CH 2 - group and -CH 2 -CH(OCH 3 )-CH 2 Selected from a group consisting of elements, (v.5) R' is (C 5 ~C 11 )When it is a heteroaryl group, L is a single bond, -CH 2 - group, -(CH 2 ) 3 -Base and -(CH 2 ) 2 - Selected from a group consisting of members, (v.6) R' is bridged (C 7 ~C 10 ) When it is a heterocycloalkyl group, L is a single bond. One of the compounds of formula (I) described in any one of claims 1 to 4, or a pharmaceutically acceptable salt thereof.

6. Here, R 1 but, Methyl group, methoxy group, hydroxyl group, fluorine atom, -OC(O)-CH 3 group, -OC(O)-C(CH 3 ) 3 group, -OC(O)-NH-C(CH 3 ) 3 group, -NH-C(O)-CH 3 group, -NH-C(O)-C 3 H 5 group, -S(O) 2 -CH 3 group, -S(O) 2 -C 3 H 5 group, -N(CH 3 ) 2 The group and -C(O)-O-CH 3 Adamantyl groups which may be substituted by 1 to 3 groups selected from the group; or, R"-O-CH 2 -CH(R"')- base, where R” is (C 1 ~C 4 ) is an alkyl group, and R"' is (C 1 ~C 4 ) is an alkyl group, or, R"' is (C 1 ~C 6 ) alkyl groups, fluoro(C 1 ~C 4 ) A phenyl group which may be substituted with 1 to 3 groups selected from the group consisting of alkyl groups, -O-fluorosubstituted (C1-C4) alkyl groups, halogen atoms, and hydroxyl groups. A compound of formula (I) according to any one of claims 1 to 5, or a pharmaceutically acceptable salt thereof, which represents the above.

7. Here, R 1 but, -COOR a Substituted with one or two groups selected from the following: (C) group, hydroxyl group, fluorine atom, -O-(C1-C4) alkyl group, -O-(C3-C4) cycloalkyl group, and benzyloxy group. 1 ~C 6 ) an alkyl group, where the benzyloxy may be substituted with 1 to 3 halogen atoms on its phenyl group, Spiro (C 5 ~C 11 ) Biring ring, or R'-L- group, here, L is a single bond or (C 1 ~C 3 ) is any of the alkanediyl groups, where (C 1 ~C 3 The alkanediyl group may be substituted with a group selected from a hydroxyl group and an -O-(C1-C3) alkyl group. It represents, and also, R' is Halogen atom, (C 1 ~C 4 ) may be substituted with one, two, or three groups selected from alkyl groups, hydroxyl groups, and -O-(C1-C3) alkyl groups (C 3 ~C 8 ) Cycloalkyl groups, and, (C 1 ~C 4 )alkyl group, -O-(C1-C4)alkyl group, halogen atom, hydroxyl group, -OC(O)-R d group, -OC(O)-NHR d Base, -NH-C(O)-R d Base, -SO 2 -R d group, -N(R e ) 2 Base, and -COOR a A cross-linked (C) which may be substituted by 1 to 3 groups selected from the group. 6 ~C 10 ) Cycloalkyl groups, Here, R a is (C 1 ~C 4 ) Represents an alkyl group, R d is, (C 1 ~C 4 ) Represents an alkyl group or a cyclopropyl group, and R e is (C 1 ~C 3 ) Represents an alkyl group Selected from the group consisting of, Here, R 2 However, hydrogen atoms or (C 1 ~C 3 ) Represents an alkyl group, Any one of the compounds of formula (I) described in claim 1 or a pharmaceutically acceptable salt thereof.

