| Title of Invention | SUBSTITUTED 2-PYRIMIDINYL-6,7,8,9-TETRAHYDROPURIMIDO[1,2-A] PYRIMIDIN-4-ONE AND 7-PYRIMIDINYL-2,3-DIHYDROIMIDAZO[1,2-A] PYRIMIDIN-5(1H) ONE DERIVATIVES FOR NEURODEGENERATIVE DISORDERS |
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| Abstract | The invention relates to a pyrimidone deriva- tive represented by formula (I) or a salt thereof wherein: X represents two hydrogen atoms, a sulphur atom, an oxygen atom or a C1-2 alkyl group and a hydrogen atom, y represents a bond, an ethenylene group, an ethynylene group, an oxygen atom, a sulphur atom, a sulfonyl group, a sulfoxide group, a carbonyl group, a nitrogen atom being optionally; or a methylene group optionally substituted; R1 represents a pyrimidine group optionally substituted; R2 may represent a C1-6 alkyl group optionally substituted by a C6,10 aryloxy or a C6,10 arylamino group; a C3-6 cycloalkyl group, a C1-4 alkylthio group, a C1-4, alkoxy group, a C1-2 perhalogenated alkyl group, a C1-3 halogenated alkyl group, a phenylthio group, a benzyl group, a benzene ring, an indan ring, a 5,6,7,8-tetrahydronaphthalene ring, a naphthalene ring, a pyridine ring, a pyrrole ring, a thiophene ring, a furan ring or an imidazole ring; R3 and R-1 represents each independently a hydrogen atom, C1-6, alkyl group, a hydroxy group, a C1-4 alkoxy group or a halogen atom; R5 represents a hydrogen atom, a C1-6 alkyl group or a halogen atom. The invention relates also to a medicament comprising the said derivative or a salt thereof as an active ingredient which is used for preventive and/or therapeutic treatment of a neurodegenerative disease caused by abnormal activity of GSK3β3 or GSK3β3 and cdk5/p25, such as Alzheimer disease. |
| Full Text | SUBSTITUTED 2-PYRIMIDINYL-6, 7, 8, 9-TETRAHYDROPYRIMIDOL{1, 2-A}PYRIMIDIN-4-ONE AND 7-PYRIMIDINYL-2,3-DIHYDROIMIDAZO{1,2-A}PYRIMIDIN-5(1H)ONE DERIVATIVES FOR NEURODEGENERATIVE DISORDERS SPECIFICATION Technical Field The present invention relates to compounds that are useful as an active ingredient of a medicament for preventive and/or therapeutic treatment of neurodegenerative diseases caused by abnormal activities of GSK3β alone or by the combined effects of GSK3β and cdk5/p25. Background Art GSK3β (glycogen synthase kinase 3β) is a proline directed serine, threonine kinase that plays an important role in the control of metabolism, differentiation and survival. It was initially identified as an enzyme able to phosphorylate and hence inhibit glycogen synthase. It was later recognised that GSK3β was identical to tau protein kinase 1 (TPK1), an enzyme that phosphorylates tau protein in epitopes that are also found to be hyperphosphorylated in Alzheimer's disease and in several tauopathies. Interestingly, protein kinase B (AKT) phosphorylation of GSK3β results in a loss of its kinase activity, and it has been hypothesised that this inhibition may mediate some of the effects of neurotrophic factors. Moreover, phosphorylation by GSK3β of β-catenin, a protein involved in cell survival, results in its degradation by an ubiquitinilation dependent proteasome pathway. Thus, it appears that inhibition 01 GSK3β activity may result in neurotrophic activity. Indeed there is evidence that lithium, an non-competitive inhibitor of GSK3β, enhances neuritogenesis in some models and also increases neuronal survival, through the induction ot survival factors such as Bcl-2 and the inhibition of the expression of proapoptotic factors such as P53 and Bax. Recent studies have demonstrated that β-amyloid increases the GSK3β activity and tau protein phosphorylation. Moreover, this hyperphosphorylation as well as the neurotoxic effects of p-am/loid are blocked by lithium chloride and by a GSK3β antisense mRNA. These observations strongly suggest that GSK3β may be the link between the two major pathological processes in Alzheimer's disease: abnormal APP (Amyloid Precursor Protein) processing and tau protein hyperphosphorylation. Although tau hyperphosphorylation results in a destabilization of the neuronal cytoskeleton, the pathological consequences of abnormal GSK3P activity are, most likely, not only due to a pathological phosphorylation of tau protein because, as mentioned above, an excessive activity of this kinase may affect survival through the modulation of the expression of apoptotic and antiapoptotic factors. Moreover, it has been shown that p-amyloid-induced increase in GSK3β activity results in the phosphorylation and, hence the inhibition of pyruvate dehydrogenase, a pivotal enzyme in energy production and acetylcholine synthesis. Cdk5/p25, also known an tau protein kinase 2 (TPK2), is a proline directed, Ser/Thr kinase essential for central nervous system development and in particular for neuronal migration and neurite outgrowth. Cdk5 is a homologue of cyclin-dependent kinases and rather ubiquitously expressed. Its activator p35 (a 305 aa protein) or a truncated form p25 (208 aa, missing an N-terminal proline- rich domain not required for activity) are selectively expressed in neurons, limiting cdk5 kinase activity essentially to the CNS. Cdk5 is completely inactive in the absence of p35 or p25. The term cdk5/p25 will be used here for the active enzyme since evidence exists suggesting that p25 and less so p35 may be involved in pathological processes. Physiological substrates of cdk5/p25 include DARPP-32, Munc-18, PAK1, synapsin 1 and perhaps some otners. In addition, it is now well established that cdk5/p25 phosphorylates tau protein epitopes which are hyperphosphorylated in Alzheimer's disease. More recently, elevated cdk5/p25 activity, mislocalization of cdk5 and an increase in p25 activator has been found in the brain of Alzheimer patients. Interestingly, prephosprorylation of tau protein by cdk5/p25 considerably enhances phosphorylation of tau by GSK3β on other epitopes, also found hyperphosphorylated in Alzheimer's disease. Moreover, neurofibrillary tangly hallmark of Alzheimer's disease, are labelled with antisera for GSK3β and cdk5, but not GSK3α and MAP kinase, also, GSK3β and cdk5 are associated with microtubules and both, more than PKA and CK, contribute to the AD-like phosphorylation of tau protein. These results taken together suggest that mixed inhibitors of GSK3β and cdk5/p25 should efficient in protecting tau protein from hyperphosphorylation. Therefore, they would be useful in the treatment of any pathological disorder associated with the abnormal phosphorylation of tau protein, in particular Alzheimer's disease, but also other tauopathies (e.g. frontotemporoparietal dementia, corticobasal degeneration, Pick's disease, progressive supranuclear palsy). Cdk5/p25 has been linked to apoptosis and neurodegeneration in more general terms. Its overexpression induces apoptosis in cultured neurons, in brain tissue apoptotic cells show strong immunoreactivity for cdk5. Neurotoxic agents, incl. Ap(1-42), neuronal injury, ischemia or growth factor withdrawal lead to activation and mislocalization of cdk5/p25, abnormal phosphorylation of cdk5 substrates, cytoskeletal disruption and cell death. Moreover, phosphorylation by cdk5/p25 transforms DARPP-32 into an inhibitor of protein kinase A, reducing signal transduction in the striatum with obvious implications for Parkinson's disease. A role for cdk5 in ALS has also been proposed based on its ability to phosphorylate neurofilaments. More recently, deregulation of cdk5 was detected in a mouse model of amyotrophic lateral sclerosis. Altogether, these experimental observations indicate that GSK3β inhibitors may find application in the treatment of the neuropathological consequences and the cognitive and attention deficits associated with Alzheimer's disease, as well as other acute and chronic neurodegenerative diseases. These include, in a non- limiting manner, Parkinson's disease, tauopathies (e.g. frontotemporoparietal dementia, corticobasal degeneration, Pick's disease, progressive supranuclear palsy) and other dementia including vascular dementia; acute stroke and others traumatic injuries; cerebrovascular accidents (e.g. age related macular degeneration); brain and spinal cord trauma; peripheral neuropathies; retinopathies and glaucoma. In addition GSK3β inhibition may find application in the treatment of other diseases such as: Non-insulin dependent diabetes (such as diabetes type II ) and obesity; manic depressive illness; schizophrenia; alopecia; cancers such as breast cancer, non- small cell lung carcinoma, thyroid cancer, T or B-cell leukemia and several virus- induced tumors. Since it appears that both, GSK3β and cdk5/p25 play a major role in the induction of apoptosis in neuronal cells, combined inhibition of these two enzymes may find application in the treatment of not only Alzheimer's disease and the other above- mentioned tauopathies, but also in a number of other neurodegenerative disorders, in particular Parkinson's disease and amyotrophic lateral sclerosis; other dementias including vascular dementia; acute stroke and other traumatic injuries; cerebrovascular accidents (e.g. age related macular degeneration); brain and spinal cord trauma; peripheral neuropathies; retinopathies and glaucoma. In addition mixed TPK1/TPK2 innibitors may find their applications in the treatment of other diseases such as : smoking cessation and other withdrawal syndromes, epilepsy. Disclosure of the Invention An object of the present invention is to provide compounds useful as an active ingredient of a medicament for preventive and/or therapeutic treatment of a disease caused by abnormal GSK3β or GSK3β and cdk5/p25 activity, more particularly of neurodegenerative diseases. More specifically, the object is to provide novel compounds useful as an active ingredient of a medicament that enables prevention and/or treatment of neurodegenerative diseases such as Alzheimer's disease. Thus, the inventors of the present invention have identified compounds possessing inhibitory activity against GSK3β or GSK3β and cdk5/p25. As a result, they found that compounds represented by the following formula (I) had the desired activity and were useful as an active ingredient of a medicament for preventive and/or therapeutic treatment of the aforementioned diseases. The present invention thus provides pyrimidone derivatives represented by formula (I) or salts thereof, solvates thereof or hydrates thereof: wherein: X represents two hydrogen a:oms, a sulphur atom, an oxygen atom or a C1-2 alkyl group and a hydrogen atom; Y represents a bond, an ethenylene group, an ethynylene group, an oxygen atom, a sulphur atom, a sulfonyl group, a sulfoxide group, a carbonyl group, a nitrogen atom being optionally substituted by a C1-6 alkyl group, a phenyl or a benzyl group; or a methylene group optionally substituted by one or two groups chosen from a C1-6 alkyl group, a benzyl group, a hydroxyl group, a C1-4 alkoxy group, a C3-6 cycloalkymethyloxy, a C1-2peihalogenated alkyl group, an amino group, an acetylamino group or a phenyl group; R1 represents a pyrimidine ring optionally substituted by a C3-6 cycloalkyl group a C1-4 alkyl group, a C1-4 alkoxy group, a benzyl group or a halogen atom; when Y represents a bond, a methylene group optionally substituted or a carbonyl group then R2 represents a C1-6 alkyl group optionally substituted by a C6,10 aryloxy or a C6,10 arylamino group ; a C3-6 cycloalkyl group, a C1-4alkylthio group, a C1-4 alkoxy group, a C1-5 perhalogenated alkyl group, a C1-3halogenated alkyl group, a phenylthio group, a benzyl group, a benzene ring, an indan ring, a 5,6,7,8-tetrahydronaphthalene ring, a naphthalene ring, a pyridine ring, a pyrrole ring, a thiophene ring, a furan rirg or an imidazole ring ; the benzyl group or the rings being optionally substituted by 1 to 4 substituents selected from a C1-6 alkyl group, a methylendioxy group, a halogen atom, a C1-2 perhalogenated alkyl group, a C1-3 halogenated alkyl group, a hydroxyl group, a C1-4 alkoxy group, a nitro, a cyano, an amino, a C1-5 monoalkylamino group, a C2-10 dialkylamino group, a C1-6 alkylcarbonylamino group, a C6,10 arylcarbonylamino group, a C1-4 alkylsulfonyl group, C1-4alkylsulfonyloxy group or a phenyl group; when Y represents an ethenylene group, an ethynylene group, an oxygen atom, a sulphur atom, a sulfonyl group, a sulfoxide group or a nitrogen atom being optionally substituted then R2 represents a C1-6alkyl group (optionally substituted by a C6,10 aryloxy or a C6,10 an/amino group), a C3-6 cycloalkyl group, a C1-2 perhalogenated alkyl group, a C1-3 halogenated alkyl group, a benzyl group, a benzene ring, an indan ring, a 5,6,7,8-tetrahydronaphthalene ring, a naphthalene ring, a pyridine ring, a pyrrole ring, a thiophene ring, a furan ring or an imidazole ring ; the benzyl group or the rings being optionally substituted by 1 to 4 substituents selected from a C1-6 alkyl group, a methylendioxy group, a halogen atom, a C1-2 perhalogenated alkyl group, a C1-3 halogenated alkyl group, a group, a C6,10 arylcarbonylamino group, a C1-4 alkylsulfonyl group, C1-4 alkylsulfonyloxy group or a phenyl group; R3 and R4 represents each independently a hydrogen atom, C1-6 alkyl group, a hydroxy group, a C1-4alkoxy group or a halogen atom; R5 represents a hydrogen atom, a C1-6 alkyl group or a halogen atom; When m equals 0, p equals 1, 2 or 3, When m equals 1, p equals 0, 1 or 2, When m equals 2, p equals 0 or 1; and n represents 0 to 3. According to another aspect of the present invention, there is provided a medicament comprising as an active ingredient a substance selected from the group consisting of the pyrimidone derivatives represented by formula (I) and the physiologically acceptable salts thereof, and the solvates thereof and the hydrates thereof. As preferred embodiments of the medicament, there are provided the aforementioned medicament which is used for preventive and/or therapeutic treatment of diseases caused by abnormal GSK3β or GSK3β and cdk5/p25 activity, and the aforementioned medicament which is used for preventive and/or therapeutic treatment of neurodegenerative diseases and