(2-(4-(1-(benzo[d]thiazol-5-YL)ethyl)piperazin-1 -YL)pyrimidin-5-YL)(IMINO)(methyl)-lamda6-sulfanone for use in the treatment of colitis, parkinson disease, tauopathy, ALS and alzheimer's disease

Abstract

The present invention relates to pharmaceutical compositions and medicaments comprising the compound of formula (I); or a stereoisomer, tautomer, pharmaceutically usable solvate or salt thereof, and dosage regimens for the administration thereof to human patients.

Description

[0001] Medicaments comprising glycosidase inhibitorsField of the invention The present invention relates to pharmaceutical compositions and medicaments comprising an O-GlcNAcase inhibitor and respective dosage regimens for the administration to human patientsfor the treatment of various disorders such as proteinopathies, including neurological disorderssuch as tauopathies, synucleinopathies and Alzheimer’s disease.Background of the inventionA wide range of cellular proteins, nuclear, cytoplasmic and mitochondrial, are post-translationallymodified by the addition of the monosaccharide 2-acetamido-2-deoxy-β-D-glucopyranoside (β-N- acetyl glucosamine) which is attached via an O-glycosidic linkage. This modification is generally referred to as O-linked N-acetylglucosamine or O-GlcNAc. The enzyme responsible for post- translationally conjugating β-N-acetylglucosamine (GIcNAc) to specific serine and threonineresidues of numerous -cytoplasmic / nucleocytoplasmic proteins is O-GIcNAc transferase (OGTor OGTase). A second enzyme, known as O-GlcNAcase, removes this post-translational modification to liberate GlcNAc making the O-GlcNAc-modification a dynamic event occurring several times during the lifetime of a protein. O-GlcNAc-modified proteins regulate a wide range of vital cellular functions including, for example, but not restricted to transcription, proteasomal degradation and cellular signaling. O- GlcNAc is also found on many structural proteins. For example, it has been found on a number of cytoskeletal proteins, including neurofilament proteins, synapsins, synapsin-specific clathrin assembly protein AP-3 and Ankyrin-G. O-GlcNAc modification has been found to be abundant inthe brain. It has also been found on proteins clearly implicated in the etiology of several diseasesincluding tauopathies, Alzheimer’s disease (AD), synucleinopathies, Parkinson’s disease, amyotrophic lateral sclerosis, and cancer. For example, it is well established that AD and a number of related tauopathies including Down’sSyndrome, progressive supranuclear palsy (PSP), Pick's disease, corticobasal degeneration(CBD), argyrophilic grain disease (AGD), globular glial tauopathy (GGT), frontotemporal dementia and parkinsonism linked to chromosome-17 (FTLD-17, Niemann-Pick Type C disease are characterized, in part, by the development of neurofibrillary tangles (NFTs). NFTs are also a histopathological hallmark of chronic traumatic encephalopathy that is a consequence of traumatic brain injury. These NFTs are aggregates of paired helical filaments (PHFs) and are composed of an abnormal form of the cytoskeletal protein "tau". Normally, tau stabilizes a key cellular network of microtubules that is essential for distributing proteins and nutrients within neurons. In AD patients, however, tau becomes hyperphosphorylated, disrupting its normalfunction, forming PHFs and ultimately aggregating to form NFTs. Six isoforms of tau are found inthe human brain. In AD patients, all six isoforms of tau are found in NFTs, and all are markedly hyperphosphorylated. Tau in healthy brain tissue bears only 2 or 3 phosphate groups, whereas those found in the brains of AD patients bear, on average, 8 phosphate groups. A clear parallel between NFT levels in the brains of AD patients and the severity of dementia strongly supports a key role for tau dysfunction in AD. The precise causes of this hyperphosphorylation of tau remainelusive. Accordingly, considerable effort has been dedicated toward: a) elucidating the molecularphysiological basis of tau hyperphosphorylation; and b) identifying strategies that could limit tau hyperphosphorylation in the hope that these might halt, or even reverse, the progression oftauopathies, synucleinopathies and Alzheimer’s disease. Several lines of evidence suggest thatup-regulation of a number of kinases may be involved in hyperphosphorylation of tau, although very recently, an alternative basis for this hyperphosphorylation has been advanced. In particular, it has recently emerged that phosphate levels of tau are regulated by the levels of O-GlcNAc on tau. The presence of O-GIcNAc on tau has stimulated studies that correlate O-GlcNAc levels with tau phosphorylation levels. The recent interest in this field stems from theobservation that O-GlcNAc modification has been found to occur on many proteins at amino acid residues that are also known to be phosphorylated. Consistent with this observation, it has been found that increases in phosphorylation levels result in decreased O-GlcNAc levels and conversely, increased O-GlcNAc levels correlate with decreased phosphorylation levels. This reciprocal relationship between O-GlcNAc and phosphorylation has been termed the "Yin-Yang hypothesis" and has gained strong biochemical support by the recent discovery that the enzyme OGT forms a functional complex with phosphatases that act to remove phosphate groups from proteins. Like phosphorylation, O-GlcNAc is a dynamic modification that can be removed and reinstalled several times during the lifespan of a protein. Suggestively, the gene encoding O- GlcNAcase has been mapped to a chromosomal locus that is linked to AD. Hyperphosphorylated tau in human AD brains has markedly lower levels of O-GlcNAc than are found in healthy human brains. Very recently, it has been shown that O-GlcNAc levels of soluble tau protein from human brains affected with AD are markedly lower than those from healthy brain. Furthermore, PHF fromdiseased brain were suggested to lack completely any O-GlcNAc modification whatsoever. Themolecular basis of this hypoglycosylation of tau is not known, although it may stem from increased activity of kinases and / or dysfunction of one of the enzymes involved in processing O-GlcNAc. Supporting this latter view, in both PC-12 neuronal cells and in brain tissue sections from mice, a nonselective N-acetylglucosaminidase inhibitor was used to increase tau O-GlcNAc levels, whereupon it was observed that phosphorylation levels decreased. Moreover, it has been described that the O-GlcNAc modification of tau directly inhibits its aggregation without perturbing the conformational properties of tau monomers. The implication of these collective results is thatby maintaining healthy O-GlcNAc levels in AD patients, such as by inhibiting the action of O-GlcNAcase (OGA), one should be able to block hyperphosphorylation of tau and all of the associated effects of tau hyperphosphorylation, including the formation of NFTs and downstream effects. However, because the proper functioning of the lysosomal β-hexosaminidases is critical, any potential therapeutic intervention for the treatment of AD that blocks the action of O- GlcNAcase would have to avoid the concomitant inhibition of both lysosomal hexosaminidases A and B. Consistent with the known properties of the hexosamine biosynthetic pathway, the enzymatic properties of O-GlcNAc transferase (OGT), and the reciprocal relationship between O-GlcNAc and phosphorylation, it has been shown that decreased glucose availability in brain leads to tau hyperphosphorylation. The gradual impairment of glucose transport and metabolism leads to decreased O-GlcNAc and hyperphosphorylation of tau (and other proteins). Accordingly, the inhibition of O-GlcNAcase should compensate for the age-related impairment of glucose metabolism within the brains of health individuals as well as patients suffering from AD or related neurodegenerative diseases. These results suggest that a malfunction in the mechanisms regulating tau O-GIcNAc levels may be vitally important in the formation of NFTs and associated neurodegeneration. Good support for blocking tau hyperphosphorylation as a therapeutically useful intervention comes from studies showing that when transgenic mice harboring human tau are treated with kinase inhibitors, they do not develop typical motor defects and, in another case, show a decreased level of insolubletau. These studies provide a clear link between lowering tau phosphorylation levels and alleviatingAD-like behavioral symptoms in a murine model of this disease.There is evidence indicating that the modification with O-GlcNAc may have a general function inpreventing harmful protein aggregation. This has been directly demonstrated for the tau proteinand also for the protein alpha-synuclein that is a toxic aggregating protein associated withsynucleinopathies, including Parkinson’s disease. Further aggregating proteins that areassociated with amyotrophic lateral sclerosis [Tar DNA binding protein-43 (TDP-43) andsuperoxide-dismutase I (SOD-I)] and frontotemporal lobar degeneration (TDP-43) are known tocarry the O-GlcNAc modification. These results indicate that increasing O-GlcNAcylation withOGA inhibitors could be in general beneficial in diseases associated with protein aggregations or,preferably, other protein misfolding and the resulting diseases or conditions, i.e. proteinopathies.There is also a large body of evidence indicating that increased levels of O-GlcNAc protein modification provides protection against pathogenic effects of stress. Humans have three genes encoding enzymes that cleave terminal β-N-acetyl-glucosamineresidues from glycoconjugates. The first of these encodes the enzyme (protein)-3-O-(N-acetyl-D-glucosaminyl)-L-serine / threonine N-acetylglucosaminyl hydrolase (O-GlcNAcase). O-GlcNAcaseis a member of family 84 of glycoside hydrolases. O-GlcNAcase acts to hydrolyze O-GlcNAc at serine and threonine residues of post-translationally modified proteins. Consistent with the presence of O-GlcNAc on many intracellular proteins, the enzyme O-GlcNAcase appears to have a role in the etiology of several diseases including type II diabetes, AD and cancer. Although O- GlcNAcase was likely isolated earlier on, about 20 years elapsed before its biochemical role in acting to cleave O-GlcNAc from serine and threonine residues of proteins was understood. More recently O-GlcNAcase has been cloned, partially characterized, and suggested to have additional activity as a histone acetyltransferase. Summary of the inventionThe present invention relates to a pharmaceutical composition or medicament comprising thecompound of formula (I)or a stereoisomer or tautomer thereof, in the respective free base form or in form of a respectivepharmaceutically usable solvate or salt and dosage regimens for the administration thereof tohuman patients. Moreover, the present invention relates to a compound of formula (I), or astereoisomer, tautomer, pharmaceutically usable solvate or salt thereof, for use in a method oftreating a human subject, the method comprising the repeated administration of one or more unit dosage forms comprising the compound of formula (I), or a stereoisomer, tautomer,pharmaceutically usable solvate or salt thereof, in a suitable dose and at a suitable daily dosingfrequency more specifically disclosed herein below. In some embodiments, the invention relates to the use of a compound of formula (I), or a stereoisomer, tautomer, pharmaceutically usablesolvate or salt thereof, in the manufacture of a medicament for the treatment of a human subject,comprising the repeated administration of one or more unit dosage forms comprising the compound of formula (I), or a stereoisomer, tautomer, pharmaceutically usable solvate or saltthereof, in a suitable dose and at a suitable daily dosing frequency more specifically disclosedherein below. Compound (I) and its use as glycosidase inhibitor is e.g. disclosed in WO2018 / 153508. Preferred acid addition salt and related polymorphic forms are disclosed in WO2020 / 039030. Objects of the invention comprise medicaments and pharmaceutical compositionscomprising the compound of formula (I), or a stereoisomer, tautomer, pharmaceutically usablesolvate or salt thereof, and dosage regimens for the treatment of neurological disorders such astauopathies, synucleinopathies and Alzheimer’s disease.Description of figures:FIG. 1: Arithmetic Mean (Mean ±SD) Plasma Concentration of Compound (I) Following a SingleOral Dose of Compound (I) at Two Dose Levels (20 mg and 50 mg) in Healthy Subject vs. Timeby Dose and Occasion (Linear and Log Scale) – Part 1 and 2, Cohort 1 and Cohort 2, Day 1.FIG. 2: Representative Individual Plasma Concentration of Compound (I) vs. Time by Dose andOccasion (Linear and Log Scale) – Part 2, Cohort 1, Day 1, 8 and 10.FIG. 3: Orthogonal cross sections of co-registered positron emission tomography and magneticresonance images from a representative subject (1411). PET = positron emission tomography; MRI = magnetic resonance imaging. From left to right columns: images are PET 1 (taken at baseline), PET 2 and PET 3 (taken after dosing with Compound (I) at the indicated doses and times relative to dosing), and structural (T1 weighted) MRI. The PET images are shown as standardised uptake value summed from 10 to 90 min. Baseline images show regional heterogeneity consistent with the expected distribution of18F-LSN3316612 signal.FIG. 4: Brain O-GlcNAcase receptor / target occupancy data plotted against plasma concentrationof Compound (I). CI = confidence interval; EC50= plasma concentration of Compound (I) that corresponds to 50% receptor / target occupancy. Plasma concentration Compound (I) (ng / ml) The plotted curve fit is to the equation for PK-occupancy analysis: RO = 100*Cp* / (Cp + EC50), where RO = Receptor Occupancy, Cp = Plasma Concentration of Compound (I), EC50 = is Cp Corresponding to 50% RO. The dashed vertical line shows the estimated EC50 value, and the vertical dotted lines show the corresponding 95% CI.FIG. 5: Dissolution Profile of Capsule and Tablet of Compound (I).FIG. 6: Characteristic X-ray powder diffraction pattern of crystalline Compound (I) fumarate salt.FIG. 7: Inhibition of Recombinant O-GlcNAcase Enzyme with Compound of Formula (I). Serialdilutions of Compound Formula (I) were incubated with recombinant full-length human O- GlcNAcase and a fluorogenic substrate. Enzymatic activity was quantified by fluorescence(wavelength settings: excitation = 485 nm; emission = 520 nm). Inhibitory potency (IC50)measured in several experiments was calculated using non-linear regression analysis andyielded a mean of 13 nM. Data are displayed as the mean + / - SEM (n = 3). Compound Formula(I) is a potent Inhibitor of human O-GlcNAcase.FIG. 8A: Lineweaver-Burk Plot of Compound of Formula (I). The enzyme kinetics experimentshows that Compound (I) does not interfere with the maximum enzyme velocity (Vmax) butdiminishes enzyme affinity (Km). These data indicate that Compound (I) is a substratecompetitive inhibitor.FIG. 8B: Compound of Formula (I) Dose Response. Pre-incubation of OGA with differentconcentrations of Compound of Formula (I) were followed by dilution prior to addition of thefluorogenic substrate. Note the decrease of potency upon dilution of the pre-formed Enzyme / Inhibitor complexes which is indicative of a reversible mechanism of enzyme inhibition.Data are displayed as the mean + / - SEM (n = 3). These data indicate that Compound (I) is areversible inhibitor.FIG. 9: Inhibition of Cellular O-GlcNAcase in HEK293 Cells Expressing Human Tau withCompound of Formula (I). The effect of Compound of Formula (I) on O-GlcNAcylation of thedisease-relevant protein tau was also confirmed in HEK293 cells expressing human tau with an immunoassay based on a proprietary antibody specifically recognizing tau O-GlcNAcylated atSerine 400 (IC50 = 195 nM). Data are displayed as the mean + / - SEM (n = 3).FIG. 10: Inhibition of Cellular O-GlcNAcase in human and rat PBMC with Compound of Formula(I). Comparable potencies were obtained with Compound of Formula (I) on human and ratperipheral mononuclear blood cells (PBMCs).FIG. 11: Ex Vivo Inhibition of Human O-GlcNAcase PBMC with Compound of Formula (I).Human blood drawn from healthy was incubated with Compound Formula (I) at different concentrations. After isolation and preparation of PBMCs, total protein O-GlcNAcylation wasquantified using a proprietary immunoassay. An average IC50 = 625 nM (+ / - 90 nM) wasobtained for five individual donors (see Figure). Correcting for human plasma protein binding with a free fraction of 24% this equates to an IC50 = 137 nM for free drug. Data are displayed asthe mean values + / - SEM (n=3 technical replicates). Compound Formula (I) elicits apharmacodynamic response in a pre-established ex vivo human blood assay.FIG. 12: PK / PD Relationship of Compound of Formula (I) in Rat Brain. Compound of Formula (I)showed an ED50 of 2.1 mg / kg for brain protein O-GlcNAcylation (A) with highly significantcorrelation (R2=0.97) with PBMC O-GlcNAcylation (B). This Pharmacodynamic responsecorresponds to an in vivo CSF EC50 of 135 nM (equivalent brain free concentration) (C). Data expressed in % over vehicle control of protein O-GlcNAcylation (***p<0.001, **** p<0.0001 versus Vehicle Groups, one-way ANOVA followed by Dunnett's post hoc test, n = 6 / group).FIG. 13A and FIG. 13B: Evaluation of Compound of Formula (I) in Line 61 Mice. Beam walkresults after chronic daily dosing (3 months) by oral gavage with Compound Formula (I) in Line 61 mice. A, B) A total of 5 different beams were tested, with schematic of 2 representative beams (10 mm wide rectangular & 16 mm rounded beam). Mean bar plots with error bars + / - standard error of the mean show results after treatment with Compound (I). N = 16 per group, statistics performed with Bonferroni’s multiple comparison’s test. *p-value < 0.05, *** p-value <0.001. Compound Formula (I) reduce the progression of motor deficits in Line 61 mice.FIG. 14A and FIG. 14B: Global protein O-GlcNAcylation in the brains of Line 61 Mice Treatedwith Different Doses of Compound of Formula (I). Line 61 mice were orally treated with 3, 10 &30 mg / kg / day for 3 months with compound Formula (I). (A) Dose dependent increase of brain protein O-GlcNAcylation. Data are expressed in % O-GlcNAcylation and displayed as mean + / - SEM (* p < 0.05. **** p<0.0001 vs vehicle-treated group, Kruskal-Wallis followed by Dunn's post hoc test). (B) Western-blot detection of O-α-synuclein as an additional α-synuclein band at higher molecular mass (≈ 30 kDa) after chemoenzymatic mass tagging in presence of GalT1(Y289L). The study indicates a dose-dependent increase of global protein O-GlcNAcylation inthe brains of Line 61 mice treated with Compound (I).FIG. 15A, FIG. 15B, FIG. 15C, and FIG. 15D: O-Tau and pTau response in hTau P301S micefollowing treatment with Compound (I). In the CNS of hTauP301S mice, Compound (I) inducesan increase of global protein and Tau O-GlcNAcylation with a peak response around 4 to 8 hours (A, B). We also observe an increase of Tau phosphorylation pTau (S356) with a similar initial kinetics but a slower rate of elimination (C). The level of total Tau remains unchanged (D).Mean bar plots with error bars + / - standard error of the mean show results after treatment withCompound (I). N = 6 per group, statistics performed using One-way ANOVA followed by Dunnett’s post hoc test (*p-value < 0.05, ** p-value <0.01, ****p-value<0,0001 versus vehicle group).