8. Here, R 1 but, (C 5 ~C 6 )Cycloalkyl or (C 5 ~C 6 ) A condensed phenyl group selected from a phenyl group condensed with a heterocycloalkyl group, where (C 5 ~C 6 )cycloalkyl and (C 5 ~C 6 ) The heterocycloalkyl group may contain unsaturated elements, and also (C 1 ~C 4 ) alkyl groups, hydroxyl groups, halogen atoms, -O-(C1-C3) alkyl groups, and -COR a It may be substituted by the group, (C 1 ~C 8 ) alkyl, (C 1 ~C 3 ) fluoroalkyl, -O-fluorosubstituted (C1-C4) alkyl, halogen atom and (C 4 ~C 7 A phenyl group substituted with one or two groups selected from heterocycloalkyl groups, wherein the (C 4 ~C 7 ) Heterocycloalkyl groups are themselves (C 1 ~C 4 ) may be substituted with an alkyl group, or R f -L f -Base, here, L f However, hydroxyl group, -O-(C1-C4) alkyl group, -NR b R c group, -COOR a It may be substituted with a group selected from the group and halogen atoms (C 1 ~C 3 ) is an alkanediyl group, and also, R f However, (C 1 ~C 6 ) alkyl groups, fluoro(C 1 ~C 4 A phenyl group which may be substituted with alkyl groups, and -O-fluorosubstituted (C1-C4) alkyl groups, halogen atoms, and hydroxyl groups, Here, R a is, (C 1 ~C 4 ) an alkyl or hydrogen atom, and R b and R c (C 1 ~C 6 ) Selected from alkyl and hydrogen atoms, It represents, and also, R 2 However, hydrogen atoms or (C 1 ~C 3 ) Represents an alkyl group, Any one of the compounds of formula (I) described in claim 1 or a pharmaceutically acceptable salt thereof.

9. R 2 However, one of the compounds of formula (I) described in any one of claims 1 to 8, or a pharmaceutically acceptable salt thereof, which represents a hydrogen atom or a methyl group.

10. R 1 This represents the R'-L- group, where, R' is a halogen atom, (C 1 ~C 4 ) may be substituted with 1 to 3 groups selected from alkyl groups, -O-(C1-C4) alkyl groups and N-methylpiperazinyl groups (C 5 ~C 11 ) is a heteroaryl group, and, L, (C 1 ~C 3 ) Alkanediyl or single bond, and Here, R 2 This represents a hydrogen atom. Any one of the compounds of formula (I) described in claim 1 or a pharmaceutically acceptable salt thereof.

11. Here, R 1 This represents the R'-L- group, where, R' is a hydroxyl group, (C 1 ~C 4 ) Alkyl group, oxo group and -COOR a It may be substituted by 1 to 3 groups selected from the group (C 3 ~C 5 ) is a heterocycloalkyl group, where R a This is as defined in claim 1, and L is methylene or a single bond, and Here, R 2 This represents a hydrogen atom. Any one of the compounds of formula (I) described in claim 1 or a pharmaceutically acceptable salt thereof.

12. (2) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-(cyclopropylamino)-1H-imidazole-5-one, (3) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-(cyclobutylamino)-1H-imidazole-5-one, (4) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-(cyclopentylamino)-1H-imidazole-5-one, (5) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-(cyclohexylmethylamino)-1H-imidazole-5-one, (6) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-(cyclohexylamino)-1H-imidazole-5-one, (7) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-(cycloheptylmethylamino)-1H-imidazole-5-one, (8) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-(cycloheptylamino)-1H-imidazole-5-one, (9) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-(cyclooctylamino)-1H-imidazole-5-one, (10) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[(3-hydroxy-2,2-dimethylpropyl)amino]-1H-imidazole-5-one, (11) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-(2-benzyloxyethylamino)-1H-imidazole-5-one, (12) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[cis-2-methylcyclohexyl]amino]-1H-imidazole-5-one, (13) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(1R)-1-cyclohexylethyl]amino]-1H-imidazole-5-one, (14) (4Z)-2-(1-adamantylmethylamino)-4-(1,3-benzothiazole-6-ylmethylene)-1H-imidazole-5-one, (15) (±)-(4Z)-2-[1-(1-adamantyl)ethylamino]-4-(1,3-benzothiazole-6-ylmethylene)-1H-imidazole-5-one, (16) (4Z)-2-(1-adamantylamino)-4-(1,3-benzothiazole-6-ylmethylene)-1H-imidazole-5-one, (17) (4Z)-2-(2-adamantylamino)-4-(1,3-benzothiazole-6-ylmethylene)-1H-imidazole-5-one, (18) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[3,5-dimethyl-1-adamantyl]amino]-1H-imidazole-5-one, (19) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[(trans-5-hydroxy-2-adamantyl)amino]-1H-imidazole-5-one, (20) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