in addition other diseases such as: Non-insulin dependent diabetes such as diabetes type II) and obesity; manic depressive illness; schizophrenia; alopecia; smoking cessation and other withdrawal syndromes, epilepsy; cancers such as breast cancer, non-small cell lung carcinoma, thyroid cancer, 1 or B-cell leukemia and several virus-induced tumors. As further preferred embodiments of the present invention, there are provided the aforementioned medicament wherein the diseases are neurodegenerative diseases and are selected from the group consisting of Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, tauopathies (e.g. frontotemporoparietal dementia, corticobasal degeneration, Pick's disease, progressive supranuclear palsy) and other dementia including vascular dementia; acute stroke and others traumatic injuries; cerebrovascular accidents (e.g. age related macular degeneration) brain and spinal cord trauma; peripheral neuropathies; retinopathies and glaucoma, and the aforementioned medicament in the form of pharmaceutical composition containing the above substance as an active ingredient together with one or more pharmaceutical additives. The present invention further provides an inhibitor of GSK3β or GSK3β and cdk5/p25 activity comprising as an active ingredient a substance selected from the group consisting of the pyrimidone derivatives of formula (I) and the salts thereof, and the solvates thereof and the hydrates thereof. According to further aspects of the present invention, there is provided a method for preventive and/or therapeutic treatment of neurodegenerative diseases caused by abnormal GSK3β or GSK3β and cdk5/p25 activity, which comprises the step of administering to a patient a preventively and/or therapeutically effective amount of a substance selected from the group consisting of the pyrimidone derivatives of formula (I) and the physiologically acceptable salts thereof, and the solvates thereof and the hydrates thereof; and a use of a substance selected from the group consisting of the pyrimidone derivatives of formula (I) and the physiologically acceptable salts thereof, and the solvates thereof and the hydrates thereof for the manufacture of the aforementioned medicament. As used herein, the C1-5 alkyl group represents a straight or branched alkyl group having 1 to 6 carbon atoms, for example, methyl group, ethyl group, n- propyl group, isopropyl group, n-butyl group, isobutyl group, sec-butyl group, tert- butyl group, n-pentyl group, isopentyl group, neopentyl group, 1,1-dimethylpropyl group, n-hexyl group, isohexy group, and the like; The ethenylene group represents the divalent group of formula: The ethynylene group represents the divalent group of formula: The C1-4 alkoxy group represents an alkyloxy group having 1 to 4 carbon atoms for example, methoxy group, ethoxy group, propoxy group, isopropoxy group, butoxy group, isobutoxy group, sec-butoxy group, tert-butoxy group, and the like; The halogen atom represents a fluorine, chlorine, bromine or iodine atom; The C1-2 perhalogenated alkyl group represents an alkyl group wherein all the hydrogen have been substitutec by a halogen atom, for example a CF3 or C2F5; The C1-3 halogenated akyl group represents an alkyl group wherein at least one hydrogen has not been substituted by a halogen atom; The C1-5 monoalkylamino group represents an amino group substituted by one C1-5 alkyl group, for example, methylamino group, ethylamino group, propylamino group, isopropylam no group, butylamino group, isobutylamino group, tert-butylamino group, pentylamino group and isopentylamino group; The C2-10 dialkylamino group represents an amino group substituted by two C1-5 alkyl groups, for example, dimethylamino group, ethylmethylamino group, diethylamino group, methyl propylamino group and diisopropylamino group; The C6-10arylamino represents a phenylamino group or naphthylamino group; a C6-10aryloxy represents a phenyioxy group or naphthyloxy group. The leaving group represents a group which could be easily cleaved and substituted, such a group may be for example a tosyloxy, a mesyloxy, a bromide and the like. The compounds represented by the aforementioned formula (I) may form a salt. Examples of the salt include, when an acidic group exists, salts of alkali metals and alkaline earth metals such as lithium, sodium, potassium, magnesium, and calcium; salts of ammonia and amines such as methylamine, dimethylamine, trimethylamine, dicyclohexylamine, tris(hydroxymethyl)aminomethane, N,N- bis(hydroxyethyl)piperazine, 2-amino-2-methyl-1-propanol, ethanolamine, N- methylglucamine, and L-glucamine; or salts with basic amino acids such as lysine, 5-hydroxy)ysine, and arginine. The base-addition salts of acidic compounds are prepared by standard procedures well known in the art. When a basic group exists, examples include salts with mineral acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid; salts with organic acids such as methanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid, acetic acid, propionic acid, tartaric acid, fumaric acid, maleic acid, malic acid, oxalic acid, succinic acid, citric acid, benzoic acid, mandelic acid, cinnamic acid, lactic acid, glycolic acid, glucuronic acid, ascorbic acid, nicotinic acid, and salicylic add; or salts with acidic amino acids such as aspartic acid, and glutamic acid. The acid-addition salts of the basic compounds are prepared by standard procedures well know in the art which include, but are not limited thereto, dissolving the free base in an aqueous alcohol solution containing the appropriate acid and isolating the salt by evaporating the solution, or by reacting the free base and an acid in an organic solvenl, in which case the salt separates directly, or is precipitated with a second organic solvent, or can be obtained by concentration of the solution. The acids which can be used to prepare the acid-addition salts include preferably those which produce, when combined with the free base, pharmaceutically-acceptable salts, that is, salts whose anions are relatively innocuous to the animal organism in pharmaceutical doses of the salts, so that the beneficial properties inherent in the free base are not compromised by side effects ascribable to the anions. Although medicinally acceptable salts of the basic compounds are preferred, all acid-addition salts are within the scope of the present invention. In addition to the pyrimidcne derivatives represented by the aforementioned formula (I) and salts thereof, their solvates and hydrates also fall within the scope of the present invention. The pyrimidone derivatives represented by the aforementioned formula (I) may have one or more asymmetric carbon atoms. As for the stereochemistry of such asymmetric carbon atoms, they may independently be in either (R) and (S) configuration, and the pyrimidone derivative may exist as stereoisomers such as optical isomers, or diastereoisomers. Any stereoisomers in pure form, any mixtures of stereoisomers, racemates and the like fall within the scope of the present invention. Examples of preferred compounds of the present invention are shown in table 1 hereinafter. However, the scope of the present invention is not limited by these compounds. Preferred compounds of the present invention represented by formula (I) include also: (1) Compounds wherein R1 represents a 4- or 5-pyrimidine ring and more preferably 4-pyrimidine ring, which may be substituted by a C1-2 alkyl group, a C1-2 alkoxy group or a halogen atom; and/or (2) X represents hydrogen atoms or a C1-2 alkyl group and a hydrogen atom; (3) Y represents a carbonyl group or a methylene group optionally substituted by one or two groups chosen from a C1-6 alkyl group, a benzyl group, a hydroxyl group, a C1-4 alkoxy group, a C3-6cycloalkylmethyloxy; and/or (4) When m equals 0, p equals 1 or 2; and/or (5) R2 represents a benzene ring, an indan ring, a 5,6,7,8-tetrahydronaphthalene ring a naphthalene ring or a cyclohexyl ring. More preferred compounds of the present invention represented by formula (I) include also: (1) Compounds wherein R1 represents an unsubstituted 4-pyrimidine ring and compounds wherein R1 represents an unsubstituted 4-pyrimidine ring and X, Y and R2 are as defined for the preferred compounds. Particularly preferred compounds of the present invention represented by formula (I) include compounds of table 1 : 1. 9-(3-Phenyl-propyl)-2-(pynmidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a] pyrimidin-4-one 2. 9-[ 2-(2-Chloro-4-fiuoro-phenyl)-ethyl]-)-(pyrimidin-4-yl)-6,7,8,9-tetrahydro- pyrimido[1,2-a] pyrimidin-4-one 3. 9-(2-Phenylsulfanyl-ethyl)-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2- a] pyrimidin-4-one 4. 9-(2-Oxo-2-phenyl-ethyl)-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1 ,2-a] pyrimidin-4-one 5. 9-(3-Hydroxy-3-phenyl-proyl)-2-(pyrimidin-4-yl)-6,7,8,9,-tetrahydro- pyrimido[1,2-a] pyrimidin-4- one 6. 9-(2-Hydroxy-2-phenyl-ethyl)-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro- pyrimido[1,2-a] pyrimidin-4-one 7. 9-(3-Oxo-3-phenyl-propyl)-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2- a] pyrimidin-4-one 8. 9-(2(R)-Hydroxy-2-phenyl-ethyl)-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro- pyrimido[1,2-a] pyrimidin-4-one 9. 9-(2(S)-Hydroxy-2-phenyl-ethyl)-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro- pyrimido[1,2-a] pyrimidin-4-one 10. 9-[2-(3-Chloro-phenyl)-2-oxo-ethyl]-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro- pyrimido[1,2-a] pyrimidin-4-one 11. 9-[2-(3-Fluoro-phenyl)-2-oxo-ethyl]-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro- pyrimido[1,2-a] pyrimidin-4-one 12. 9-[2-(3-Fluoro-phenyl)-2-hycroxy-ethyl]-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro- pyrimido[1,2-a] pyrimidin-4-one 13. 9-[2-(3-Chloro-phenyl)-2-hydroxy-ethyl]2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro- pyrimido[1,2-a] pyrimidin-4-one 14. 9-(1 -Methyl-2-oxo-2-phenyl-ethyl)2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro- pyrimido[1,2-a] pyrimidin-4-one 15. 9-(2-Hydroxy-1 -methyl-2-phenyl-ethyl )2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro- pyrimido[1,2-a] pyrimidin-4-one 16. 9-[2-(3-Chloro-phenyl)-2(R)-hydroxy-ethyl]2-(pyrimidin-4-yl)-6,7,8,9- tetrahydro-pyrimido[1,2-a] pyrimidin-4-one 17. 7,7-Difluoro-9-(2-oxo-2-phenyl-ethyl)-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro- pyrimido[1,2-a] pyrimidin-4-one 18. 7,7-Dimethyl-9-(2-oxo-2-phenyl-ethyl)-2-pyrimidin-4-yl)-6,7,8,9-tetrahydro- pyrimido[1,2-a] pyrimidin-4-one 19. 9-[2(S)-Hydroxy-2-pheny-ethyl)-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9- tetrahydro-pyrimido[1,2-a| pyrimidin-4-one 20. 9-[2-(3-Chloro-phenyl)-2-oxo-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9- tetrahydro-pyrimido[1,2-a] pyrimidin-4-one 21. 9-[2-(3-Chloro-phenyl)-2-hydroxy-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)- 6,7,8,9-tetrahydro-pyrimido[1,2-a] pyrimidin-4-one 22. 9-[2-(3-Fluoro-phenyl)-2-oxo-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9- tetrahydro-pyrimido[1,2-a] pyrimidin-4-one 23. 3-Methyl-9-(2-oxo-2-phenvl-ethyl)-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro- pyrimido[1,2-a] pyrimidin-4-one 24. 3-Chloro-9-(2(S)-hydroxy-2-phenyl-ethyl)-2-(pyrimidin-4-yl)-6,7,8,9- tetrahydropyrimido[1,2-a] pyrimidin-4-one 25. 9-[2-(2(S)-Hydroxy-2-phenyl-ethyl)-3-methyl-2-(pyrimidin-4-yl)-6,7,8,9- tetrahydro-pyrimido[1,2-a] pyrimidin-4-one 26. 9-[2-(3-Fluoro-phenyl)-2-hydroxy-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)- 6,7,8,9-4etrahydro-pyrimido[1,2-a] pyrimidin-4-one 27. 9-[2-Oxo-2-(5,5,8,8-tetramethyl-5,6,7,8,tetrahydro-naphthalen-2-yl-ethyl]-2- (pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one 28. 9-[2-(4-Chloro-phenyl)-2-oxo-ethyl]-2-{pyrimidin-4-yl)-6,7,8,9-tetrahydro- pyrimido[1,2-a] pyrimidin-4-one 29. 9-[2-(4-Fluoro-phenyl)-2-oxo-ethyl]-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro- pyrimido[1,2-a]pyrimidin-4-one 30. 9-(2-Naphthalen-2-yl-2-oxo-ethy)-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro- pyrimido[1,2-a] pyrimidin-4-one 31. 9-(2-Oxo-2-p-tolyl-ethyl)-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a] pyrimidin-4-one 32. 9-(2-Biphenyl-4-yl-2-oxo-ethyl)-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro- pyrimido[1,2-a] pyrimidin-4-one 33. 9-[2-(3-Methoxy-phenyl)-2-oxo-ethyl]-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro- pyrimido[1,2-a] pyrimidin-4-one 34. 9-[2-(7-Methoxy-benzo-[1,3]dioxol-5-yl)-1-methyl-2-oxo-ethyl]-2-(pyrimidin-4- yl)-6,7,8,9-tetrahydro-pyrimido{1,2-a] pyrimidin-4-one 35. 9-[2-(7-Methoxy-benzo-[1,3]dioxol-5-yl)-1 -methyl-2-oxo-ethyl]-7,7-dimethyl-2- (pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a)pyrimidin-4-one 36. 9-[2-(4-Chloro-phenyl)-2-oxo-ethy)]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9- tetrahydro-pyrimido[1 ,2-a] pyrimidin-4-one 37. 7,7-Dimethyl-9-[2-oxo-2-(5,5,8,8-tetramethyl-5,6,7,8,-tetrahydro-naphthalen-2- yl)-ethyl)-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrim|din-4-one 38. 9-[2-Fluoro-phenyl)-2-oxo-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9- tetrahydro-pyrimido[1,2-a] pyrimidin-4-one 39. 9-[2-Biphenyl-4-yl-2-oxo-ethyl)-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9- tetrahydro-pyrimido[1,2-a] pyrimidin-4-one 40. 7,7-Dimethyl-9-(2-oxo-2-p-to|yl-ethyl)-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro- pyrimido[1,2-a] pyrimidin-4-one 41. 9-[2-(3-Methoxy-phenyl)-2-oxo-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9- tetrahydro-pyrimido[1,2-a] pyrimidin-4-one 42. 7,7-Dimethyl-9-(2-naphthalen-2-yl-2-oxo-ethyl]-2-(pyrimidin-4-yI)-6,7,8,9- tetrahydro-pyrimido[1,2-a] pyrimidin-4-one 43. 9-[2-Hydroxy-2-(7-methoxy-benzo-[1,3]dioxol-5-yl)-1 -methyl-ethyl]-7,7- dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one 44. 9-[2-Hydroxy-2-(7-methoxy-benzo-[1,3]dioxol-5-yl)-1-methyl-ethyl]-2- (pyrimidin-4-yl)-6,7,8,9-tetrahydropyrimido[1,2-a]pyrimidin-4-one 45. 9-(2-Hydroxy-2-phenyl-propyl)-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9- tetrahydro-pyrimido[1,2-a] pyrimidin-4-one 46. 