[0002] Details of the inventionAccording to the invention, the medicaments and pharmaceutical compositions comprising the compound of formula (I), and dosage regimens for its administration to humans is particularly suited for the prophylactic or therapeutic treatment and / or monitoring of diseases that are caused, mediated and / or propagated by O-GlcNAcase activity. Diseases included in the present scope of the present invention are neurological and neurodegenerative diseases, diabetes, cancer,cardiovascular diseases and stroke. In some embodiments, the disease is a neurodegenerativedisease. In some embodiments, the diseases are selected from synucleinopathies andtauopathies. In some embodiments, the disease is Alzheimer’s disease or dementia. Diseasesincluded in the present scope of the present invention are neurological and neurodegenerative diseases, diabetes, cancer, cardiovascular diseases and stroke, more preferably neurodegenerative diseases, most preferably one or more synucleinopathies and tauopathies, highly preferably Alzheimer’s disease and dementia.Further diseases to which the compounds of formula (I), or medicaments or pharmaceuticalcompositions comprising formula (I), can be applied in prophylaxis or therapy according to the invention include diseases or conditions selected from one or more proteinopathies. Such proteinopathies are selected from the group comprising tauopathies, such as but not limited to Alzheimer’s disease (AD), corticobasal degeneration (CBD), progressive supranuclear palsy (PSP), chronic traumatic encephalopathy or synucleinopathies (also called α-synucleinopathies),such as but not limited to Parkinson’s disease or multiple system atrophy. Such proteinopathiesare preferably selected from the group comprising tauopathies, such as but not limited to Alzheimer’s disease (AD), corticobasal degeneration (CBD), progressive supranuclear palsy (PSP), chronic traumatic encephalopathy or synucleinopathies (also called α-synucleinopathies), such as but not limited to Parkinson’s disease, multiple system atrophy. Another aspect of the invention relates to a method for treating neurodegenerative diseases, diabetes, cancer, cardiovascular diseases and stroke, e.g., a tauopathy, wherein a medicamentor pharmaceutical composition comprising the compound of formula (I) and / or a physiologicallyacceptable salt thereof is administered according to the dosage regimens disclosed herein to ahuman in need of such treatment. In some embodiments, the compound of formula (I) isadministered orally. Medicaments and pharmaceutical compositions according to the invention,comprising the compound of formula (I) are especially preferred. The preferred way ofadministration is an oral administration. Medicaments and pharmaceutical compositions accordingto the invention, comprising the compound of formula (I) are especially preferred. The neurodegenerative disease or condition is selected from the group of one or moretauopathies, synucleinopathies, Alzheimer’s disease (AD), amyotrophic lateral sclerosis (ALS),amyotrophic lateral sclerosis with cognitive impairment (ALSci), argyrophilic grain disease, behavioral variant frontotemporal dementia (bvFTD), non-fluent and semantic variant primary progressive aphasia (nfv & svPPA), Bluit disease, corticobasal degeneration (CBD), Dementia pugilistica, Dementia with Lewy Bodies (DLB), diffuse neurofibrillary tangles with calcification, Down's syndrome, Familial British dementia, Familial Danish dementia, frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17), frontotemporal lobar degeneration (FTLD), ganglioglioma, gangliocytoma, Gerstmann-Straussler-Scheinker disease, globular glialtauopathy, Guadeloupean parkinsonism, Hallevorden-Spatz disease (neurodegeneration withbrain iron accumulation type 1), lead encephalopathy, lipofuscinosis, meningioangiomatosis, multiple system atrophy (MSA), myotonic dystrophy, Niemann-Pick disease (type C), Pallido- ponto-nigral degeneration, Parkinson’s disease, Parkinson’s disease dementia (PDD), Parkinsonism-dementia complex of Guam, Pick's disease (PiD), postencephalitic parkinsonism (PEP), Prion diseases (including Creutzfeldt-Jakob Disease (GJD), variant Creutzfeldt-Jakob Disease (vCJD)), fatal Familial Insomnia, Kuru, progressive supercortical gliosis, progressivesupranuclear palsy (PSP), pure autonomic failure, Richardson's syndrome also named PSPRichardson’s syndrome, subacute sclerosing panencephalitis, Tangle-only dementia, tuberous sclerosis, Huntington's disease or mild cognitive impairment (MCI), Chronic traumatic encephalopathy, Primary progressive aphasia, Progressive nonfluent aphasia, Semantic dementia, Steele-Richardson-Olszewski syndrome, epilepsy, chronic and acute inflammation such as Crohn disease, neuroinflammation, subarachnoid hemorrhage (SAH), multiple sclerosis (MS), progressive forms of MS, such as primary or secondary progressive MS, Friedreich’s Ataxiaand Adenoleukodystrophy. Most preferred are one or more tauopathies, PSP, synucleinopathies,Parkinson’s disease and Alzheimer’s disease.It has now been found that the compound of formula (I), or a pharmaceutically usable solvate, saltor tautomer thereof, can be advantageously administered to a human subject, such as a patientin need thereof, following the dose and dosage regimens according to the present invention.Throughout the specification, a dosage regimen according to the invention refers to or comprisesthe repeated administration of one or more unit dosage forms comprising the compound of formula(I), or a stereoisomer, tautomer, pharmaceutically usable solvate or salt thereof to a humansubject, in a suitable dose and at a suitable daily dosing frequency.In some embodiments, a dosage regimen according to the invention refers to a method of treating a human subject, the method comprising the repeated administration of one or more unit dosageforms comprising the compound of formula (I), or a stereoisomer, tautomer, pharmaceuticallyusable solvate or salt thereof in a suitable dose and at a suitable daily dosing frequency.Preferably,a dosage regimen according to the invention refers to a method of treating a human subject, the method comprising the repeated administration of one or more unit dosage forms comprising thecompound of formula (I), or a stereoisomer, tautomer, pharmaceutically usable solvate or saltthereof in a suitable dose and at a suitable daily dosing frequency. The invention also relates to the use of the compound of formula (I), or a stereoisomer, tautomer,pharmaceutically usable solvate or salt thereof, and the dose regimens disclosed herein for thetreatment of and a method of treating retinal degenerative diseases, e.g., selected from glaucoma,age-related macular degeneration (AMD), retinitis pigmentosa and diabetic retinopathy. The invention also relates to the use of the compound of formula (I), or a stereoisomer, tautomer,pharmaceutically usable solvate or salt thereof, and the dose regimens disclosed herein for thetreatment of and a method of treating retinal degenerative diseases, preferably selected from glaucoma, age-related macular degeneration (AMD), retinitis pigmentosa and diabetic retinopathy. The invention also relates to the use of the compound of formula (I), or a stereoisomer, tautomer,pharmaceutically usable solvate or salt thereof, and the dose regimens disclosed herein for thetreatment of and a method of treating inflammatory bowel diseases, e.g., selected from colitis,such as ulcerative colitis, and Cohn’s disease. The invention also relates to the use of the compound of formula (I), or a stereoisomer, tautomer,pharmaceutically usable solvate or salt thereof, and the dose regimens disclosed herein for thetreatment of and a method of treating inflammatory bowel diseases, preferably selected from colitis, such as ulcerative colitis, and Cohn’s disease.It is to be understood that the disclosure relating to the medical use of a compound per se shallapply analogously to the use of that compound when comprised in a pharmaceutical composition or medicament, or when that compound is used in a method of treatment or dose regimen as disclosed herein. The same applies in the converse, for instance it is understood that disclosuresof the use of a compound as comprised in a pharmaceutical composition, in a medicament, or ina method of treatment involving administration of a compound, or as part of a dose regimen, shallapply analogously to medical uses of that compound per se. As used herein the term “about” when referring to a particular value, e.g. an endpoint or endpoints of a range, encompasses and discloses, in addition to the specifically recited value itself, a certain variation around that specifically recited value. Such a variation may for example arise from normal measurement variability. The term “about” shall be understood as encompassing and disclosing,in addition to the exact referenced value itself, a range of variability above and below an indicatedspecific value, said variability being relative to the specific recited value itself, for example: The term “about” may encompass and disclose variability of ± 5.0%. The term “about” may encompass and disclose variability of ± 4.5%. The term “about” may encompass and disclose variability of ± 4.0%. The term “about” may encompass and disclose variability of ± 3.5%. The term “about” may encompass and disclose variability of ± 3.0%. The term “about” may encompass and disclose variability of ± 2.5%. The term “about” may encompass and disclose variability of ± 2.0%. The term “about” may encompass and disclose variability of ± 1.5%. The term “about” may encompass and disclose variability of ± 1.0%. The term “about” may encompass and disclose variability of ± 0.5%. Unless stated otherwise, where the term “about” is recited before the first endpoint of a numerical range, but not before the second endpoint of that range, this term, and the variability it implies in disclosure, refers to both the first endpoint of the range and the second endpoint of therange. For instance, a recited range of “about X to Y” should be read as “about X to about Y”. It isalso understood that when the term “about” is applied to both the upper and lower endpoints of a range, different degrees of variability may apply for the upper and lower endpoints of the same range. All such possible different degrees of variability are also within the disclosure of the presentapplication. For instance, in a range of “about X to about Y”, the application discloses i.e. a rangein which the lower endpoint X varies within a tolerance of 1.5% of the stated value, while the upper endpoint varies within a tolerance of 2% of the stated value. Of course, this is merely exemplary, it being understood that all combinations of tolerances as set out above are included in the disclosure of the present application. The term “human subject” is preferably taken to mean a patient having a disease or a humansubject being at increased risk of acquiring a disease, wherein diseases are preferably selectedfrom the diseases mentioned throughout this specification. In some embodiments, the term“human subject” is taken to mean a patient having a condition selected from neurological disorders or neurodegenerative diseases, diabetes, cancer, cardiovascular diseases and stroke, or a human subject being at increased risk of acquiring said disorders or diseases. As used herein, the term “treating” or “treat” describes the management and care of a patient for the purpose of combating a disease, condition, or disorder and includes the administration of acompound of the present disclosure, or a pharmaceutically usable salt, polymorph or solvatethereof, to alleviate the symptoms or complications of a disease, condition or disorder, or to eliminate the disease, condition or disorder. The term “treat” can also include treatment of a cellin vitro or an animal model. It is to be appreciated that references to “treating” or “treatment”include the alleviation of established symptoms of a condition. “Treating” or “treatment” of a state, disorder or condition therefore includes: (1) preventing or delaying the appearance of clinical symptoms of the state, disorder or condition developing in a human that may be afflicted with or predisposed to the state, disorder or condition but does not yet experience or display clinical orsubclinical symptoms of the state, disorder or condition, (2) inhibiting the state, disorder orcondition, i.e., arresting, reducing or delaying the development of the disease or a relapse thereof (in case of maintenance treatment) or at least one clinical or subclinical symptom thereof, or (3) relieving or attenuating the disease, i.e., causing regression of the state, disorder or condition or at least one of its clinical or subclinical symptoms.As used herein, the term “pharmaceutically usable salt” refers to a derivative of the compound ofthe present disclosure wherein the parent compound is modified by making an acid or base salt thereof. Examples of pharmaceutically acceptable salts include, but are not limited to, mineral or organic acid salts of basic residues such as amines, alkali or organic salts of acidic residues such as carboxylic acids, and the like. The pharmaceutically acceptable salts include the conventional non-toxic salts or the quaternary ammonium salts of the parent compound formed, for example, from non-toxic inorganic or organic acids. For example, such conventional non-toxic salts include, but are not limited to, those derived from inorganic and organic acids selected from 2- acetoxybenzoic, 2-hydroxyethane sulphonic, acetic, ascorbic, benzene sulphonic, benzoic, bicarbonic, carbonic, citric, edetic, ethane disulphonic, 1,2-ethane sulphonic, fumaric, glucoheptonic, gluconic, glutamic, glycolic, glycollyarsanilic, hexylresorcinic, hydrabamic, hydrobromic, hydrochloric, hydroiodic, hydroxymaleic, hydroxynaphthoic, isethionic, lactic, lactobionic, lauryl sulphonic, maleic, malic, mandelic, methane sulphonic, napsylic, nitric, oxalic, pamoic, pantothenic, phenylacetic, phosphoric, polygalacturonic, propionic, salicylic, stearic, subacetic, succinic, sulphamic, sulphanilic, sulphuric, tannic, tartaric, toluene sulphonic, and the commonly occurring amine acids, e.g., glycine, alanine, phenylalanine, arginine, etc. Preferably, the risk of acquiring a neurological disorder or neurodegenerative disease, such asPSP or Alzheimer is in some embodiments, a subject can be identified as being at increased riskof developing a neurological disorder or neurodegenerative disease, such as PSP, or identified as having a neurological disorder or neurodegenerative disease, such as e.g., at least in part, by detecting a genetic alteration in a gene encoding the microtubule-associated protein tau (MAPT) (e.g., any of the inversion polymorphisms in the MAPT gene, any of the haplotype--specific polymorphisms in the MAPT gene, the rare-coding MAPT variant (A152T), or mutations that enhance splicing of exon 10 in the MAPT gene described, e.g., in Hoglinger et al., Nature Genet. 43 :699-705, 2011, and Hinz et al., Cold Spring Harb. Perspect Biol.). Non-limiting examples of genetic alterations in a gene encoding MAPT include mutations that result in the production of MAPT protein that include one or more point mutations of: S285R, L284R, P301L, and G303V. Additional specific genetic mutations in a gene encoding MAPT protein that can be used to identifya subject as having an increased risk of developing a neurological disorder or neurodegenerativedisease, such as PSP, or can be used to identify a subject as having a neurological disorder or neurodegenerative disease, such as PSP are described in, e.g., Boxer et al., Lancet 16:552-563, 2017. In some embodiments, a subject can be identified as being at increased risk of developing aneurological disorder or neurodegenerative disease, such as Alzheimer by genetic alterations inthe presenilin 1 (PSEN1) or 2 (PSEN2) or β-amyloid precursor protein (APP) genes or by thepresence of the ε4 allele of the apolipoprotein E (APOE) gene or by having relatives bearing these alterations in their genes.In some embodiments, a subject can be identified as having an increased risk of developing aneurological disorder or neurodegenerative disease, such as PSP or identified as having a neurological disorder or neurodegenerative disease, such as PSP, e.g., at least in part, by detecting tau protein deposits (e.g., 4-repeat tau protein deposits), detecting of atrophy of the midbrain and / or superior cerebellar peduncles (e.g., using any of the imaging techniques described herein or known in the art, e.g., magnetic resonance imaging (MRI) or positron emission tomography (PET) scans), and / or detecting of hypometabolism in the frontal cortex, caudate, and / or thalamus in the subject (e.g., using any of the imaging techniques described herein or known in the art, e.g., MRI, CT scan, or PET scan). In some embodiments, a subject can be identified as being at increased risk of developing a neurological disorder or neurodegenerative disease, such as PSP or identified as having aneurological disorder or neurodegenerative disease, such as PSP, e.g., at least in part, by detecting the presence of, or an elevated level (e.g., as compared to a level in a healthy control subject) of, one or more biomarkers in a subject. In some embodiments, a subject can be identified as being at increased risk of developing a neurological disorder or neurodegenerative disease, by having had concussions / brain trauma asa result of sport activities (e.g. boxing, American football), military blast injuries or traffic accidents.In some embodiments, a subject can be identified as being at increased risk of developing a neurological disorder or neurodegenerative disease, by having reached an age over 65 years. In some embodiments, a subject can be identified as being at increased risk of developing a neurological disorder or neurodegenerative disease, by having predisposing diseases such as heart disease, stroke, hypercholesterolemia, obesity, hypertension and diabetes. The term “solvates” of the compounds is taken to mean adductions of inert solvent molecules ontothe compounds, which are formed owing to their mutual attractive force. Solvates are, for example,mono- or dihydrates or alkoxides. The invention also comprises solvates of salts of the compoundsaccording to the invention.In some embodiments, the compound of formula (I) is used in its non-racemic form. In someembodiments, an optically enriched mixture denotes the compound of Formula (I). The compound of formula (I) are preferably used in its non-racemic form. Most preferably, an optically enriched mixture denotes the compound of Formula (I). Compounds that have the same molecular formula but differ in the nature or sequence of bonding of their atoms or the arrangement of their atoms in space are termed “isomers”. Isomers that differ in the arrangement of their atoms in space are termed “stereoisomers”. Stereoisomers that are not mirror images of one another are termed “diastereomers” and those that are non-superimposable mirror images of each other are termed “enantiomers”. When a compound has an asymmetric centre, for example, it is bonded to four different groups, a pair of enantiomersis possible. An enantiomer can be characterised by the absolute configuration of its asymmetriccentre and is described by the R- and S-sequencing rules of Cahn and Prelog, or by the mannerin which the molecule rotates the plane of polarised light and designated as dextrorotatory or levorotatory (i.e., as (+) or (-)-isomers respectively). A chiral compound can exist as either individual enantiomer or as a mixture thereof. A mixture containing equal proportions of the enantiomers is called a “racemic mixture”. As used herein, the term “stereoisomer” includes“diastereoisomer” and “enantiomer”. The compounds of this disclosure may possess one or more asymmetric centres; suchcompounds can therefore be produced as individual (R)- or (S)-stereoisomers or as mixturesthereof. Unless indicated otherwise, the description or naming of a particular compound in the specification and claims is intended to include both individual enantiomers and mixtures, racemic or otherwise, thereof. The methods for the determination of stereochemistry and the separation of stereoisomers are well-known in the art (see discussion in Chapter 4 of “Advanced Organic Chemistry”, 4th edition J. March, John Wiley and Sons, New York, 2001), for example by synthesis from optically active starting materials or by resolution of a racemic form. Some of the compoundsof the disclosure may have geometric isomeric centres (E- and Z- isomers).As used herein, the term “tautomer” is one of two or more structural isomers that exist in equilibrium and is readily converted from one isomeric form to another. This conversion results inthe formal migration of a hydrogen atom accompanied by a switch of adjacent conjugated doublebonds. Tautomers exist as a mixture of a tautomeric set in solution. In solutions where tautomerisation is possible, a chemical equilibrium of the tautomers will be reached. The exact ratio of the tautomers depends on several factors, including temperature, solvent and pH. Theconcept of tautomers that are interconvertible by tautomerisations is called tautomerism.In some embodiments, the compositions of the invention are substantially comprising a singleisomer of the compound of formula (I). In one aspect, substantially free of corresponding isomersmeans at least 90% by weight of the compound of formula (I), or a stereoisomer, tautomer,pharmaceutically usable solvate or salt thereof, to 10% by weight or less of a corresponding isomerin said pharmaceutical composition. In another aspect, substantially free of corresponding isomers means at least 95% by weight of the compound of formula (I), or a stereoisomer, tautomer,pharmaceutically usable solvate or salt thereof, to 5% by weight or less of a corresponding isomerin the pharmaceutical composition. In yet another aspect, substantially free of correspondingisomers means at least 99% by weight of the compound of formula (I) s to 1% by weight or lessof a corresponding isomer in the pharmaceutical composition.The compound of Formula (I), or a stereoisomer or tautomer thereof, can be used in their finalnon-salt form. On the other hand, the present invention also encompasses the use of thecompound (I), or a stereoisomer or tautomer thereof, in the form of their pharmaceuticallyacceptable acid-addition salt, which can be formed by treating the respective compound withpharmaceutically acceptable organic and inorganic acids, for example hydrogen halides, such as hydrogen chloride, hydrogen bromide or hydrogen iodide, other mineral acids and correspondingsalts thereof, such as sulfate, nitrate or phosphate and the like, and alkyl- and monoarylsulfonates,such as methanesulfonate, ethanesulfonate, toluenesulfonate and benzenesulfonate, and other organic acids and corresponding salts thereof, such as carbonate, acetate, trifluoroacetate, tartrate, maleate, succinate, citrate, benzoate, salicylate, ascorbate and the like. Accordingly, pharmaceutically acceptable acid-addition salts of the compounds according to the invention include the following: acetate, adipate, alginate, arginate, aspartate, benzoate, benzenesulfonate (besylate), bisulfate, bisulfite, bromide, butyrate, camphorate, camphorsulfonate, caprate, caprylate, chloride, chlorobenzoate, citrate, cyclamate, cinnamate, cyclopentanepropionate, digluconate, dihydrogenphosphate, dinitrobenzoate, dodecylsulfate, ethanesulfonate, formate, glycolate, fumarate, galacterate (from mucic acid), galacturonate, glucoheptanoate, gluconate, glutamate, glycerophosphate, hemisuccinate, hemisulfate, heptanoate, hexanoate, hippurate, hydrochloride, hydrobromide, hydroiodide, 2-hydroxyethanesulfonate, iodide, isethionate, isobutyrate, lactate, lactobionate, malate, maleate, malonate, mandelate, metaphosphate, methanesulfonate, methylbenzoate, monohydrogenphosphate, 2-naphthalenesulfonate, nicotinate, nitrate, oxalate, oleate, palmoate, pectinate, persulfate, phenylacetate, 3-phenylpropionate, phosphate, phosphonate, phthalate, but this list is not intending to represent arestriction. In a preferred embodiment of the invention, a compound of formula (I) is selected from formula Chemical bonds that in formula (I) and (I’) are drawn as follows: indicate a defined, i.e. R or S, stereochemistry at at least one of the atoms to which they areattached to. Thus, formula (I) and (I’) refer to individual stereochemically defined compounds asopposed to a mixture of diastereoisomers and / or enantiomers. The compound of formula (I) is more specifically selected from the following compounds of formulaIa), (Ib), (Ic) and (Id): The compounds of formula (Ia) and (Ib) are preferred. The compound of formula (Ia) is the mostpreferred embodiment of formula (I) and (I’).In some embodiments, an acid addition salt of fumaric acid, succinic acid, benzoic acid, methyl sulfonic acid, hydrochloric acid, maleic acid, tartaric acid, sulfuric acid phosphoric acid malic acid,citric acid or p-toluolsulfonic acid with a compound of formula (I) is especially preferred. In someembodiments, a salt of the compound of formula (I) is the fumarate or the succinate. Very preferredsalts of the compound of formula (I), i.e. salts of compounds of formula (I’), (Ia), (Ib), (Ic), (Id) arethe fumarate and the succinate salts.A preferred fumaric acid salt of formula (I) is shown below: A very preferred fumaric acid salt of formula (Ia) is shown below: The compound of formula (I) is obtainable and preferably prepared according to example 35 ofWO 2018 / 153508 and example C04 of WO 2020 / 039030. The compound (I) is more preferablyemployed as its fumarate salt form and its corresponding polymorphic form as disclosed in WO 2020 / 039030, claim 8. The compound of formula (I) can be obtained by carrying out the following synthesis steps: a) Racemic 5-(1-(piperazin-1-yl)ethyl)benzo[d]thiazole is resolved preferably by using D-di-p- anisoyltartaric acid or D-di-p-toluyltartaric acid or (R)-(+)-chlocyphos to form a crystalline saltthat is isolated. From the crystalline salt, the enantiomerically pure or enriched 5-(1-(piperazin-1-yl)ethyl)benzo[d]thiazole is obtained after removal of the chiral resolution agent via basic treatment. b) Racemic 2-chloro-5-(methylsulfinyl)pyrimidine is separated into its enantiomers by chiral chromatography, preferably using as a chiral stationary phase a polymeric support comprisingamylose as immobilized polysaccharide selectors, such as amylose based phenyl carbamatederivative, such as but not limited to Chiralpak IE-20 CSP as chiral stationary phase, containingamylose tris(3,5-dichlorophenylcarbamate), or Phenomenex Lux Amylose-1 column (250 x 30mm, 5 μm), containing amylose tris(3,5-dimethylphenylcarbamate).The first eluting enantiomer of 2-chloro-5-(methylsulfinyl)pyrimidine is treated withtrifluroacetamide, Rh2(OAc)4 and PhI(OAc)2 and the resulting product is purified through conventional means. c) The products under a) and b) above are combined in a suitable solvent in the presence of a base, such as an amine, to produce an intermediate that is optionally purified and treated again with a base, such as potassium carbonate, in a solvent such as methanol. The compound of formula (I) is obtained after conventional purification from the aforementioned mixture. The compound of formula (Ia) is most preferably obtained according to the steps a), b) and c) above. A preferred method for the preparation of an acid addition salt of succinic acid or fumaric acid with compounds of formula (I) comprise the following steps: i) suspending or dissolving the compound of formula (I) and the respective acid in a suitable solvent or solvent mixture; ii) heating the mixture obtained in step i) to a temperature of between about 30 °C to about the boiling point of the selected solvent or solvent mixture, and allowing the mixture to cool to room temperature; iii) optionally repeating step ii) several times; iiii) separating and drying the solid thus obtained. The fumarate of the compound of formula (Ia) is most preferably obtained according to the method above. A further aspect of the invention relates to the use of the medicaments and pharmaceutical compositions comprising the compound of formula (I), or a stereoisomer, tautomer,pharmaceutically usable solvate or salt thereof, and the respective dosage regimens for itsadministration to humans for inhibiting a glycosidase. Such use may be therapeutic or non- therapeutic in character. The term “inhibition” denotes any reduction in glycosidase activity, which is based on the action of the specific inventive compounds capable to interact with the target glycosidase in such a manner that makes recognition, binding and blocking possible. In some embodiments, the glycosidase comprises glycoside hydrolases, more preferably family 84 glycoside hydrolases, most preferably (protein)-3-O-(N-acetyl-D-glucosaminyl)-L-serine / threonine N-acetylglucosaminyl hydrolase (O-GlcNAcase), highly preferably a mammalianO-GlcNAcase. It is particularly preferred that the compounds of formula (I) according to the invention selectively bind an O-GlcNAcase, e.g. thereby selectively inhibiting the cleavage of 2-acetamido-2-deoxy-β-D-glucopyranoside (O-GlcNAc) while they do not substantially inhibit alysosomal β-hexosaminidase. It is particularly preferred that the compounds of formula (I)according to the invention selectively bind an O-GlcNAcase, e.g. thereby selectively inhibiting the cleavage of 2-acetamido-2-deoxy-β-D-glucopyranoside (O-GlcNAc) while they do not substantially inhibit a lysosomal β-hexosaminidase. As discussed herein, the glycosidase-signaling pathways are relevant for various diseases, e.g., neurodegenerative diseases, diabetes, cancer, cardiovascular diseases and stroke. As discussed herein, the glycosidase-signaling pathways are relevant for various diseases, preferably neurodegenerative diseases, diabetes, cancer, cardiovascular diseases and stroke. Accordingly, the compounds according to the invention are useful in the prophylaxis and / or treatment of diseases that are dependent on the said signaling pathways by interaction with one or more of them. The present invention therefore relates to the therapeutic and non-therapeutic use of compounds according to the invention as inhibitors of the signaling pathways described herein, preferably of the OGA-mediated signaling. A further aspect of the invention relates to a medicament comprising the compound of formula (I),or a stereoisomer, tautomer, pharmaceutically usable salt, or solvate thereof. A “medicament” inthe meaning of the invention is any agent in the field of medicine, which comprises the compoundof formula (I) or preparations thereof (e.g. a pharmaceutical composition or pharmaceutical formulation) and can be used in prophylaxis, therapy, follow-up or aftercare of patients who sufferfrom diseases, which are associated with OGA activity, in such a way that a pathogenicmodification of their overall condition or of the condition of particular regions of the organism couldestablish at least temporarily. In some embodiments, the medicament is prepared in a non-chemical manner, e.g. by combining the active ingredient with at least one solid, fluid and / or semi- fluid carrier or excipient, and optionally in conjunction with a single or more other active substancesin an appropriate dosage form. The medicament is preferably prepared in a non-chemical manner,e.g. by combining the active ingredient with at least one solid, fluid and / or semi-fluid carrier or excipient, and optionally in conjunction with a single or more other active substances in an appropriate dosage form. In the meaning of the invention, an “adjuvant” denotes every substance that enables, intensifies or modifies a specific response against the active ingredient of the invention if administered simultaneously, contemporarily or sequentially. Known adjuvants for injection solutions are, for example, aluminum compositions, such as aluminum hydroxide or aluminum phosphate, saponins, such as QS21, muramyldipeptide or muramyltripeptide, proteins, such as gamma- interferon or TNF, M59, squalen or polyols.In some embodiments, the present invention provides dosing regiments for the administration ofthe medicament or the pharmaceutical composition according to the present invention to human patients in need thereof. The dose regimens are especially suited for the treatment of neurological or neurodegenerative diseases including tauopathies such as PSP, Alzheimer's Disease or dementia.In some embodiments, concerning O-GlcNAcase inhibition as therapeutic mechanism, a highdegree of enzyme or target occupancy and / or inhibition over 24 hours is preferred. In this respect,maintaining sufficient O-GlcNAcase inhibitor concentrations at trough is a significant determinantto ensure minimal recovery of enzyme activity during treatment.In some embodiments, therapeutically effective doses of the compound of formula (I), or astereoisomer, tautomer, pharmaceutically usable solvate or salt thereof, ensure targetoccupancies of at least about 35% at trough, (e.g., at least about 40% or 50% at trough, (e.g., atleast about 60%, or 70% at trough, (e.g., at least about 80%, 90% or 98% at trough))). In some embodiments, therapeutically effective doses of the compound of formula (I), or astereoisomer, tautomer, pharmaceutically usable solvate or salt thereof, preferably ensure targetoccupancies of at least about 35% at trough, preferably at least about 40% or 50% at trough, more preferably at least about 60%, or 70% at trough, most preferably at least about 80%, 90% or 98% at trough.In some embodiments, a single dose of 20 mg yields enzyme occupancy (EO) which is still above85% at 72 h. In some embodiments, more than 95% EO can be maintained over 24 h with a dose of or lessthan 10 mg once daily QD of compound (I).In some embodiments, the ratio of mean maximum concentration to trough concentration at steadystate is lower than 2, both in fed and fasted conditions.In some embodiments, the range of target occupancy at trough is about 40 % to about 95%. Insome embodiments, the target occupancy at trough is about 60% to about 95%. In some embodiments, the target occupancy at trough is at least about 70% to about 95%. In some embodiments, the target occupancy at trough is at least about 80% to about 98%. In some embodiments, therapeutically effective doses of the compound of formula (I), or astereoisomer, tautomer, pharmaceutically usable solvate or salt thereof, ensure average targetoccupancies over a period of 24 hours during treatment with the medicament or formulationcomprising the compound of formula (I), of at least about 70% (e.g., at least about 80% or 85%,(e.g., at least about 90%, (e.g., at least about 98%))).In some embodiments, therapeutically effective doses of the compound of formula (I), or astereoisomer, tautomer, pharmaceutically usable solvate or salt thereof, preferably ensureaverage target occupancies over a period of 24 hours during treatment with the medicament orformulation comprising the compound of formula (I), of at least about 70%, preferably at leastabout 80% or 85%, more preferably at least about 90%, most preferably at least about 98%. In some embodiments, the range of average target occupancy over a period of 24 hours duringtreatment with the medicament or formulation comprising the compound of formula (I), or astereoisomer, tautomer, pharmaceutically usable solvate or salt thereof, is about 80 % to about99.5% or higher. In some embodiments, the average target occupancy over a period of 24 hoursduring treatment with the medicament or formulation comprising the compound of formula (I), ora stereoisomer, tautomer, pharmaceutically usable solvate or salt thereof, is about 85% to about99% or higher. In some embodiments, the average target occupancy over a period of 24 hoursduring treatment with the medicament or formulation comprising the compound of formula (I), ora stereoisomer, tautomer, pharmaceutically usable solvate or salt thereof, is about 90% to about99% or higher.Preferably, a therapeutically effective dose ensures at least about 78% target occupancy in thebrain at trough, and at least about 80% average target occupancy over a period of 24 hours duringtreatment with the medicament or formulation comprising the compound of formula (I), or astereoisomer, tautomer, pharmaceutically usable solvate or salt thereof.Preferably, a therapeutically effective dose ensures at least about 85% target occupancy in thebrain at trough, and at least about 90% average target occupancy over a period of 24 hours during treatment with the medicament or formulation comprising the compound of formula (I), or astereoisomer, tautomer, pharmaceutically usable solvate or salt thereof.In some embodiments, target occupancy leads to clinical efficacy, that results in reduced orameliorated progression of the signs and symptoms of a disease including neurological disordersor neurodegenerative diseases, diabetes, cancer, cardiovascular diseases and stroke and e.g., aneurological disorder or neurodegenerative disease such as PSP. In preferred embodiments target occupancy leads to clinical efficacy, that results in reduced or ameliorated progression ofthe signs and symptoms of a disease including neurological disorders or neurodegenerativediseases, diabetes, cancer, cardiovascular diseases and stroke and preferably a neurologicaldisorder or neurodegenerative disease such as PSP. In some embodiments, the dose regimencomprising the compound of formula (I), or a stereoisomer, tautomer, pharmaceutically usablesolvate or salt thereof, reduces or ameliorate the progression of the signs and symptoms of aneurological disorder or neurodegenerative disease, such as PSP, in particular brain tau burden, whole brain and regional midbrain atrophy, reduced ability to perform daily activities, cognitive impairment. Moreover, the dose regimen comprising the compound of formula (I), or astereoisomer, tautomer, pharmaceutically usable solvate or salt thereof, improve biomarkerresults, overall clinical status and quality of life. In some embodiments, the dose regimen comprising the compound of formula (I), or astereoisomer, tautomer, pharmaceutically usable solvate or salt thereof, reducesneuroinflammation. In some embodiments, the dose regimen comprising the compound of formula(I), or a stereoisomer, tautomer, pharmaceutically usable solvate or salt thereof, isneuroprotective. In some embodiments, the dose regimen comprising the compound of formula(I), or a stereoisomer, tautomer, pharmaceutically usable solvate or salt thereof, treats neuronaldegeneration. In some embodiments, the dose regimen comprising the compound of formula (I),or a stereoisomer, tautomer, pharmaceutically usable solvate or salt thereof, reduces atrophy ordegeneration of the brain. In some embodiments, the dose regimen comprising the compound offormula (I), or a stereoisomer, tautomer, pharmaceutically usable solvate or salt thereof, reducesatrophy or degradation of the substantia nigra, globus pallidus, subthalamic nucleus and orcerebellum. In some embodiments, the dose regimen comprising the compound of formula (I), ora stereoisomer, tautomer, pharmaceutically usable solvate or salt thereof, improves mitochondrialfunction. This results in improved behavior, improved survival (i.e. lifespan) and reduced braindegeneration. In some embodiments, the dose regimen comprising the compound of formula (I),or a stereoisomer, tautomer, pharmaceutically usable solvate or salt thereof, reduces theaggregation of abnormal Tau protein, or fragments of Tau protein. In some embodiments, the doseregimen comprising the compound of formula (I), or a stereoisomer, tautomer, pharmaceuticallyusable solvate or salt thereof, ameliorates the reduction of neuroprotective proteins in the brain.In some embodiments, the dose regimen comprising the compound of formula (I), or astereoisomer, tautomer, pharmaceutically usable solvate or salt thereof, reduces the reduction ofbrain-derived neurotrophic factor and Bcl 2. In some embodiments, the dose regimen comprisingthe compound of formula (I), or a stereoisomer, tautomer, pharmaceutically usable solvate or saltthereof, ameliorates the reduction of cerebral glucose metabolism as e.g. assessed by [18F]-fluoro-deoxyglucose PET. Moreover, in preferred embodiments, the dose regimen comprising the compound of formula (I),or a stereoisomer, tautomer, pharmaceutically usable solvate or salt thereof, results inimprovement of one or more of the following disease parameters, biomarkers and scores compared to baseline values: -PSP Rating Scale (PSPRS) (28-item scale)- Modified PSPRS (10-item subscale)- Cortical Basal ganglionic Functional Scale (CBFS)- PSP Functional Disability Scale (PSPFDS)- Schwab and England Activities of Daily Living Scale (SEADL)- Clinical Global Impression of Change (CGI-C)- Progressive Supranuclear Palsy Quality of Life Scale (PSP-QoL)- Montreal Cognitive Assessment (MoCA)- ADAS-Cog (The Alzheimer's Disease Assessment Scale–Cognitive Subscale)- Dimensional Apathy Scale (DAS)- Color Trails Test Parts 1 and 2 (CTT-1 and CTT-2)- Letter Fluency Test- Tau PET imaging- Neurodegeneration and neuroinflammation CSF biomarkers, such asneurodegeneration panel: total tau, p-tau, NfL and neuroinflammation panel -Whole brain volumes as measured by volumetric brain MRI- Regional volumes as measured by volumetric brain MRI- Plasma and CSF (NfL, total tau, p-tau) concentrations- Gobal O-GlcNAcylation levels- Digital biomarkers of neurodegenerationIn some embodiments, in order to meet the required target occupancies in the brain establishedabove, certain concentrations of the compound of formula (I), or a stereoisomer, tautomer,pharmaceutically usable solvate or salt thereof, in the plasma need to be achieved in a humanpatient. The brain enzyme, receptor or target occupancy was quantified by competitive displacement of a selective radiolabelled O-GlcNAcase inhibitor used as positron emissiontomography (PET) tracer by compound of formula (I). [18F]-LSN3316612 has been chosen as [18F]-radiolabelled, selective O-GlcNAcase inhibitor as it has been shown to exhibit a suitable selectivityand pharmacokinetics for quantification of O-GlcNAcase enzyme in the brain in preclinical studiesand as a PET tracer for human studies (Paul S. et al. J. Nucl. Med. 2019, 60(1), 129-134). Othersuitable PET tracers provide similar results. A correlation of the required target occupancies withplasma concentrations of the drug is established by measuring the plasma concentration of the compound of formula (I), or a stereoisomer, tautomer, pharmaceutically usable solvate or saltthereof, during competitive displacement of the PET tracer by compound of formula (I), or astereoisomer, tautomer, pharmaceutically usable solvate or salt thereof.In some embodiments, it has been found that the preferred target occupancies in the brain can beachieved when the plasma concentrations of the compound of formula (I), or a stereoisomer,tautomer, pharmaceutically usable solvate or salt thereof, are as mentioned below. The plasmaconcentrations, if not indicated