[(3-hydroxy-1-adamantyl)amino]-1H-imidazole-5-one, (21) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[(3-methoxy-1-adamantyl)amino]-1H-imidazole-5-one, (22) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(1R,2R,3R,5S)-2,6,6-trimethylnorpinan-3-yl]amino]-1H-imidazole-5-one, (23) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(1S,2S,3S,5R)-2,6,6-trimethylnorpinan-3-yl]amino]-1H-imidazole-5-one, (24) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(1R,2R,5R)-6,6-dimethylnorpinan-2-yl]methylamino]-1H-imidazole-5-one, (25) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-(spiro[2.5]octane-2-ylamino)-1H-imidazole-5-one, (26) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-(spiro[3.3]heptan-2-ylamino)-1H-imidazole-5-one, (27) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(2R)-1,7,7-trimethylnorbornan-2-yl]amino]-1H-imidazole-5-one, (28) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-(norbornan-2-ylamino)-1H-imidazole-5-one, (29) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(1R,2S,5R)-2-isopropyl-5-methylcyclohexyl]amino]-1H-imidazole-5-one, (30) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(1R)-1-(cyclohexylmethyl)-2-hydroxy-ethyl]amino]-1H-imidazole-5-one, (31) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(1R)-1-(cyclopentylmethyl)-2-hydroxy-ethyl]amino]-1H-imidazole-5-one, (32) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(1R)-1-(cyclobutylmethyl)-2-hydroxy-ethyl]amino]-1H-imidazole-5-one, (33) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(1R)-1-(cyclopropylmethyl)-2-hydroxy-ethyl]amino]-1H-imidazole-5-one, (34) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(1R)-1-(hydroxymethyl)-3-methyl-butyl]amino]-1H-imidazole-5-one, (35) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(1R)-1-(methoxymethyl)-3-methyl-butyl]amino]-1H-imidazole-5-one, (36) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(1S)-1-(hydroxymethyl)-3-methyl-butyl]amino]-1H-imidazole-5-one, (37) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(1S)-1-(methoxymethyl)-3-methyl-butyl]amino]-1H-imidazole-5-one, (38) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(1R)-1-(hydroxymethyl)propyl]amino]-1H-imidazole-5-one, (39) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(1S)-1-(hydroxymethyl)propyl]amino]-1H-imidazole-5-one, (40) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[1-(fluoromethyl)-3-methyl-butyl]amino]-1H-imidazole-5-one, (41) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[(1-cyclohexyl-2-hydroxyethyl)amino]-1H-imidazole-5-one, (42) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[(1-cyclohexyl-2-methoxyethyl)amino]-1H-imidazole-5-one, (43) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[(2-cyclohexyl-2-hydroxyethyl)amino]-1H-imidazole-5-one, (44) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[(2-cyclohexyl-2-methoxyethyl)amino]-1H-imidazole-5-one, (45) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[cis-2-hydroxycyclopentyl]amino]-1H-imidazole-5-one, (46) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[trans-2-hydroxycyclopentyl]amino]-1H-imidazole-5-one, (47) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[cis-2-methoxycyclopentyl]amino]-1H-imidazole-5-one, (48) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[trans-2-methoxycyclopentyl]amino]-1H-imidazole-5-one, (49) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[cis-2-hydroxycyclohexyl]amino]-1H-imidazole-5-one, (50) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[trans-2-hydroxycyclohexyl]amino]-1H-imidazole-5-one, (51) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(1R,2S)-2-hydroxycyclohexyl]amino]-1H-imidazole-5-one, (52) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(1S,2R)-2-hydroxycyclohexyl]amino]-1H-imidazole-5-one, (53) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(1R,2R)-2-hydroxycyclohexyl]amino]-1H-imidazole-5-one, (54) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(1S,2S)-2-hydroxycyclohexyl]amino]-1H-imidazole-5-one, (55) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[cis-3-hydroxycyclohexyl]amino]-1H-imidazole-5-one, (56) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[trans-3-hydroxycyclohexyl]amino]-1H-imidazole-5-one, (57) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[(trans-4-hydroxycyclohexyl)amino]-1H-imidazole-5-one, (58) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