9-[2-(2-Methoxy- phenyl)-2-oxo-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9- tetrahydro-pyrimido[1,2-a] pyrimidin-4 one 47 9-[2-(2-Methoxy- phenyl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9- tetrahydro-pyrimido[1,2-a] pyimidin-4-one 48. 9-[2-Hydroxy-2-(2-methoxy-phenyl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)- 6,7,8,9-tetrahydro-pyrimidol[1,2-a] pyrimidin-4-one 49. 9-[2-(2,5-Dimethoxy-phenyl)-2-oxo-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)- 6,7,8,9-tetrahydro-pyrimido[1,2-a] pyrimidin-4-one 50. 9-[2-(2,5-Dimethoxy-phenyl)-2-hydroxy-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)- 6,7,8,9-tetrahydro-pyrimido[1,2-al pyrimidin-4-one 51. 9-(2(S)-Cyclopropylmethoxy-2-phenyl-ethyl)-7,7-dimethyl-2-(pyrimidin-4-yl)- 6,7,8,9-tetrahydro-pyrimido[1,2-a] pyrimidin-4-one 52. 9-{2-(2,5-Dimethoxy-phenyl)-2-ethoxy-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)- 6,7,8,9-tetrahydro-pyrimido[1,2-a] pyrimidin-4-one 53. 9-[2-(3-Phenyl-2-hydroxy-propyl]-7,7-dimethyl-2-pyrimidin-4-yl)-6,7,8,9- tetrahydro-pyrimido[1,2-a] pyrimidin-4-one 54. 9-(2(S)-Ethoxy-2-phenyl-ethyl)-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9- tetrahydro-pyrimido[1,2-a] pyrimidin-4-one 55. 9-[2-Ethoxy-2-(2-methoxy-f)henyl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)- 6,7,8,9-tetrahydro-pyrimidc[1,2-a] pyrimidin-4-one 56. 9-[2-Hydroxy-2-(2-methoxy-phenyl)-propyl]-7,7-dimethyl-2-(pyrimidin-4-yl)- 6,7,8,9-tetrahydro-pyrimidc[1,2-a] pyrimJdin-4-one 57. 9-[2-{2-Chloro-4-fluoro-phenyl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9- tetrahydro-pyrimido[1,2-a] pyrimidin -4-one 58. 9-(2-(Benzo-[1,3]dioxol-5-yl)-2-hydroxy-propyl)-7,7-dimethyl-2-(pyrimidin-4- yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a] pyrimidin-4-one 59. 9-[2-Hydroxy-2-(3-methoxy-phenyl)-propyl]-7,7-dimethyl-2-(pyrimidin-4-yl)- 6,7,8,9-tetrahydro-pyrimidc[1,2-a] pyrimidin-4-one 60. 9-[2-(4-Fluoro-phenyl)-2-hydroxy-propyl]-7,7-dimethyl-2-(pyrimidin-4-y!)- 6,7,8,9-tetrahydro-pyrimidc[1,2-a] pyrimidin-4-one 61. 9-[2-(4-Fluoro-phenyl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9- tetrahydro-pyrimido[1,2-a] pyrimidin-4-one 62. 9-[2-(3-Fluoro-phenyl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9- tetrahydro-pyrimido[1,2-a] pyrimidin-4-one 63. 9-[2-(2-Fluoro-phenyl)-ethyl]-7,7-dimethyl-2-pyrimidin-4-yl)-6,7,8,9- tetrahydro-pyrimido[1,2-a] pyrimidin-4-one 64. 4-[2-(3,3-Dimethyl-6-oxo-8-pyrimidin-4-yl-3,4,dihydro-2H,6H-pyrimido[1,2-a] pyrimidin-1-yl)ethyl]benzonitrile 65. 9-[2-(4-Methoxy-phenyl)-thyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9- tetrahydro-pyrimido[1,2-a]-pyrimidin-4-one 66. 9-[2-(3,4-Dimethoxy-phenyl)-ethyl]-7,7-dimethyl-2-pyrimidin-4-yl)-6,7,8,9- tetrahydro-pyrimido[1,2-a] pyrimidin-4-one 67. 7,7-Dimethyl-2-(pyrimidin-4-yl)-9-(2-o-tolyl-ethyl)-6,7,8,9-tetrahydro- pyrimido[1,2-a] pyrimidin-4-one 68. 7,7-Dimethyl-2-(pyrimidin-4-yl)-9-(2-p-tolyl-ethyl)-6,7,8,9-tetrahydro- pyrimido[1,2-a] pyrimidin-4-one 69. 9-[2-{4-Fluoro-2-methoxy-phenyl)-2-hydroxy-ethyl]-7,7-dimethyl-2-(pyrimidin- 4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a] pyrimidin-4-one 70. 9-[2-{4-Fluoro-2-methoxy-phenyl)-2-oxo-ethyl]-7,7-dimethyl-2-(pyrimidin-4- yl)-6,7,8,9-tetrahydro-pyrimido[1 ,2-a] pyrimidin-4-one 71. 9-[2-(4-Chloro-phenyl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9- tetrahydro-pyrimido[1,2-a] pyrimidin-4-one 72. 9-[2-(2-Chloro-phenyl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9- tetrahydro-pyrimido[1,2-a] pyrimidin -4-one 73. 9-[2-(2,4-Dichloro-phenyl)-ethyl]-7,7-dimethyl-2-{pyrimidin-4-yl)-6,7,8,9- tetrahydro-pyrimido[1,2-a] pyrimidin-4-one 74. 9-[2-(4-Bromo-phenyl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9- tetrahydro-pyrimido[1,2-a] pyrimidin-4-one 75. 9-[2-(4-Ethoxy-phenyl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9- tetrahydro-pyrimido[1,2-a] pyrimidin-4-one 76. 9-[2-Cyclohexyl-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro- pyrimido[1,2-a] pyrimidin-4-one 77. 9-[2-(4-Nitro-phenyl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro- pyrimido[1,2-a] pyrimidin-4-one 78. 9-[2-{2-Trifluoromethyl-phenyl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9- tetrahydro-pyrimido[1,2-a] pyrimidin-4-one 79. 9-[2-(3-Chloro-phenyl)-ethyl|-7,7'-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9- tetrahydro-pyrimido[1,2-a] pyrimidin-4-one 80. 9-[2-(2,5-Dimethoxy-phenyl)-ethyl]-7,7-dimethyl--2-(pyrimidin-4-yl)-6,7,8,9- tetrahydro-pyrimido[1,2-a| pyrimidin-4-one 81. 7,7-Dimethyl-2-(pyrimidin-4-yl)-9-[2-(3,4,5-trimethoxy-phenyl)-ethyl]-6,7,8,9- tetrahydro-pyrimido[1,2-a]pyrimidin-4-one 82. 9-[2-(3-Methoxy-phenyl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9- tetrahydro-pyrimido[1,2-a] pyrimidin-4-one 83. 9-[2-Methoxy-2-(2-methoxy-phenyl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)- 6,7,8,9-tetrahydro-pyrimido[1,2-a] pyrimidin-4-one 84. 9-(2(R)-Methoxy-2-phenyl-ethyl)-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9- tetrahydro-pyrimido[1,2-a] pyrimidin-4-one 85. 9-[2-(2,5-Dimethoxy-phenyl)-2-methoxy-ethyl]-7,7-dimethyl-2-(pyrimidin-4- yl)-6,7,8,9-tetrahydro-pyrlmido[1,2-a] pyrimidin-4-one 86. 9-[2-(4-Fluoro-2-methoxy-phenyl)-2-methoxy-ethyl]-7,7-dimethyl-2- (pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a] pyrimidin-4-one 87. 7,7-Dimethyl-9-(2-phenyl-ethyl)-(pyrimidin-4-yl)-6,7,8,9-tetrahydro- pyrimido[1,2-a]pyrimidjn-4-one 88. 9-[2-(3-Chloro-phenyl)-2-methoxy-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)- 6,7,8,9-tetrahydro-pyrimido[1,2-a] pyrimidin-4-one 89. 9-[2-(3-Fluoro-phenyl)-2-methoxy-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)- 6,7,8,9-tetrahydro-pyrimido[1,2-a] pyrimidin-4-one 90. 9-[2-(4-Fluoro-2-methoxy-phenyl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)- 6,7,8,9-tetrahydro-pyrimido[1,2-a] pyrimidin-4-one 91. 9-[2-{4-Fluoro-2-methoxy-phenyl)-ethyl]-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro- pyrimido[1,2-a] pyrimidir-4-one 92. 9-{2-(2,6-Dichloro-phenyl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9- tetrahydro-pyrimido[1,2-a] pyrimidin-4-one 93. 7,7-Dimethyl-9-(2-naphthalen-1-yl-ethyl)-2-(pyrimidin-4-yl)-6,7,8,9- tetrahydro-pyrimido[1,2-a]pyrimidin-4-one 94. 9-[2-{2,6-Dimethoxy-phenyl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9- tetrahydro-pyrimido[1,2-a] pyrimidin-4-one 95. 7,7-Dimethyl-2-(pyrimidin-4-yl)-9-[2-{2-trifluoromethoxy-phenyl)-ethyl]- 6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one 96. 9-[2-{2,4-Dichloro-5-fluorophenyl)-ethyl]-7,7-climethyl-2-(pyrimidin-4-yl)- 6,7,8,9-tetrahydro-pyrimido[1,2-a] pyrimidin-4-one 97. 7,7-Dimethyl-2-(pyrimidin-4-yl)-9-[2-(2,4,5-trifluoro-phenyl)-ethyl]-6,7,8,9- tetrahydro-pyrimido[1,2-a]pyrimidin-4-one 98. 9-[2-(2,4-Difluoro-phenyl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9- tetrahydro-pyrimido[1,2-a] pyrimidin-4-one 99. 9-lndan-2-ylmethyl-7,7-diinethyl-2-pyrimidin-4-yl)-6,7,8,9-tetrahydro- pyrimido[1,2-a] pyrimidin-4-one 100. 3-Chloro-9-indan-2-ylmethyl-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9- tetrahydro- pyrimido[1,2-a] pyrimidin-4-one 101. 9-[2-(2-Ethoxy-4-fluoro-phenyl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9- tetrahydro-pyrimido[1,2-a] pyrimidin-4-one 102. 9-[2-(4-Fluoro-2-isopropoxy-phenyl)-ethyl]-7,7-dimethyl-2-{pyrimidin-4-yl)- 6,7,8,9-tetrahydro-pyrimido[1,2-a] pyrimidin-4-one 103. 9-{2-(4-Fluoro-2-hydroxy-phenyl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)- 6,7,8,9-tetrahydropyrimido[1,2-a] pyrimidin-4-one 104. 9-[2-(5-Chloro-2,3-dihydro-benzofuran-7-yl)-ethyl]-7,7-dimethyl-2-(pyrimidin- 4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a] pyrimidin-4-one and compounds of table 2 : 1. 1 -(3-Phenyl-propyl)-7-pyrimidin-4-yl-2,3-dihydro-1H-imidazo[1,2-a]pyrimidin- 5-one 2. 1 -[3-{2-Fluoro-phenyl)-pi opyl]-2,2-dimethyl-7-pyrimidin-4-yl-2,3-dihydro-1 H- imidazo[1,2-a]pyrimidin- 3-one 3. 1 -(2-Oxo-2-phenyl-ethyl -7-pyrimidin-4-yl-2,3-dihydro-1H-imidazo[1,2- a]pyrimidin-5-one 4. 1 -(2-Hydroxy-2-phenyl-e thyl)-7-pyrimidin-4-yl-2,3-dihydro-1 H-imidazo[1,2- a]pyrimidin-5-one 5. 1-[2-{3-Methoxy-phenyl]-2-oxo-ethyl]-2,2-dimethyl-7-pyrimidin-4-yl-2,3- dihydro-1H-imidazo[1,2a]pyrimidin-5-one 6. 1-[2-(7-Methoxy-benzo-1,3]dioxol-5-y|)-1-methyl-2-oxo-ethyl]-2,2-dimethyl-7- pyrimidin-4-yl-2,3-dihydro-1H-imidazo[1,2-a]pyrimidin-5-one 7. 1 -(2-Biphenyl-4-yl-2-oxo-ethyl)-2,2-dimethyl-7-pyrimidin-4-yl-2,3-dihydro-1H- imidazo[1,2-a]pyrimidin-5-one 8. 1-[2-(4-Fluoro-phenyl)-2-oxo-ethyl]-2,2-dimethyl-7-pyrimidin-4-yl-2,3-dihydro- 1 H-imidazo[1,2-a]pyrimidin-5-one 9. 2,2-Dimethyl-1 -(2-oxo-2-p-tolyl-ethyl)-7-pyrimidin-4-yl-2,3-dihydro-1H- imidazo[1,2-a]pyrimidin-5-one 10. 2,2-Dimethyl-1 -(2-naphthalen-2-yl-2-oxo-ethyl)-7-pyrimidin-4-yl-2,3-dihydro- 1H-imidazo[1,2-a]pyrimidin-5-one 11. 1 -[2-(4-Chloro-phenyl)-2-oxo-ethyl]-2,2-dimethyl-7-pyrimidin-4-yl-2,3-dihydro- 1 H-imidazo[1,2-a]pyrimidin-5-one 12. 2,2-Dimethyl-1 -[2-oxo-2-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-naphthalen- 2-yl)ethyl}-7-pyrimidin-4-yl-2,3-dihydro-1H-imidazo[1,2-a]pyrimidin-5-one; and compounds of table 3 : 1. 9-[2-(4-Fluoro-2-methoxy-pheny!)-ethyl]-8-methyl-2-(pyrimidin-4-yl)-6,7,8,9- tetrahydro-pyrimido[1,2-a]pyrimidin-4-one 2. 9-{2-(4-Fluoro-2-methoxy-phenyl)-ethyl]-8,8-dimethyl-2-(pyrimidin-4-yl)- 67,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one 3. 9-[2-{4-Fluoro-phenyl)-ethyl]-8-methyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro- pyrimido[1,2-a]pyrimidin-4 -one 4. 8-Methyl-9-(2-oxo-2-phenyl-ethyl)-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro- pyrimido[1,2-a]pyrimidin-4-one 5. 9-[2-(2,5-Dimethoxy-phenyl)-ethyl]-8-methyl-2-(pyrimidin-4-yl)-6,7,8,9- tetrahydro-pyrimido[1,2-a]pyrimidin-4-one. 6. 9-[2-(2-Methoxy-phenyl)-€thyl]-8-methyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro- pyrimido[1,2-a]pyrimidin-4-one; 7. 9-[2(S)-Hydroxy-2-phenylethyl]-8-methyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro- pyrimido[1,2-a]pyrimidin-4-one; 8. 9-[2(R)-Methoxy-2-pheny -ethyl]-8-methyl-2-(pyrimidin-4-yl)-6,7,8,9- tetrahydro-pyrimido[1,2-a|pyrimidin-4-one; 9. 9-[2-(2,5-Dimethoxy-phenyl)-ethyl]-8,8-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9- tetrahydro-pyrimido[1,2-a]pyrimidin-4-one; 10. 8-Methyl-9-[naphthalen-l-ylmethyl]-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro- pyrimido[1,2-a]pyrimidin-4-one; 11. 9-[2(S)-Hydroxy-2-phenyl-ethyl]-8,8-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9- tetrahydro-pyrimido[1,2-a]pyrimidin-4-one; 12. 8-Methyl-9-[naphthalene-2-ylmethyl]-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro- pyrimido[1,2-a]pyrimidin-4-one; 13. 9-[2(R)-Hydroxy-2-phenyl-ethyl]-8,8-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9- tetrahydro-pyrimido[1,2-a]pyrimidin-4-one; 14. 9-[2-Fluoro-phenyl)-ethyl]-8,8-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9- tetrahydro-pyrimido[1,2-a]pyrimidin-4-one; 15. 8,8-Dimethyl-9-[2-oxo-2-phenyl-ethyl]-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro- pyrimido[1,2-a]pyrimidin-4-one; 16. 9-[2-(3-Methoxy-phenyl)-2-oxo-ethyl]-8-methyl-2-(pyrimidin-4-yl)-6,7,8,9- tetrahydro-pyrimido[1,2-a]p yrimidin-4-one; 17. 9-[2-(3-Chloro-phenyl)-2-oxo-ethyl]-8-methyl-2-(pyrimidin-4-yl)-6,7,8,9- tetrahydro-pyrimido[1,2-a]pyrimidin-4-one; 18. 8,8-Dimethyl-9-[naphthalen-1-ylmethyl]-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro- pyrimido[1,2-a]pyrimidin-4-one; 19. 8-Ethyl-9-[2-oxo-2-phenyl-ethyl]-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro- pyrimido[1,2-a]pyrimidin-4 one; 20. 9-[2-(4-Fluoro-phenyl)-2(S)-hydroxy-ethyl]-8,8-dimethyl-2-(pyrimidin-4-yl)- 6,7,8,9-tetrahydro-pyrimidio[1,2-a]pyrimidin-4-one; 21. 8-Ethyl-9-[2(S)-hydroxy-2-phenyl-ethyl]-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro- pyrimido[1,2-a]pyrimidin-4 -one; 22. 9-[2(S)-Hydroxy-2-(4-methoxy-phenyl)-ethyl]-8,8-dimethyl-2-(pyrimidin-4-yl)- 6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one; 23. 9[2-(3-Fluoro-phenyl)-2-hydroxy-ethyl]-8-methyl-2-(pyrimidin-4-yl)-6,7,8,9- tetrahydro-pyrimido[1,2-a]pyrimidin-4-one; 24. 9-[2-{2,4-Dimethoxy-phen/l)-2(S)-hydroxy-ethyl]-8,8-dimethyl-2-(pyrimidin-4- yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one; 25. 9-[2-(3-Bromo-phenyl)-2(S)-hydroxy-ethyI]-8,8-dimethyl-2-(pyrimidin-4-yI)- 6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one; 26. 9-[2-Benzo[1,3]dioxol-5-yl-2-oxo-ethyl]-8-methyl-2-(pyrimidin-4-yl)-6,7,8,9- tetrahydro-pyrimido[1,2-a]pyrimidin-4-one 27. 9-[2-(2,3-Dihydro-benzo[1,4]dioxin-6-yl)-2-oxo-ethyl]-8-methyl-2-(pyrimidin-4- yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one 28. 9-{2-(3,5-Dichloro-phenyl)-2-hydroxy-ethyl]-8-methyl-2-(pyrimidin-4-yl)-6,7,8,9- tetrahydro-pyrimido[1,2-a]pyrimidin-4-one 29. 9-[2-(3-Fluoro-phenyl)-2-(Si-hydroxy-ethyl]-8,8-dimethyl-2-pyrimidin-4-yl)- 6,7,8,9-etrahydro-pyrimido[1,2-a]pyrimidin-4-one 30. 9-(2(S)-Hydroxy-2-naphthalen-2-yl-ethyl]-8,8-dimethyl-2-(pyrimidin-4-yl)- 6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one 31. 9-(2-Biphenyl-4-yl-2(S)-hydroxy-ethyl)-8,8-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9- tetrahydro-pyrimido[1,2-a]byrimidin-4-one 32. 9-[2-(2,5-Dimethoxy-phenyl)-2(S)-hydroxy-ethyl]-8,8-dimethyl-2-(pyrimidin-4- yl)-6,7,8,9-tetrahydro-pyrirnido[1,2-a]pyrimidin-4-one 33. 9(2(S)-Hydroxy-2-p-tolyl-ethyl)-8,8-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9- tetrahydro-pyrimido[1,2-a]pyrimidin-4-one 34. 9-[2(S)-Hydroxy-2-(3-methoxy-phenyl)-ethyl]-8,8-dimethyl-2-(pyrimidin-4-yl)- 6,7,8,9-tetrahydro-pyrimidoI[1,2-a]pyrimidin-4-one 35. 9-[2-{4-Chloro-phenyl)-2(S)-hydroxy-ethyl]-8,8-dimethyl-2-(pyrimidin-4-yl)- 6,7,8,9-etrahydro-pyrimico[1,2-a]pyrimidin-4-one 36. 9-[2-(2,4-Dichloro-phenyr-2(S)-hydroxy-ethyl]-8,8-dimethyl-2-(pyrimidin-4-y!)- 6,7,8,9-tetrahydro-pyrimiclo[1,2-a]pyrimidin-4-one 37. 3-Bromo-8-methyl-9-(2-oxo-2-phenyl-ethyl)-2-pyrimidin-4-yl-6,7,8,9- tetrahydro-pyrimido[1,2-a|pyrimidin-4-one; 38. 8,8-Dimethyl-9-(2-oxo-2-p-tolyl-ethyl)-2-pyrimidin-4-yl-6,7,8,9-tetrahydro- pyrimido[1,2-a]pyrimidin-4-one; 39. 9-[2-(3,4-Dichloro-phenyl)-2(S)-hydroxy-ethyl]-8,8-dimethyl-2-(pyrimidin-4-yl)- 6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one 40. 