otherwise, are measured and indicated at steady state.In some aspects, the present disclosure provides methods of treating a subject, the method comprising administering to the subject a compound of formula (I), or a stereoisomer, tautomer,pharmaceutically usable solvate or salt thereof.In some aspects, the present disclosure provides a compound of formula (I), or a stereoisomer,tautomer, pharmaceutically usable solvate or salt thereof, for use in treating a subject.In some aspects, the present disclosure provides a use of a compound of formula (I), or astereoisomer, tautomer, pharmaceutically usable solvate or salt thereof, in the manufacture of amedicament for treating a subject. In some aspects, the present disclosure provides a use of a compound of formula (I), or astereoisomer, tautomer, pharmaceutically usable solvate or salt thereof, for treating a subject.Throughout the specification, all embodiments of the present invention can be combined with any other embodiments of the invention disclosed in this specification, unless explicitly excluded. In some embodiments, the plasma concentration of the compound of formula (I), or astereoisomer, tautomer, pharmaceutically usable solvate or salt thereof, is least about 5 ng / mL at trough, or at least about 7.5 ng / mL or 10 ng / mL or 12.5 ng / mL or 20 ng / mL at trough, at leastabout 60 ng / mL, or at least about 100 ng / mL or 200 ng / mL or 300 ng / mL at trough, at least about400 ng / mL, 500 ng / mL, 600 ng / mL, 700 ng / mL, 800 ng / mL or 1000 ng / mL at trough. In someembodiments, the plasma concentration of the compound of formula (I), or a stereoisomer,tautomer, pharmaceutically usable solvate or salt thereof, is least about 5 ng / mL at trough,preferably at least about 7.5 ng / mL or 10 ng / mL or 12.5 ng / mL or 20 ng / mL at trough, at leastabout 60 ng / mL, or at least about 100 ng / mL or 200 ng / mL or 300 ng / mL at trough, at least about 400 ng / mL, 500 ng / mL, 600 ng / mL, 700 ng / mL, 800 ng / mL or 1000 ng / mL at trough. In some embodiments, the plasma concentration of the compound of formula (I), or astereoisomer, tautomer, pharmaceutically usable solvate or salt thereof, may be at least about 10ng / mL at trough or at last about 20 ng / mL or 100 ng / mL at trough, at least about 150 ng / mL, or200 ng / mL at trough, at least about 300 ng / mL or 400 ng / mL at trough. In a preferred embodiment,the plasma concentration of the compound of formula (I), or a stereoisomer, tautomer,pharmaceutically usable solvate or salt thereof, may be at least about 10 ng / mL at trough or atlast about 20 ng / mL or 100 ng / mL at trough, at least about 150 ng / mL, or 200 ng / mL at trough, at least about 300 ng / mL or 400 ng / mL at trough.In some embodiments, average plasma concentrations of the compound of formula (I), or astereoisomer, tautomer, pharmaceutically usable solvate or salt thereof, over a period of 24 hoursduring treatment with the medicament or formulation comprising the compound of formula (I) atsteady state, are at least about 6.5 ng / mL, at least about 10 ng / mL or at last about 15 ng / mL, 80ng / mL, 125 ng / mL or 250 ng / mL, at least about 500 ng / mL or 1300 ng / mL. In some embodiments,average plasma concentrations of the compound of formula (I), or a stereoisomer, tautomer,pharmaceutically usable solvate or salt thereof, over a period of 24 hours during treatment withthe medicament or formulation comprising the compound of formula (I) at steady state, arepreferably at least about 6.5 ng / mL, at least about 10 ng / mL or preferably at last about 15 ng / mL,80 ng / mL, 125 ng / mL or 250 ng / mL, at least about 500 ng / mL or 1300 ng / mL. In a preferred embodiment, average plasma concentrations of the compound of formula (I), or astereoisomer, tautomer, pharmaceutically usable solvate or salt thereof, over a period of 24 hoursduring treatment with the medicament or formulation comprising the compound of formula (I), areat least about 12 ng / mL, at last about 80 ng / mL, 120 ng / mL or 250 ng / mL, at least about 520ng / mL.In some embodiments, plasma concentrations of the compound of formula (I), or a stereoisomer,tautomer, pharmaceutically usable solvate or salt thereof, at steady state are at least about 30ng / mL or 50 ng / mL at trough, while average plasma concentrations of the compound of formula(I), or a stereoisomer, tautomer, pharmaceutically usable solvate or salt thereof, over a period of24 hours are at least about 35 ng / mL or 85 ng / mL.In a preferred embodiment, plasma concentrations of the compound of formula (I), or astereoisomer, tautomer, pharmaceutically usable solvate or salt thereof, at steady state are atleast about 90 ng / mL at trough, while average plasma concentrations of the compound of formula(I), or a stereoisomer, tautomer, pharmaceutically usable solvate or salt thereof, over a period of24 hours are at least about 125 ng / mL.In some embodiments, plasma concentrations of the compound of formula (I), or a stereoisomer,tautomer, pharmaceutically usable solvate or salt thereof, at steady state are at least about 190ng / mL at trough, while average plasma concentrations of the compound of formula (I), or astereoisomer, tautomer, pharmaceutically usable solvate or salt thereof, over a period of 24 hoursare at least about 250 ng / mL.In a preferred embodiment, plasma concentrations of the compound of formula (I), or astereoisomer, tautomer, pharmaceutically usable solvate or salt thereof, at steady state are atleast about 400 ng / mL at trough, while average plasma concentrations of the compound of formula(I), or a stereoisomer, tautomer, pharmaceutically usable solvate or salt thereof, over a period of24 hours are at least about 520 ng / mL.In some aspects, the present invention provides for a dose regimen for the administration of amedicament or a pharmaceutical composition comprising of formula (I), or a stereoisomer,tautomer, pharmaceutically usable solvate or salt thereof, to an individual in need thereof, forexample, and individual having a neurological disorder or neurodegenerative disease, such asmild to moderate AD or PSP, so as to obtain a desired pharmacokinetic profile of a desiredconcentration of the compound of formula (I), or a stereoisomer, tautomer, pharmaceuticallyusable solvate or salt thereof, in the plasma over a period of time. By maintaining a preferredplasma concentration of the compound of formula (I), or a stereoisomer, tautomer,pharmaceutically usable solvate or salt thereof, a preferred target occupancy is achieved.Ppreferred pharmacokinetic profiles and / or endpoints may be achieved through the administration of one or more unit dosage forms comprising, for example, about 0.25 mg, about 0.5 mg, about 1 mg, about 2 mg, about 3 mg, about 5 mg, about 7.5 mg, about 10 mg, about 15 mg, about 20 mg,about 25 mg or about 50 mg of the compound of formula (I), or a stereoisomer or tautomer thereof,which may also be administered in the form of a pharmaceutically useable solvate or salt thereof. In some embodiments, pharmacokinetic profiles and / or endpoints may be achieved through theadministration of specific daily doses of the compound of formula (I), or a stereoisomer, tautomer,pharmaceutically usable solvate or salt thereof, for example daily oral doses ranging from about0.25 mg to about 50 mg per day (e.g., about 1 mg to about 25 mg per day, (e.g., about 3 mg toabout 20 mg per day)). In some embodiments, the daily dose is about 5 mg or about 7.5 mg orabout 10 mg or about 12.5 mg or about 15 mg or about 20 mg per day. Preferred pharmacokineticprofiles and / or endpoints may more specifically be achieved through the administration of specificdaily doses of the compound of formula (I), or a stereoisomer, tautomer, pharmaceutically usablesolvate or salt thereof, preferably daily oral doses, preferably ranging from about 0.25 mg to about 50 mg per day, more preferably about 1 mg to about 25 mg per day and most preferably about 3 mg to about 20 mg per day. In a further preferred embodiment, the daily dose is about 5 mg or about 7.5 mg or about 10 mg or about 12.5 mg or about 15 mg or about 20 mg per day. In preferred embodiments, the daily dose of the compound of formula (I), or a stereoisomer,tautomer, pharmaceutically usable solvate or salt thereof, is achieved by a once daily QD doseregimen of the compound of formula (I), or a stereoisomer, tautomer, pharmaceutically usablesolvate or salt thereof. This is preferably achieved by administration of one or two unit dosageforms comprising of the compound of formula (I), or a stereoisomer, tautomer, pharmaceuticallyusable solvate or salt thereof, such as a tablet or capsule per administration.In a preferred embodiment, wherein once daily QD dose regimens are applied, immediate releaseformulations of the compound of formula (I), or a stereoisomer, tautomer, pharmaceutically usablesolvate or salt thereof, are administered. In some embodiments, immediate release formulations and immediate release unit dosage forms according to the present invention are designed to release the compound of formula (I), or astereoisomer, tautomer, pharmaceutically usable solvate or salt thereof, immediately after theouter shell such as a coating of the respective dosage form, such as a tablet or a capsule dissolve. This preferably results in rapid absorption and fast systemic entry into the body, i.e. a prompt increase in blood concentration of the compound of formula (I), or a stereoisomer, tautomer,pharmaceutically usable solvate or salt thereof. Immediate release formulations and immediaterelease unit dosage forms according to the present invention also comprise a sachet or a sachet formulation. In some embodiments, the immediate release dosage form according to the invention hasreleased at least 75%, (e.g., at least 95%) of the compound of formula (I), or a stereoisomer,tautomer, pharmaceutically usable solvate or salt thereof, at 45 minutes and / or at least 90% of thecompound of formula (I), or a stereoisomer, tautomer, pharmaceutically usable solvate or saltthereof, at 15 minutes in the USP Paddle test, e.g., in 0.1 % cetyltrimethylammonium bromide(CTAB) in 0.01 M hydrochloric acid as dissolution medium, and paddle speed of 75 rpm.Preferably, the immediate release dosage form according to the invention has released at least 75%, preferably at least 95% of the compound of formula (I), or a stereoisomer, tautomer,pharmaceutically usable solvate or salt thereof, at 45 minutes and / or at least 90% of the compoundof formula (I), or a stereoisomer, tautomer, pharmaceutically usable solvate or salt thereof, at 15minutes in the USP Paddle test, preferably in 0.1 % cetyltrimethylammonium bromide (CTAB) in 0.01 M hydrochloric acid as dissolution medium, and paddle speed of 75 rpm. Most preferably, the immediate release dosage form according to the invention has released at least 75% of the compound of formula (I), or a stereoisomer, tautomer, pharmaceutically usable solvate or saltthereof, at 45 minutes in the USP Paddle test as described in example 5.In preferred embodiments, the dose regimen of the medicament or formulation comprising thecompound of formula (I), or a stereoisomer, tautomer, pharmaceutically usable solvate or saltthereof comprises a respective dose and a dosing frequency as follows: A dose of the compoundof formula (I), or a stereoisomer, tautomer, pharmaceutically usable solvate or salt thereof, ofabout 5 mg once daily QD or 10 mg once daily QD.In some embodiments, the invention provides for a medicament comprising the compound offormula (I), or a stereoisomer, tautomer, pharmaceutically usable solvate or salt thereof, and a method of administering a medicament or a pharmaceutical composition comprising thecompound of formula (I), or a stereoisomer, tautomer, pharmaceutically usable solvate or saltthereof to an individual, wherein said compound of formula (I), or a stereoisomer, tautomer,pharmaceutically usable solvate or salt thereof, is provided in an amount sufficient to result in aplasma C max of the compound of formula (I), or a stereoisomer, tautomer, pharmaceuticallyusable solvate or salt thereof, of about 9 ng / mL to about 1900 ng / mL. In some embodiments, theplasma C max of the compound of formula (I), or a stereoisomer, tautomer, pharmaceuticallyusable solvate or salt thereof, is e.g., from about 20 ng / mL to about 750 ng / mL. In someembodiments, the C max of the compound of formula (I), or a stereoisomer, tautomer,pharmaceutically usable solvate or salt thereof, is about 45 ng / mL to about 550 ng / mL, or about100 ng / mL to about 370 ng / mL, or about 185 ng / mL to about 370 ng / mL. In some embodiments,the plasma C max of the compound of formula (I), or a stereoisomer, tautomer, pharmaceuticallyusable solvate or salt thereof, is preferably from about 20 ng / mL to about 750 ng / mL. In anothermore preferred embodiments, the C max of the compound of formula (I), or a stereoisomer,tautomer, pharmaceutically usable solvate or salt thereof, is about 45 ng / mL to about 550 ng / mL,or preferably about 100 ng / mL to about 370 ng / mL, or most preferably about 185 ng / mL to about370 ng / mL. In some embodiments, the invention provides for a medicament comprising the compound offormula (I), or a stereoisomer, tautomer, pharmaceutically usable solvate or salt thereof and amethod of administering a medicament or a pharmaceutical composition comprising thecompound of formula (I), or a stereoisomer, tautomer, pharmaceutically usable solvate or saltthereof to an individual, wherein said compound of formula (I), or a stereoisomer, tautomer,pharmaceutically usable solvate or salt thereof, is provided in an amount sufficient to result in aplasma AUC over 24 hours of the compound of formula (I), or a stereoisomer, tautomer,pharmaceutically usable solvate or salt thereof, of about 150 ng*h / mL to about 31000 ng*h / mL. Insome embodiments, the AUC over 24 hours of the compound of formula (I), or a stereoisomer,tautomer, pharmaceutically usable solvate or salt thereof, is about 350 ng*h / mL to about 13000ng*h / mL or about 740 ng*h / mL to about 9200 ng*h / mL, or about 1800 ng*h / mL to about 6200ng*h / mL, or about 3000 ng*h / mL to about 6200 ng*h / mL. In another more preferred embodiment,the AUC over 24 hours of the compound of formula (I), or a stereoisomer, tautomer,pharmaceutically usable solvate or salt thereof, is about 350 ng*h / mL to about 13000 ng*h / mL orabout 740 ng*h / mL to about 9200 ng*h / mL, or preferably about 1800 ng*h / mL to about 6200ng*h / mL, or most preferably about 3000 ng*h / mL to about 6200 ng*h / mL. In some embodiments, the invention encompasses repeated dosing of the compound of formula(I), or a stereoisomer, tautomer, pharmaceutically usable solvate or salt thereof, to achieve theselevels for about 1 week, two weeks, three weeks, four weeks, one month, two months, three months, four months, five months, six months, seven months, eight months, nine months, ten months, eleven months, one year, or preferably more than one year. All dosages given throughout the specification are referring to the amount of the compound offormula (I), or a stereoisomer, tautomer, pharmaceutically usable solvate or salt thereof, or inrespective free base form. Thus, any dose or dosage of an acid-addition salt of the compound offormula (I), or a stereoisomer or tautomer thereof, is to be adapted accordingly, taking theadditional molecular weight of the respective acid into account. The same applies correspondinglyto solvates of the compound of formula (I), or a stereoisomer, tautomer, or pharmaceuticallyusable salt thereof.It is understood that while the compound of formula (I), or a stereoisomer or tautomer thereof, maybe administered in form of one or more respective pharmaceutically usable solvate or salt, plasma concentrations are given throughout the specification in the respective base form, i.e. as freecompound of formula (I), or a stereoisomer or tautomer thereof.In preferred embodiments the compound of formula (I), or a stereoisomer or tautomer thereof, isadministered in a form of the respective fumarate salt.In some embodiments, intervals between administrations are regular or follow a regular pattern.In some embodiments, the medicament of the present invention is administered once daily. Insome embodiments, the interval between administrations is about 24 hours.Preferred intervals between administrations are regular or follow a regular pattern. More preferably, the medicament of the present invention is administered once daily. Most preferably, the interval between administrations is about 24 hours. In some embodiments, oral administration of a dose of the compound of formula (I), or astereoisomer, tautomer, pharmaceutically usable solvate or salt thereof, is once daily for at leastabout 4 months, at least about 6 or at least about 8 months, or at least about 1 year, or at leastabout 2 years. In some embodiments, oral administration of a dose of the compound of formula (I), or a stereoisomer, tautomer, pharmaceutically usable solvate or salt thereof, preferably once daily for at least about 4 months, preferably at least about 6 or at least about 8 months, and morepreferably at least about 1 year, or at least about 2 years. In some embodiments, oraladministration provides an improvement or lessening of decline in cognitive function, biochemicaldisease marker progression, and / or plaque pathology. In some embodiments, a dosage form is a unit dosage form, such as a capsule. In some embodiments, a dosage form is a tablet. In some embodiments, a dosage form is a powder, (e.g., contained in a sachet). In one aspect, a preferred dosage form is a unit dosage form, such as a capsule. In another aspect, a preferred dosage form is a tablet. In another aspect, a preferred dosage form is a powder, preferably contained in a sachet. In some embodiments, the medicament or composition provides an improvement or lessening in decline in biochemical disease marker progression, plaque pathology, quality of life indicators or combinations of any disease parameters. In some embodiments, the decline in cognitive function preferably can be characterized bycognition tests. In some embodiments, the lessening in decline in cognitive function is at least25% as compared to individuals treated with placebo, (e.g., at least 40%, (e.g., at least 60%)). It is preferred that the lessening in decline in cognitive function is at least 25% as compared to individuals treated with placebo, more preferably at least 40%, and even more preferably at least 60%. For example, an individual treated with placebo having probably mild-to-moderate Alzheimer's disease is expected to score approximately 5.5 points higher on the ADAS-cog test after a specified period of time (e.g.1 year) whereas an individual treated with a composition of the invention for the same period of time will score only approximately 3.3 points higher on theADAS-cog scale, i.e., will show 60% of the decline in cognitive function relative to untreatedindividuals, or 2.2 points higher i.e., will show 40% of the decline in cognitive function relative to untreated individuals, when treated for the same specified period of time. In some embodiments, the dosage is provided as a medicament or a pharmaceutical composition that is composed of the compound of formula (I), or a stereoisomer, tautomer, pharmaceuticallyusable solvate or salt thereof, an optional release agent, and additional optional ingredients.In some embodiments, the dosage is provided as a medicament or pharmaceutical composition that is a unit dosage form, e.g., a tablet or a capsule. The unit dosage form is preferably composed of the compound of formula (I), or a stereoisomer, tautomer, pharmaceutically usable solvate orsalt thereof, microcrystalline cellulose, Silica, colloidal hydrated, and magnesium stearate. In someembodiments, the dosage is provided as a pharmaceutical composition that is a capsule is composed of the compound of formula (I), microcrystalline cellulose, Silica, colloidal hydrated, and magnesium stearate, all encapsulated in hard HPMC capsule.In some embodiments, pharmaceutical formulations can be adapted for administration via anydesired suitable method, for example by oral (including buccal or sublingual), rectal, nasal, topical (including buccal, sublingual or transdermal), vaginal or parenteral (including subcutaneous, intra- muscular, intravenous or intradermal) methods. Such formulations can be prepared using proc- esses known in the pharmaceutical art by, e.g., combining the active ingredient with the excipient(s) or adjuvant(s). In some embodiments, the pharmaceutical composition of the invention is produced in a known way using common solid or liquid carriers, diluents and / or additives and usual adjuvants for pharmaceutical engineering and with an appropriate dosage. The amount of excipient material that is combined with the active ingredient to produce a single dosage form varies depending upon the host treated and the particular mode of administration. Suitable excipients include organic or inorganic substances that are suitable for the different routes of administration, such as enteral (e.g. oral), parenteral or topical application, and which do not react with compounds of formula (I) or salts thereof. Examples of suitable excipients are water, vegetable oils, benzyl alcohols, alkylene glycols, polyethylene glycols, glycerol triacetate, gelatin, carbohydrates, e.g. lactose or starch, magnesium stearate, talc and petroleum jelly.In preferred embodiments, the pharmaceutical composition is adapted for oral administration. Thepreparations can be sterilized and / or can comprise auxiliaries, such as carrier proteins (e.g. serum albumin), lubricants, preservatives, stabilizers, fillers, chelating agents, antioxidants, solvents, bonding agents, suspending agents, wetting agents, emulsifiers, salts (for influencing the osmoticpressure), buffer substances, colorants, flavorings and one or more further active substances, forexample one or more vitamins. Additives are well known in the art, and they are used in a variety of formulations. In some embodiments, pharmaceutical formulations adapted for oral administration can be administered as separate units, such as, for example, capsules or tablets; powders or granules; solutions or suspensions in aqueous or non-aqueous liquids; edible foams or foam foods; or oil-in-water liquid emulsions or water-in-oil liquid emulsions. In some embodiments, the formulations may also comprise other agents usual in the art with respect to the particular type of formulation; thus, for example, formulations which are suitable for oral administration may comprise flavors.A preferred example of a capsule or tablet core formulation according to the invention comprisesthe compound of formula (I), or a stereoisomer, tautomer, or pharmaceutically acceptable saltthereof (e.g., in a salt form such as the fumarate salt), a filler, a binder, a disintegrant, a glidant, adry binder, a lubricant and optionally a solvent. A preferred example of a capsule or tablet core formulation comprises the compound of formula(I), or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof (e.g., in a salt formsuch as the fumarate salt), microcrystalline cellulose, silica, and magnesium stearate andoptionally a solvent, such as water. In some embodiments, the pharmaceutical compositions and medicaments according to the invention may be administered alone or in combination with other treatments. A synergistic effectmay be achieved by using more than one active pharmaceutical ingredient in the pharmaceuticalcomposition or medicament, i.e. in this case, the compound of formula (I), or a stereoisomer,tautomer, pharmaceutically usable solvate or salt thereof, is combined with at least another agentas active ingredient. The active ingredients can be used either simultaneously or sequentially andcan be formulated into a single unit dosage form comprising both, the compound of formula (I) and a further pharmaceutically active ingredient or agent. The present compounds are suitable for combination with agents known to those of skill in the art (e.g., WO 2008 / 025170) and are useful with the pharmaceutical compositions and medicaments according to the invention. In some embodiments, pharmaceutical compositions and medicaments according to the invention,and the dose regimens according to the invention, may be provided in combination with any otheractive agents or pharmaceutical compositions where such combined therapy may be useful to modulate O-GlcNAcase activity, for example to treat neurodegenerative, inflammatory,cardiovascular, or immunoregulatory diseases or any condition described herein. In someembodiments, pharmaceutical compositions and medicaments according to the invention, and the dose regimens according to the invention, may be provided in combination with one or moreagents useful in the prevention or treatment of tauopathies, synucleinopathies and Alzheimer’sdisease. Examples of such agents may include, without limitation,- Acetylcholine esterase inhibitors (AChEIs) such as Aricept® (Donepezil), Exelon®(Rivastigmine), Razadyne® (Razadyne ER®, Reminyl®, Nivalin®, Galantamine), Cognex® (Tacrine), NMDA antagonists such as memantine (Axura®, Ebixa®), Huperzine A, Phenserine, Debio-9902 SR (ZT-1 SR), Zanapezil (TAK0147), ganstigmine, NP7557, ^7 nicotinic acetylcholine receptor agonists, 5-HT6 receptor antagonists, M1 muscarinicacetylcholine receptor agonists and positive allosteric modulators, and other agents which restore / potentiate cholinergic signaling or show pro-cognitive effects- Tau aggregation inhibitors such as methylene blue, morphomers, and others- Agents blocking intra- and extracellular tau seeding and transcellular propagation bysequestration of tau by directly binding to tau such as tau antibodies and other protein / peptide derived tau binding agents- Vaccines inducing a titer of tau binding / sequestering antibodies- Microtubule stabilizers such as AL-108, AL-208, paclitaxel and others- Neuroprotective agents or claimed as such (e.g. AZP2006)- Anti-inflammatory agents such as non-steroidal anti-inflammatory drugs, TNFα / anti-rheumatic drugs such as Enbrel, Humira and others- siRNAs, shRNAs, gene therapies or CRISPER derived therapeutic agents that reduce ormodify the expression of tau and / or downregulate the generation of Aβ- Amyloid-β (Aβ) peptide lowering agents such as β-secretase (BACE-1) or γ-secretaseinhibitors or modulators- Senile plaque-clearing, Aβ monomer or oligomer binding biologics such as Aβ antibodiesand Aβ vaccines inducing a titer of such antibodies, e.g. aducanumab- Compounds that inhibit tau phosphorylation by inhibiting kinases such as GSK3 inhibitors(Tideglusib)- TREM2 and CD33 binding / modulating drugs / antibodies / vaccines- Cholesterol lowering drugs such as Zocor / Lipitor, ApoE4 targeting drugs- Anti-hypertensive drugs such a diuretics, angiotensin-1 receptor blockers, angiotensin-converting enzyme inhibitors, calcium channel blockers, or β-blockers- Mood stabilizing drugs such as anti-depressants (e.g. fluoxetine, duloxetine, bupropion,amitriptyline, imipramine)- Insomnia drugs such as Zolpidem- Dietary supplements such as Coenzyme Q10- Dopaminergic drugs such as Carbiodopa / Levodopa, monoaminooxidase inhibitors(Razagiline), COMPT inhibitors, gene therapies and others- Lewy body / α-synuclein binding biologics such as α-synuclein antibodies and α-synucleinvaccines inducing a titer of such antibodies- TDP43 or FUS binding biologics such as TDP43 or FUS antibodies and TDP43 or FUSvaccines inducing a titer of such antibodies -Progranulin modulating agents- Cell-based therapies to enhance synaptic plasticity and / or neuronal networks with theaim to improve cognition -Deep brain stimulation (DBS) consists of implanting electrodes in key brain areas, butwithout limitation, such as the fornix and / or the nucleus basalis of Meynert with the aim tostimulate neuronal pathways involved in memory and cognition. (Mirzadeh Z. et al. (2016)J. Neural Transm (Vienna) 123: 775-783 ; Ponce FA et al. (2016) J Neurosurg 125 :75-84;Sankar T et al. (2015) Brain Stimulat 8 :645-654; Lozano AM et al. (2016) J AlzheimersDis 54 :777-787 ; Kuhn J et al. (2015) Brain Stimulat 8 :838-839)In addition to the chronically applied pharmacological therapies listed above, there may be benefitsto either short or long-term O-GlcNAcase inhibition in more invasive brain therapies including cell-based therapies, gene therapies, deep brain stimulation and targeted lesioning of brain circuits. For instance, cell transplantation of iPSC cells in diseases like Parkinson’s disease may produce cellular stresses in the cultured cells that may be mitigated by treatment with an O-GlcNAcase inhibitor to improve function and survival concomitant to and after the procedure. As reviewed by Martinez et al (2017), O-GlcNAc has been implicated in mediating cell survival decisions via numerous pathways that include transcription, stress granule formation, Heat Shock Protein synthesis, altered metabolic flux, reduced endoplasmic reticulum (ER) stress, and improved mitochondrial function which all may play a role in determining the immediate and long-term function and survival of the transplanted cells. In addition, reduced cellular stresses in the operative site and reduction of subsequent neuroinflammatory responses may also be of benefit. In some embodiments, pharmaceutical compositions and medicaments according to the invention, and the dose regimens according to the invention, may be provided in combination with one ormore agents useful in the prevention or treatment of tauopathies, synucleinopathies andAlzheimer’s disease. Examples of such agents may include, without limitation, cell replacementtherapies which consist of generation of neuronal cells that are transplanted in any affected brain areas with the aim to improve cognition. The neuronal cells can be generated directly from somaticcells (Vierbuchen T. et al. (2010) Nature 463:1035-1041; Zhang SZ. et al. (2016) Stem Cells Int.2016: 2452985; Addis RC. et al. (2011) PLoS ONE 6: e28719; Zhao J. et al. (2012) PLoS ONE 7: e41506; Lim MS. et al. (2015) J. Biol. Chem.290:17401-17414) and / or from induced pluripotentstem cells (iPSCs) (Kim J. et al. (2011) Proc Natl Acad Sci USA 108 :7838-7843; Matsui T. et al.(2012) Stem Cells 30: 1109-1119; Sheng C. et al. (2012) Cell Res 22: 208-218; Lujan E. et al.(2012) Proc Natl Acad Sci USA 109 :2527-2532; Lim MS et al. (2015) J Biol Chem 290:17401-17414; Han DW et al. (2012) Cell Stem Cell 10: 465-472) by using any combination of neural- specific transcription factors.In some embodiments, the invention also relates to a set (kit) consisting of separate packs of aneffective amount of the compound of formula (I) and / or pharmaceutically usable solvate or saltthereof and an effective amount of a further medicament comprising a pharmaceutically active ingredient. The set comprises suitable containers, such as boxes, individual bottles, bags or ampoules. The set may, for example, comprise separate unit dosage forms, each containing aneffective amount of the compound of formula (I) and / or pharmaceutically usable solvate or saltthereof and an effective amount of a further medicament comprising a pharmaceutically activeingredient in further unit dosage forms as tablets or e.g. dissolved or in lyophilized form.In some embodiments, the pharmaceutical compositions and medicaments according to the invention can be administered before or following an onset of disease once or several times acting as therapy. The aforementioned pharmaceutical compositions and medicaments are particularly used for the therapeutic treatment. A therapeutically relevant effect relieves to some extent one or more symptoms of a disorder, or returns to normality, either partially or completely, one or more physiological or biochemical parameters associated with or causative of a disease or pathological condition. Monitoring is considered as a kind of treatment provided that the pharmaceuticalcompositions and medicaments are administered in distinct intervals, e.g. in order to booster theresponse and eradicate the symptoms of the disease completely.In the meaning of the invention, prophylactic treatment is advisable if the subject possesses any preconditions for the aforementioned physiological or pathological conditions, such as a familialdisposition, a genetic defect, or a previously passed disease.In some embodiments, a unit dosage form comprising a compound of formula (I), or astereoisomer, tautomer, pharmaceutically usable solvate or salt thereof, in an amount selectedfrom about 0.25 mg, about 0.5 mg, about 1 mg, about 2 mg, about 3 mg, about 5 mg, about 7.5mg, about 10 mg, about 15 mg, about 20 mg, about 25 mg or about 50 mg of the compound offormula (I), or a stereoisomer, tautomer, pharmaceutically usable solvate or salt thereof, andoptionally one or more pharmaceutically acceptable excipients. In some embodiments, a unit dosage form comprising a compound of formula (I), or a stereoisomer, tautomer, pharmaceutically usable solvate or salt thereof, in an amount selected from about 0.25 mg, about 0.5 mg, about 1 mg, about 2 mg, about 3 mg, preferably about 5 mg, preferably about 7.5 mg, preferably about 10 mg, preferably about 15 mg, about 20 mg, about 25 mg or about 50 mg of the compound offormula (I), or a stereoisomer, tautomer, pharmaceutically usable solvate or salt thereof, andoptionally one or more pharmaceutically acceptable excipients. The unit dosage form according to one of the above embodiments, said unit dosage form beingadapted to be administered orally.The unit dosage form according to any one of the above embodiments, said unit dosage form being in the form of a tablet or capsule or sachet.A compound of formula (I), or a stereoisomer, tautomer, pharmaceutically usable solvate or saltthereof, for use in a method of treating a human subject suffering from or being at increased riskof developing a disease or condition, the method comprising the administration BID (twice daily)or once daily QD, (e.g., once daily QD) of an oral dose of the compound of formula (I), or astereoisomer, tautomer, pharmaceutically usable solvate or salt thereof, in an amount selectedfrom about 0.25 mg, about 0.5 mg, about 1 mg, about 2 mg, about 3 mg, about 5 mg, about 7.5mg, about 10 mg, about 15 mg, about 20 mg, about 25 mg or about 50 mg of the compound offormula (I), or a stereoisomer, tautomer, pharmaceutically usable solvate or salt thereof, andoptionally one or more pharmaceutically acceptable excipients. A compound of formula (I), or astereoisomer, tautomer, pharmaceutically usable solvate or salt thereof, for use in a method oftreating a human subject suffering from or being at increased risk of developing a disease orcondition, the method comprising the administration preferably BID (twice daily) or once daily QD,most preferably once daily QD of an oral dose of the compound of formula (I), or a stereoisomer,tautomer, pharmaceutically usable solvate or salt thereof, in an amount selected from about 0.25 mg, about 0.5 mg, about 1 mg, about 2 mg, about 3 mg, preferably about 5 mg, preferably about 7.5 mg, preferably about 10 mg, preferably about 15 mg, about 20 mg, about 25 mg or about 50 mg of the compound of formula (I), or a stereoisomer, tautomer, pharmaceutically usable solvate or salt thereof, and optionally one or more pharmaceutically acceptable excipients. Further exemplary embodiments of the present invention are the following: 1. A dose regimen comprising the repeated administration of one or more unit dosage forms comprising the compound of formula (I), or a stereoisomer, tautomer, pharmaceutically usable solvate or salt thereof to a human subject, in a dose and at a daily dosing frequency sufficient to maintain the plasma concentration of the compound of formula (I) and / or its tautomers at steady state of at least about 5 ng / mL at trough. 2. A dose regimen according to embodiment 1, wherein the plasma concentration of the compoundof formula (I), or a stereoisomer, tautomer, pharmaceutically usable solvate or salt thereof, ismaintained in a range of about 5 ng / mL or about 7 ng / mL to about 1000 ng / mL at trough. 3. A dose regimen comprising the repeated administration of one or more unit dosage forms comprising the compound of formula (I), or a stereoisomer, tautomer, pharmaceutically usable solvate or salt thereof to a human subject, in a dose and at a daily dosing frequency sufficient to maintain the average plasma concentration of the compound of formula (I), or a stereoisomer,tautomer, pharmaceutically usable solvate or salt thereof, over a period of 24 hours at steady stateat least about 6.5 ng / mL. 4. A dose regimen according to embodiment 3, wherein the average plasma concentration of the compound of formula (I), or a stereoisomer, tautomer, pharmaceutically usable solvate or saltthereof, is maintained over a period of 24 hours in a range of about 6.5 ng / mL to about 1300ng / mL. 5. A dose regimen comprising the repeated administration of one or more unit dosage formscomprising the compound of formula (I), or a stereoisomer, tautomer, pharmaceutically usablesolvate or salt thereof to a human subject, in a dose and at a daily dosing frequency sufficient to maintain at steady state a plasma C max of the compound of formula (I) and / or its tautomers of about 9 or about 10 to about 1900 ng / mL. 6. A dose regimen comprising the repeated administration of one or more unit dosage formscomprising the compound of formula (I), or a stereoisomer, tautomer, pharmaceutically usablesolvate or salt thereof to a human subject, in a dose and at a daily dosing frequency sufficient to maintain at steady state a plasma AUC over 24 hours of the compound of formula (I) and / or its tautomers of about 150 to about 31000 ng*h / mL. 7. A dose regimen according to one of the aforementioned embodiments, wherein the dose to be administered at said daily dosing frequency is orally administered and is in the range of about 0.25 mg to about 50 mg.8. A dose regimen according to embodiment 5, wherein the plasma C max of the compound offormula (I), or a stereoisomer, tautomer, pharmaceutically usable solvate or salt thereof, is about20 to about 750 ng / mL and preferably about 185 to about 370 ng / mL ng / mL. 9. A dose regimen according to embodiment 6, wherein the plasma AUC over 24 hours of the compound of formula (I), or a stereoisomer, tautomer, pharmaceutically usable solvate or saltthereof, is about 350 to about 13000 ng*h / mL and preferably about 3000 to about 6200 ng*h / mL.10. A dose regimen according to any one of the aforementioned embodiments, wherein the dose to be administered at said daily dosing frequency is orally administered and is in the range of about 1 mg to about 20 mg and preferably about 5 mg to about 10 mg. The said doses arepreferably administered once daily QD.11. A dose regimen according to the aforementioned embodiments, wherein the repeatedly administered dose remains constant. 12. A dose regimen according to the aforementioned embodiments, wherein the daily dosing frequency is once a day. 13. Method of treatment of a condition selected from neurological disorders or neurodegenerative diseases, diabetes, cancer, cardiovascular diseases and stroke, comprising the dose regimens according to any one of embodiments 1 to 12. 14. Method of treatment of a condition selected from neurological disorders or neurodegenerative diseases, diabetes, cancer, cardiovascular diseases and stroke, comprising the administration of an oral dose of the compound of formula (I), or a stereoisomer, tautomer, pharmaceutically usablesolvate or salt thereof, to a human subject, of about 5 mg once a day or about 10 mg once a day.15. A method of treatment of a condition according to embodiment 13 or 14, wherein the condition is selected from the group of one or more tauopathies, synucleinopathies, Alzheimer’s disease (AD), amyotrophic lateral sclerosis (ALS), amyotrophic lateral sclerosis with cognitive impairment (ALSci), argyrophilic grain disease, behavioral variant frontotemporal dementia (bvFTD), non- fluent and semantic variant primary progressive aphasia (nfv & svPPA), Bluit disease, corticobasal degeneration (CBD), Dementia pugilistica, Dementia with Lewy Bodies (DLB), diffuse neurofibrillary tangles with calcification, Down's syndrome, Familial British dementia, Familial Danish dementia, frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP- 17), frontotemporal lobar degeneration (FTLD), ganglioglioma, gangliocytoma, Gerstmann- Straussler-Scheinker disease, globular glial tauopathy, Guadeloupean parkinsonism, Hallevorden-Spatz disease (neurodegeneration with brain iron accumulation type 1), lead encephalopathy, lipofuscinosis, meningioangiomatosis, multiple system atrophy (MSA), myotonic dystrophy, Niemann-Pick disease (type C), Pallido-ponto-nigral degeneration, Parkinson’s disease, Parkinson’s disease dementia (PDD), Parkinsonism-dementia complex of Guam, Pick's disease (PiD), postencephalitic parkinsonism (PEP), Prion diseases (including Creutzfeldt-Jakob Disease (GJD), variant Creutzfeldt-Jakob Disease (vCJD)), fatal Familial Insomnia, Kuru, progressive supercortical gliosis, progressive supranuclear palsy (PSP), pure autonomic failure, Richardson's syndrome, subacute sclerosing panencephalitis, Tangle-only dementia, tuberous sclerosis, Huntington's disease or mild cognitive impairment (MCI), Chronic traumatic encephalopathy, Primary progressive aphasia, Progressive nonfluent aphasia, Semanticdementia, Steele-Richardson-Olszewski syndrome, epilepsy, chronic and acute inflammation,Crohn disease, neuroinflammation, subarachnoid hemorrhage (SAH), multiple sclerosis (MS), Friedreich’s Ataxia and Adrenoleukodystrophy. 16. A unit dosage form comprising an amount of a compound of formula (I), or a stereoisomer,tautomer, pharmaceutically usable solvate or salt thereof, selected from about 0.25 mg, about 0.5mg, about 1 mg, about 2 mg, about 3 mg, about 5 mg, about 7.5 mg, about 10 mg, about 15 mg, about 20 mg, about 25 mg or about 50 mg of the compound of formula (I), or a stereoisomer,tautomer, pharmaceutically usable solvate or salt thereof, and optionally one or morepharmaceutically acceptable excipients. 17. The unit dosage form of embodiment 16, comprising an amount of about 2.5 or about 3 mg, about 5 mg, about 7.5 mg or about 10 mg of a compound of formula (I), or a stereoisomer,tautomer, pharmaceutically usable solvate or salt thereof.18. The unit dosage form of embodiment 16 or embodiment 17, which is adapted to be administered orally. 19. The unit dosage form of embodiments 16, 17 or 18, which is a tablet or capsule or sachet. 20. The unit dosage form of embodiments 16, 17, 18 or 19 for use in a dose regimen according to embodiments 1 to 12 or a method according to embodiment 13 to 15. All the references cited herein are incorporated by reference in the disclosure of the inventionhereby. The terms “compound of formula (I)” and “compound (I)” are used interchangeablythroughout the specification. Most preferably, compound (I) is used in its fumarate salt form andcorresponding polymorphic form as disclosed in WO 2020 / 039030, claim 8.