[cis-2-methoxycyclohexyl]amino]-1H-imidazole-5-one, (59) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[trans-2-methoxycyclohexyl]amino]-1H-imidazole-5-one, (60) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[(trans-4-methoxycyclohexyl)amino]-1H-imidazole-5-one, (61) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[cis-2-hydroxycycloheptyl]amino]-1H-imidazole-5-one, (62) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[trans-2-hydroxycycloheptyl]amino]-1H-imidazole-5-one, (63) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(1R,2R)-2-hydroxycycloheptyl]amino]-1H-imidazole-5-one, (64) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(1S,2S)-2-hydroxycycloheptyl]amino]-1H-imidazole-5-one, (65) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[cis-3-hydroxycycloheptyl]amino]-1H-imidazole-5-one, (66) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[trans-3-hydroxycycloheptyl]amino]-1H-imidazole-5-one, (67) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[cis-2-methoxycycloheptyl]amino]-1H-imidazole-5-one, (68) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[trans-2-methoxycycloheptyl]amino]-1H-imidazole-5-one, (69) (2S)-2-[[(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-5-oxo-1H-imidazole-2-yl]amino]-3-methylbutanoate methyl, (70) (2S)-2-[[(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-5-oxo-1H-imidazole-2-yl Methyl aminopropanoate, (71) (2S)-2-[[(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-5-oxo-1H-imidazole-2-yl]amino]-4-methylpentanoate methyl, (72) (2R)-2-[[(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-5-oxo-1H-imidazole-2-yl]amino]-4-methylpentanoate methyl, (73) (2S)-2-[[(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-5-oxo-1H-imidazole-2-yl]amino]-3-hydroxybutanoate methyl (75) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-(indan-2-ylamino)-1H-imidazole-5-one, (76) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[(3,4-dimethylphenyl)methylamino]-1H-imidazole-5-one, (77) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[(2,4-dimethylphenyl)methylamino]-1H-imidazole-5-one, (78) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[2-(trifluoromethyl)phenyl]methylamino]-1H-imidazole-5-one, (79) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[2-(trifluoromethoxy)phenyl]methylamino]-1H-imidazole-5-one, (80) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[cis-2-hydroxyindan-1-yl]amino]-1H-imidazole-5-one, (81) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[trans-2-hydroxyindan-1-yl]amino]-1H-imidazole-5-one, (82) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(1R,2R)-2-hydroxyindan-1-yl]amino]-1H-imidazole-5-one, (83) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(1S,2S)-2-hydroxyindan-1-yl]amino]-1H-imidazole-5-one, (84) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[cis-2-methoxyindan-1-yl]amino]-1H-imidazole-5-one, (85) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[trans-2-methoxyindan-1-yl]amino]-1H-imidazole-5-one, (86) (2S)-2-[[(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-5-oxo-1H-imidazole-2-yl]amino]-3-phenyl-propanoate methyl, (87) (2R)-2-[[(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-5-oxo-1H-imidazole-2-yl]amino]-3-phenyl-propanoate methyl, (88) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[(2-fluoro-1-phenyl-ethyl)amino]-1H-imidazole-5-one, (89) (±)-(4Z)-2-[(2-amino-1-phenyl-ethyl)amino]-4-(1,3-benzothiazole-6-ylmethylene)-1H-imidazole-5-one dihydrochloride, (90) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[2-(methylamino)-1-phenylethyl]amino]-1H-imidazole-5-one dihydrochloride, (91) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[2-(dimethylamino)-1-phenyl-ethyl]amino]-1H-imidazole-5-one, (92) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[(1-benzyl-2-hydroxyethyl)amino]-1H-imidazole-5-one, (93) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(1R)-1-benzyl-2-hydroxyethyl]amino]-1H-imidazole-5-one, (94) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[(1-benzyl-2-methoxyethyl)amino]-1H-imidazole-5-one, (95) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[(2-hydroxy-1-phenylethyl)amino]-1H-imidazole-5-one, (96) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(1R)-2-hydroxy-1-phenylethyl]amino]-1H-imidazole-5-one, (97) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(1S)-2-hydroxy-1-phenylethyl]amino]