9-[2-(3-Methoxy-phenyl)-2-oxo-ethyl]-8,8-dimethyl-2-pyrimidin-4-yl-6,7,8,9- tetrahydro-pyrimido[1,2-a]pyrimidin-4-one; 41. 4-[2-(2,2-Dimethyl-6-oxo-8-pyrimidin-4-yl-3,4-dihydro-2H,6H-pyrimido[1,2- a]pyrimidin-1-yl)-1 (S)-hydroxy-ethy]- benzonitrile; 42. 9-[2-(4-Fluoro-phenyl)-2-oxo-ethyl]-8,8-dimethyl-2-pyrimidin-4-yl-6,7,8,9- tetrahydro-pyrimido[1,2-a]pyrimidin-4-one; 43. 9-[2-(4-Chloro-phenyl)-2-oxo-ethyl]-8,8-dimethyl-2-pyrimidin-4-yl-6,7,8,9- tetrahydro-pyrimido[1,2-a]pyrimidin-4-one; 44. 9-[2-(4-Methoxy-phenyl)-2-oxo-ethyl]-8,8-dimethyl-2-pyrimidin-4-yl-6,7,8,9- tetrahydro-pyrimido[1,2-a]pyrimidin-4-one; 45. 8,8-Dimethyl-9-(2-naphtaren-2-yl-2-oxo-ethyl)-2-pyrimidin-4-yl-6,7,8,9- tetrahydro-pyrimido[1,2-a]pyrimidin-4-one; 46. 9-[2-(3,4-Dichloro-phenyl)-2-oxo-ethyl]-8,8-dimethyl-2-pyrimidin-4-yl-6,7,8,9- tetrahydro-pyrimido[1,2-a]pyrimidin-4-one; 47. 9-[2-(2,5-Dimethoxy-phenyl)-2-oxo-ethyl]-8,8-dimethyl-2-pyrimidin-4-yl- 6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one; 48. 9-(2-Biphenyl-4-yl-2-oxo-elhyl)-8,8-dimethyl-2-pyrimidin-4-yl-6,7,8,9- tetrahydro-pyrimido[1,2-a]pyrimidin -4-one; 49. 9-[2-(3-Bromo-phenyl)-2-oxo-ethyl]-8,8-dimethyl-2-pyrimidin-4-yl-6,7,8,9- tetrahydro-pyrimido[1,2-a]pyrimidin-4-one; 50. 9-[2-(3-Fluoro-phenyl)-2-oxo-ethyl]-8,8-dimethyl-2-pyrimidin-4-yl-6,7,8,9- tetrahydro-pyrimido[1,2-a)pyrimidin-4-one; 51. 8-Ethyl-9-(2-hydroxy-2-p-tolyl-ethyl)-2-pyrimidin-4-yl-6,7,8,9-tetrahydro- pyrimido[1,2-a]pyrimidin-4-one; 52. 9-[2-(4-Chloro-phenyl)-2-oxo-ethyl]-8,8-dimethyl-2-pyrimidin-4-yl-6,7,8,9- tetrahydro-pyrimido[1,2-a |pyrimidin-4-one; 53. 9-[2-(4-Chloro-phenyl)-2-hydroxy-ethyl] 8-ethyl -2-pyrimidin-4-yl-6,7,8,9- tetrahydro-pyrimido[1,2-a|pyrimidin-4-one. As a further object, the present invention concerns also methods for preparing the compounds represented by the aforementioned formula (I). These compounds can be prepared, for example, according to methods explained below. Preparation method Pyrimidone compounds represented by the aforementioned formula (I) may be prepared according to scheme 1. The pyrimidin-5(1H)-one derivative represented by the above formula (III), wherein R1 is as defined for compound of formula (I), is allowed to react with a base such as sodium hydride, sodium carbonate or potassium carbonate in a solvent such as N,N-dimethylformamide, N-methylpyrrolidine, N,N- dimethylacetamide or chloroform at a suitable temperature ranging from 0 to 130°C under ordinary air, then with a compound of formula (II), wherein R2, X, Y and n are as defined for compound of formula (I) and L represents a leaving group preferably bromide or mesyloxy group, is added to obtain the compound of the aforementioned formula (I). Compound of formula (II) are commercially available or may be synthesised according to wel-known methods of one skilled in the art. The compound of formula (III) may be prepared according to the method defined in scheme 2. (In the above scheme the definition of R1, R3, R4, R5, p and m are the same as already described.) According to this method, the 3-ketoester of formula (IV) is allowed to react with a compound of formula (V). The reaction may be carried out in the presence of potassium carbonate, in an alcoholic solvent such as methanol, ethanol and the like or without, at a suitable temperature ranging from 25°-140°C under ordinary air. Alternatively, compounds, of formula (III) wherein R5 represents a hydrogen atom may be halogenated in order to give compounds of formula (III) wherein R5 is a halogen atom such as a bromine atom or a chlorine atom. The reaction may be carried out in an acidic medium such as acetic acid or propionic acid, in presence of bromosuccinimide or chlorosuccinimide, or bromine. In addition, compounds of formula (III) wherein R5 represents a fluorine atom may be obtained by analcgy to the method described in Tetrahedron Letters, Vol.30,N°45,pp6113-6116, 1989. Compounds of formula (V) or (IV) are commercially available or may be synthesised according to well-Known methods of one skilled in the art. For example compounds of formula (IV), wherein R1 represent a pyrimidine ring optionally substituted by a C1-4 alkyl group, C1-4 alkoxy group or a halogen atom, can be prepared by reacting a pyrimidine-4-carboxylic acid optionally substituted by a C1-4 alkyl group, C1-4 alkoxy group or a halogen, with a malonic acid monoester. The reaction can be carried out using methods well known to one skilled in the art, such as for example in presence of a coupling agent such as 1,1'-carbonylbis-1H-imidazole in a solvent such as tetrahydrofuran at a temperature ranging from 20 to 70°C. Compounds of formula (I) may also be obtained starting from another compound of formula (I) using well-known methods of one skilled in the art. In the above reactions protection or deprotection of a functional group may sometimes be necessary. A suitable protecting group Pg can be chosen depending on the type of the functional group, and a method described in the literature may be applied. Exanples of protecting groups, of protection and deprotection methods are given for example in Protective groups in Organic Synthesis Greene et al., 2nd Ed. (John Wiley & Sons, Inc., New York). The compounds of the present invention have inhibitory activity against GSK3β or GSK3β and cdk5/p25. Accordingly, the compounds of the present invention are useful as an active ingredient for the preparation of a medicament, which enables preventive and/or therapeutic treatment of a disease caused by abnormal GSK3β or GSK3β and cdk5/p25 activity and more particularly of neurodegenerative diseases such as Alzheimer's disease. In addition, the compounds of the present invention are also useful as an active ingredient for the preparation of a medicament for preventive and/or therapeutic treatment of neurodegenerative diseases such as Parkinson's disease, amyotrophic lateral sclerosis, tauopathies (e.g. frontotemporoparietal dementia, corticobasal degeneration, Pick's disease, progressive supranuclear palsy) and other dementia including vascular dementia; acute stroke and others traumatic injuries; cerebrovascular accidents (e.g. age related macular degeneration); brain and spinal cord trauma; peripheral neuropathies; retinopathies and glaucoma; and other diseases such as non-insulin dependent diabetes (such as diabetes type II) and obesity; manic depressive illness; schizophrenia; alopecia; smoking cessation and other withdrawal syndromes, epilepsy; cancers such as breast cancer, non- small cell lung carcinoma, thyroid cancer, T or B-cell leukemia and several virus- induced tumors. The present invention further relates to a method for treating neurodegenerative diseases caused by abnormal activity of GSK3β or GSK3β and cdk5/p25 and of the aforementioned diseases which comprises administering to a mammalian organism in need thereof an effective amount of a compound of the formula (I). As the active ingredient of the medicament of the present invention, a substance may be used which is selected from the group consisting of the compound represented by the aforementioned formula (I) and pharmacologically acceptable salts thereof, and solvates thereof and hydrates thereof. The substance, per se, may be administered as the medicament of the present invention, however, it is desirable to administer the medicament in a form of a pharmaceutical composition which comprises the aforementioned substance as. an active ingredient and one or more pharmaceutical additives. As the active ingredient of the medicament of the present invention, two or more of the aforementioned substances nray be used in combination. The above pharmaceutical composition may be supplemented with an active ingredient of another medicament for the treatment of the above mentioned diseases. The type of pharmaceutical composition is not particularly limited, and the composition may be provided as any formulation for oral or parenteral administration. For example, the pharmaceutical composition may be formulated, for example, in the form of pharmaceutical compositions for oral administration such as granules, fine granules, powders, hard capsules, soft capsules, syrups, emulsions, suspensions, solutions and the like, or in the form of pharmaceutical compositions for parenteral administrations such as injections for intravenous, intramuscular, or subcutaneous administration, drip infusions, transdermal preparations, transmucosal preparations, nasal drops, inhalants, suppositories and the like. Injections or drip infusions may be prepared as powdery preparations such as in the form of lyophilised preparations, and may be used by dissolving just before use in an appropriate aqueous medium such as physiological saline. Sustained-release preparations such as those coated with a polymer may be directly administered intracerebrally. Types of pharmaceutical additives used for the manufacture of the pharmaceutical composition, content ratios of the pharmaceutical additives relative to the active ingredient, and methods for preparing the pharmaceutical composition may be appropriately chosen by those skilled in the art. Inorganic or organic substances, or solid or liquid substances may be used as pharmaceutical additives. Generally, the pharmaceutical additives may be incorporated in a ratio ranging from 1 % by weight to 90% by weight based on the weight of an active ingredient. Examples of excipients used for the preparation of solid pharmaceutical compositions include, for example, lactose, sucrose, starch, talc, cellulose, dextrin, kaolin, calcium carbonate and the like. For the preparation of liquid compositions for oral administration, a conventional inert diluent such as water or a vegetable oil may be used. The liquid composition may contain, in addition to the inert diluent, auxiliaries such as moistening agents, suspension aids, sweeteners, aromatics, colorants, and preservatives. The liquid composition may be filled in capsules made of an absorbable material such as gelatin. Examples of solvents or suspension mediums used for the preparation of compositions for parenteral administration, e.g. injections, suppositories, include water, propylene glycol, polyethylene glycol, benzyl alcohol, ethyl oleate, lecithin and the like. Examples of base materials used for suppositories include, for example, cacao butter, emulsified cacao butter, lauric lipid, witepsol. The dose and frequency of administration of the medicament of the present invention are not particularly limited, and they may be appropriately chosen depending on conditions such as a purpose of preventive and/or therapeutic treatment, a type of a disease, the body weight or age of a patient, severity of a disease and the like. Generally, a daily dose for oral administration to an adult may be 0.01 to 1,000 mg (the weight of an active ingredient), and the dose may be administered once a day or several times a day as divided portions, or once in several days. When the medicament is used as an injection, administrations may preferably be performed continuously or intermittently in a daily dose of 0.001 to 100 mg (the weight of an active ingredient) to an adult. Chemical Examples The present invention will be explained more specifically with reference to the following general examples, however, the scope of the present invention is not limited to these examples. Example 1 (Compound No. 24 of table 1) 3-Chloro-9-(2(S)-hydroxy-2-phenyl- ethyl)-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one 1.1 2-(Pyrimidin-4-yl)-6,7,8,9-tetrahydro-4H-pyrimido[1,2-a]pyrimidin-4-one A mixture of 1.75g (9.0 mmol) of ethyl 3-(4-pyrimidinyl)-3-oxopropionate, (prepared by analogy to the method described in patent DE 2705582), 5.0g (30.55 mmol) 1,4,5,6-tetrahydro-2-pyrimidinamine dihydrochloride (prepared by analogy to US Patent No. 4,262,122) and 2.49g (18.0 mmol) of potassium carbonate in 30ml of methanol were heated at reflux temperature during 18 h. The reaction mixture was cooled and the solvent removed by evaporation. The residue obtained was treated with water and the precipitate recovered by filtration to give 1.15g (56%) of product. Mp.: 268-272°C. 1.2 3-Chloro-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-4H-pyrimido[1,2-a]pyrimidin-4- one A suspension of 3.0g (13.09 mmol) of 2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-4H- pyrimido[1,2-a]pyrimidin-4-ore in 60ml of acetic acid was treated with 1.75g (15.7 mmol) of N-chlorosuccinimide. The reaction mixture was heated at 90°C during 18h. The cooled solution was evaporated to remove the solvent and water was added. The product was recovered, rised with diethylether and dried to give 2.95g (86%) of solid. Mp.: 208-210°C. 1.3 3-Chloro-9-(2(S)-hydroxy-2-phenyl-ethyl)-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro- pyrimido[1,2-a] pyrimidin-4-one To a solution of 0.6g (2.27 mmol) of 3-chloro-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro- 4H-pyrimido[1,2-a]pyrimidin-4-one in 6.7ml of anhydrous dimethylformamide was added 0.20g (5.10 mmol) of sodium hydride (60% suspension in mineral oil) and the mixture allowed to stir at 50°C for 20min. 0.361ml (2.73 mmol) of (S)-2-chloro- 1-phenylethanol was added and stirring continued for 18h. Water was added and the mixture extracted with dichloromethane. The extracts were washed with a saturated aqueous solution of sodium chloride, dried and evaporated to give crude product. Purification by chromatography on silica gel eluting with a mixture of dichloromethane/methanol in the proportions 100/0 to 96/4 gave 0.598g (69%) of pure product. Mp. : 158-160°C. Example 2 (Compound No. 23 in table 1) 3-Methyl-9-(2-oxo-2-phenyl-ethyl)-2- (pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one 2.1 3-Methyl-2-(pyrimidin-4-7l)-6,7,8,9-tetrahydro-4H-pyrimido[1,2-a]pyrimidin-4- one A mixture of 10.72g (51.48 mmol) of ethyl 3-(4-pyrimidinyl)-2-methyl-3- oxopropionate, (prepared by analogy to the method described in patent DE 2705641 and US 4110450) 6 98g (51.48 mmol) of 1,4,5,6-tetrahydro-2- pyrimidinamine