[0003] ExamplesThe compound of formula (I) as used in the following examples is prepared according to example35 of WO 2018 / 153508 and example C04 of WO 2020 / 039030. Throughout the experimentscompound (I) has been employed as its fumarate salt form and its corresponding polymorphicform as disclosed in WO 2020 / 039030, claim 8, if not stated otherwise in the examples.Preparation of the compound of formula (I)The compounds according to Formula (I), such as the compound of formula (Ia), can beprepared from readily available starting materials by several synthetic approaches, using both solution-phase and solid-phase chemistry protocols or mixed solution and solid phase protocols.Examples of synthetic pathways are described below in the examples. All reported yields arenon-optimized yields. Unless otherwise stated, compounds of Formula (I) and related formulae obtained as a racemic mixture can be separated to provide an enantiomerically enriched mixture or a pure enantiomer. Preferably, the compound of formula (I) and especially the compound of formula (Ia) areprepared as follows and especially according to example 35 below:The commercially available starting materials used in the following experimental description were purchased from Aldrich, Sigma, ACROS, ABCR, Combi-Blocks, Matrix, Apollo scientific, Alfa Aesar, etc. unless otherwise reported. The HPLC, MS and NMR data provided in the examples described below are obtained as followed:1H NMR analyses were carried out using BRUKER NMR, model AV-II and AV-III 400 MHz FT-NMR. Residual signal of deuterated solvent was used as internal reference. Chemical shifts (δ)are reported in ppm in relative to the residual solvent signal (δ = 2.50 for 1H NMR in DMSO-d6,and 7.26 in CDCl3). s (singlet), d (doublet), t (triplet), q (quadruplet), br (broad), quint (quintuplet). LCMS analysis condition:Instrument name: Agilent Technologies 1290 infinity 11.Method A: Method: A-0.1% TFA in H2O, B-0.1% TFA in ACN; flow rate: 2.0 mL / min; column: XBridge C8 (50 x 4.6 mm, 3.5 µm), +ve mode HPLC analysis condition: Instrument name: Agilent 1200 Series instruments as followed using % with UV detection (maxplot). Method A: Method: A-0.1% TFA in H2O, B-0.1% TFA in ACN; flow rate: 2.0 mL / min; column: XBridge C8 (50 x 4.6 mm, 3.5 µm). Method B: Method: A-10 mM NH4HCO3 in H2O, B-ACN; flow rate: 1.0 mL / min; column: XBridgeC8 (50 x 4.6 mm, 3.5 µm).Chiral HPLC analysis condition:Instrument name: Agilent 1260 infiinity IIMethod A: Mobile Phase: 0.1% DEA in n-Hexane: EtOH: 60:40; flow rate: 1.0mL / min; column: Chiralcell OD-H (250 x 4.6 mm, 5 μm). Chiral SFC analysis condition: Instrument name: THAR-SFC 80 and THAR-SFC 200 (analytical) Ratio between CO2 and co-solvent is ranging between 60:40 and 80:20 Method B: Mobile Phase: 20 mM ammonia in methanol, flow rate: 10 mL / min; column: YMC Cellulose C (250 x 4.6 mm, 5 μm). Method E: Mobile Phase: IPA, flow rate: 3 mL / min; column: Lux A1 (250 x 4.6 mm, 5 μm). Chiral Preparative SFC analysis condition: Instrument name: THAR-SFC 80, THAR-SFC 200 and PIC SFC 10-150 Ratio between CO2 and co-solvent is ranging between 60:40 and 80:20 Method E: Mobile Phase: IPA, flow rate: 100 mL / min; column: Phenomenex Lux Amylose-1 (250x 30 mm, 5 μm).General flash chromatography conditions used for the purification of intermediates orcompounds of Formula I: silica gel 230-400 mesh; gradients used as elutent: 10 to 80% EtOAc in petroleum ether or 1 to 15% MeOH in DCM. Intermediate 7: (S)-5-(1-(piperazin-1-yl)ethyl)benzo[d]thiazole or (R)-5-(1-(piperazin-1- yl)ethyl)benzo[d]thiazoleTo a stirred mixture of racemic 5-(1-(piperazin-1-yl)ethyl)benzo[d]thiazole (100 g, 405.0 mmol) inEtOH (2 L, 20V), D-di-p-anisoyltartaric acid (42.31 g, 101.2 mmol) was added at RT and heatedat 90 °C for 20 min. (Note: Salt formation was observed slowly after 3 to 5 min after addition of D- di-p-anisoyltartaric acid). Then the reaction mixture was stirred at RT overnight. The resulting mixture was filtered and the filtration cake was washed with EtOH (2 x 250 mL, 5V), diethyl ether (250 mL) and dried under high vacuum. To increase the ee, the salt (66 g, 79% ee) was further refluxed in EtOH (1 L, 10V) for 24 h and stirred at RT overnight. The obtained salt was filtered, washed with EtOH (200 mL, 2V), diethyl ether (200 mL) and dried under high vacuum. The same procedure was repeated to achieve the ee of 96.1% (21.2 g). This step was repeated on 300 g scale to obtain the salt (113.2 g). The above obtained salts (134.4 g) were dissolved in water (300 mL), basified to pH ~14 with 6N NaOH solution (350 mL) and the aqueous layer was extracted with EtOAc (2 x 1 L). The combined EtOAc layer was washed with brine solution (2 x 1 L), water (300 mL), dried over anhydrous Na2SO4 and concentrated under vacuum to obatin the title compound (enantiomer ratio97.41:2.58%). Yield: 85% (63.0 g, pale brown gummy solid). 1H NMR (400 MHz, DMSO-d6): δ9.38 (s, 1H), 8.09 (d, J = 8.4 Hz, 1H), 7.97 (s, 1H), 7.45 (d, J = 8.0 Hz, 1H), 3.55 (q, J = 6.8 Hz, 1H), 2.67-2.66 (m, 4H), 2.34-2.25 (m, 4H), 1.34 (d, J = 6.8 Hz, 3H). LCMS: (Method A) 248.2 (M+H), Rt. 1.5 min, 98.5% (Max). HPLC: (Method A) Rt. 1.6 min, 98.7% (Max). Chiral HPLC: (Method A) Rt.11.1 min, 97.4% (Max). Chiral resolution agent D-di-p-anisoyltartaric acid can be exchanged for D-di-p-toluyltartaric acid or (R)-(+)-chlocyphos to obtain the identical products. Racemic 5-(1-(piperazin-1-yl)ethyl)benzo[d]thiazole, dihydrochloride salt (15.57 g, 48.60 mmol) was mixed with sodium acetate trihydrate (26.45 g, 194.4 mmol, 400 mol%), R-(+)- chlocyphos (8.11 g, 29.32 mmol, 99% ee, 60.3 mol%), water (120 mL) and ethanol (16 mL). The mixture, becoming a thick suspension on stirring, was warmed up, resulting in a clear solution when it reached reflux temperature. The solution was allowed to cool with stirring and some seedcrystals (small spatula, ca.10 – 20 mg) were added about every 5 – 10 minutes, until crystallizationstarted (between 5 and 10 times). Crystallization of the salt started at ca.45 °C. The suspension was stirred at 20 °C overnight, then filtered, the solid was washed with water / ethanol 10 / 1 (55 mL) and water (20 mL). It was dried for 2 d at 20°C (11.12 g, 21.22 mmol, 44%). The ee was 97.5 %. This salt was heated under gentle reflux with water (90 mL) and ethanol (10 mL). Further ethanol (2 mL) was added, and the solution was allowed to cool to 20 °C and stirred for 6 h. The resulting solid was filtrated and washing with water (50 mL). After drying at 20°C for 3 d, Chlorcyphos salt was isolated (9.50 g, 18.13 mmol, 37%). The ee was 100%. The above obtained chlocyphos-salt with 100% ee (8.50 g, 16.22 mmol) was stirred for 1.5 h in amixture of toluene (100 mL), water (50 mL), and sodium hydroxide (4.04 g, 101 mmol). Sodiumchloride (20 g) was added and the mixture was stirred for 15 min, then filtered. The filtrate layers were separated. The solid isolated on the filter and in the aqueous layer were stirred with toluene (125 mL). It was filtered and the filtrate layers were separated again. The combined toluene layers were dried and evaporated at 60 °C to yield the desired free amine as a solidifying oil (3.60 g, 14.55 mmol, 90%, pure by NMR), and with 99.6% ee. Intermediate 11: N-((2-chloropyrimidin-5-yl)-(R)-(methyl)(oxo)-^6-sulfanylidene)-2,2,2-trifluoroacetamide or N-((2-chloropyrimidin-5-yl)-(S)-(methyl)(oxo)-^^6-sulfanylidene)-2,2,2-trifluoroacetamide Step 1: 2-chloro-5-(methylsulfinyl)pyrimidine: Racemic 2-chloro-5-(methylsulfinyl)pyrimidine (502 g, 2.84 mol) was separated by SFC analysis(Pic SFC 10-150; CO2: IPA (70:30); column: Lux A1 (250 x 30); flow rate: 100 mL / min; wavelength: 210 nm; cycle time: 5 min; back pressure: 100 bar, Method E). The first eluting peak (250.0L of IPA) was concentrated at 40 °C. Yield: 40% (201.0 g, white solid).1H NMR (400 MHz, DMSO-d6): δ 9.05 (s, 2H), 2.98 (s, 3H). LCMS: (Method A) 177.0 (M+H), Rt.0.7 min, 99.9% (Max). HPLC: (Method B) Rt.2.04 min, 99.8% (Max). Chiral SFC: (Method E) Rt 2.1 min,100% (Max). Step 2: N-((2-chloropyrimidin-5-yl)-(S)-(methyl)(oxo)-λ6-sulfanylidene)-2,2,2-trifluoroacetamide or N-((2-chloropyrimidin-5-yl)-(R)-(methyl)(oxo)-λ6-sulfanylidene)-2,2,2-trifluoroacetamide To the stirred solution of the first eluting compound isolated in step 1 (0.5 g, 2.8 mmol) in DCM (5mL), trifluroacetamide (0.64 g, 5.66 mmol), MgO (0.45 g, 11.3 mmol), Rh2(OAc)4 (0.062 g, 0.14mmol) and PhI(OAc)2 (1.36 g, 4.20 mmol) were added and the reaction mixture was stirred at RT overnight. Completion of the reaction was monitored by TLC. The reaction mixture was then filtered through celite, washed with DCM. The organic layer was concentrated under vacuum and the resulting crude material was purified by flash chromatography (Biotage Isolera, eluent: 25-28% EtOAc in pet ether) to afford Intermediate 11. Yield: 86 % (0.69 g, white solid). 1H NMR(400 MHz, DMSO-d6): δ 9.39 (s, 2H), 3.98 (s, 3H). LCMS: (Method A) 191.9 (M–COCF3+H), Rt.3.8 min, 73.8%. Example 35: (S)-(2-(4-((S)-1-(benzo[d]thiazol-5-yl)ethyl)piperazin-1-yl)pyrimidin-5- yl)(imino)(methyl)-λ6-sulfanone or (R)-(2-(4-((S)-1-(benzo[d]thiazol-5-yl)ethyl)piperazin-1- yl)pyrimidin-5-yl)(imino)(methyl)-λ6-sulfanone or (S)-(2-(4-((R)-1-(benzo[d]thiazol-5- yl)ethyl)piperazin-1-yl)pyrimidin-5-yl)(imino)(methyl)-λ6-sulfanone or (R)-(2-(4-((R)-1- (benzo[d]thiazol-5-yl)ethyl)piperazin-1-yl)pyrimidin-5-yl)(imino)(methyl)-λ6-sulfanone To a stirred solution of intermediate 7 (400 mg, 1.41 mmol) in ACN (5 mL), TEA (0.6 mL, 4.23mmol) and intermediate 11 (445 mg, 1.54 mmol) were added at RT and stirred overnight.Completion of the reaction was monitored by TLC, then the reaction mixture was evaporated at 50 °C under vacuum. To the resulting mixture, water (10 mL) was added and the aqueous layer was extracted with EtOAc (2 x 50 mL). The combined organic layer was dried over anhydrous Na2SO4 and concentrated under vacuum. The resulting crude material was purified by flash chromatography (silica gel: 230-400 mesh, eluent: 50% EtOAc in pet-ether) to obtain the pureintermediate. Yield: 39% (273 mg, off white solid).To this intermediate methanol (7 mL, 20 V) and K2CO3 (414 mg, 4.53 mmol) were added andstirred at RT for 20 min. After 20 min, the reaction mixture was filtered through celite and concentrated under vacuum. To the resulting mixture, water (50 mL) was added and the aqueus layer was extracted with DCM (2 x 100 mL). The combined organic layer was dried over anhydrous Na2SO4 and concentrated under vacuum. The resulting crude material was purified by flash chromatography (Biotage Isolera, gradient: 1-2% methanol in DCM) to afford the title compound.Yield: 10% (15 mg, off white solid). 1H NMR (400 MHz, DMSO-d6): δ 9.39 (s, 1H), 8.65 (s, 2H),8.13 (d, J = 8.0 Hz, 1H), 8.03 (s, 1H), 7.51-7.49 (m, 1H), 4.24 (s, 1H), 3.86-3.83 (m, 4H), 3.69-3.67 (m, 1H), 3.07 (s, 3H), 2.54-2.39 (m, 4H), 1.41 (d, J = 6.8 Hz, 3H). LCMS: (Method A) 403.3(M +H), Rt. 1.8 min, 99.6% (Max). HPLC: (Method A) Rt. 1.8 min, 99.2% (Max). Chiral SFC:(Method B) Rt 9.3 min, 99.9% (Max). [α]25D = -107.69, c 0.104 (MeOH). The compound obtainedaccording to this Example 35 is further used in Examples 1, 2, 3, 4, 5, 6, 7, 8 and 9 below, if notstated otherwise.Example 1: In vitro cell-free assaysA. e.g. Human O-GlcNAcase enzyme inhibition assay5 µl of the appropriate concentration of a solution of compound of formula (I) in McIlvaine’s Buffer(pH 6.5) in 2 % DMSO (for a dose response curve calculation) is added into each well of a 384- well plate (Greiner, 781900). Then, 20 nM of His-Tagged hOGA and 10 µM of FL-GlcNAc (Fluorescein mono-beta-D-(2-deoxy-2-N-acetyl) glucopyranoside; Marker Gene Technologies Inc,M1485) are added to the 384-well plate for a final volume of 20 µl. After incubation for 60 min atroom temperature, the reaction is terminated by the addition of 10 µL of stop buffer (200 mMglycine, pH 10.75). The level of fluorescence (λexc 485 nm; (λemm 520 nm) is read on a PHERAstarmachine. The amount of fluorescence measured is plotted against the concentration of inhibitorto produce a sigmoidal dose response curve to calculate an IC50. All individual data is correctedby subtraction of the background (Thiamet G 3 uM = 100 % inhibition) whilst 0.5% DMSO isconsidered as the control value (no inhibition). The average value (EC50) for the compound offormula (I) is 13 nM in this enzymatic assay. In one instance, EC50 for compound of formula (I) hasbeen found at 11.6 nM in this assay. The data are depicted in FIG. 7.B. e.g. Substrate competition and reversibility assay For substrate competition, enzyme velocity is measured in the same McIlvaine buffer described inExample 1.A using increasing concentrations of 4-Methylumbelliferyl N-acetyl-β-D-glucosaminideor 4 MU-NAG (Sigma, 69585) as substrate in presence of various concentrations of compound offormula (I). During incubation of the plate for 60 min in the dark, the fluorescence is quantifiedevery 2 min on a Pherastar fluorescence reader (Ex / Em: 350 / 450 nm). The enzyme kinetics datais plotted using the Lineweaver-Burk transformation to determine Vmax and Km for eachconcentration of compound of formula (I). For the reversibility assay, His-tagged OGA enzyme ispre-incubated for 1 h at RT with increasing concentrations of compound of formula (I). Fluorogenicsubstrate for determination of enzyme activity is added to either undiluted or diluted (1:3 and 1:5)preincubation reactions. In the substrate competition assay, the compound of formula (I) does not interfere with the maximum enzyme velocity (Vmax) while diminishing the enzyme affinity (Km) which means that the compound of formula (I) is a substrate competitive inhibitor of OGA. In the reversibility assay, the compound of formula (I) shows a decrease of potency upon dilution of the enzyme reaction which means that the compound of formula (I) demonstrates a reversiblemechanism of enzyme inhibition. The data are depicted in FIG. 8A and FIG. 8B.Example 2: In vitro potency of compound of formula (I) on cell-based assays:A. In vitro HEK293 tau cell-based assay (quantification of O-proteins and O-Tau)The potency of compound of formula (I) is determined in HEK293 cells stably transfected with wild-type human tau441 [2N4R tau] plated in 96-well plates at a density of 100,000 cells / well.HEK293 tau cells are incubated for 16 h at 37 °C with increasing concentrations of compound offormula (I). On the following day, the cells are washed with PBS and lysed in RIPA buffer [25 mM Tris-HCl pH 7.6, 150 mM NaCl, 1% NP-40, 1% sodium deoxycholate, 0.1% SDS + ProteaseInhibitor, PI (Roche, 11836145001)]. O-GlcNAcylated tau (O-Tau) present in the cell lysate arequantified by immunoassays according to the following procedures. To quantify O-Tau, a multi-array 96-well avidin Mesoscale® plate (MSD, L15AA-1) is precoated with 25 μl (2.5 μg / ml) of thebiotinylated rabbit monoclonal O-Tau (Ser400) antibody (Cameron, B. Et al. (2013) FEBSLett., 587 (2013), pp. 3722-3728). Then, fifty μl of HEK293 tau cell lysate (6 μg total protein) aretransferred into each well followed by 16 h incubation at 4 °C. After three washing steps with PBS- T, 25 μl / well of SULFO-TAG™labelled anti-tau polyclonal antibody (DAKO, A0024) is added followed by 1 h incubation at RT under light protection.In one instance the EC50 value for compound of formula (I) has been found at 195 nM in theHEK293 tau cell-based assay. The data are depicted in FIG. 9.B. In vitro PBMC cell-based assay (quantification of O-proteins)The potency of compound of formula (I) is also determined in isolated and plated human (h) and / or rat (r) PBMC. After isolation following the Ficoll® density gradient method, human and / or rat PBMC are plated in 96-well plates (ThermoFisher, 07-000-162) at a density of 200,000 cells / well and incubated in presence of increasing concentrations of compound of formula (I) for 4 h at 37°C. After compound incubation, PBMCs are collected and resuspended in lysis buffer [50 mM Tris-HCl pH 7.4, 150 mM NaCl, 1% Triton X-100, 0.1% SDS, 0.2% sodium deoxycholate + PI]. Thelevel of total protein O-GlcNAcylation is then quantified in PBMC cell lysates using a sandwich O-protein immunoassay. For this, a multi-array 96-well avidin Mesoscale® plates (MSD, L15AA-1)is coated with 50 µl (5 µg / ml) of biotinylated wheat germ agglutinin, WGA (Vector Biology, B1025)in PBS-T. After 1 h incubation at RT followed by 1 h of blocking, the plates are incubated overnightat 4°C with 50 µl of PBMC cell lysate (60 µg protein). After washing, the plates are incubated for 2 h at RT under light protection with 50 ul of the pan O-GlcNAc monoclonal antibody RL2 (1:1,000 dilution) mixed with a SULFO-TAG™labelled goat anti-mouse antibody in PBS-T. After a finalwash, the plates are read on Sector Imager 6000In this PBMC assay, the average value (EC50) for the compound of formula (I) is 121 nM and 346nM on plated human and rat PBMCs, respectively. The data are depicted in FIG. 10.Example 3: Ex vivo potency of compound of formula (I) on whole blood assayFresh, heparinized human blood is incubated with increasing concentrations of compound offormula (I) for 2 hours under continuous rolling at 37 °C, 5% CO2. After incubation, the peripheralblood mononuclear cells (PBMC) are isolated by density gradient centrifugation with Ficoll® using15 ml SepmateTMtubes (Stemcell Technologies, 15420) and according to the manufacturer’s instructions. Briefly, samples are diluted with an equal volume of PBS, 2% foetal bovine serum (FBS) and mixed gently. The diluted blood is layered onto a Ficoll solution (GE Healthcare, 17-1440-02) and centrifuged at 1,200 g for 10 min. The top layer, which contained the enrichedPBMC, is poured off into a new tube containing 8 ml of PBS, 2% FBS and centrifuged at 800 g for10 min at 37 °C. The PBMC is washed twice with 2 ml PBS by centrifugation at 400 g for 10 min.After the last centrifugation, the supernatant is discarded and the PBMC are snap frozen forstorage at -80 °C. The quantification of O-proteins is performed with the O-protein immunoassayfollowing the procedure described in Example 2B.In average value (EC50) for compound of formula (I) on the ex vivo whole blood assay (7 donors)is 700 nM. The data are depicted in FIG. 11.Example 4: Pharmacodynamic Model: Pharmacokinetic / Pharmacodynamic model of Wistar ratThe compound of formula (I) is administered orally to Wistar rats at different concentrations and / orat different time intervals. After compound administration, typically at a time ranging between 2and 48 hours, preferably between 4 and 24 hours, rats are deeply anesthetized to collect brain tissue, blood, and cerebrospinal fluid (CSF) according to the following procedure. After deep anaesthesia with pentobarbital, 50 µl of CSF is collected from the cisterna magna and stored at -80 °C for PK analyses. Four milliliters (ml) of blood are taken by cardiac puncture with Sarstedttubes containing 35 IU of Heparin.400 µl of heparinized blood is used for the isolation of rat PBMC following the standard procedure with Ficoll® density gradient as described in example 3.100 µl of heparinized blood is centrifuged at 3,800 g for 10 min to isolate the plasma which is stored at - 80 °C for PK analyses. After brain dissection, the right frontal lobe of the cortex is homogenizedusing Precellys tubes (VWR, 432-3752) in ice-cold Cytobuster reagent buffer (Merck, 71009) withPI. The left frontal cortex is directly snap frozen in dry ice and stored at -80 °C for PK analyses.The brain tissue homogenate was submitted to a first centrifugation at 18,000 g for 15 min, 4 °C.Finally, the resulting supernatants is submitted to an ultracentrifugation (100,000 g, 60 min, 4 °C)to isolate the soluble fraction of the cortex. After protein determination (BCA), O-proteins arequantified in brain soluble fractions and in PBMC cell lysates by using the O-protein immunoassay described in Example 2B.The concentration of compound of formula (I) present in the brain, CSF and plasma is performedby using the following bioanalytical methodology: Plasma and CSF samples were processed byprotein precipitation. 50 µl of sample are mixed with 150 µl of acetonitrile containing an internalstandard (0.5 µg / ml Tolbutamide) on a vortex mixer for 5 min. After centrifugation for 10 min at3,800 g, the supernatant is transferred into 96 well LC-MS / MS sample plates for analysis. Braintissue is homogenized in PBS, pH 7.4 (1 g tissue in 5 ml buffer) using a bullet blender at 4 °C. Asample of 50 µl of each homogenate is processed as described for plasma above by protein precipitation. Samples are analysed by LC-MS / MS system consisting of Nexera ™ UHPLC (Shimadzu) coupled to an AB Sciex API 4000 mass spectrometer. Samples are separated using a Phenomenex Synergi polar RP 80A (75*2 mm, 4 µm) column with a mobile phase (MP) consisting of 0.1% formic acid in Milli-Q water (A) and 0.1% formic acid in 100% acetonitrile (B). The MS instrument was operated in positive mode (ESI+). Multiple reactions monitoring (MRM) transition are selected for the test and reference compounds (Tolbutamide) for the LC-MS / MS analysis. For analysis, 5 µl of processed sample are injected into the LC-MS / MS instrument. The collected data are analysed using the Analyst 1.6.1 software. The lower limit of quantitation (LLOQ) of this method to quantify the compound of formula (I) in the plasma, CSF and brain samples is 1 ng / ml (calibration range 1 to 10,000 ng / ml). The accuracy of back-calculated standards as well as QC samples is within ±15%.Four hours after administration in our PK / PD Wistar rat model, the compound of formula (I)administrated orally at the concentrations of 0.3, 1, 3, 10 and 30 mg / kg / day demonstrates an ED50of 2.1 mg / kg (brain protein O-GlcNAcylation) corresponding to an in vivo CSF EC50 of 135 nM(equivalent brain free concentration). Additionally, there is an excellent correlation (R2= 0.97).between the level O-GlcNAcylation in the brain and in periphery (PBMC). The brain / plasma ratiofor compound of formula (I) is between 0.5 and 1.4 demonstrating high brain penetration. CSFconcentrations of compound of formula (I) show a dose proportionality and confirm a rapid andpassive blood-brain barrier (BBB) penetration (Table 1). The data are depicted in FIG. 12A - FIG.12C).Table 1: Compound of formula (I) plasma, brain and CSF concentrations at t = 4 hours after asingle, oral dose in the rat Compound (I) Drug Concentration Dose Plasma Brain CSF CSF / (mg / kg) (nM) (nM) (nM) Plasma 0.3 72 73 16 0.231.0 246 345 49 0.203 1232 703 272 0.2210 4167 1898 825 0.2030 16263 10070 4339 0.27 Example 5: Preclinical Models A. In vivo treatment efficacy on DSS colitis model:Zhao M, et al. (2018) EMBO Mol. Med. 10: e8736The dextran sodium sulfate (DSS) is a negatively charged sulfated polysaccharide ofapproximately 36-50 kDa which induces colitis when administered at 5% (weight / volume) indrinking water for several days (Okayasu I. et al. (1990) Gastroenterology 98:694–702).Adult (balb / c) mice are randomized and are allowed to a period of acclimatization for one week. After this, the compound of formula (I) or vehicle is administered for 21 days by oral gavage, starting 2 weeks before the DSS treatment (Day -14) and continuing during DSS treatment and until the end of the experiment (Day +9). At Day 0, animals are getting access to a 5% (weight / volume) DSS solution in drinking water until Day + 5. The DSS solution is then removedand replaced by drinking water for 4 more days until Day + 9. From Day 0 until the end of theexperiment (Day +12), animals are monitored daily for clinical signs of colitis including bodyweight loss, loose stools and / or diarrhoea and presence of occult or gross blood in the stools. At Day +12 or when animals reach humane endpoints, colons are dissected out, to measure their lengths and observe their content. A sample of distal colon is processed for histopathology. Another sample is homogenised and stored at -80°C for tissue cytokine analysis. Treatment efficacy of the testedcompound is evaluated according to Alenghat et al. 2013 (Alenghat T. et al. (2013) Nature 504:153 – 157), by the determination of a disease score which included, i) body weight loss, ii) stoolappearance iii) presence of blood in feces and iv) general appearance of the animal : -weight loss (no loss = 0; < 5% = 1; 5–10% = 2; 10–20% = 3; > 20% = 4);- stool (normal = 0; soft, watery =1; very soft, semi-formed = 2; liquid, sticky, or unable todefecate = 3); -blood in feces (no blood = 0; visible blood in rectum = 1; visible blood on fur = 2);- General appearance (normal = 0; piloerection = 1; lethargy and piloerection = 2; motionless = 4). Histological injury and inflammation are scored as described in Gilbert S. et al (2012)(Gilbert S. et al. (2012) EMBO Mol. Med.4: 109 – 124). Scoring parameters includeoedema (scale: 1–4), erosion / ulceration of the epithelial monolayer (scale: 1–4), crypt loss / damage (scale: 1–4), and infiltration of immune cells into the mucosa (scale: 1–4).A decrease in the disease score resulting from less body weight loss, absence or less blood infeces, better stool consistency and better general appearance is observed after treatment with thecompound of formula (I). By histology examination, treatment with the compound of formula (I) results in a significant decrease of tissue inflammation. B. In vivo treatment efficacy on motoric functions of the Parkinson disease model (Line61):Levine PM. et al. (2019) Proc. Natl. Acad. Sci. U S A. 116(5):1511-1519.The transgenic Thy1-αSyn “Line 61” mouse model of Parkinson Disease (PD) or Line 61 whichoverexpresses wildtype human alpha-synuclein protein (hAsyn) under the regulatory control of themurine Thy-1 promoter is a widely used PD animal model. With time, this model showsaccumulation of hAsyn and aggregated deposits of hAsyn phosphorylated on serine 129 (pser129- Asyn) in cortical and subcortical regions of the brain, including the substantia nigra (RockensteinE. et al. (2002) J. Neurosci. Res. 68(5):568–78). Another pathological feature in this transgenicmodel is the presence of astrogliosis (GFAP) in the cortex and hippocampus starting at around 3to 4 months of age. In addition, motor deficits such as lack of coordination, diminution of strength,and unbalance are also observed from 2 to 4 months of age (Fleming S.M. et al. (2004) J. Neurosc.24 (42): 9434-40). Treatment effect of compound of formula (I) is evaluated by the assessment ofthe motoric functions using beam walk or rotarod test, and / or immunohistology (quantification ofaggregated hAsyn, pser129-Asyn deposits and astrogliosis) and / or biochemical analysis (GFAP,aggregated hAsyn) of “soluble” and “insoluble” brain fraction of compound of formula (I)-treatedanimals. For this, transgenic Line 61 mice (4 weeks of age) and age / sex-matched non-transgenic littermates are first tested in the Irwin testing battery test, rotarod, wire suspension, beam walk and pasta gnawing test at baseline. Animals are daily treated by oral gavage with the compound of formula (I) for 24 weeks. During treatment period, animals undergo two additional rounds of behaviour tests (as described above) after 12 weeks and 24 weeks of treatment. At the end of the treatment period, all mice are euthanized under deep anesthesia and receive a transcardial perfusion with saline. Brains are removed and hemisected: left hemibrains are snap frozen on dry ice for biochemical analysis whilst the right hemibrains are post fixed in 4% PFA, embedded and frozen in cryomolds for histological evaluations. Right hemibrains are embedded in OCT medium and 10 μm cryosections are collected to quantify the level of GFAP, hAsyn and pser129-Asyn deposits by immunohistochemistry in the hippocampus and in the cortex of treated animals. For biochemical analysis of soluble and insoluble hAsyn, snap frozen hemibrains are homogenized in 10 volumes of lysis buffer [20 mM Tris-HCl, pH7.4, 50 mM NaCl, 1% Triton X- 100, 0.2 mM Sodium-orthovanadate, protease inhibitor cocktail and phosphatase inhibitor cocktail] and incubated for 30 min on wet ice. After centrifugation (15,000 g, 60 min, 4°C) supernatants are collected and referred as “Triton X-100 soluble fraction”. The Triton X-100-insoluble pellet is washed once in lysis buffer and resuspended in lysis buffer containing 2% sodium dodecyl sulfate (SDS). The resulting homogenate in 2% SDS is collected and referred as the “Triton X-100 insoluble fraction”. Levels of human alpha-synuclein present in “Triton-X-100 soluble fraction” and “Triton X-100 insoluble fractions” are quantified by electrochemilumiscence using a hAsynimmunosorbent assay kit (cat no. K151TGD) from MesoScale Discovery (MSD). Levels of GFAPare evaluated in the Triton X-100 soluble fraction of cortex using a sandwich MSD immunoassaywith a biotinylated mouse monoclonal anti-GFAP antibody (Synaptic system, 173211BT) as capture and a rat monoclonal anti-GFAP antibody (Invitrogen, 13-0300) as detection antibody. The detection of O-GlcNAcylated α-synuclein (O-α-Syn) is performed by using chemo-enzymaticmass tagging. For this, 10% (wt / vol) homogenates from Line 61 α-synuclein transgenic micetreated with vehicle or with compound of formula (I) are prepared by homogenizing half of a cortexin ice-cold buffer comprised of 25 mM Tris (pH 7.5), 150 mM NaCl, 1% Triton X-100, 20 μMPUGNAC (Tocris) and EDTA-free protease inhibitor cocktail (Roche) using a Precellys homogenizer 5,000 rpm with 2 cycles of 30 s with 1 s pause between the 2 cycles. Thehomogenates are incubated for 30 min in ice before centrifugation at 18,500 g, 4 °C for 15 minand the supernatants processed for chemoenzymatic mass tagging. 300 µg protein of eachsample is precipitated by standard methanol / chloroform extraction and resuspended in 100 µl of20 mM HEPES (pH 7.9), 1% SDS. The terminal N-acetyl-β-D-glucosamine (GlcNAc) residues ofglycoproteins present in these samples are labelled with N-azido-galactose using the Click-IT kitwith GalT1(Y289L) enzyme according to the manufacturer’s instructions (ThermoFisher, 33368). Sample reactions without GalT1(Y289L) enzyme are used as controls. After 20 h labelling with N-azido-galactose, 7.5 µl of freshly made iodoacetamide (600 mM) are added to each sample andincubated for 30 min in the dark under rotation. The samples are precipitated withmethanol / chloroform, solubilized in 10 mM triethanolamine (pH 7.4) (TEA, Sigma-Aldrich), 150 mM NaCl, 1% SDS and finally 10 µl of 10 mM DBCO-PEG 5kDa (Click Chemistry Tools, A118-100) are added for mass tagging using click chemistry. After boiling for 5 min at 98 °C, thereactions are precipitated with methanol / chloroform and resulting pellets are resuspended in 20µl of 10 mM TEA (pH 7.4), 150 mM NaCl, 1% SDS and 10 µl 1.5x Tricine-SDS sample buffer(NuPage, Novex) containing 200 mM DTT (Sigma-Aldrich) and boiled for 5 min at 98°C. Equalvolumes of the samples (20 μl) are separated on 10-20% Tricine gels (NuPage Novex) andtransferred onto nitrocellulose membranes. For detection of O-synuclein by Western-blot,nitrocellulose membranes are incubated in presence of a rabbit polyclonal α-Synuclein antibody(Cell signaling, 2642) at 1:1,000 dilution followed by an IRDye 680-conjugated goat anti-rabbitsecondary antibody at 1:8,000 dilution (Li-Cor, 926-68071). The blots are scanned using anOdyssey Infrared Imager at 700 nm, and the α-synuclein bands are quantified by densitometry.The treatment with the compound of formula (I) is 1) showing in the brain of treated mice thepresence of O-α-synuclein by using chemo-enzymatic mass tagging coupled to western-blotdetection; 2) showing by histology a reduction of the number of intraneuronal aggregated pser129-Asyn deposits; 3) demonstrates a decrease in the level of astrogliosis (GFAP) by immunohistologyand by ECL immunoassay and 4) showing a functional benefit (motor improvement) in any of thebehavioural tests among Irwin battery, rotarod, wire suspension, beam walk and / or pasta gnawingtest. The data are depicted in FIG. 13A, FIG. 13B, FIG. 14A and FIG. 14B.C. In vivo treatment efficacy in Parkinson (PD) model (Line A53T)The transgenic hA53T-Sud mice (hA53T-Sud mice) has been developed by Dr. Thomas C.Sudhof, first described by Chandra S. et al. (2005) (Chandra S. et al. (2005) Cell Nov 4;123(3):383-96) and carry a mutated human α-synuclein gene (SNCA) with the A53T (alanine-53 -> threonine)point mutation under the control of the thymus cell antigen 1 (THY1) promoter. Hemizygous transgenic mice are viable and fertile and develop a Parkinson’s Disease-like phenotype with aging. At about 5 to 6 months of age, A53T mice start to demonstrate a progressive motor deficit in the rotarod and other gait tests, anxiety-related symptoms, increased activity, and sleepdisturbances (Rothman S.M. et al. (2013) J. Parkinsons Dis. ;3(2):215-29). A complete immobilityand death occurs in A53T mice around 10 to 12 months of age. A53T mice express 10- to 20-foldmore α-synuclein protein (A53T-hα-syn) in the brain and spinal cord, respectively, as comparedwith wild type mice (Chandra S. et al. (2005) Cell Nov 4;123(3):383-96). High molecular weight,aggregated forms of A53T human α-synuclein also appear in the spinal cord, brainstem,cerebellum and hippocampus at 6 months of age and later in the striatum. In parallel, the A53Tmodel displays neurodegeneration in the cortex and hippocampus with loss of TH-positive dopaminergic (TH) neurons in the substantia nigra (SA) and striatum, reaching a total loss ofapproximately 60% by the end stage (Martin L.J. et al. (2014) Neurobiol. Aging. May;35(5):1132- 52). While the Line 61 model shows reduced striatal dopamine production, it does not displaydopaminergic neuronal loss. Thus, the A53T mouse model represents an ideal PD model toconfirm the functional motor benefits of compound of formula (I) in the setting of both human αsynuclein aggregation and dopaminergic neuronal loss.For this, male transgenic A53T-Sud mice at an age of 4 weeks and age / sex-matched non- transgenic littermates are first tested in the Wire Hanging test, Beam Walk and the Pasta Gnawingtest at baseline, at treatment week 10, and at treatment week 20. Additionally Elevated Plus Mazetest is performed to evaluated changes in emotion at treatment week 20. Animals are daily treatedvia oral gavage with the compound of formula (I) or vehicle for a total of 20 weeks. Invivo blood(plasma) samples are taken at baseline and at treatment week 10 from all animals via mandibularbleeding. At the end of the treatment period all mice are euthanized under deep anesthesia, CSF and blood samples are collected and brains are removed and hemisected. One hemi brain is dissected into cortex, hippocampus, striatum which are snap frozen on dry ice for biochemical analysis. The other hemi brain is post fixed in 4% PFA, cryoprotected and embedded in OCT medium for histological evaluations as the quantification of phospho-Serine129 α-synuclein, human α-synuclein, GFAP and Iba1 in the hippocampus, in the cortex, and striatum. For biochemical analyses, Neurofilament light chain (NF-L) levels in the CSF and plasma (baseline, treatment week 10 and week 20) are measured using the NF-L ELISA by Uman Diagnostics.The treatment with the compound of formula (I) generally shows 1) functional benefit (motorimprovement) in any of the behavioural tests such as the wire hanging, beam walk, pasta gnawingand elevated plus maze test; 2) a reduction of the dopaminergic neuronal loss found in thesubstantia nigra and striatum; 3) a diminution of the quantity of insoluble hAsyn present in TritonX-100 insoluble fractions from cortex and hippocampus. D. In vivo treatment efficacy in the acute glaucoma induced ischemia-reperfusion (I / R)model: Chen YJ et al. (2015), Invest Ophthalmol. Vis Sci.56(3):1506-16 The efficacy of compound of formula (I) is evaluated in the acute glaucoma animal model. Eight- week-old male Sprague-Dawley (SD) rats weighing 250 to 300 g are housed in a temperature- and humidity-controlled animal room under a 12-hour light / 12-hour dark cycle, with food and water provided ad libitum. Before any experiment, animals are allowed for one week of acclimatization. The SD rats are randomly allocated to control group and / or treatment groups. Compound offormula (I) is administrated by oral (gavage) route. Two protocols are considered, where thetreatment is initiated 24 hours before or 1 hour after the induction of acute glaucoma-induced I / Rinjury. To induce I / R injury, a general anesthesia is induced via i.p. injection of a mixture of 50 mg / kg of ketamine and 2 mg / kg of xylazine. Corneal analgesia is administered using a drop of topical 0.5% proparacaine hydrochloride ophthalmic solution, and pupillary dilatation is maintained with 0.5% tropicamide and 0.5% phenylephrine. After analgesia and dilation of the pupil, the anterior chamber of the left eye is cannulated with a 30-gauge needle connected to a saline reservoir at 150 cm above the eye, leading to a high intraocular pressure (IOP) of 110 mm Hg. The presence of retinal ischemia is examined by the fundus. The cannulation is lasting 60 minutes. Afterremoving the infusion needle from the anterior chamber, the IOP returns to normal. Antibioticophthalmic gel with tobramycin is topically applied to the eye before and after the procedure. The rats are sacrificed 7 days after I / R injury to observe the long-term effect of the compound of formula (I) treatment. After collection, the thickness of the retinas is examined by histological staining(Mayer P, (1896), Mitt. zool. Stn. Neapel.,12,303). The number of retinal ganglion cells is alsoquantified by immunohistochemistry. Finally, the function of the retina is also evaluated 7 daysafter I / R injury by electroretinography (ERG). The treatment with the compound of formula (I) is 1) mitigating the reduction of thickness of theretina measured by H&E staining; 2) showing an increased number of retinal ganglion cells stainedby immunohistochemistry and 3) improving retinal function by analysing the different electrical responses obtained by electroretinography. E. In vivo treatment efficacy in the kainate-induced temporal lobe epilepsy (TLE) modelSanchez et al. (2019) Neurobiology of Disease 124: 531–543Compound of formula (I) is evaluated in the kainate-induced seizure rat model. Sprague-Dawleyrats are treated with intraperitoneal injection of kainate (10 mg / kg) to induce seizure or with salineas vehicle control. The severity of behavioral seizures following kainate injection is scored according to the Racine scale (Racine R.J. (1972). Electroencephalogr. Clin. Neurophysiol.32 (3), 269–279), from less (score 1) to more severe (score 5): 1) mouth and face clonus and head nodding; 2) clonic jerks of one forelimb; 3) bilateral forelimb clonus; 4) forelimb clonus and rearing; 5) forelimb clonus with rearing and falling. The onset of status epilepticus (SE) is defined as the time from kainate injection to the occurrence of continuous seizure activity (Racine score 4–5)over a period of 4 h. Four weeks following the administration of kainate, animals undergo EEG surgery for electrodes implantation at the surface of the dura mater. Five weeks post-kainateadministration a baseline (EEG) is recorded during 24 hours. Then, the animals receive a dailyadministration (oral gavage) of compound of formula (I) for 3 consecutive days during which,cerebral activity is monitored by EEG recording. Animals are finally sacrificed ninety-six hours (4days) post-baseline.The treatment with the compound of formula (I) is reducing the epileptic activity of treated animalswhich is determined by EEG and characterised by a reduction of the number of seizures, seizure duration, or interictal spike frequency (Sanchez et al. (2019) Neurobiology of Disease 124: 531– 543). F. In vivo chronic and acute effects of compound of formula (I) on the hTau.P301S-Tgmouse model of Tauopathy The hTau.P301S-Tg model is characterized by an early onset of tau pathology in the brain and spinal cord, starting at the age of 3 months and displays a progressive age-dependent increase in tau hyperphosphorylation in the spinal cord, brainstem, cerebral cortex and hippocampus from3 months onwards (Hampton D.W. et al (2010) J Neurosci, 30 (30), 9973-83:63). Concomitant tothe pathology, these mice progressively develop motoric deficits like clasping, reduced general mobility, weight loss and die prematurely around the age of 6 months. To study the chronic effect of compound of formula (I) on tau pathology, homozygous female hTau.P301S mice (2 months of age) are treated every day for 3.5 months either with vehicle (0.5% HPMC / 0.25% Tween 20) or with compound of formula (I) (n=15 per group). Twenty-four hoursafter the last compound administration, the mice are anaesthetized, and brains are removed andprocessed for histology (one half brain) and for biochemistry (one half brain). For biochemicalanalysis of the cortex and hippocampus, the methodology of Greenberg and Davies is followed with few modifications to isolate the soluble and sarkosyl insoluble cortical and hippocampal fractions of the brain. In brief, cortex and hippocampus tissues are homogenized in 10 % wt / vol of ice-cold PhosphoSafeTMreagent buffer (Merck Millipore, 71296-4) with protease inhibitor cocktailto obtain a crude tissue homogenate (S0). 300 μl of homogenates are spun at 80,000 g at 4 °Cfor 20 min to obtain the supernatants S1 (soluble fraction) and the pellets P1. The P1 pellets arehomogenized in 5% wt / vol of sucrose extraction buffer (10 mM Tris HCl pH 7.4, 0.8 M NaCl, 10%sucrose, protease inhibitors) and spun at 4,000 g at 4 °C for 20 min. The resulting supernatantsare incubated for 1 h at 37 °C in presence of 1% sarkosyl (final concentration) before ultracentrifugation at 80,000 g at 4 °C for 1h. Finally, the resulting pellets (sarkosyl-insolublefractions or P3 pellets) are resuspended in 50 µl of TBS (10 mM Tris-HCl pH 7.4, 0.8 M NaCl +PI) to quantify the level of O-Proteins and / or O-Tau using the immunoassays described in example2B and 2A, respectively. Total tau proteins are also quantified for normalisation. For this, abiotinylated mouse monoclonal anti-tau HT7 (ThermoFisher, MN 1000B) is used for capture while a SULFO-TAG™ labelled Tau-5 antibody is used for detection. For the detection of ptauSer202 / Thr205 (AT8) a biotinylated anti-tau HT7 is used for capture and a SULFO-TAG™ labelled AT8 antibody (ThermoFisher, MN1020) for detection. The detection of ptauS356 and ptauS396 are performed by direct (ECL) immunoassay using a high-bind Mesoscale® plates (MSD, L15XB-3) and a mouse monoclonal anti-ptauS356 (Abcam, ab75603) or anti-ptauS396 (Invitrogen, 44-752G) for detection. For pathological analyses, 40 µm thickness brain sections are silver-impregnated following themethod of Gallyas-Braak to visualize filamentous tau pathology. The sections are also incubatedwith AT8 (anti-ptauSer202 / Thr205) or with AT100 (anti-ptauThr212 / Thr214) to quantify thepresence of hyperphosphorylated pathological tau proteins in brain tissue.The chronic treatment (3,5 months) of hTau.P301S-Tg mice with the compound of formula (I) is1) diminishing the extent of neuronal pathology in the hippocampus (NFTs) observed byimmunohistology (AT8 and / or AT100 immunostaining) and by Gallyas-Braak silver staining and2) reducing the level of pathological tau in the sarkosyl insoluble cortical and hippocampal fractionsusing AT8, ptau356 and ptau396 phospho-tau assays.To study the pharmacodynamic effect of an acute treatment with the compound of formula (I), 42homozygous female hTau.P301S mice (2 months of age) are treated every day for 4 days eitherwith vehicle or compound of formula (I). After treatment, animals are sacrificed at different time-points (n=6 / group) after last administration and brain tissues are dissected out for biochemicalquantification of brain O-proteins, O-Tau and ptauS356 by ECL immunoassay.The acute treatment (4 days) of hTau.P301S-Tg mice with the compound of formula (I) is 1)increasing the level of O-Proteins and O-Tau in soluble cortical fractions and 2) demonstrates asignificant elevation of ptau species such as ptau356 in soluble cortical fraction of the brain ofhTau.P301S-Tg mice. The data are depicted in FIG. 15A - FIG. 15D)G. In vivo chronic and acute effect of compound of formula (I) in the hTau.P301L-Tgmouse model of TauopathyThe hTau.P301L-Tg model used in this study displays an age-dependent neuronal tauopathywhich is characterized by a hyperphosphorylation of tau (detected by AT8 and AT100) in thebrainstem, in the midbrain and, to a lesser extend in the cortex and hippocampus.Hyperphosphorylated tau proteins show conformational changes which lead to tau aggregation, and the mice develop neurofibrillary tangles from the age of 6 months. Concomitant to taupathology, these mice progressively develop central breathing impairments, motoric deficits likeclasping behaviour accompanied by a diminution of general mobility and die prematurely at theage of 8-11 months (reMYND unpublished data, Borghgraef P. et al. (2013) Dec 23;8(12):e84442,Terwel D. et al (2005) J Biol Chem 280:3963–3973)To study the chronic effect of compound of formula (I) on hTau.P301L-Tg mice, homozygousfemale hTau.P301L-Tg mice (3,5 months old) are treated every day for 6 months with vehicle orcompound of formula (I). From the age of 7 months, motoric functions are tested every day byclasping test until sacrifice. Clasping of the hind and fore limbs is scored for each limb separatelyusing the 4-point rating scale. Fore limb scores are also used to determine humane end pointsand sacrifice decisions. For survival analysis, hTauP301L mice showing a severe claspingphenotype (fore limb score at stage 4) accompanied with a weight loss of 20% and bodytemperature below 34 °C are sacrificed before study termination.The chronic treatment of hTau.P301L-Tg mice with the compound of formula (I) is 1)demonstrating a significant benefit in survival rate; 2) showing an improvement in motoric function(clasping behaviour, beam walk).To study the acute effect of compound of formula (I) on breathing capacities, female hTau.P301L- Tg mice (7 months old) are treated every day for 4 days with vehicle of compound of formula (I).Two hours after last administration, animals are anesthetized, and the breathing functions (ForcedExpiratory, FE-parameters) are investigated using the fllexiVent FX system (SCIREQ Inc.)equipped with a FX1 module with a mice adapter (NPFE extension) and operated by the flexiWarev7.2 software. From the FE parameters, the forced expiratory volume and flow at 0.1 s (FEV0.1) and 0.2 s (FEV0.2), forced vital capacity (FVC), and peak expiratory flows (PEF) are considered as well as the FEV0.1 / FVC (Tiffeneau index at 0.1 s) and FEV0.2 / FVC (Tiffeneau index at 0.2s).The acute treatment of hTau.P301L-Tg mice with the compound of formula (I) is showing animprovement of the upper airway dysfunction with a significant increase of the Tiffeneau index at0.2 s (FEV0.2 / FVC) in compound of formula (I) treated animals compared to vehicle treated ones.H. In vivo treatment effect of compound of formula (I) on a mouse model ofAmyotrophic Lateral Sclerosis (ALS) Hsieh YL et al. (2019) Cell Rep Nov 19;29(8):2134-2143 Nonselenocysteine-containing Phospholipid hydroperoxide Glutathione Peroxidase (NPGPx) serves as a redox sensor / transmitter against oxidative stress by regulating biological functions oftarget proteins via disulfide bond shuffling in endoplasmic reticulum (ER) (Utomo A. et al. (2004)J. Biol. Chem. Oct 15;279(42):43522-9). Aged NPGPx knock-out (KO) mice, develop ALS-like phenotypes, including paralysis, muscle denervation, and motor neurons loss (Hsieh YL et al. (2019) Cell Rep Nov 19;29(8):2134-2143)Nine months old female homozygous NPGPx knockout (NPGPx- / -) mice and wild-type littermates(NPGPx+ / +) are orally treated every day by the compound of formula (I) for a period of 3 months.During treatment period all mice (KO and WT littermate) are placed on an accelerating rotarodonce per month from the age of 9 to 12 months. After the last round of rotarod test, animals areperfused with 4% (wt / vol) PFA in PBS (pH 7.4), and their L3-L5 lumbar spinal cords, brains, and hindlimb gastrocnemius muscles are collected. Spinal cords and brains are sectioned into 20 μm thick slices using a cryostat. For detection of the neuromuscular junction (NMJ) architecture, the gastrocnemius muscles are teased into layers of 5-10 fibers in thickness for staining. The muscles are incubated with the anti-NF-200 ab against presynaptic nerve terminals and a- Bungarotoxin-Alexa 594 against acetylcholine receptors (AChRs) to estimate the level of innervation at the neuromuscular junction. The spinal cord slices are incubated with the anti- ChAT antibody to evaluate (count) the number of ChAT-positive motoneuron (MN) present in the ventral horn of the spinal cord. Images are acquired using identical confocal settings, and then analyzed quantitatively using ImageJ.Treatment of aged NPGPx KO mice with compound of formula (I) demonstrates: 1) an increaseof the number of ChAT positive motoneuron in the spinal cord.2) an improvement of motoneuron denervation at the NMJ of the gastrocnemius muscles and 3) an improvement of the locomotor activity on rotarod test. Example 6: Unit Dosage Form (Drug Product, DP,) Preparation A. Description and Manufacturing of Capsule of Compound (I)The fumarate salt of compound (I), which can be obtained according to example C04 of WO2020039030 (hereinafter also the “Drug Substance”), can be formulated as an immediate release capsule, as hard capsules containing for example, but not limited to 5 mg or 50 mg of compound (I) (free base equivalents) per capsule. The manufacturing principle comprises various dry blending and sieving steps of the micronized fumarate salt of compound (I) with requiredexcipients, followed by a semi-automated capsule filling process. The resulting hard capsules arepackaged into HDPE bottles with desiccant pouches, induction seal and a child-proof screw cap.The qualitative and quantitative compositions are provided in the Tables 2 and 3:Table 2: Qualitative and Quantitative Composition of Drug Product, eq. 5 mg Strength, HardCapsule, Size 5c bCorrection factor: 1.388.cNote that “eq.” (equivalent) refers to the free base equivalent form of compound (I) fumarate salt.Table 3: Qualitative and Quantitative Composition of Drug Product, eq. 50 mg Strength,Hard Capsule, Size 00c aDrug Substance quantity may be adjusted by the correction factor for fumarate salt and purity.bCorrection factor: 1.388.cNote that “eq.” (equivalent) refers to the free base equivalent form of Compound (I) fumarate salt. The Drug Substance comprising compound (I) has suitable physical, biopharmaceutical, and chemical characteristics for development of an immediate release capsule formulation. It is suitably stable. The blend powder to be filled into the capsules contains common excipients: microcrystallinecellulose, Silica, colloidal hydrated and magnesium stearate. The function and quality of theseexcipients are summarized in Tables 2 and 3. All ingredients are used in concentrations typical forsolid oral formulations. The selection of excipients, for the capsule powder, are based on compatibility studies and short-term stability studies. These studies show no incompatibility with the chosen excipients. For the manufacturing of the powder blend, excipients and Drug Substance are sieved prior to use. Sieved Drug Substance is blended together with the filler, microcrystalline cellulose, Theglidant, silica, colloidal hydrated and the lubricant, magnesium stearate, are added sequentially,with blending time after each addition to obtain a homogeneous mixture.For the encapsulation, the blend is filled into Size 5, white opaque, HPMC capsules or Size 00swedish orange, HPMC capsules using encapsulation equipment. The capsules are de-dusted,weight-sorted and filled into HDPE bottles with desiccant pouches, induction seal and a child-proofscrew cap. Similar procedures as described above can be followed to produce capsules with different strengths of compound (I). Method to Monitor Dissolution Rate by HPLC Dissolution testing conditions A method to monitor the rate of dissolution has been established. Dissolution conditions are described below: Type of dissolution apparatus: USP apparatus type II (Paddle)Medium: 0.01 M HClVolume: 900 mLTemperature: 37°CSinker use: Suitable sinker devices for both capsule sizesRotation speed: 50 ± 2 rpmSampling time points: 5, 10, 15, 30, 45, 60, 90 minutesSampling information: Flow rate: 15 mL / min, in-line filter with 45 mm filter disk, with1.5 mL Sample volume: 5ml Typical chromatographic conditions Column: C18, 50 x 2.1 mm ID, 1.7 μm particle size + guard columnColumn temperature: 60 °CFlow rate: 0.4 mL / minDilution solvents: 1: MQ water / ACN (80 / 20; v / v) + 0.1% (v / v) TFA2: MQ water + 0.1% (v / v) TFA Injection volume: 10 µLDetection: UV 260 nm, 10 p / s.Mobile phases: A: 0.05 % TFA (v / v) in MQ waterB: 0.05 % TFA (v / v) in acetonitrile Peak retention time: Compound (I): approx. 5.5 minPeak retention time: Peak corresponding to compound of formula (I) elutes at about 5.5 minutes.A dissolution profile of the capsule can be found in FIG. 5.