-1H-imidazole-5-one, (98) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[(2-methoxy-1-phenylethyl)amino]-1H-imidazole-5-one, (99) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[(2-hydroxy-2-phenylethyl)amino]-1H-imidazole-5-one, (100) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[(2-methoxy-2-phenylethyl)amino]-1H-imidazole-5-one, (101) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[(2-hydroxy-3-phenylpropyl)amino]-1H-imidazole-5-one, (102) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[(2-methoxy-3-phenylpropyl)amino]-1H-imidazole-5-one, (103) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[(5-methylpyrazine-2-yl)methylamino]-1H-imidazole-5-one, (104) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-(2-pyridylmethylamino)-1H-imidazole-5-one, (105) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-(3-pyridylmethylamino)-1H-imidazole-5-one, (106) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-(4-pyridylmethylamino)-1H-imidazole-5-one, (107) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[(5-methyl-2-furyl)methylamino]-1H-imidazole-5-one, (108) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[(4-methylthiazole-2-yl)methylamino]-1H-imidazole-5-one, (109) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-(3-imidazole-1-ylpropylamino)-1H-imidazole-5-one, (110) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[2-(2-pyridyl)ethylamino]-1H-imidazole-5-one, (111) (4Z)-2-(1,3-benzothiazole-2-ylmethylamino)-4-(1,3-benzothiazole-6-ylmethylene)-1H-imidazole-5-one, (112) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[(1-methyl-4-piperidyl)methylamino]-1H-imidazole-5-one, (113) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-(tetrahydropyran-4-ylmethylamino)-1H-imidazole-5-one, (114) 4-[[[(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-5-oxo-1H-imidazole-2-yl]amino]methyl]piperidine-1-carboxylate Tert-butyl, (115) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[(7-methyl-7-azaspiro[3.5]nonan-2-yl)amino]-1H-imidazole-5-one, (116) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-(3-fluoro-4-methyl-anilino)-1H-imidazole-5-one, (117) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-(4-fluoroanilino)-1H-imidazole-5-one, (118) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-(4-hexylanilino)-1H-imidazole-5-one, (119) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[4-(4-methylpiperazine-1-yl)anilino]-1H-imidazole-5-one, (120) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[3-(difluoromethoxy)anilino]-1H-imidazole-5-one, (121) (4Z)-2-[(1-acetylindoline-6-yl)amino]-4-(1,3-benzothiazole-6-ylmethylene)-1H-imidazole-5-one, (122) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[3-(trifluoromethyl)anilino]-1H-imidazole-5-one, (123) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-(indan-5-ylamino)-1H-imidazole-5-one, (124) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-(4-morpholinoanilino)-1H-imidazole-5-one, (125) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[(1-methylindazole-7-yl)amino]-1H-imidazole-5-one, (126) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-(pyrimidine-2-ylamino)-1H-imidazole-5-one, (127) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-(2-pyridylamino)-1H-imidazole-5-one, (128) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[(1-methylpyrazole-3-yl)amino]-1H-imidazole-5-one, (129) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[(2-methoxy-6-methyl-3-pyridyl)amino]-1H-imidazole-5-one, (130) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-(pyrimidine-5-ylamino)-1H-imidazole-5-one, (131) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-(3-pyridylamino)-1H-imidazole-5-one, (132) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-(1,3,4-thiadiazole-2-ylamino)-1H-imidazole-5-one, (133) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[5-(4-methylpiperazine-1-yl)-2-pyridyl ]amino]-1H-imidazole-5-one, (134) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[6-(4-methylpiperazine-1-yl)-3-pyridyl ]amino]-1H-imidazole-5-one, (135) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[2-(4-methylpiperazine-1-yl)pyrimidine-5-yl ]amino]-1H-imidazole-5-one, (136) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[5-(4-methylpiperazine-1-yl)pyrimidine-2-yl ]amino]-1H-imidazole-5-one, (137) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[5-(4-methylpiperazine-1-yl)pyrazine-2-yl]amino]-1H-imidazole-5-one, (138) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[6-(4-methylpiperazine-1-yl)pyridazin-3-yl]amino]-1H-imidazole-5-one, (139) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-(tetrahydropyran-4-ylamino)-1H-imidazole-5-one, (140) 4-[[(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-5-oxo-1H-imidazole-2-yl ]amino]piperidine-1-carboxylate tert-butyl, (141) 4-[[(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-5-oxo-1H-imidazole-2-yl ]amino]piperidine-1-carboxylate ethyl, (142) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[(1-methyl-4-piperidyl)amino]-1H-imidazole-5-one, (143) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[(1-methyl-3-piperidyl)amino]-1H-imidazole-5-one, (144) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-(oxetane-3-ylamino)-1H-imidazole-5-one, (145) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(3R)-tetrahydrofuran-3-yl]amino]-1H-imidazole-5-one, (146) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(3S)-tetrahydrofuran-3-yl]amino]-1H-imidazole-5-one, (147) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(3R)-tetrahydropyran-3-yl]amino]-1H-imidazole-5-one, (148) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(3S)-tetrahydropyran-3-yl]amino]-1H-imidazole-5-one, (149) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[(6,6-dimethyltetrahydropyran-3-yl)amino]-1H-imidazole-5-one, (149A) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(3R) / (3S)-6,6-dimethyltetrahydropyran-3-yl]amino]-1H-imidazole-5-one, (149B) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(3R) / (3S)-6,6-dimethyltetrahydropyran-3-yl]amino]-1H-imidazole-5-one, (150) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(3R,4R)-4-hydroxytetrahydropyran-3-yl]amino]-1H-imidazole-5-one, (151) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-(oxepan-3-ylamino)-1H-imidazole-5-one, (152) (±)-3-[[(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-5-oxo-1H-imidazole-2-yl]amino]piperidine-2-one, (153) (3S)-3-[[(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-5-oxo-1H-imidazole-2-yl]amino]piperidine-2-one, (154) (5S)-5-[[(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-5-oxo-1H-imidazole-2-yl]amino]piperidine-2-one, (155) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[(3,3-difluorocyclopentyl)amino]-1H-imidazole-5-one, (156) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[(4,4-difluorocyclohexyl)amino]-1H-imidazole-5-one, (157) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[(3,3-difluorocyclohexyl)amino]-1H-imidazole-5-one, (158) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[(2,2-difluorocyclohexyl)amino]-1H-imidazole-5-one, (159) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[(3,3-difluorocycloheptyl)amino]-1H-imidazole-5-one, (160) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(1R)-1-(fluoromethyl)-3-methyl-butyl]amino]-1H-imidazole-5-one, (161) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(1S)-1-(fluoromethyl)-3-methyl-butyl]amino]-1H-imidazole-5-one, (162) [3-[[(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-5-oxo-1H-imidazole-2-yl ]amino]-1-adamantyl]acetate, (163) [3-[[(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-5-oxo-1H-imidazole-2-yl ]amino]-1-adamantyl]2,2-dimethylpropanoate, (164) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(1R,2R)-2-methoxycyclopentyl]amino]-1H-imidazole-5-one, (165) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(1S,2S)-2-methoxycyclopentyl]amino]-1H-imidazole-5-one, (166) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(1R,2R)-2-methoxycyclohexyl]amino]-1H-imidazole-5-one, (167) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(1S,2S)-2-methoxycyclohexyl]amino]-1H-imidazole-5-one, (168) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[cis-3-methoxycyclohexyl]amino]-1H-imidazole-5-one, (169) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[trans-3-methoxycyclohexyl]amino]-1H-imidazole-5-one, (169A) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(1R,3R) / (1S,3S)-3-methoxycyclohexyl]amino]-1H-imidazole-5-one, (169B) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(1R,3R) / (1S,3S)-3-methoxycyclohexyl]amino]-1H-imidazole-5-one, (170) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[cis-4-hydroxycycloheptyl]amino]-1H-imidazole-5-one, (171) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[trans-4-hydroxycycloheptyl]amino]-1H-imidazole-5-one, (171A) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(1R,4R) / (1S,4S)-4-hydroxycycloheptyl]amino]-1H-imidazole-5-one, (171B) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(1R,4R) / (1S,4S)-4-hydroxycycloheptyl]amino]-1H-imidazole-5-one, (172) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[cis-3-methoxycycloheptyl]amino]-1H-imidazole-5-one, (173) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[trans-3-methoxycycloheptyl]amino]-1H-imidazole-5-one, (174) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[cis-4-methoxycycloheptyl]amino]-1H-imidazole-5-one, (175) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[trans-4-methoxycycloheptyl]amino]-1H-imidazole-5-one, (176) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(1R)-2-methoxy-1-phenylethyl]amino]-1H-imidazole-5-one, (177) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(1S)-2-methoxy-1-phenylethyl]amino]-1H-imidazole-5-one, (178) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(2R)-2-hydroxy-2-phenylethyl]amino]-1H-imidazole-5-one, (179) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(2S)-2-hydroxy-2-phenylethyl]amino]-1H-imidazole-5-one, (180) (4Z)-2-[[(1R)-2-amino-1-phenylethyl]amino]-4-(1,3-benzothiazole-6-ylmethylene)-1H-imidazole-5-one dihydrochloride, (181) (4Z)-2-[[(1S)-2-amino-1-phenylethyl]amino]-4-(1,3-benzothiazole-6-ylmethylene)-1H-imidazole-5-one dihydrochloride, (182) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(3R)-quinuclidin-3-yl]amino]-1H-imidazole-5-one, (183) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(3S)-quinuclidin-3-yl]amino]-1H-imidazole-5-one, (184) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-(tetrahydrothiopyran-3-ylamino)-1H-imidazole-5-one, (185) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-(1,4-dioxepan-6-ylamino)-1H-imidazole-5-one, (186) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[(2-oxopyrrolidine-3-yl)amino]-1H-imidazole-5-one, (187) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[(1-methyl-2-oxo-pyrrolidine-3-yl)amino]-1H-imidazole-5-one, (188) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[(4,4-dimethyl-2-oxo-pyrrolidine-3-yl)amino]-1H-imidazole-5-one, (189) (3R)-3-[[(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-5-oxo-1H-imidazole-2-yl]amino]piperidine-2-one, (190) (±)-3-[[(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-5-oxo-1H-imidazole-2-yl]amino]-1-methyl-piperidine-2-one, (191) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[(3-methyl-2-oxo-pyrrolidine-3-yl)amino]-1H-imidazole-5-one, (192) (±)-(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[(1,3-dimethyl-2-oxo-pyrrolidine-3-yl)amino]-1H-imidazole-5-one, (192A) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(3R) / (3S)-1,3-dimethyl-2-oxo-pyrrolidine-3-yl]amino]-1H-imidazole-5-one, (192B) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(3R) / (3S)-1,3-dimethyl-2-oxo-pyrrolidine-3-yl]amino]-1H-imidazole-5-one, (193) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(3S,4S)-4-hydroxytetrahydropyran-3-yl]amino]-1H-imidazole-5-one, (194) (4Z)-2-(3-noadamantylamino)-4-(1,3-benzothiazole-6-ylmethylene)-1H-imidazole-5-one, (195) 3-[[(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-5-oxo-1H-imidazole-2-yl ]amino]-1-adamantyl]N-tert-butylcarbamate, (196) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[(3-fluoro-1-adamantyl)amino]-1H-imidazole-5-one, (197) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(1R)-1-(tert-butoxymethyl)-3-methyl-butyl]amino]-1H-imidazole-5-one, (198) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(1R)-2-tert-butoxy-1-phenylethyl]amino]-1H-imidazole-5-one, (199) N-[3-[[(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-5-oxo-1H-imidazole-2-yl ]amino]-1-adamantyl]acetamide, (200) N-[3-[[(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-5-oxo-1H-imidazole-2-yl ]amino]-1-adamantyl]cyclopropanecarboxamide, (201) N-[3-[[(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-5-oxo-1H-imidazole-2-yl ]amino]-1-adamantyl]methanesulfonamide, (202) N-[3-[[(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-5-oxo-1H-imidazole-2-yl ]amino]-1-adamantyl]cyclopropanesulfonamide, (203) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[3-(dimethylamino)-1-adamantyl]amino]-1H-imidazole-5-one, (204) 2-[[(4Z)-4-(1,3-benzothiazole-6-ylmethylene)-5-oxo-1H-imidazole-2-yl ]amino]adamantane-2-carboxylate methyl, (205) (4Z)-2-(cyclohexylamino)-4-[(2-methyl-1,3-benzothiazole-6-yl)methylene]-1H-imidazole-5-one, (206) (4Z)-2-(cycloheptylamino)-4-[(2-methyl-1,3-benzothiazole-6-yl)methylene]-1H-imidazole-5-one, (207) (4Z)-2-[[(1R)-1-(methoxymethyl)-3-methyl-butyl]amino]-4-[(2-methyl-1,3-benzothiazole-6-yl)methylene]-1H-imidazole-5-one, (208) (4Z)-2-[[(1R)-2-methoxy-1-phenylethyl]amino]-4-[(2-methyl-1,3-benzothiazole-6-yl)methylene]-1H-imidazole-5-one, (209) (4Z)-2-(1-adamantylamino)-4-[(2-methyl-1,3-benzothiazole-6-yl)methylene]-1H-imidazole-5-one, and (210) (4Z)-2-[(3-hydroxy-1-adamantyl)amino]-4-[(2-methyl-1,3-benzothiazole-6-yl)methylene]-1H-imidazole-5-one, (211) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[(3,5-dihydroxy-1-adamantyl)amino]-1H-imidazole-5-one, (212) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[(3,5,7-trifluoro-1-adamantyl)amino]-1H-imidazole-5-one, (213) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(1R)-1-(ethoxymethyl)-3-methyl-butyl]amino]-1H-imidazole-5-one, (214) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(1R)-1-(benzyloxymethyl)-3-methyl-butyl]amino]-1H-imidazole-5-one, (215) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(1R)-1-[(4-fluorophenyl)methoxymethyl]-3-methyl-butyl]amino]-1H-imidazole-5-one, and (216) (4Z)-4-(1,3-benzothiazole-6-ylmethylene)-2-[[(1R)-1-(cyclopropoxymethyl)-3-methyl-butyl]amino]-1H-imidazole-5-one, A compound of formula (I) according to any one of claims 1 to 5, or any pharmaceutically acceptable salt thereof, selected from the above.

13. A pharmaceutical composition comprising one of at least one compound or a pharmaceutically acceptable salt thereof as described in any one of claims 1 to 11, or one of at least one compound or a pharmaceutically acceptable salt thereof as described in claim 12.

14. A synthesis method for producing one of the compounds of formula (I) described in any one of claims 1 to 11 or a pharmaceutically acceptable salt thereof, or the compound described in claim 12 or a pharmaceutically acceptable salt thereof, wherein the compound of formula (II) below is R 1 NH 2 The process includes at least the step of coupling with an amine, 【Chemistry 2】 Here, Alk is (C 1 ~C 5 ) is alkyl, R 1 and R 2 The method, wherein is as defined in any one of claims 1 to 11.

15. The synthetic intermediate of the following equation (II), 【Transformation 3】 Here, Alk is (C 1 ~C 5 ) is alkyl, and also R 2 The synthetic intermediate is as defined in any one of claims 1 to 11. However, the following compounds are excluded. 【Transformation 5】

16. A compound of formula (I) as defined in any one of claims 1 to 11 or a pharmaceutically acceptable salt thereof, for use as a pharmaceutical, or at least one compound as defined in claim 12 or one pharmaceutically acceptable salt thereof.

17. A pharmaceutical product comprising one of the compounds of formula (I) as defined in any one of claims 1 to 11 or a pharmaceutically acceptable salt thereof, or at least one of the compounds defined in claim 12 or a pharmaceutically acceptable salt thereof, intended to treat and / or prevent diseases selected from cognitive impairment associated with Down syndrome; Alzheimer's disease; dementia; tauopathy; other neurodegenerative diseases; CDKL5 deficiency disorder; McDermid syndrome; autism; type 1 and type 2 diabetes mellitus; folic acid and methionine metabolic disorders; osteoarthritis; Duchenne muscular dystrophy; several cancers; viral infections; neuroinflammation; anemia; infections caused by unicellular parasites; and diseases of livestock caused by unicellular pathogens, and to regulate body temperature.

18. A pharmaceutical product comprising one of the compounds of formula (I) as defined in any one of claims 1 to 11 or a pharmaceutically acceptable salt thereof, or at least one of the compounds defined in claim 12 or a pharmaceutically acceptable salt thereof, intended to treat and / or prevent Down syndrome, Alzheimer's disease, dementia, tauopathy, Parkinson's disease, Niemann-Pick disease type C, CDKL5 deficiency and Phelan-McDermid syndrome, and cognitive and motor conditions associated therewith, and diseases selected from type 1 and type 2 diabetes, or at least one of the compounds defined in claim 12 or a pharmaceutically acceptable salt thereof.

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