dihydrochloride (prepared by analogy to US F'atent No. 4,262,122) and 7.11g (51.48 mmol) of potassium carbonate in 250ml of ethanol were heated at reflux temperature during 5h. The reaction mixture was coded and the solvent removed by evaporation. The residue obtained was treated with water and the precipitate recovered by filtration. The filtrate was dissolved in chloroform and the solution filtered and evaporated to give 8.6g (69%) of product. Mp.: 206-207°C. 2.2 3-Methyl-9-(2-oxo-2-phenyl-ethyl)-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro- pyrimido[1,2-a] pyrimidin-4-one A solution containing 0.608g (2.5 mmol) of 3-methyl-2-(pyrimidin-4-yl)-6,7,8,9- tetrahydro-4H-pyrimido[1,2-a]pyrimidin-4-one in anhydrous dimethylformamide was treated with 0.11g (2.5 mmol) of sodium hydride (60 % suspension in mineral oil) and the mixture warmed to 40°C during 1h. 0.497g (2.5 mmol) of phenacyl bromide dissolved in 5ml of dimethylformamide was added dropwise and the resulting solution stirred at room temperature for 3h. The reaction mixture was treated with a saturated aqueous solution of sodium chloride and then extracted with ethyl acetate. The organic extracts were dried and evaporated to give a crude product, which was purified by chromatography on silica gel eluting with dichlorornethane/methanol/ammonia in the proportions 100/0/0 to 98/2/0.2. A pure pioduct was obtained which was triturated in diethylether to give 0.309g (34%) of yellow solid. Mp. : 184-185°C. Example 3 (Compound No. 17 in table 1) 7,7-Difluoro-9-(2-oxo-2-phenyl-ethyl)-2- (pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one 3.1 5,5-Difluoro-1,4,5,6-tetrahydro-2-pyrimidinamine A mixture of 2.95g (16.12 mmol) of 2,2-difluoro-1,3-propandiamine dihydrochloride (Tetrahedror (1994) 50(29), 8617-8632), 1.54g (16.12 mmol) of guanidine hydrochloride and 2.19g (32.23 mmol) of sodium methylate was heated at 150°C during 18h. The cooled mixture was used as such in the subsequent step. 3.2 77-Difluoro-2-(pyrimidin-2-yl)-6,7,8,9-tetrahydro-4H-pyrimido[1,2-a]pyrimidin- 4-one To a suspension of 2.17g (16.12 mmol) of 5,5-difluoro-1,4,5,6-tetrahydro-2- pyrimidinamine and 1.81g (16.12g) of potassium carbonate in 30ml of ethanol was treated with 2.55g (13.13 mmol) of ethyl 3-(4-pyrimidinyI)-3-oxopropionate. The reaction mixture was heated at reflux temperature during 32h. The cooled reaction mixture was evaporated and the resulting residue treated with water and extracted with dichloromethane. The extracts were dried and evaporated and the residue was purified by chromatography on silica gel eluting with a mixture of dichloromethane/methanol/ammonia in the proportions 97.5/2.5/0.25. 0.22g (6.3%) of product was thus obtained. 3.3 7,7-Difluoro-9-(2-oxo-2-phenyl-ethyl)-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro- pyrimido[1,2-a] pyrimidin-4-one. A solution of 0.22g (0.829 mmol) of 7,7-difluoro-2-(pyrimidin-4-yl)-6,7,8,9- tetrahydro-4H-pyrimido[1,2-a]pyrimidin-4-one in 4ml of anhydrous dimethylformamide was treated with 36.2mg (0.829 mmol) of sodium hydride (60% suspension in mineral oil) and the mixture warmed to 40°C during 30min. The cooled solution (-10°C) was treated with 0.165g (0.829 mmol) of phenacyl bromide and the resulting mixture stirred at room temperature for 1h. Water was added and the reaction mixture extracted with ethyl acetate. The extracts were dried and evaporated to leave a residue which was purified by chromatography on silica gel eluting with a mixture of dichloromethane/methanol/ammonia in the proportions 98/2/0.2 to give 56mg (17%) of product. Mp.: 233-234°C. Example 4 (Compound No. 19 in table 1) 9-(2(S)-Hydroxy-2-phenyl-ethyl)-7,7- dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one 4.1 7,7-Dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-4H-pyrimido[1,2- a]pyrimidin-4-one A mixture containing 5.15g (26.52 mmol) of ethyl 3-(4-pyrimidinyl)-3- oxopropionate, (prepared by analogy to the method described in patent DE 2705582), 4.34g (26.52 mmol) of 5,5-dimethyl-1,4,5,6-tetrahydro-2- pyrimidinamine monohydrochloride (prepared by analogy to US Patent US 4,262,122) and 3.66g (26.5 mmol) of potassium carbonate in 60ml of methanol were heated at reflux temperature during 18 h. The cooled reaction mixture was evaporated and water was added. The resulting precipitate was recovered by filtration and dried to give 4.86g (71 %) of product. Mp. : 194-196°C. 4.2 9-(2(S)-Hydroxy-2-phenyl-ethyl)-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9- tetrahydro-pyrimido[1,2-a] pyrimidin-4-one To a solution of 0.40g (1.55 mmol) of 7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9 tetrahydro-4H-pyrimido[1,2-a]pyrimidin-4-one in 10ml of anhydrous dimethylformamide was added 0.132g (3.42 mmol) of sodium hydride (60% suspension in mineral oil) and the resulting mixture stirred for 15min. at room temperature. 0.535g (3.42 mmol) of (S)-2-chloro-1-phenylethanol was added and the reaction mixture was heated at 50°C for 7h. The cooled reaction mixture was treated with water and extracted with ethyl acetate. The extracts were dried and evaporated and the residue obtained was purified by chromatography or silica gel eluting with a mixture of dichloromethane/methanol in the proportions 100/0 to 95/5 to give 0.084g (14%) of product which was transformed into the hyrdochloride salt in the usual manner. Mp. : 113-115°C. [α]D+54.7° ;c=0.6, CH3OH). Example 5 (Compound No. 54 in table 1) 9-(2(S)-Ethoxy-2-phenyl-ethyl)-7,7- dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-4H-pyrimido[1,2-a]pyrimidin-4-one To a solution of 0.092g (0.244 mmol) of 7,7-dimethyI-9-[2-(2(S)-hydroxy-phenyl- ethyl)]-2-(pyrimidin-4-yl)-6,7,8 9-tetrahydro-4H-pyrimido[1,2-a]pyrimidin-4-one in 3ml of anhydrous dimethylfornamide was added 0.010g (0.244 mmol) of sodium hydride (60% suspension in mineral oil) and the mixture stirred at room temperature during 1h. To this, solution cooled to 0°C was added 0.019ml (0.244 mmol) of iodoethane and the mixture heated at 60°C during 2h. Water was added and the mixture extracted with dichloromethane. The extracts were washed with a saturated aqueous solution of sodium chloride and dried and evaporated. The residue was purified by chromatography on silica gel eluting with a mixture of dichloromethane/methanol/ammonia in the proportions 95/5/0.5 to give 57mg (56%) of product. Mp.: 113-115°C. [α]D +19.4° (c=0.82, CH3OH). Example 6 (Compound No. 58 in table 1) 9-(2-Benzo[1,3]dioxol-5-yl-2-hydroxy- propyl)-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1.2-a]pyrimidin- 4-one 6.1 7,7-Dimethyl-9-(2-oxo-propyl)-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro- pyrimido[1,2-a]pyrimidin-4-one To a solution of 3.815g (14.83 mmol) of 7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9- tetrahydro-pyrimido[1,2-a]pyrimidn-4-one in 50ml of anhydrous dimethylformamide was added 0.771g (19.28 mmol) of sodium hydride (60% suspension in mineral oil). The suspension was stirred at room temperature for 30min. at room temperature. 1.54ml (19.28 mmol) of 1-chloropropanone was added and the solution was heated at 60°C during 4h. Water was added to the cooled solution and the mixture extracted with dichloromethane. The extracts were washed with a saturated aqueous solution of sodium chloride and dried and evaporated. The residue was purified by chromatography on silica gel eluting with a mixture of dichloromethane/methanol in the proportions 100/0 to 90/10 to give 2.58g (85%) of product. 6.2 9-(2-Benzo[1,3]dioxol-5-yl-2-hydroxy-propyL)-7,7-dimethyl-2-(pyrimidin-4-yl)- 6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one To a solution of 0.3g (0.957 mmol) of 7,7-dimethyl-9-(2-oxo-propyl)-2-(pyrimidin-4- yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidn-4-one in 2ml of anhydrous tetrahydrofuran at -2°C was added 2.1 ml (9.57 mmol) of a solution of 3,4- (methylenedioxy)phenylmagnesiumbromide (1M solution in tetrahydrofuran/toluene 50/50) during 20min. After stirring for 15min. at room temperature the reaction was quenched by the addition of a saturated aqueous solution of ammonium chloride. The reaction mixture was extracted with dichloromethane and the extracts washed with a saturated aqueous solution of sodium chloride, dried and evaporated. The residue was purified by chromatography on silica geleluting with a mixture of ethyl acetate/cyclohexane in the proportions 50/50 to 100/0 to give 0.21 Og (50%) of product. Mp.: 194-196°C. Example 7 (Compound No. 2 in table 2) 1-{3-(2-Fluoro-phenyl)-propyl]-2,2- dimethyl-7-pyrimidin-4-yl-2,3-clihydro-1H-imidazo[1,2-a]pyrimidin-5-one hydrochloride (1:1) 7.1 5,5-Dimethyl-4,5-dihydro-1H-imidazol-2-ylamine hydrobromide (1:1) To a solution of 15g (0.17 mol) of 1,2-diamino-2-methylpropane in 150ml of water at 0°C, was added 18g (0.17 rnol) of cyanogen bromide portionwise and the temperature was allowed to warm to room temperature during 4h. The water was removed by evaporation and ethanol was added and evaporated. Trituration in a mixture of diethyl ether and ethanol gave 29.5g (89%) of product as an amorphous hygroscopic solid. 7.2 2,2-Dimethyl-7-pyrimidin 4-yl-2,3-dihydro-1 H-imidazo[1,2-a]pyrimidin-5-one A mixture containing 2.0g (10.3 mmol) of ethyl 3-(4-pyrimidinyl)-3-oxopropionate, 2.0g (10.3 mmol) of 5,5-dimethyl-4,5-dihydro-1H-imidazol-2-ylamine hydrobromide and 2.85g (20.6 mmol) of potassium carbonate in 15ml of methanol were heated at reflux temperature during 18h. The solvent was removed by evaporation and the residue was treated with water and extracted with dichloromethane. The extracts were dried and evaporated to give 0.960g (39%) of product. Mp.: 238-240°C. 7.3 1 -[3-(2-Fluoro-phenyl)-propyl]-2,2-dimethyl-7-pyrimidin-4-yl-2,3-dihydro-1H- imidazo[1,2-a]pyrimidin-5-one hydrochloride (1:1) A solution of 0.2g (0.822 mmol) of 2,2-dimethyl-7-pyrimidin-4-yl-2,3-dihydro-1H- imidazo[1,2-a]pyrimidin-5-one in 6ml of anhydrous dimethylformamide was treated with 39mg (0.986 mmol) of sodium hydride (60% suspension in mineral oil) and the mixture heated at 60°C for 10min. To the cooled reaction mixture was added 0.210g (0.904 mmol) of 1-[3-(methylsulfonyloxy)propyl]-2-fluorobenzene and heating maintained at 130°C for 1 h. Water was added and the reaction mixture was extracted with ethyl acetate. The combined extracts were washed with a saturated aqueous solution of sodium chloride, dried and evaporated The residue obtained was purified by chromatography on silica gel e uting with a mixture of dichloromethane/methanol in the proportions 99/1 to 90/10 to give 0.25g (80%) of product which was treated with one equivalent of hydrogen chloride in isopropanol to give the monohydrochloride. Mp. : 170-172°C. Example 8 (Compound No.1 in table 3) 9-[2-(4-Fiuoro-2-methoxy-phenyl)-ethyl]- 8-methyl-2-(pyrimidin-4-yl-6,7,8,9-tetrahydro-pyrimido[1,2-a]primidin-4-one 8.1 8-Methyl-2-pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one A mixture of 7.76g (40.0 mmol] of ethyl 3-(4-pyrimidinyl)-3-oxopropionate, (prepared by analogy to the method described in patent DE 2705582), 6.0g (40.0 mmol) 6-methyl-1,4,5,6-tetrahydro-pyrimidin-2-ylamine hydrochloride (prepared according to J.Org. Chem., 20, 1955, 829-838) and 8.29g (60.0 mmol) of potassium carbonate in 50ml of ethanol were heated at reflux temperature during 18 h. The reaction mixture was cooled and the solvent removed by evaporation. The residue obtained was treated with water and the precipitate recovered by filtration to give 3.81 g (39%) of product. Mp.: 199-201 °C. 8.2 (4-Fluoro-2-methoxy-phenyl)-acetic acid methyl ester To a suspension of 14.34g (32.47 mmol) of lead (IV) acetate in 100ml of anhydrous toluene was added a mixture of 5.2g (30.92 mmol) of 1-(4-fluoro-2- methoxy-phenyl)-ethanone and 15.02 ml (123.13 mmol) of boron trifluoride etherate in 9ml of methanol. The reaction mixture is further stirred at room temperature for 16h. Water was added to the cooled mixture and the resulting solution extracted with toluene. The extracts were washed with saturated sodium hydrogen carbonate solution, saturated sodium chloride solution and dried with sodium sulphate. The solvent was evaporated to dryness to give 6g of product as an oil, which was used in the subsequent step without further purification. 8.3 2-(4-Fluoro-2-methoxy-phenyl)-ethanol To a suspension of 1.72g ( 45 41 mmol) of lithium aluminum hydride in 120ml of tetrahydrofuran at 0°C was added dropwise 6g (30.27 mmol) of dissolved in 120 ml of (4-Fluoro-2-methoxy-phenyl)-acetic acid methyl ester and the resulting mixture stirred at room temperature for 1h. The reaction mixture was diluted with 100ml of diethylether at 0°C and treated with excess of a saturated aqueous solution of sodium sulfate. Further solid sodium sulfate was added and the organic phase was filtered to remove salts. The solvent was evaporated to dryness to give 5.1 g (99%) of product as an oil. 8.4 Methanesulfonic acid 2-(4-fluoro-2-methoxy-phenyl)-ethyl ester To a solution of 5.1 g (29.97 mmol) of 2-(4-Fluoro-2-methoxy-phenyl)-ethanol in 30 ml of anhydrous dichloromethane was added at 0°C 6.26ml (44.95 mmol) of triethylamine and 3.5ml (44.95 mmol) of methanesulfonyl chloride. The resulting mixture was stired at 0°C for 1h. The mixture was then diluted with water and dichloromethane and extracted with dichloromethane. Organic layer was dried and evaporated to give 7g(100%) of methanesulfonic acid 2-(4- fluoro-2-methoxy-phenyl)-ethyl ester. 