[0004] Example 7: Phase 1 Clinical TrialsAll unit dosage forms used for the clinical trials described hereafter are prepared in accordance toExample 5. In all cases, where the compound of formula (I) is administered to a human subject, it is comprised in its respective dosage form disclosed above.A Randomized, Double-Blind, Placebo-Controlled, Phase 1, Safety, Tolerability,Pharmacokinetics and Pharmacodynamics Study of Oral Compound of Formula (I) inHealthy Young Adult and Elderly Subjects and Elderly Subjects with Alzheimer’s DiseaseThe study is a multi, randomized, placebo-controlled single- and multiple ascending dose study inhealthy male and female (no childbearing potential) volunteers and patients with Alzheimer’sdisease. Study objectives are safety, tolerability, food effect and pharmacokinetics, andpharmacodynamics. Following identification of safe and tolerable single doses in healthy subjects aged 18-55 years, multiple-dose safety, tolerability, pharmacokinetics, CSF drug levels andpharmacodynamics are assessed in elderly (age 55-80 years) volunteers. Furthermore, multiple-dose safety, tolerability, pharmacokinetics, CSF drug levels and pharmacodynamics are investigated in a cohort of Alzheimer patients (see Example 7) The different parts of the study are illustrated schematically in the following table.

[0005] Table 4: Summary of the first in man study Pharmacokinetics in Humans 1. Single Dose PharmacokineticsThe single-dose pharmacokinetics of two, ascending, dose levels of compound of Formula (I) (20,and 50 mg of compound (I) fasted state) are evaluated in part 1of a randomized, placebo-controlled, time lagged, parallel group study in healthy young volunteersCompound (I) pharmacokinetic data are measured in plasma and in urine up to 216 hours postdose. Compound (I) pharmacokinetics is characterized by consistent dose-dependent profiles which demonstrate rapid absorption, nearly dose-proportional increase in Cmax and AUC from 20to 50 mg, and terminal half-life (t½), ranging from mean 43.9 h to mean 49.7 h at the different doselevels. Exposure (AUC over 24 hours) show dose proportionality at the two dose levels 20, 50 mgas suggested by the dose normalized AUC not deviating more than approximately 3% at thesedose levels. Cmax show dose proportionality at the two dose levels as suggested by the dosenormalized Cmaxnot deviating more than approximately 8% at these dose levels.Table 5: Summary (N, Arithmetic Mean (AM) and Standard Deviation (SD)) of PlasmaPharmacokinetic Parameters of Compound (I) Following a Single Oral Dose of Compound (I) atTwo Dose Levels (20 mg, and 50 mg) in Healthy Subjects – Part 1 (based on scheduled blooddraws) *: Median (min, max) reported for Tmax.In summary, Peak concentrations (Cmax) and systemic exposures (AUC0-t and AUC0-inf) of plasmacompound (I) increase after single dose administration of compound (I) doses in proportion to thedose of 20 mg to 50 mg.Median Tmax of compound (I) is between 1.0 hour and 1.50 hours, with comparable ranges ofindividual values for the dose levels from 20 mg to 1000 mg (ranging between 0.50 hour and 3 hours).The mean terminal half-life of compound (I) ranges from 43.9 hours to 49.7 hours over the 2 doselevels.Dose proportionality is observed for Cmax and AUC of compound (I) from dosing range of 20 mgto 50 mg.2. Multiple Dose PharmacokineticsThe multiple-dose pharmacokinetics of one dose level of compound (I) (20 mg compound (I) givenQD i.e. once daily for 10 days) are evaluated in part 2 of a randomized, placebo-controlled, timelagged, parallel group study in healthy elderly volunteers.Compound (I) pharmacokinetic data are measured in plasma and in urine up to 240 hours postlast dose. The compound (I) pharmacokinetics are characterized by consistent profiles whichdemonstrate rapid absorption, and a terminal mean half-life (t½) of 42 hours, consistent with thehalf-life calculated for single doses.Accumulation of compound (I) plasma concentrations from day 1 to day 10 is consistent with thecalculated terminal half-life (t½), ie the accumulation ratios are between 2.1 for Cmax and 2.6 forAUC(0-tau), comparing day 1 and day 10 exposure (tau = 24 hours for once daily QD dosing).Table 6: Summary (N, Arithmetic Mean and Standard Deviation) of Plasma PharmacokineticParameters of Compound (I) Following Once Daily QD Doses of 20 mg Compound (I) in Male andFemale Elderly Subjects for 10 Days – Part 2 (based on scheduled blood draws) reported for Day 10; Dosing interval (tau) is 24 h for multiple dose study;*: Median (min, max) reported for Tmax;***: Accumulation ratio (AR), calculated by AUC0-tauat Day 10 / AUC0-tauat Day 1;a: t1 / 2 and λz are not reliably estimable on Day 1 due to an insufficient number of data points at theterminal phase due to the long half-life;