8.5 9-[2-(4-Fluoro-2-methoxy-phenyl)-ethyl]-8-methyl-2-(pyrimidin-4-yl)-6,7,8,9- tetrahydro-pyrimido[1,2-a]primidin-4-one To a solution of 0.18g (0.74 mmol) of 8-methyl-2-(pyrimidin-4-yl)-6,7,8,9- tetrahydro-pyrimido[1,2-a]pynmidin-4-one in 4ml of anhydrous dimethylformamide was added 0.033g (0.81 mmol) of sodium hydride (60% suspension in mineral oil) and the mixture allowed to stir at 50°C for 20min. 0.202g (0.81 mmol) of methanesulfonic acid 2-(4-fluoro-2-methoxy-phenyl)-ethyl ester was added and stirring continued for 18h. Water was added and the mixture extracted with dichloromethane. The extracts were washed with a saturated aqueous solution of sodium chloride, dried and evaporated to give crude product. Purification by chromatography on silica gel eluting with a mixture of dichloromethane/methanol in the proportions 100/0 to 96/4 gave 0.154g (53%) of pure product. Mp.: 148-150°C. Example 9 (Compound No.2 in table 3) 9-{2-(4-Fluoro-2-methoxy-phenyl)-ethyl]- 8,8-dimethyl-2-pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one 9.1 8,8-Dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4- one A mixture of 2.39g (12.31 mmol) of ethyl 3-(4-pyrimidinyl)-3-oxopropionate, (prepared by analogy to the nethod described in patent DE 2705582), 2.33g (11.19 mmol) 6,6-dimethyl-1,4,5,6-tetrahydro-pyrimidin-2-ylamine hydrobromide (prepared according to Bull. Soc. Chim. Belg., 1950, 59, 573-587) and 3.25g (23.5 mmol) of potassium carbonate n 25ml of ethanol were heated at reflux temperature during 18 h. The reaction mixture was cooled and the solvent removed by evaporation. The residue obtained was treated with water and the precipitate recovered by filtration to give 1g (35%) of product. Mp.: 265-267°C. 9.2 9-{2-(4-Fluoro-2-methoxy-phenyl)-ethyl]-8,8-dimethyl-2-(pyrimidin-4-yl)- 6,7,8,9-tetrahydro-pyrimido[1,2 -a]pyrimidin-4-one To a solution of 0.2g ( 0.78 mmol) of 8,8-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9- tetrahydro-pyrimido[1,2-a]pyrimidin-4-one in 5ml of anhydrous dimethylformamide was added 0.035g ( 0.86 mmol) of sodium hydride (60% suspension in mineral oil) and the mixture allowed to stir at 50°C for 20min. 0.212g ( 0.86 mmol) of methanesulfonic acid 2-(4-fIuoro-2-methoxy-phenyl)-ethyl ester was added and stirring continued for 18h. Water was added and the mixture extracted with dichloromethane. The extracts were washed with a saturated aqueous solution of sodium chloride, dried and evaporated to give crude product. Purification by chromatography on silica gel eluting with a mixture of dichlcromethane/methanol in the proportions 100/0 to 96/4 gave 0.136g (43%) of pure product. Mp. : 196-198°C. Example 10 (Compound No. 1 in table 3) 9-(2(S)-Hydroxy-2-phenyl-ethyl)-8,8- dimethyl-2-pyrimidin-4-yl-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one To a solution of 0.2g (0.78 mmol) of 8,8-dimethyl-2-pyrimidin-4-yl-6,7,8,9- tetrahydro-pyrirnido[1,2-a]pyrirnidin-4-one in 3ml of anhydrous dimethylformamide was added 0.07g (1.71 mmol) of sodium hydride (60% suspension in mineral oil) and the mixture was allowed to stir at 50°C for 1h. 0.158g (1.01 mmol) of (1-S)-2- chloro-1-phenyl ethanol was added and the mixture allowed to stir at 120°C for 12h. Water was added and the mixture extracted with ethyl acetate. The extracts were washed with a saturated aqueous solution of sodium chloride, dried and evaporated to give crude product. Purification by chromatography on silica gel eluting with a mixture of dichloromethane/methanol in the proportions 100/0 to 96/24 gave 0.21g (72%) of pure product. Mp. : 178-179°C, [α]D=+45.7 ° (c=0.784, CHCI3). Example 11 (Compound No. 15 in table 3) 8,8-Dimethyl-9-(2-oxo-2-phenyl-ethyl)- 2-pyrimidin-4-yl-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one To a solution of 0.24ml (3.3mmol) of dimethyl sulphoxide in 3ml of anhydrous dichloromethane at -78°C was added 0.42ml (2.93 mmol) of trifluoroacetic anhydride in 2ml of anhydrous dichloromethane and the mixture allowed to stir at -78°C for 20 min. 0.201 g (0.53 mmol) of 9-(2(S)-Hydroxy-2-phenyl-ethyl)-8,8- dimethyl-2-pyrimidin-4-yl-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one in 2ml of anhydrous dichloromethane was added at -78°C and stirring continued for 30 min. 0.62ml (4.47 mmol) of triethylamine was added and the mixture allowed to stir at room temperature for 12h. Water was added and the mixture extracted with ethyl acetate, the extracts were washed with a saturated aqueous solution of ammonium chloride, a saturated aqueous solution of sodium chloride, dried and evaporated to give crude product. Purification by chromatography on silica gel eluting with ethyl acetate gave 0.045g (23%) of pure product. Mp.: 203-205°C. Example 12 (Compound No. 19 in table 3) 8-Ethyl-9-(2-oxo-2-phenyl-ethyl)-2- pyrimidin-4-yl-6,7,8,9-tetrahy(lro-pyrimido[1,2-a]pyrimidin-4-one. 12.1 8-Ethyl-2-pyrimidin-4-yl-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one A mixture of 5g (25.75 mmol) of ethyl 3-(4-pyrimidinyl)-3-oxopropionate, 3.83g (23.41 mmol) of 6-ethyl-1,4,5,6-tetrahydro-pyrirnidin-2-ylamine hydrochloride (prepared according to J. Org. Chem., 20, 1955, 829-838) and 6.794g (49.16 mmol) of potassium carbonate in 50ml of ethanol were heated at reflux temperature during 18 h. The reaction mixture was cooed and the solvent removed by evaporation. The residue obtained was treated with water and the precipitate recovered by filtration to give 3.62g (60%) of product Mp. : 226-228°C. 12.2 8-Ethyl-9-(2-oxo-2-phenyl-ethyl)-2-pyrimidin-4-yl-6,7,8,9-tetrahydro- pyrimido[1,2-a]pyrimidin-4-one. To a solution of 0.35g (1.36 mmol) of 8-ethyl-2-pyrimidin-4-yl-6,7,8,9-tetrahydro- pyrimido[1,2-a]pyrimidin-4-one in 7ml of anhydrous dimethylformamide was added 0.071 g (1.77 mmol) of sodium hydride (60% suspension in mineral oil) and the mixture allowed to stir at 25°G for 15 min. At 0°C, 0.352g (1.77 mmol) of phenacyl bromide was added. The mixture was allowed to stir at 0°C for 3h and the temperature was allowed to warm to room temperature during 12h. Water was added and the mixture extracted with ethyl acetate. The extracts were washed with a saturated aqueous solution of sodium chloride, dried and evaporated to give crude product. Purification by chromatography on silica gel eluting with a mixture of dichloromethane/methanol in the proportions 100/0 to 98/2 gave 0.163g (32%) of pure product. Mp: 187-189°C. Example 13 (Compound No. 20 in table 3) 9-[2-(4-Fluoro-phenyl)-2(S)-hydroxy- ethyl]-8,8-dimethyl-2-pyrimidin-4-yl-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4- one 13.1 (1S)-2-Bromo-1 -phenyl- ethanol To a solution of 2.30ml (2 30 mmol) of borane tetrahydrofuran complex (1 M solution in tetrahydrofuran) was added at -30°C 0.46ml (0.46 mmol) of (S)-2- methyl-CBS-oxazaborolidine (1M solution in toluen). 0.5g (2.30 mmol) of 4'- Fluoro-phenacyl bromide in 1.85ml of anhydrous dichloromethane was added to the solution over 1 hour while the internal temperature was maintained at -30°C. The mixture was stirred at -20°C for 1 hour. 1.85ml of methanol was added to the reaction mixture. The solution was warmed to room temperature, 5.55 ml of aqueous hydrochloric acid (1N) was added. The mixture extracted with ethyl acetate, the extracts were dried over sodium sulphate and concentrated in vacuo to give 0.498g of 2-Bromo-1-phenyl-ethanol, which was used without purification in the next reaction. 13.2 9-[2-{4-Fluoro-phenyl)-2(S)-hydroxy-ethyl]-8,8-dimethyl-2-pyrimidin-4-yl- 6,7,8,9-tetrahydro-pyrimkdo[1,2-a]pyrimidin-4-one To a solution of 0.3g (1.17 mmol) of 8,8-dimethyl-2-pyrimidin-4-yl-6,7,8,9- tetrahydro-pyrimido[1,2-a]pyrimidin-4-one in 5ml of anhydrous dimethylformamide was added 0.105g (2.57 mmol) of sodium hydride (60% suspension in mineral oil) and the mixture allowed to stir at 50°C for 1h. 0.332g (1.01 mmol) of (1-S)-2- bromo-1-phenyl ethanol was added and the mixture allowed to stir at 120°C for 12h. Water was added and the mixture extracted with ethyl acetate. The extracts were washed with a saturated aqueous solution of sodium chloride, dried and evaporated to give crude product. Purification by chromatography on silica gel eluting with ethyl acetate gave 0.24g (52%) of pure product. Mp. : 176-178°C, [a]D = +51.6 º (c=0.844, CHCI3). A list of chemical structures and physical data for compounds of the aforementioned formula (I) illustrating the present invention is given in tables 1, 2 and 3. The compounds have been prepared according to the methods of the example. In the tables, R1 is an unsutstituted pyrimidin-4-yl group, Ph represents a phenyl group, Et represents an ethyl group, Me represents a methyl group, (S), (R) or (Rac.) indicates in the column "Y" the stereochemistry of the carbon atom. (rac.) means racemic mixture (R) means absolute R configuration (S) means absolute S configuration In table 1 for compounds of formula (I) "m" and "p" equal 1; in table 2 for compounds of formula (I) "m" equals 0 and p equals 1 and In table 3 for compounds of formula (I) "m" equals 0 and "p" equals 2. Test Example 1: Inhibitory activity of the medicament of the present invention against GSK3β: Two different protocols can be used. In a first protocol: 7.5 uM of prephosphorylated GS1 peptide and 10 μM ATP (containing 300,000 cpm of 33P-ATP) were incubated in 25 mM Tris-HCI, pH 7.5, 0.6 mM DTT, 6 mM MgCI2, 0.3 mM EGTA, 0.05 mg/ml BSA buffer for 1 hour at room temperature in the presence of GSK3β (total reaction volume : 100 microliters). In a second protocol: 4.1 μM of prephosphorylated GS1 peptide and 42 μM ATP (containing 260,000 cpm 33F -ATP) were incubated in 80 mM Mes-NaOH, pH 6.5, 1 mM Mg acetate, 0.5 mM EGTA, 5 mM 2-mercaptoethanol, 0.02% Tween 20, 10% glycerol buffer for 2 hours at room temperature in the presence of GSK3β. Inhibitors were solubilised in DMSO (final solvent concentration in the reaction medium, 1%). The reaction was stopped with 100 microliters of a solution made of 25 g polyphosphoric acid (85% P2O5), 126 ml 85% H3PO4, H2O to 500 ml and then diluted to 1:100 before use. An aliquot of the reaction mixture was then transferred to Whatman P81 cation exchange filters and rinsed with the solution described above. Incorporate 33P radioactivity was determined by liquid scintillation spectrometry. The phosphorylated GS-1 peptide had the following sequence : NH2-YRRAAVPPSPSLSRHxSSPHQS(P)EDEE-COOH. The GSK3β inhibitory activity of the compounds of the present invention are expressed in IC50, and as an illustration the range of IC50's of the compounds in table 1 is between 2 nanomolar to 2 micromolar concentrations, of the compounds in table 2 is between 30 nanomolar to 2 micromolar concentrations and of the compounds in table 3 is between 1 nanomolar to 2 micromolar concentrations. Test Example 2: Inhibitory activity of the medicament of the present invention against cdk5/p25: The following protocol may be used: 0.4 mg/ml Histone H1 and 10 μM ATP (containing 300,000 cpm of 33P-ATP) were incubated in 50 mM Hepes, pH 7.2, 1 mM DTT, 1 mM MgCl2, 1 mM EGTA, 0.02% Tween 20 buffer for 1 hour at room temperature in the presence of cdk5/p25 (total reaction volume: 100 microliters). Inhibitors were solubilised in DMSO (final solvent concentration in the reaction medium, 1%). The reaction was stopped witn 100 microliters of a solution of 25 g polyphosphoric acid (85% P2O5), 126 ml 85% H3PO4, H2O to 500 ml (diluted to 1:100 before use). An aliquot of the reaction mixture was then transferred to Whatman P81 cation exchange filters and rinsed with the solution described above. Incorporated 33P radioactivity was determined by liquid scintillation spectrometry. The cdk5/p25 inhibitory activity of the compounds of the present invention are expressed as IC50 values. Typically, 3-fold serial dilutions of the inhibitor over at least a 1000-fold concentration range are used. As an illustration the range of IC50S of the compounds in table 1 is between 200 nanomolar to 5 micromolar concentrations, of the compounds in table 2 is between 100 nanomolar to 5 micromolar concentrations and of the compounds in table 3 is between 100 nanomolar to 5 micromolar concentrations. As an illustration the specific IC50's of some compounds of the aforementioned formula (I) illustrating the present invention are given in table 4. Formulation Example (1) Tablets The ingredients below were mixed by an ordinary method and compressed by using a conventional apparatus. Compound of Example 1 30 mg Crystalline cellulose 60 mg Corn starch 100 mg Lactose 200 mg Magnesium stearate 4 mg (2) Soft capsules The ingredients below were mixed by an ordinary method and filled in soft capsules. Compound of Example 1 30 mg Olive oil 300 mg Lecithin 20 mg (1) Parenteral preparations The ingredients below were mixed by an ordinary method to prepare injections contained in a 1 ml ampoule. Compound of Example 1 3 mg Sodium chloride 4 mg Distilled water for injection 1 ml Industrial Applicability The compounds of the present invention have GSK3β or GSK3β and cdk5/p25 inhibitory activity and are useful as an active ingredient of a medicament for preventive and/or therapeutic treatment of diseases caused by abnormal activity of GSK3β or GSK3β and cdk5/p25 and more particularly of neurodegenerative diseases. We claim : 1. A pyrimidone derivative represented by formula (I) or a salt thereof, or a solvate thereof or a hydrate thereof: wherein: X represents two hydrogen atoms, a sulphur atom, an oxygen atom or a C1-2 alkyl group and a hydrogen atom; Y represents a bond, an ethenylene group, an ethynylene group, an oxygen atom, a sulphur atom, a sulfonyl group, a sulfoxide group, a carbonyl group, a nitrogen atom being optionally substituted by a C1-6 alkyl group, a phenyl or a benzyl group; or a methylene group optionally substituted by one or two groups chosen from a C1-6 alkyl group, a bonzyl group, a hydroxy group, a C1-4 alkoxy group, a C3-6 cycloalkymethyloxy, a C1-2 perhalogenated alkyl group, an amino group, an acetylamino group or a phenyl group; R1 represents a pyrimidine ring optionally substituted by a C3-6 cycloalkyl group a C1-4 alkyl group, a C1-4 alkcxy group, a benzyl group or a halogen atom; when Y represents a bond, a methylene group optionally substituted or a carbonyl group then R2 represents a C1-6 alkyl group optionally substituted by a C6,10 aryloxy or a C6,10 arylamino group ; a C 3-6cycloalkyl group, a C1-4alkylthio group, a C1-4 alkoxy group, a C1-2perhalogenated alkyl group, a C1-3halogenated alkyl group, a phenylthio group, a benzyl group, a benzene ring, an indan ring, a 5,6,7,8-tetrahydronaphthalene ring, a naphthalene ring, a pyridine ring, a pyrrole ring, a thiophene ring, a furan ring or an imidazole ring ; the benzyl group or the rings being optionally substituted by 1 to 4 substituents selected from a C1-6 alkyl group, a methylendioxy grouo, a halogen atom, a C1-2 perhalogenated alkyl group, a C1-3 halogenated alkyl group, a hydroxy group, a C1-4alkoxy group, a nitro, a cyano, an amino, a C1-5 monoalkylamino group, a C2-10 dialkylamino group, a C1-6 alkylcarbonylamino group, a C6,10 arylcarbonylamino group, a C1-4 alkylsulfonyl group, C1-4 alkylsulfonylexy group or a phenyl group; when Y represents ar ethenylene group, an ethynylene group, an oxygen atom, a sulphur atom, a sulfonyl group, a sulfoxide group or a nitrogen atom being optionally substituted then R2represents a C1-6 alkyl group (optionally substituted by a C6,10 aryloxy or a C6,10 arylamino group), a C3-6cycloalkyl group, a C1-2 perhalogenated alkyl group, a C1-3 halogenated alkyl group, a benzyl group, a benzene ring, an indan ring, a 5,6,7,8-tetrahydronaphthalene ring, a naphthalene ring, a pyridine ring, a pyrrole ring, a thiophene ring, a furan ring or an imidazole ring ; the benzyl group or the rings being optionally substituted by 1 to 4 substituents selected from a C1-6 alkyl group, a methylendioxy group, a halogen atom, a C1-2 perhalogenatec alkyl group, a C1-3 halogenated alkyl group, a hydroxy group, a C1-4 alkoxy group, a nitro, a cyano, an amino, a C1-5 monoalkylamino group, a C1-10 dialkylamino group, a C1-6 alkylcarbonylamino group, a C6,10 arylcarbonylamino group, a C1-4 alkylsulfonyl group, C1-4 alkylsulfonyloxy group or a phenyl group; R3 and R4 represents each independently a hydrogen atom, C1-6 alkyl group, a hydroxy group, a C1-4 alkoxy group or a halogen atom; R5 represents a hydrogen atom, a C1-6 alkyl group or a halogen atom; When m equals 0, p equals 1, 2 or 3, When m equals 1, p equals 0,1 or 2, When m equals 2, p equals 0 or 1; and n represents 0 to 3. 