[0006] In summary, -Half-lifes of compound (I) are comparable under single dose and multiple dose conditions- Accumulation of compound (I) is consistent with the half-life: 2.1 for Cmax, and 2.6 for AUC(0-tau)- With a half-life of approximately 42 hours, steady-state is reached within approximately 8days. 3. Effect of food on pharmacokineticsThe effect of food on pharmacokinetics is assessed in part 2 by administering compound (I) at day8 under fed conditions and at day 10 under fasted conditions, assuming that steady-state is reached. Table 7: Summary (N, Arithmetic Mean and Standard Deviation) of Plasma PharmacokineticParameters of Compound (I) following a Single Oral Dose of 20 mg Compound (I) in HealthyElderly Subjects under Fasted (Day 10) and Fed Conditions (Day 8) - Part 2 (based on scheduledblood draws) In summary, there is no relevant food effect, if compound (I) is administered under fed or fasted conditions. The extent of exposure is basically unchanged, the maximum exposure is just slightly lower and the maximum concentration is delayed. 4. Effect of age on pharmacokineticsThe effect of age on pharmacokinetics is assessed by comparing the single dosepharmacokinetics of the first dose level in part 1 in healthy adult subjects (20 mg single dose ofcompound (I) under fasted conditions, aged 18 – 55 years according to the protocol) with thepharmacokinetics at day 1 of the multiple dose part 2 (20 mg single dose of compound (I) underfasted conditions) in healthy elderly subjects, aged 55 – 80 years according to the protocol.Table 8: Summary (N, Arithmetic Mean and Standard Deviation) of Plasma PharmacokineticParameters of Compound (I) following a Single Oral Dose of 20 mg Compound (I) in Healthy Adult Subjects as compared to a Single Oral Dose of 20 mg Compound (I) in Healthy Elderly Subjectsunder Fasted Conditions– Parts 1 and 2 (based on scheduled blood draws) *: Median (min, max) reported for Tmax. In summary, there is no relevant effect of age on pharmacokinetics, if compound (I) is administeredto adult or elderly subjects. The extent of exposure and the maximum exposure are slightly lowerin elderly subjects, which is a safety feature for indications in elderly populations. Pharmacokineticconclusions derived from studies in healthy adult subjects can be applied to elderly populations.

[0007] 5. Cerebrospinal Fluid (CSF) PharmacokineticsThe multiple-dose pharmacokinetics of compound (I) in CSF is assessed in a randomized,placebo-controlled, time lagged, parallel group study at one dose level of compound (I) (20 mgcompound (I) given QD i.e. once daily for 10 days) in healthy elderly volunteers.Compound (I) plasma concentrations are measured in CSF at day 10Mean concentrations of compound (I) in the morning of day 10 of dosing with 20 mg of compound(I) in CSF are 157 ng / mL. The concentrations of compound (I) in plasma at day 10 four hours afterdosing with 20 mg compound (I) are 673 ng / mL; the ratio is 0.23, pointing to an excellentpenetration of compound (I) into the brain. A phase 1, open-label, positron emission tomography study in healthy subjects to determine the relationship between plasma concentration and brain target occupancy of Compound (I) following a single oral dose The human brain O-linked-N-acetylglucosaminidase (O-GlcNAcase) enzyme occupancy isquantified by competitive displacement of a selective radiolabelled O-GlcNAcase inhibitor used aspositron emission tomography (PET) tracer by compound of formula (I). A PET tracer can typically bear a18F or a12C as radiolabelled atom. [18F]-LSN3316612, but not limited to, may be chosen as[18F]-radiolabelled, selective O-GlcNAcase inhibitor as it has been shown to exhibit a suitableselectivity and pharmacokinetics for quantification of O-GlcNAcase enzyme in the brain inpreclinical studies and as a PET tracer for human studies (Paul S. et al. (2019) J. Nucl. Med. 60:129-134).The primary objective of this study is to determine the brain O-GlcNAcase occupancy using [18F]-LSN3316612 Positron Emission Tomography (PET), following a single oral dose of compound (I).The secondary objective is the determination of the relationship between the plasma concentrationof compound (I) and the time-course of brain O-GlcNAcase occupancy using [18F]-LSN3316612 PET, following a single oral dose of compound (I).PET imaging data are acquired and analysed for three healthy volunteers, male. Each subject hasa baseline PET scan and two post-dose PET scans taken. The O-GlcNAcase receptor occupancyis explored around 6 hours to 48 hours after oral doses of compound (I) (ranged from 5 – 15 mg),and the corresponding estimates of occupancy ranged from 68.2 – 92.2%.The relationship between plasma concentration of compound (I) and O-GlcNAcase is welldescribed by a simple saturation model, with an EC50 of 9.4 ng / ml (95% confidence interval: 6.4 –12.3 ng / ml). A plasma concentration of 199 ng / mL of compound (I) is sufficient to obtain a receptoroccupancy of 92.2 % in the brain, which can be obtained by well tolerated doses of compound (I).

[0008] Example 8: Phase 1 in Alzheimer Dementia (AD) Patient (Protocol)Part 3 of a Randomized, Double-Blind, Placebo-Controlled, Phase 1 Safety, Tolerability,Pharmacokinetics and Pharmacodynamics Study of Oral Compound of Formula (I) in Healthy Young Adult and Elderly Subjects and Elderly Subjects with Alzheimer’s Disease The part 3 of the study is a multi-center, randomized, placebo-controlled multiple dose study in patients with Alzheimer’s disease. Multiple-dose safety, tolerability, pharmacokinetics, CSF druglevels and pharmacodynamics are investigated in a cohort of Alzheimer patientsThe different parts of the study are illustrated schematically in the following table. Table 9: Summary of the first in man study PRIMARY OBJECTIVE: To evaluate the safety and tolerability of one dose level (10 mg oncedaily QD for 28 days) of compound (I) compared with placebo for the treatment of ADSECONDARY OBJECTIVES: To evaluate the following:• To assess the plasma and urine pharmacokinetics of Compound (I)• To assess the effect of multiple doses of Compound (I) on the quantitative electroencephalogramand the P300 • To assess the CSF pharmacokinetics of Compound (I) • To assess the effect of food on the plasma pharmacokinetics of Compound (I) • To assess the pharmacodynamic effects of Compound (I) on CSF TauEXPLORATORY OBJECTIVES: To evaluate the following:• To assess the effects of Compound (I) on CSF and plasma biomarkers • To assess the effects of Compound (I) on functional outcomes (i.e., cognition, sleep, and activity)STUDY DESIGN: This is a randomized, multi-centre, double-blind, placebo-controlled trial to studythe safety and tolerability of compound (I) in AD patients. Approximately 10 AD patients arerandomized in a 5:1 ratio to orally administered 10 mg or placebo once daily QD.After assessing eligibility during a 6-week screening period, 10 elderly male or female AD subjectsparticipate in Part 3 of the study. Each eligible subject is assigned either to receive Compound (I)(8 subjects) or to receive placebo (2 subjects). A hospitalization is optional; however, subjects whoare not hospitalized are under supervision by a caregiver at all times. Starting at Day 1, subjectsreceive Compound (I) or placebo. The subjects are dosed once daily QD for 28 days. Blood andCSF samples for PK and biomarker analysis are collected pre-dose and at 648 h post first dosebefore last drug administration. Physical and neurological examinations, vital signs, ECG, telemetry, cognitive testing, upper motor function testing, actigraphy, sleep analysis, and EEG withERP (P300) are performed at specified times. Adverse events are recorded throughout the study.A follow-up visit takes place 10 days (±3 days) after receiving the last dose.ENDPOINTSSafety Endpoints Safety are assessed over the entire study period for the incidence of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs), including clinically significant changes in vital signs, clinical laboratory evaluations, physical examination findings, ECG parameters, and suicidal ideation / behavior. Primary Outcome Measures • TEAEs and SAEs up to follow-up • SAEs up to 4 weeks after last administration • Laboratory tests • Vital signs • ECG and telemetry • Physical examination Secondary Outcome Measures • Pharmacokinetics of Compound (I) in CSF and plasma • Change from Baseline in CSF phosphorylated tau 181 • Event-related potential (ERP) P300 latency • Quantitative Electroencephalogram, Gamma Power Exploratory Outcome Measures • Pharmacodynamic biomarkers (Part 1 Plasma only, Parts 2 and 3 both CSF and Plasma) • Sleep (Dreem headband, Karolinska Sleep Scale) and activity (Philips actigraphy watch) • Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog13, Part 3) • Montreal Cognitive Assessment (MoCA, Part 3) • Cognitive test battery (CogState) • Anxiety (Generalized Anxiety Visual Analogue Scale STATISTICAL CONSIDERATIONS A full description of the statistical evaluations, general considerations, and procedures for handlingmissing data are provided in the Statistical Analysis Plan (SAP). In general, trial data are reportedusing summary tables, figures, and data listings. Descriptive statistics are used to summarize thedata. For continuous variables, the mean, standard deviation, median, minimum, and maximumare provided. For discrete data, incidence and percentages are provided. Statistical tests are 2-sided at the alpha level of 0.05, unless stated otherwise. For the primary endpoints, TEAEs are tabulated and summarized by Medical Dictionary for Regulatory Activities (MedDRA) System Organ Class (SOC) and Preferred Term (PT). The number and percentage of patients whoexperience AEs coded with the same PT and SOC are summarized by treatment group (indescending order according to the incidence in the investigational study drug group). Adverseevents are also tabulated by severity and by relationship to study drug. Summary tables areaccompanied by individual subject listings broken down by treatment group, including pre-doseevents. SAEs are listed and summarized similarly to AEs. Reasons for death are only listed.Reasons for premature discontinuation of study drug are listed and summarized by frequencytables. ECG variables, vital sign measurements and laboratory measurements are summarized ateach time point using mean, median, standard deviation, min, max, number of available observations, and change from baseline. Individual patient listings of ECG data, vital signs dataand laboratory measurements are provided. For PK and PD secondary endpoints, individualsubject listings are provided. Mean and individual plasma concentration-time profiles forCompound (I) are presented graphically for each group. PK variables are summarized usingarithmetic mean, STD, geometric mean, median, minimum, maximum, and %CV. Exploratorydata-driven analyses are performed with the caveat that any statistical inference have not anyconfirmatory value. Listings of all individual subject data are produced. An SAP are written andfinalized before the study closure, i.e., database closure and unblinding of the randomization codeof the study, if applicable. The SAP provide full details of the analyses, the data displays, and thealgorithms to be used for data derivations. REFERENCES Boxer AL, Lang AE, Grossman M, et al. Davunetide in patients with progressive supranuclear palsy: a randomised, double-blind, placebo-controlled phase 2 / 3 trial. Lancet Neurol. 2014;13(7):676-85. Höglinger GU, Respondek G, Stamelou M, et al. (2017) Clinical diagnosis of progressivesupranuclear palsy: The movement disorder society criteria. Mov Disord. a;32:853-64.Höglinger GU, Schöpe J, Stamelou M, Kassubek J, Del Ser T, Boxer AL, et al. (2017) Longitudinalmagnetic resonance imaging in progressive supranuclear palsy: A new combined score for clinicaltrials. Mov Disord. 32(6):842-52.Stamelou M, Schöpe J, Wagenpfeil S, Del Ser T, Bang J, Lobach IY, Luong P, et al. (2016) Powercalculations and placebo effect for future clinical trials in progressive supranuclear palsy. Mov Disord.31(5):742-7. Tolosa E, Litvan I, Höglinger GU, et al. (2014) A phase 2 trial of the GSK-3 inhibitor tideglusib inprogressive supranuclear palsy. Mov Disord. 29(4):470-8.Wahlund LO, Barkhof F, Fazekas F, et al. (2001) A new rating scale for age-related white matter changes applicable to MRI and CT. Stroke.32(6):1318-22. Example 9: Pasma protein binding determination. Compound (I) (0.5, 2, 10 and 30 μM) in 100 % species-specific plasma was added to one side of the membrane and buffer (pH 7.4) was added to the other side. The experiment was performed using equilibrium dialysis with the two compartments separated by a semi-permeable membrane. Compound (I) incubations were performed in triplicate. After equilibration (4 hr), samples were taken from both sides of the membrane and analysed by LC-MS / MS. Samples were quantified using standard curves prepared in the equivalent matrix. Fraction unbound (fu) in human, rat and dog plasma ranged between 0.153-0.290, 0.272-0.344 and 0.340-0.496 respectively. No concentration-dependence was observed under these experimental conditions. Plasma protein binding was greatest in human followed by rat and then dog. Compound (I) was 24% free in average (fu = 0.24) when 10 μM of compound (I) was used.

Claims

CLAIMS 1. A compound of formula (I)or a stereoisomer, tautomer, pharmaceutically usable solvate or salt thereof, for use in a methodof treating a subject, the method comprising the repeated administration of one or more unit dosage forms comprising the compound of formula (I), or a stereoisomer, tautomer,pharmaceutically usable solvate or salt thereof, in a dose and at a daily dosing frequency sufficientto maintain the plasma concentration of the compound of formula (I), or a stereoisomer, tautomer,pharmaceutically usable solvate or salt thereof, at steady state of at least about 5 ng / mL at trough.

2. Use of a compound of formula (I)or a stereoisomer, tautomer, pharmaceutically usable solvate or salt thereof, for treating a subject,comprising the repeated administration of one or more unit dosage forms comprising the compound of formula (I), or a stereoisomer, tautomer, pharmaceutically usable solvate or saltthereof, in a dose and at a daily dosing frequency sufficient to maintain the plasma concentrationof the compound of formula (I), or a stereoisomer, tautomer, pharmaceutically usable solvate orsalt thereof, at steady state of at least about 5 ng / mL at trough.

3. A method of treating a subject, the method comprising the repeated administration of one or more unit dosage forms comprising a compound of formula (I)or a stereoisomer, tautomer, pharmaceutically usable solvate or salt thereof, in a dose and at adaily dosing frequency sufficient to maintain the plasma concentration of the compound of formula(I), or a stereoisomer, tautomer, pharmaceutically usable solvate or salt thereof, at steady state ofat least about 5 ng / mL at trough.

4. Use of a compound of formula (I)or a stereoisomer, tautomer, pharmaceutically usable solvate or salt thereof, in the manufacture of a medicament for treating a subject, comprising the repeated administration of one or more unit dosage forms comprising the compound of formula (I), or a stereoisomer, tautomer, pharmaceutically usable solvate or salt thereof, in a dose and at a daily dosing frequency sufficientto maintain the plasma concentration of the compound of formula (I), or a stereoisomer, tautomer,pharmaceutically usable solvate or salt thereof, at steady state of at least about 5 ng / mL at trough.

5. The compound, use or method according to any one of claims 1-4, wherein the plasmaconcentration of the compound of formula (I), or a stereoisomer, tautomer, pharmaceuticallyusable solvate or salt thereof, is maintained in a range of about 5 ng / mL to about 1000 ng / mL attrough.

6. A compound of formula (I)or a stereoisomer, tautomer, pharmaceutically usable solvate or salt thereof, for use in a methodof treating a subject, the method comprising the repeated administration of one or more unit dosage forms comprising the compound of formula (I), or a stereoisomer, tautomer,pharmaceutically usable solvate or salt thereof, in a dose and at a daily dosing frequency sufficientto maintain the average plasma concentration of the compound of formula (I), or a stereoisomer,tautomer, pharmaceutically usable solvate or salt thereof, over a period of 24 hours at steady stateof at least about 6.5 ng / mL.

7. Use of a compound of formula (I)or a stereoisomer, tautomer, pharmaceutically usable solvate or salt thereof, for treating a subject,comprising the repeated administration of one or more unit dosage forms comprising the compound of formula (I), or a stereoisomer, tautomer, pharmaceutically usable solvate or saltthereof, in a dose and at a daily dosing frequency sufficient to maintain the average plasmaconcentration of the compound of formula (I), or a stereoisomer, tautomer, pharmaceuticallyusable solvate or salt thereof, over a period of 24 hours at steady state of at least about 6.5 ng / mL.

8. A method of treating a subject, the method comprising the repeated administration of one ormore unit dosage forms comprising a compound of formula (I)or a stereoisomer, tautomer, pharmaceutically usable solvate or salt thereof, in a dose and at adaily dosing frequency sufficient to maintain the average plasma concentration of the compoundof formula (I), or a stereoisomer, tautomer, pharmaceutically usable solvate or salt thereof, over aperiod of 24 hours at steady state of at least about 6.5 ng / mL.

9. Use of a compound of formula (I)or a stereoisomer, tautomer, pharmaceutically usable solvate or salt thereof, in the manufactureof a medicament for treating a subject, comprising the repeated administration of one or more unit dosage forms comprising the compound of formula (I), or a stereoisomer, tautomer,pharmaceutically usable solvate or salt thereof, in a dose and at a daily dosing frequency sufficientto maintain the average plasma concentration of the compound of formula (I), or a stereoisomer,tautomer, pharmaceutically usable solvate or salt thereof, over a period of 24 hours at steady stateof at least about 6.5 ng / mL.

10. The compound, use or method according to any one of claims 6-9, wherein the averageplasma concentration of the compound of formula (I), or a stereoisomer, tautomer,pharmaceutically usable solvate or salt thereof, is maintained over a period of 24 hours in a rangeof about 6.5 ng / mL to about 1300 ng / mL.

11. A compound of formula (I)or a stereoisomer, tautomer, pharmaceutically usable solvate or salt thereof, for use in a methodof treating a subject, the method comprising the repeated administration of one or more unit dosage forms comprising the compound of formula (I), or a stereoisomer, tautomer,pharmaceutically usable solvate or salt thereof, in a dose and at a daily dosing frequency sufficientto maintain at steady state a plasma C max of the compound of formula (I), or a stereoisomer,tautomer, pharmaceutically usable solvate or salt thereof, of about 9 ng / mL to about 1900 ng / mL.

12. Use of a compound of formula (I)or a stereoisomer, tautomer, pharmaceutically usable solvate or salt thereof, for treating a subject,comprising the repeated administration of one or more unit dosage forms comprising the compound of formula (I), or a stereoisomer, tautomer, pharmaceutically usable solvate or saltthereof, in a dose and at a daily dosing frequency sufficient to maintain at steady state a plasmaC max of the compound of formula (I), or a stereoisomer, tautomer, pharmaceutically usablesolvate or salt thereof, of about 9 ng / mL to about 1900 ng / mL.

13. A method of treating a subject, the method comprising the repeated administration of one ormore unit dosage forms comprising the compound of formula (I)or a stereoisomer, tautomer, pharmaceutically usable solvate or salt thereof, in a dose and at adaily dosing frequency sufficient to maintain at steady state a plasma C max of the compound offormula (I), or a stereoisomer, tautomer, pharmaceutically usable solvate or salt thereof, of about9 ng / mL to about 1900 ng / mL.

14. Use of a compound of formula (I)or a stereoisomer, tautomer, pharmaceutically usable solvate or salt thereof, in the manufacture of a medicament for treating a subject, comprising the repeated administration of one or more unit dosage forms comprising the compound of formula (I), or a stereoisomer, tautomer,pharmaceutically usable solvate or salt thereof, in a dose and at a daily dosing frequency sufficientto maintain at steady state a plasma C max of the compound of formula (I), or a stereoisomer,tautomer, pharmaceutically usable solvate or salt thereof, of about 9 ng / mL to about 1900 ng / mL.

15. A compound of formula (I)or a stereoisomer, tautomer, pharmaceutically usable solvate or salt thereof, for use in a methodof treating a subject, the method comprising the repeated administration of one or more unit dosage forms comprising the compound of formula (I), or a stereoisomer, tautomer,pharmaceutically usable solvate or salt thereof, in a dose and at a daily dosing frequency sufficientto maintain at steady state a plasma AUC over 24 hours of the compound of formula (I), or astereoisomer, tautomer, pharmaceutically usable solvate or salt thereof, of about 150 ng*h / mL toabout 31000 ng*h / mL.

16. Use of a compound of formula (I)or a stereoisomer, tautomer, pharmaceutically usable solvate or salt thereof, for treating a subject,comprising the repeated administration of one or more unit dosage forms comprising the compound of formula (I), or a stereoisomer, tautomer, pharmaceutically usable solvate or saltthereof, in a dose and at a daily dosing frequency sufficient to maintain at steady state a plasmaAUC over 24 hours of the compound of formula (I), or a stereoisomer, tautomer, pharmaceuticallyusable solvate or salt thereof, of about 150 ng*h / mL to about 31000 ng*h / mL.

17. A method of treating a subject, comprising the repeated administration of one or more unit dosage forms comprising the compound of formula (I)or a stereoisomer, tautomer, pharmaceutically usable solvate or salt thereof, in a dose and at adaily dosing frequency sufficient to maintain at steady state a plasma AUC over 24 hours of the compound of formula (I), or a stereoisomer, tautomer, pharmaceutically usable solvate or saltthereof, of about 150 ng*h / mL to about 31000 ng*h / mL.

18. Use of a compound of formula (I)or a stereoisomer, tautomer, pharmaceutically usable solvate or salt thereof, in the manufacture of a medicament for treating a subject, comprising the repeated administration of one or more unitdosage forms comprising the compound of formula (I), or a stereoisomer, tautomer,pharmaceutically usable solvate or salt thereof, in a dose and at a daily dosing frequency sufficientto maintain at steady state a plasma AUC over 24 hours of the compound of formula (I), or astereoisomer, tautomer, pharmaceutically usable solvate or salt thereof, of about 150 ng*h / mL toabout 31000 ng*h / mL.

19. The compound, use or method according to any one of the preceding claims, wherein the doseof the compound of formula (I), or a stereoisomer, tautomer, pharmaceutically usable solvate orsalt thereof, to be administered at said daily dosing frequency is orally administered and is in therange of about 0.25 mg to about 50 mg.

20. The compound, use or method according to any one of claims 11-14, wherein the plasma Cmax of the compound of formula (I), or a stereoisomer, tautomer, pharmaceutically usable solvateor salt thereof, is about 20 ng / mL to about 750 ng / mL.

21. The compound, use or method according to any one of claims 15-18, wherein the plasma AUCover 24 hours of the compound of formula (I), or a stereoisomer, tautomer, pharmaceuticallyusable solvate or salt thereof, is about 350 ng*h / mL to about 13000 ng*h / mL.

22. The compound, use or method according to any one of the preceding claims, wherein the doseof the compound of formula (I), or a stereoisomer, tautomer, pharmaceutically usable solvate orsalt thereof, to be administered at said daily dosing frequency is orally administered and is in therange of about 1 mg to about 20 mg.

23. The compound, use or method according to any one of the preceding claims, wherein therepeatedly administered dose of the compound of formula (I), or a stereoisomer, tautomer,pharmaceutically usable solvate or salt thereof, remains constant.

24. The compound, use or method according to any one of the preceding claims, wherein the dailydosing frequency of the compound of formula (I), or a stereoisomer, tautomer, pharmaceuticallyusable solvate or salt thereof, is once a day QD.

25. The compound, use or method according to any one of the preceding claims, wherein the dailydose of the compound of formula (I), or a stereoisomer, tautomer, pharmaceutically usable solvateor salt thereof, is about 1 mg to about 20 mg per day, when orally administered.

26. The compound, use or method according to any one of the preceding claims, comprising theadministration of an oral dose of the compound of formula (I), or a stereoisomer, tautomer,pharmaceutically usable solvate or salt thereof, of about 3 mg once a day QD or about 5 mg oncea day QD, or about 7.5 mg once a day QD or about 10 mg once a day QD.

27. The compound, use or method according to any one of the preceding claims, wherein thehuman subject suffers from a disease or condition, or is at increased risk of developing a disease or condition.

28. The compound, use or method according to claim 27, wherein the disease or condition isselected from one or more proteinopathies.

29. The compound, use or method according to claims 27 or 28, wherein the disease or conditionis selected from neurological disorders or neurodegenerative diseases, diabetes, cancer, cardiovascular diseases and stroke.

30. The compound, use or method according to any one of claims 27-29, wherein the disease orcondition is selected from the group of one or more tauopathies, synucleinopathies, Alzheimer’sdisease (AD), amyotrophic lateral sclerosis (ALS), amyotrophic lateral sclerosis with cognitive impairment (ALSci), argyrophilic grain disease, behavioral variant frontotemporal dementia (bvFTD), non-fluent and semantic variant primary progressive aphasia (nfv & svPPA), Bluit disease, corticobasal degeneration (CBD), Dementia pugilistica, Dementia with Lewy Bodies (DLB), diffuse neurofibrillary tangles with calcification, Down's syndrome, Familial British dementia, Familial Danish dementia, frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17), frontotemporal lobar degeneration (FTLD), ganglioglioma, gangliocytoma, Gerstmann-Straussler-Scheinker disease, globular glial tauopathy, Guadeloupean parkinsonism, Hallevorden-Spatz disease (neurodegeneration with brain iron accumulation type 1), lead encephalopathy, lipofuscinosis, meningioangiomatosis, multiple system atrophy (MSA), myotonic dystrophy, Niemann-Pick disease (type C), Pallido-ponto-nigral degeneration, Parkinson’s disease, Parkinson’s disease dementia (PDD), Parkinsonism- dementia complex of Guam, Pick's disease (PiD), postencephalitic parkinsonism (PEP), Prion diseases (including Creutzfeldt-Jakob Disease (GJD), variant Creutzfeldt-Jakob Disease (vCJD)), fatal Familial Insomnia, Kuru, progressive supercortical gliosis, progressive supranuclear palsy (PSP), pure autonomic failure, Richardson's syndrome, subacute sclerosing panencephalitis,Tangle-only dementia, tuberous sclerosis, Huntington's disease or mild cognitive impairment (MCI), Chronic traumatic encephalopathy, Primary progressive aphasia, Progressive nonfluent aphasia, Semantic dementia, Steele-Richardson-Olszewski syndrome, epilepsy, chronic and acute inflammation, Crohn disease, neuroinflammation, subarachnoid hemorrhage (SAH), multiple sclerosis (MS), Friedreich’s Ataxia and Adrenoleukodystrophy.

31. The compound, use or method according to any one of the preceding claims, wherein thecompound, or a stereoisomer, tautomer, pharmaceutically usable solvate or salt thereof, isadministered in form of a pharmaceutically usable solvate and / or salt thereof.

32. The compound, use or method according to claim 31, wherein the compound is administeredin form of its fumarate salt.

33. The compound, use or method according to claim 32, wherein its fumarate salt is in a solidform having the characteristic X-ray powder diffraction pattern as shown in FIG. 6.

34. The compound, use or method according to any one of the preceding claims, wherein thesubject is a human subject.

35. The compound, use or method according to any one of the preceding claims, wherein thecompound of formula (I) is selected from a compound of formula (I’)36. The compound, use or method according to any one of the preceding claims, wherein thecompound of formula (I), is selected from the following compounds of formula (Ia), (Ib), (Ic) and37. The compound, use or method according to any one of the preceding claims, wherein thecompound of formula (I) is the compound of formula (Ia).

38. The compound, use or method according to any one of the preceding claims, wherein thecompound of formula (I) is used as its fumarate salt.

39. The compound, use or method according to any one of the preceding claims, wherein thecompound of formula (Ia) is used as its fumarate salt.

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