2. A pyrimidone derivative or a salt thereof, or a solvate thereof or a hydrate thereof as claimed in claim 1, wherein Rl represents an unsubstituted 4-pyrimidine ring. 3. A pyrimidone derivative represented by the formula (I), as claimed in claim 1, which is selected from the group consisting of: • 9-(3-Phenyl-propyl)-2-(pypimidin-4-yl)-6,7,8,9,-tetrahydro-pyrimido[1,2-a] pyrimidin-4-one • 9-[ 2-(2-Chloro-4-fluoro-phenyl)-ethyl] )-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro- pyrimido[1,2-a] pyrimidin-4-one • 9-(2-Phenylsulfanyl-ethyl i-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a] pyrimidin-4-one • 9-(2-Oxo-2-phenyl-ethyl) -2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a] pyrimidin-4-one • 9-(3-Hydroxy-3-phenyl-propyl)-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro- pyrimido[1,2-a] pyrimidir-4-one • 9-(2-Hydroxy-2-phenyl-ethyl)-2-(pyrimidin-4-yl)-6,7,8,9-tetfahydro- pyrimido[1,2-a] pyrimidin-4-one • 9-(3-Oxo-3-phenyl-propyl)-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a] pyrimidin-4-one • 9-(2(R)-Hydroxy-2-phenyl-ethyl)-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro- pyrimido[1,2-a] pyrimidin-4-one • 9-(2(S)-Hydroxy-2-phenyl-ethyl)-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro- pyrimido[1,2-a] pyrimid n-4-one • 9-[2-(3-Chloro-phenyl)-2-oxo-ethyl]-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro- pyrimido[1,2-a] pyrimidin-4-one • 9-[2-(3-Fluoro-phenyl)-2-oxo-ethyl]-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro- pyrimido[1,2-a] pyrimidin-4-one • 9-[2-(3-Fluoro-phenyl)-2-hydroxy-ethyl]-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro- pyrimido[1,2-a] pyrimidin-4-one • 9-[2-(3-Ch!oro-phenyl)-2-hydroxy-ethyl]2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro- pyrimido[1,2-a] pyrimidin-4-one • 9-(1-Methyl-2-oxo-2-phenyl-ethyl)2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro- pyrimido[1,2-a] pyrimidin-4-one • 9-(2-Hydroxy-1-methyl-2-phenyl-ethyl)2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro- pyrimido[1,2-a] pyrimidin-4-one • 9-[2-(3-Chloro-phenyl)-2(R)-hydroxy-ethyl]2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro- pyrimido[1,2-a] pyrimidin-4-one • 7,7-Difluoro-9-(2-oxo-2-phenyl-ethyl)-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro- pyrimido[1,2-a] pyrimidin-4-one • 7,7-Dimethyl-9-(2-oxo-2phenyl-ethyl)-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro- pyrimido[1,2-a] pyrimidir-4-one • 9-(2(S)-Hydroxy-2-phenyl-ethyl)-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9- tetrahydro-pyrimido[1,2-a] pyrimidin-4-one • 9-[2-(3-Chloro-phenyl)-2-oxo-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9- tetrahydro-pyrimido[1,2-a] pyrimidin-4-one • 9-[2-(3-Chloro-phenyl)-2-hydroxy-ethyl]-7,7-dimethyl-2-pyrimidin-4-yl)-6,7,8,9- tetrahydro-pyrimido[1,2-a] pyrimidin-4-one • 9-[2-(3-Fluoro-phenyl)-2-oxo-ethyl]-7,7-dimethyl-2-pyrimidin-4-yl]-6,7,8,9- tetrahydro-pyrimido[1,2-a] pyrimidin-4-one • 3-Methyl-9-(2-oxo-2-phenyl-ethyl)-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro- pyrimido[1,2-a] pyrimidin-4-one • 3-Chloro-9-(2(S)-hydroxy-2-phenyl-ethyl)-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro- pyrimido[1,2-a] pyrimidin-4-one • 9-[2-(2(S)-Hydroxy-2-phenyl-ethyl)-3-methyl-2-(pyrimidin-4-yl)-6,7,8,9- tetrahydro-pyrimido[1,2-a] pyrimidin-4-one • 9-[2-(3-Fluoro-phenyl)-2-hydroxy-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9- tetrahydro-pyrimido[1,2-a] pyrimidin-4-one • 9-[2-Oxo-2-(5,5,8,8-tetremethyl-5,6,7,8-tetrahydro-naphthalen-2-yl-ethyl]-2- (pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one • 9-[2-(4-Chloro-phenyl)-2-oxo-ethyl]-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro- pyrimido[1,2-a] pyrimidir-4-one • 9-[2-{4-Fluoro-phenyl)-2 oxo-ethyl]-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro- pyrimido[1,2-a] pyrimidin-4-one • 9-(2-Naphthalen-2-yl-2-oxo-ethyl-2-(pyrimidin-4-yI)-6,7,8,9-tetrahydro- pyrimido[1,2-a] pyrimidin-4 one • 9-(2-bxo-2-p-tolyl-ethyl)-2-pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a] pyrimidin-4-one • 9-(2-Biphenyl-4-yl-2-oxo-ethyl)-2-pyrimidin-4-yl)-6,74,8,9-tetrahydro- pyrimido[1,2-a] pyrimidin-4-one • 9-[2-(3-Methoxy-phenyl)-2-oxo-ethyl]-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro- pyrimido[1,2-a] pyrimidin-4- one • 9-[2-(7-Methoxy-benzo-[1,3]dioxol-5-yl)-1-methyl-2-oxo-ethyl]-2-(pyrirnidin-4- yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a] pyrimidin-4-one • 9-[2-(7-Methoxy-benzo-[1,3]dioxol-5-yl)-1-methyl-2-oxo-ethyI]-7,7-dimethyl-2- (pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one • 9-[2-(4-Chloro-phenyl)-2-oxo-ethyl]-7,7-dimethyl-2-{pyrimidin-4-yl)-6,7,8,9- tetrahydro-pyrimido[1,2-a] pyrimidin-4-one • 7,7-Dimethyl-9-[2-oxo-2-(5,5,8,8-tetraimethyl-5,6,7,8,-tetrahydro-naphthalen-2- yl)-ethyl)-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one • 9-[2-(4-Fluoro-phenyl)-2-oxo-ethyl]-7,7-dimethy l-2-(pyrimidin-4-yl)-6,7,8,9- tetrahydro-pyrimido[1,2-a] pyrimidin-4-one • 9-[2-Biphenyl-4-yl-2-oxo-ethyl)-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9- tetrahydro-pyrimido[1,2-a] pyrimidin-4-one • 7,7-Dimethyl-9-(2-oxo-2-p-tolyl-ethyl)-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro- pyrimido[1,2-a] pyrtmidin-4-one • 9-[2-(3-Methoxy-phenyl)-2-oxo-ethyl)-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9- tetrahydro-pyrimido[1,2-a] pyrimidin-4-one • 7,7-Dimethyl-9-(2-naphthalen-2-yl-2-oxo-ethyl]-2-(pyrimidin-4-yl)-6,7,8,9- tetrahydro-pyrimido[1,2-a] pyrimidin-4-one • 9-[2-Hydroxy-2-(7-methoxy-t enzo-[1,3]dioxol-5-yl)-1 -methyl-ethyl]-7,7- dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one • 9-[2-Hydroxy-2-(7-methoxy-benzo-[1,3]dioxol-5-yl)-1-methyl-ethyl]-2- (pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one • 9-(2-Hydroxy-2-phenyl-propy )-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9- tetrahydro-pyrimido[1,2-a] pyimidin-4-one • 9-[2-(2-Methoxy-phenyl-2-oxo-ethyl]-7,7-dimethyl-2-pyrimidin-4-yl)-6,7,8,9- tetrahydro-pyrimido[1,2-a] pyrimidin-4-one • 9-[2-(2-Methoxy-phenyl]-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9- tetrahydro-pyrimido[1,2-a] pyrimidin-4-one • 9-[2-Hydroxy-2-(2-methoxy-phenyl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)- 6,7,8,9-tetrahydro-pyrimido[1,2-a] pyrimidin-4-one • 9-[2-{2,5-Dimethoxy-phenyl)-2-oxo-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)- 6,7,8,9-tetrahydro-pyrimiclo[1,2-a] pyrimidin-4-one • 9-[2-(2,5-Dimethoxy-pheryl)-2-hydroxy-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)- 6,7,8,9-tetrahydro-pyrimico[1,2-a] pyrimidin-4-one • 9-(2(S)-Cyclopropylmethoxy-2-phenyl-ethyl)-7,7-dimethyl-2-(pyrimidin-4-yl)- 6,7,8,9-tetrahydro-pyrimido[1,2-a] pyrimidin-4-one • 9-[2-{2,5-Dimethoxy-phenyl)-2-ethoxy-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)- 6,7,8,9-tetrahydro-pyrimido[1,2-a] pyrimidin-4-one • 9-[2-(3-Phenyl-2-hydroxy-propyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9- tetrahydro-pyrimido[1,2-a] pyrimidin-4-one • 9-(2(S)-Ethoxy-2-phenyl-ethyl)-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9- tetrahydro-pyrimido[1,2-a] pyrimidin-4-one • 9-[2-Ethoxy-2-(2-me{hoxy-phenyl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)- 6,7,8,9-tetrahydro-pyrimido[1,2-a] pyrimidin-4-one • 94,2-Hydroxy-2-(2-methoxyphenyl)-propyl]-7,7-dimethyl-2-(pyrimidin-4-yl)- 6,7,8,9-tetrahydro-pyrimidol ,2-a] pyrimidin-4-one • 9-[2-(2-Chloro-4-fluoro-phenyl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9- tetrahydro-pyrimido[1,2-a] pyrimidin-4-one. • 9-(2-(Benzo-[1,3]dioxol-5-yl -2-hydroxy-propyl)-7,7-dimethyl-2-(pyrimidin-4-yl)- 6,7,8,9-tetrahydro-pyrimido[1,2-a] pyrmidin-4-one • 9-[2-Hydroxy-2-(3-methoxy-phenyl)-propyl]-7,7-dimethyl-2-(pyrimidin-4-yl)- 6,7,8,9-tetrahydro-pyrimido[ 1,2-a] pyrimidin-4-one • 9-[2-(4-Fluoro-phenyl)-2-hydroxy-propyl]-7,7-dimethyl-2-(pyrimidin-4-yl)- 6,7,8,9-tetrahydro-pyrimido[1,2-a] pyrimidin-4-one • 9-[2-(4-Fluoro-phenyl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro- pyrimido[1,2-a] pyrimidin-4-one • 9-[2-(3-Fluoro-phenyl)-ethyl]-7,7-dimethyl-2-pyrimidin-4-yl)-6,7,8,9-tetrahydro- pyrimido[1,2-a] pyrimidin-4-one • 9-[2-(2-Fluoro-phenyl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro- pyrimido[1,2-a] pyrimidin-4-one • 4-[2-(3,3-Dimethyl-6-oxo-8 pyrimidin-4-yl-3,4,dihydro-2H,6H-pyrimido[1,2-a] pyrimidin-1-yl)ethyl]benzonitrile • 9-[2-(4-Methoxy-phenyl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9- tetrahydro-pyrimido[1,2-a] pyrimidin-4-one • 9-[2-(3,4-Dimethoxy-phenyl)-ethyl)-7,7-dimethyl-2-pyrimidin-4-yl)-6,7,8,9- tetrahydro-pyrimido[1,2-a] pyrimidin 4-one • 7,7-Dimethyl-2-(pyrimidin-4-yl)-9-(2-o-tolyI-ethyl)-6,7,8,9-tetrahydro- pyrimido[1,2-a] pyrimidin-4-one • 7,7-Diethyl-2-(pyrimidin-4-yl)-9-(2-p-tolyl-ethyl)-6,7,8,9-tetrahydro- pyrimido[1,2-a] pyrimidin-4-one • 9-[2-(4-Fluoro-2-methoxy-phenyl)-2-hydroxy-ethyl]-7,7-dimethyl-2-(pyrimidin-4- yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a] pyrimidin-4-one • 9-[2-(4-Fluoro-2-methoxy-phenyl)-2-oxo-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)- 6,7,8,9-tetrahydro-pyrimido[1,2-a] pyrimidin-4-one • 9-[2-(4-Chloro-phenyl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro- pyrimido[1,2-a] pyrimidin-4-one • 9-[2-(2-Chloro-phenyl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro- pyrimido[1,2-a] pyrimidin-4-one • 9-[2-(2,4-Dichloro-phenyl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9- tetrahydro-pyrimido[1,2-a] pyrimidin-4-one • 9-[2-(4-Bromo-phenyl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro- pyrimido[1,2-a] pyrimidin-4-one • 9-[2-(4-Ethoxy-phenyl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro- pyrimido[1,2-a] pyrimidin-4-one • 9-[2-Cyclohexyl-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro- pyrimido[1,2-a] pyrimidin 4-one • 9-[2-(4-Nitro-phenyl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro- pyrimido[1,2-a] pyrimidin-4-one • 9-[2-{2-Trifluoromethyl-phenyl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9- tetrahydro-pyrimido[1,2-a] pyrimidin-4-one • 9-[2-(3-Chloro-phenyl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro- pyrimido[1,2-a] pyrimidir-4-one • 9-[2-(2,5-Dimethoxy-phenyl)-ethyl)-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9- tetrahydro-pyrimido[1,2-a] pyrimidin-4-one • 7,7-Dimethyl-2-(pyrimidin-4-yl)-9-[2-{3,4,5-trimethoxy-phenyl)-ethyl]-6,7,8,9- tetrahydro-pyrimido[1,2-a]pyrimidin-4-one • 9-[2-(3-Methoxy-phenyl)-ethyl-7,7-dimethyl-2-pyrimidin-4-yl)-6,7,8,9- tetrahydro-pyrimido[1,2-a] pyrimidin-4-one • 9-[2-Methoxy-2-(2-methoxy-phenyl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)- 6,7,8,9-tetrahydro-pyrimido[1,2-a] pyrimidin-4-one • 9-(2(R)-Methoxy-2-phenyl-ethyl)-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9- tetrahydro-pyrimido[1,2-a] pyrimidin-4-one • 9-[2-(2,5-Dimethoxy-phenyl)-2-methoxy-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)- 6,7,8,9-tetrahydro-pyrimido[1,2-a] pyrimidin-4-one • 9-[2-(4-Fluoro-2-methoxyphenyl)-2-methoxy-ethyl]-7,7-dimethyl-2-(pyrimidin- 4-yi)-6,7,8,9-tetrahydro-pyrimido[1,2-a] pyrimidin-4-one • 7,7-Dimethyl-9-(2-phenyl-ethyl)-(pyrimidin-4-yl)-6,7,8,9-tetrahydro- pyrimido[1,2-a]pyrimidin-4 -one • 9-[2-(3-Chloro-phenyl)-2-methoxy-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)- 6,7,8,9-tetrahydro-pyrimido[1,2-a] pyrimidin-4-one • 9-[2-(3-Fluoro-phenyl)-2-methoxy-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9- tetrahydro-pyrimido[1,2-a] pyrimidin-4-one • 9-[2-(4-Fluoro-2-methoxy-|)henyl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9- tetrahydro-pyrimido[1,2-a] pyrimidin-4-one • 9-[2-(4-Fluoro-2-methoxy-|)henyl)-ethyl]-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro- pyrimido[1,2-a] pyrimidin-4-one • 9-[2-(2,6-Dichloro-phenyl)-3thyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9- tetrahydro-pyrimido[1,2-a] pyrimidin-4-one • 7,7-Dimethyl-9-(2-naphthalan-1-yl-ethyl)-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro- pyrimido[ 1,2-a]pyrimidin-4-one • 9-[2-(2,6-Dimethoxy-phenyl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9- tetrahydro-pyrimido[1,2-a] pyrimidin-4-one • 7,7-Dimethyl-2-(pyrimidin-4-yl)-9-[2-(2-trifluoromethoxy-phenyl)-ethyl]-6,7,8,9- tetrahydro-pyrimido[1,2-a]pyrimidin-4-one • 9-[2-(2,4-Dichloro-5-fluoro-phenyl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)- 6,7,8,9-tetrahydro-pyrimido 1,2-a] pyrimidin-4-one • 7,7-Dimethyl-2-(pyrimidin-4-yl)-9-[2-(2,4,5-trifluoro-phenyl)-ethyl]-6,7,8,9- tetrahydro-pyrimido[1,2-a]pyrimidin-4-one • 9-[2-(2,4-Difluoro-phenyl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9- tetrahydro-pyrimido[1,2-a] pyrimidin-4-one • 9-Indan-2-ylmethyl-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro- pyrimido[1,2-a] pyrimidin-4-one • 3-Chloro-9-indan-2-ylmethyl-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro- pyrimido[1,2-a] pyrimidin-4-one • 9-[2-(2-Ethoxy-4-fluoro-phenyl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9- tetrahydro-pyrimido[1,2-a] pyrimidin-4-one • 9-[2-(4-Fluoro-2-isopropoxy-phenyl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)- 6,7,8,9-tetrahydro-pyrimido[1,2-a] pyrimidin-4-one • 9-[2-{4-Fluoro-2-hydroxy-phenyl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9- tetrahydro-pyrimido[1,2-a] pyrimidin-4-one • 9-[2-{5-Chloro-2,3-dihydrc-benzofuran-7-yl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4- yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a] pyrimidin-4-one or a salt thereof, or a solvate thereof or a hydrate thereof. 4. A pyrimidone derivative represented by the formula (I), as claimed in claim 1, which is selected from the group consisting of: • 1 -(3-Phenyl-propyl)-7-pyrimidin-4-yl-2,3-dihydro-1H-imidazo[1,2-a]pyrimidin-5- one • 1-[3-(2-Fluoro-phenyl)-propyl]-2,2-dimethyl-7-pyrimidin-4-yl-2,3-dihydro-1H- imidazo[1,2-a]pyrimidin-5-one • 1 -(2-Oxo-2-phenyl-ethyl)-7 -pyrimidin-4-yl-2,3-dihydro-1H-imidazo[1,2- a]pyrimidin-5-one • 1 -(2-Hydroxy-2-phenyl-ethyl)-7-pyrimidin-4-yl-2,3-dihydro-1 H-imidazo[1,2- a]pyrimidin-5-one • 1-[2-(3-Methoxy-phenyl)-2-oxo-ethyl]-2,2-dimethyl-7-pyrimidin-4-yl-2,3-dihydro- 1H-imidazo[1,2-a]pyrimidin-5-one • 1-[2-(7-Methoxy-benzo-[1,3]dioxol-5-yl)-1-methyl-2-oxo-ethyl]-2,2-dimethyl-7- pyrimidin-4-yl-2,3-dihydro-1H-imidazo[1,2-a]pyrimidin-5-one • 1-(2-Biphenyl-4-yl-2oxo-ethyl)-2,2-dimethyl-7-pyrimidin-4-yl-2,3-dihydro-1H- imidazo[1,2-a]pyrimidin-5-one • 1-[2-(4-Fluoro-phenyl)-2-oxo-ethyl]-2,2-dimethyl-7-pyrimidin-4-yl-2,3-dihydro- 1H-imidazo[1,2-a]pyrimidin-5-one • 2,2-Dimethyl-1-(2-oxo-2-p-tolyl-ethyl)-7-pyrimidin-4-yl-2,3-dihydro-1H- imidazo[1,2-a]pyrimidin-5-one • 2,2-Dimethyl-1-(2-naphthalen-2-yl-2-oxo-ethyl)-7-pyrimidin-4-yl-2,3-dihydro- 1H-imidazo[1,2-a]pyrimidin-5-one • 1-[2-(4-Chloro-phenyl)-2-oxo-ethyl]-2,2-dimethyl-7-pyrimidin-4-yl-2,3-dihydro- 1 H-imidazo[1,2-a]pyrimidin-5-one • 2,2-Dimethyl-1-[2-oxo-2-(5,5,8,8-tetramethyl-5,5,7,8-tetrahydro-naphthalen-2- yl)ethyl]-7-pyrimidin-4-yl-2,3-dihydro-1H-imidazo[1,2-a]pyrimidin-5-one; or a salt thereof, or a solvate thereof or a hydrate thereof. 5. A pyrimidone derivative represented by the formula (I), as claimed in claim 1, which is selected from the group consisting of: • 9-[2-(4-Fluoro-2-methoxy-phenyl)-ethyl]-8-methyl-2-(pyrimidin-4-yl)-6,7,8,9- tetrahydro-pyrimido[1,2-a]pyrimidin-4-one • 9-[2-(4-Fluoro-2-methoxy-phenyl)-ethyl]-8,8-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9- tetrahydro-pyrimido[1,2-a]pyrimidin-4-one • 9-[2-(4-Fluoro-phenyl)-ethyl-8-methyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro- pyrimido[1,2-a]pyrimidin-4-one • 8-Methyl-9-(2-oxo-2-pheny-ethyl)-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro- pyrimido[1,2-a]pyrimidin-4-one • 9-[2-(2,5-Dimethoxy-phenyl)-ethyl]-8-methyl-2-(pyrimidin-4-yl)-6,7,8,9- tetrahydro-pyrimido[1,2-a]pyrimidin-4-one. • 9-[2-(2-Methoxy-phenyl)-ehyl]-8-methyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro- pyrimido[1,2-a]pyrimidin-4-one; • 9-[2(S)-Hydroxy-2-phenyl-ethyl]-8-methyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro- pyrimido[1,2-a]pyrimidin-4- one; • 9-{2(R)-Methoxy-2-phenyl-ethyl]-8-methyl-2-(pyrimidin-4-yl)-6,7,8,9- tetrahydro-pyrimido[1,2-a]|)yrimidin-4-one; • 9-[2-(2,5-Dimethoxy-phenyl)-ethyl]-8,3-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9- tetrahydro-pyrimido[1,2-a]pyrimidin-4-one; • 8-Methyl-9-[naphthalen-1-ylmethyl]-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro- pyrimido[1,2-a]pyrimidin-4-one; • 9-[2(S)-Hydroxy-2-phenyl-ethyl]-8,8-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9- tetrahydro-pyrimido[1,2-a]pyrimidin-4-one; • 8-Methyl-9-[naphthalene-2-ylmethyl]-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro- pyrimido[1,2-a]pyrimidin-4-one; • 9-[2(R)-Hydroxy-2-phenyl-ethyl]-8,8-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9- tetrahydro-pyrimido[1,2-a] pyrimidin-4-one; • 9-[2-(4-Fluoro-phenyl)-ett-yl]-8,8-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro- pyrimido[1,2-a]pyrimidin-4 -one; • 8,8-Dimethyl-9-[2-oxo-2-phenyl-ethyl]-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro- pyrimido[1,2-a]pyrimidin-4-one; • 9-[2-(3-Methoxy-phenyl)-2-oxo-ethyl]-8-methyl-2-pyrimidin-4-yl)-6,7,8,9- tetrahydro-pyrimido[1,2-a]pyrimidin-4-one; • 9-[2-(3-Chloro-phenyl)-2-oxo-ethyl]-8-methyl-2-(pyrimidin-4-yl)-6,7,8,9- tetrahydro-pyrimido[1,2-a]pyrimidin-4-one; • 8,8-Dimethyl-9-[naphthalon-1-ylmethyl]-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro- pyrimido[1,2-a]pyrimidin-4-one; • 8-Ethyl-9-[2-oxo-2-phenyl-ethyl]-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro- pyrimido[1,2-a]pyrimidin-4-one; • 9-[2-(4-Fluoro-phenyl)-2(S)-hydroxy-ethyl]-8,8-dimethyl-2-(pyrimidin-4-yl)- 6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one; • 8-Ethyl-9-[2(S)-hydroxy-2-phenyl-ethyl]-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro- pyrimido[1,2-a]pyrimidin-2-one; • 9-[2(S)-Hydroxy-2-(4-methoxy-phenyl)-ethyl]-8,8-dimethyl-2-(pyrimidin-4-yl)- 6,7,8,9-tetrahydro-pyrimidon[1,2-a]pyrimidin-4-one; • 9-[2-(3-Fluoro-phenyl)-2-hydroxy-ethyl]-8-methyl-2-(pyrimidin-4-yl)-6,7,8,9- tetrahydro-pyrimido[1,2-a]pyrimidin-4-one; • 9-[2-{2,4-Dimethoxy-phenyl)-2(S)-hydroxy-ethyl]-8,8-dimethyl-2-(pyrimidin-4- yl)-6,7,8,9-tetrahydro-pyrinido[1,2-a]pyrimidin-4-one; • 9-[2-{3-Bromo-phenyl)-2(S)-hydroxy-ethyl]-8,8-dimethyl-2-(pyrimidin-4-yl)- 6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one; • 9-[2-Benzo[1,3]dioxol-5-yl-2-oxo-ethyl]-8-methyl-2-(pyrimidin-4-yl)-6,7,8,9- tetrahydro-pyrimido[1,2-a]pyrimidin-4-one • 9-[2-(2,3-Dihydro-benzo[1,4]dioxin-6-yl)-2-oxo-ethyl]-8-methyl-2-(pyrimidin-4- yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one • 9-[2-(3,5-Dichloro-phenyl)-2-hydroxy-ethyl]-8-methyl-2-(pyrimidin-4-yl)-6,7,8,9- tetrahydro-pyrimido[1,2-a]pyrimidin-4-one • 9-[2-(3-Fluoro-phenyl)-2(S)-hydroxy-ethyl]-8,8-dimethyl-2-(pyrimidin-4-yl)- 6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one • 9-(2(S)-Hydroxy-2-naphthalen-2-yl-ethyl]-8,8-dimethyl-2-(pyrimidin-4-yl)- 6,7,8,9-tetrahydro-pyrimido [1,2-a]pyrimidin-4-one • 9-(2-Biphenyl-4-yl-2(S)-hydroxy-ethyl)-8,8-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9- tetrahydro-pyrimido[1,2-a]pyrimidin-4-one • 9-[2-(2,5-Dimethoxy-phenyl)-2(S)-hydroxy-ethyl]-8,8-dimethyl-2-(pyrimidin-4- yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one • 9(2(S)-Hydroxy-2-p-tolyl-ethyl)-8,8-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9- tetrahydro-pyrimido[1,2-a]pyrimidin-4-one • 9-[2(S)-Hydroxy-2-(3-methcxy-phenyl)-ethyl]-8,8-dimethyl-2-(pyrimidin-4-yl)- 6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one • 9-[2-(4-Chloro-phenyl)-2(S)-hydroxy-ethyl]-8,8-dimethyl-2-(pyrimidin-4-yl)- 6,7,8,9-tetrahydro-pyrimido [1,2-a]pyrimidin-4-one • 9-[2-(2,4-Dichloro-pnenyl)-2(S)-hydroxy-ethyl]-8,8-dimethyl-2-(pyrimidin-4-yl)- 6,7,8,9-tetrahydro-pyrimido [1,2-a]pyrimidin-4-one • 3-Bromo-8-methyl-9-(2-oxo-2-phenyl-ethyl)-2-pyrimidin-4-yl-6,7,8,9-tetrahydro- pyrimido[1,2-a]pyrimidin-4-one; • 8,8-Dimethyl-9-(2-oxo-2-p-tolyl-ethyl)-2-pyrimidin-4-yl-6,7,8,9-tetrahydro- pyrimido[1,2-a]pyrimidin-4-one; • 9-[2-(3,4-Dichloro-phenyl)-2(S)-hydroxy-ethyl]-8,8-dimethyl-2-(pyrimidin-4-yl)- 6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one • 9-[2-(3-Methoxy-phenyl)-2-oxo-ethyl]-8,8-dimethyl-2-pyrimidin-4-yl-6,7,8,9- tetrahydro-pyrimido[1,2-a]pyrimidin-4-one; • 4-[2-(2,2-Dimethyl-6-oxo-8-pyrimidin-4-yl-3,4-dihydro-2H,6H-pyrimido[1,2- a]pyrimidin-1-yl)-1 (S)-hydroxy-ethy]- benzonitrile; • 9-[2-(4-Fluoro-phenyl)-2-oxo-ethyI]-8,8-dimethyl-2-pyrimidin-4-yl-6,7,8,9- tetrahydro-pyrimido[1,2-a]pyrimidin-4-one; • 9-[2-(4-Chloro-phenyi)-2-o>:o-ethyl]-8,8-dimethyl-2-pyrimidin-4-yl-6,7,8,9- tetrahydro-pyrimido[1,2-a]pyrimidin-4-one; • 9-[2-(4-Meth0xy-phenyl)-2-oxo-ethyl]-8,8-dimethyl-2-pyrimidin-4-yl-6,7,8,9- tetrahydro-pyrimido[1,2-a]pyrimidin-4-one; • 8,8-Dimethyl-9-(2-naphtalen-2-yl-2-oxo-ethyl)-2-pyrimidin-4-yl-6,7,8,9- tetrahydro-pyrimido[1,2-a]pyrimidin-4-one; • 9-[2-(3,4-Dichloro-phenyl)-2-oxo-ethyl]-8,8-dimethyl-2-pyrimidin-4-yl-6,7,8,9- tetrahydro-pyrimido[1,2-a]pyrimidin-4-one; • 9-[2-(2,5-Dimethoxy-phenyl)-2-oxo-ethyl]-8,8-dimethyl-2-pyrimidin-4-yl-6,7,8,9- tetrahydro-pyrimido[1,2-a]pyrimidin-4-one; • 9-(2-Biphenyl-4-yl-2-oxo-ethyl)-8,8-dimethyl-2-pyrimidin-4-yl-6,7,8,9- tetrahydro-pyrimido[1,2-a]pyrimidin-4-one; • 9-[2-(3-Bromo-phenyl)-2-oxo-ethyl]-3,8-dimethyl-2-pyrimidin-4-yl-6,7,8,9- tetrahydro-pyrimido[1,2-a]pyrimidin-4-one; • 9-[2-(3-Fluoro-phenyl)-2-oxo-ethyl]-8,8-dimethyl-2-pyrimidin-4-yl-6,7,8,9- tetrahydro-pyrimido[1,2-a]|)yrimidin-4-one; • 8-Ethyl-9-(2-hydroxy-2-p-tolyl-ethyl)-2-pyrimidin-4-yl-6,7,8,9-tetrahydro- pyrimido[1,2-a]pyrimidin-4- one; • 9-[2-(4-Chloro-phenyl)-2-oxo-ethyl]-8,8-dimethyl-2-pyrimidin-4-yl-6,7,8,9- tetrahydro-pyrimido[1,2-a]pyrimidin-4-one; • 9-[2-(4-Chloro-phenyl)-2-hydroxy-ethyl] 8-ethyl -2-pyrimidin-4-yl-6,7,8,9- tetrahydro-pyrimido[1,2-a]pyrimidin-4-one; or a salt thereof, or a solvate thereof or a hydrate thereof. 6. A medicament comprising as an active ingredient a substance selected from the group consisting of a pyrimidone derivative represented by formula (I) or salts thereof, or a solvate thereof or a hydrate thereof as claimed in claims 1 to 5 . 7. A GSK3β or GSK3β and cdk5/p25 inhibitor selected from the group of a pyrimidone derivative represented by formula (I) or salts thereof, or a solvate thereof or a hydrate thereof as claimed in claims 1 to 5 . 8. A medicament as claimed in claim 6 for preventive and/or therapeutic treatment of a disease caused by abnormal GSK3β or GSK3β and cdk5/p25 activity. 9. A medicament as claimed in claim 6, for preventive and/or therapeutic treatment of a neurodegenerativ: disease. 10. A medicament as claimed in claim 9, wherein the neurodegenerative disease is selected from the group consisting of Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, tauopathies, vascular dementia; acute stroke, traumatic injuries; cerebrovascular accidents, brain cord trauma, spinal cord trauma; peripheral neuropathies; retinopathies or glaucoma. 11. A medicament as claimed in claim 6 for preventive and/or therapeutic treatment of non-insulin depencent diabetes ; obesity ; manic depressive illness, schizophrenia ; alopecia ; smoking cessation, epilepsy ; or cancers. 12. A medicament as claimed in claim 11, wherein cancer is breast cancer, non- small cell lung carcinoma, thyrc id cancer, T or B-cell leukemia or virus-induced tumors. The invention relates to a pyrimidone deriva- tive represented by formula (I) or a salt thereof wherein: X represents two hydrogen atoms, a sulphur atom, an oxygen atom or a C1-2 alkyl group and a hydrogen atom, y represents a bond, an ethenylene group, an ethynylene group, an oxygen atom, a sulphur atom, a sulfonyl group, a sulfoxide group, a carbonyl group, a nitrogen atom being optionally; or a methylene group optionally substituted; R1 represents a pyrimidine group optionally substituted; R2 may represent a C1-6 alkyl group optionally substituted by a C6,10 aryloxy or a C6,10 arylamino group; a C3-6 cycloalkyl group, a C1-4 alkylthio group, a C1-4, alkoxy group, a C1-2 perhalogenated alkyl group, a C1-3 halogenated alkyl group, a phenylthio group, a benzyl group, a benzene ring, an indan ring, a 5,6,7,8-tetrahydronaphthalene ring, a naphthalene ring, a pyridine ring, a pyrrole ring, a thiophene ring, a furan ring or an imidazole ring; R3 and R-1 represents each independently a hydrogen atom, C1-6, alkyl group, a hydroxy group, a C1-4 alkoxy group or a halogen atom; R5 represents a hydrogen atom, a C1-6 alkyl group or a halogen atom. The invention relates also to a medicament comprising the said derivative or a salt thereof as an active ingredient which is used for preventive and/or therapeutic treatment of a neurodegenerative disease caused by abnormal activity of GSK3β3 or GSK3β3 and cdk5/p25, such as Alzheimer disease. |
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204-kolnp-2004-granted-abstract.pdf
204-kolnp-2004-granted-assignment.pdf
204-kolnp-2004-granted-claims.pdf
204-kolnp-2004-granted-correspondence.pdf
204-kolnp-2004-granted-description (complete).pdf
204-kolnp-2004-granted-examination report.pdf
204-kolnp-2004-granted-form 1.pdf
204-kolnp-2004-granted-form 13.pdf
204-kolnp-2004-granted-form 18.pdf
204-kolnp-2004-granted-form 3.pdf
204-kolnp-2004-granted-form 5.pdf
204-kolnp-2004-granted-gpa.pdf
204-kolnp-2004-granted-reply to examination report.pdf
204-kolnp-2004-granted-specification.pdf
| Patent Number | 231465 | |||||||||||||||||||||||||||
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| Indian Patent Application Number | 204/KOLNP/2004 | |||||||||||||||||||||||||||
| PG Journal Number | 10/2009 | |||||||||||||||||||||||||||
| Publication Date | 06-Mar-2009 | |||||||||||||||||||||||||||
| Grant Date | 04-Mar-2009 | |||||||||||||||||||||||||||
| Date of Filing | 16-Feb-2004 | |||||||||||||||||||||||||||
| Name of Patentee | SANOFI-AVENTIS | |||||||||||||||||||||||||||
| Applicant Address | 174 AVENUE DE FRANCE, F-75013, PARIS | |||||||||||||||||||||||||||
Inventors:
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| PCT International Classification Number | C07D 487/04 | |||||||||||||||||||||||||||
| PCT International Application Number | PCT/EP02/11127 | |||||||||||||||||||||||||||
| PCT International Filing date | 2002-09-19 | |||||||||||||||||||||||||||
PCT Conventions:
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