RU2003105827A - AGENTS AGAINST DECIDENCE, CONTAINING 2-ARIL-8-OXODYHYDROPURINE DERIVATIVES, AS AN ACTIVE INGREDIENT - Google Patents

Claims (14)

1. A medicament for the treatment or prevention of dementia containing a 2-aryl-8-oxo-dihydropurin derivative of the formula (I)

where W represents a hydrogen atom, a C _1-6 alkyl group, a halogen atom, a C _1-6 alkoxy group, an amino group, a mono or di (C _1-4 alkyl) amino group, or a phenyl group, which may optionally have 1 or 2 substituents selected from halogen, C _1-6 alkyl, C _1-6 alkoxy, trifluoromethyl, hydroxy, amino, mono or di (C _1-4 alkyl) amino, cyano and nitro; X represents a hydrogen atom, a C _1-6 alkyl group, a C _3-8 cycloalkyl-C _1-4 alkyl group, a C _1-4 alkyl group substituted with a phenyl group, which may optionally have 1 or 2 substituents selected from halogen, C _1-6 alkyl, C _1-6 alkoxy, trifluoromethyl, hydroxy, amino, mono- or di (C _1-4 alkyl) amino, cyano and nitro, C _3-6 alkenyl group, carbamoyl group, di (C _{1- 4} alkyl) carbamoyl group or a group of the formula [Q]

where R ¹ represents a C _1-6 alkyl group, a C _3-6 alkenyl group; A C _3-8 cycloalkyl group, a C _3-8 cycloalkyl-C _1-4 alkyl group or a hydroxy-C _1-4 alkyl group; R ² represents a C _1-6 alkyl group, a C _3-8 cycloalkyl group, a phenyl group which may optionally have 1 or 2 substituents selected from halogen, C _1-6 alkyl, C _1-6 alkoxy, trifluoromethyl, hydroxy, amino, mono- or di (C _1-4 alkyl) amino, cyano and nitro, C _1-4 alkyl group substituted by a phenyl group, which may optionally have 1 or 2 substituents selected from halogen, C _1-6 alkyl, C _1-6 alkoxy, trifluoromethyl, hydroxy, amino, mono- or di (C _1-4 alkyl) amino, cyano and nitro, or monocyclic 5- or 6-membered heteroaryl groups or a bicyclic heteroaryl group consisting of 5- or 6-membered heteroaryls which have at least one heteroatom selected from a nitrogen atom, an oxygen atom or a sulfur atom and optionally substituted with C _1-3 alkyl or trifluoromethyl, or R ¹ and R ² may optionally be taken together with the adjacent nitrogen atom to form a piperidine ring, pyrrolidine ring, morpholine ring or piperazine ring, which may optionally be substituted with 1 or 2 C _1-6 alkyl, respectively; R ³ represents a hydrogen atom, a C _1-6 alkyl group or a hydroxy-C _1-4 alkyl group; Y represents a hydrogen atom, a C _1-6 alkyl group, a C _3-8 cycloalkyl group, a C _3-8 cycloalkyl-C _1-4 alkyl group, a C _3-8 alkenyl group, a C _1-4 alkyl group substituted with a phenyl group which may optionally have 1 or 2 substituents selected from halogen, C _1-6 alkyl, C _1-6 alkoxy, trifluoromethyl, hydroxy, amino, mono or di (C _1-4 alkyl) amino, cyano and nitro, or a group of the formula [Q]

where R ¹ R ² and R ³ are as described above); A is a phenyl group, which may optionally have 1 or 2 substituents selected from halogen, C _1-6 alkyl, C _1-6 alkoxy, trifluoromethyl, hydroxy, amino, mono or di (C _1-6 alkyl) amino, cyano and nitro; or a monocyclic 5- or 6-membered heteroaryl group or a bicyclic heteroaryl group consisting of 5- or 6-membered heteroaryls which have at least one heteroatom selected from a nitrogen atom, an oxygen atom or a sulfur atom and optionally substituted with C _{1 -3} alkyl or trifluoromethyl, with the proviso that either X or Y of the indicated formula (I) is a group of the above formula [Q], and when X is a group of the formula [Q], then Y represents a hydrogen atom, a C _1-6 alkyl group, C _{3- 8} cycloalkyl group, C _3-8 cycloalkyl-C _1-4 alkyl group, C _3-6 alkenyl group, or C _1-4 alkyl group substituted with a phenyl group, which may optionally have 1 or 2 substituents selected from halogen, C _1-6 alkyl, C _1-6 alkoxy, trifluoromethyl, hydroxy, amino, mono- or di (C _1-4 alkyl) amino, cyano and nitro, and when Y is g a group of the formula [Q], then X represents a hydrogen atom, a C _1-6 alkyl group, a C _3-8 cycloalkyl-C _1-4 alkyl group, a C _1-4 alkyl group substituted with a phenyl group, which may optionally have 1 or 2 substituents selected from halogen, C _1-6 alkyl, C _1-6 alkoxy, trifluoromethyl, hydroxy, amino, mono or di (C _1-4 alkyl) amino, cyano and nitro, C _3-6 alkenyl group, carbamoyl a group or di (C _1-4 alkyl) carbamoyl group, or a pharmaceutically acceptable acid addition salt thereof. 2. The medicament for the treatment or prevention of dementia according to claim 1, wherein said 2-aryl-8-oxodihydropurin derivative has the formula (Ia)

where R ¹² and R ²² are the same or different and represent an ethyl group, a propyl group or a butyl group, or R ¹² represents a methyl group, an ethyl group or a propyl group, and R ²² represents a phenyl group, a halogen phenyl group, a methoxyphenyl group, a benzyl group, a halogenbenzyl group or a methoxybenzyl group; R ³² represents a hydrogen atom, a methyl group or an ethyl group; Y ¹ represents a hydrogen atom, a methyl group or an ethyl group; R ⁴² represents a hydrogen atom, a halogen atom, a methyl group, a methoxy group, a nitro group or a trifluoromethyl group, or a pharmaceutically acceptable acid addition salt thereof. 3. The medicament for the treatment or prevention of dementia according to claim 1, wherein said 2-aryl-8-oxodihydropurin derivative has the formula (Ib)

where X ¹ represents a hydrogen atom, a methyl group, an ethyl group or a propyl group; R ¹³ and R ²³ are the same or different and represent an ethyl group, a propyl group or a butyl group, or R ¹³ represents a methyl group, an ethyl group or a propyl group, and R ²³ represents a phenyl group, a halogen phenyl group, a methoxyphenyl group, a benzyl a group, a halogenbenzyl group or a methoxybenzyl group; R ³³ represents a hydrogen atom, a methyl group or an ethyl group; R ⁴³ represents a hydrogen atom, a methyl group, a methoxy group, a nitro group or a trifluoromethyl group, or a pharmaceutically acceptable acid addition salt thereof. 4. The medicament for treating or preventing dementia according to claim 1, wherein said derivative is N-ethyl-8,9-dihydro-9-methyl-8-oxo-2-phenyl-N-phenyl-7H-purin-7 -acetamide or a pharmaceutically acceptable acid addition salt thereof. 5. The medicament for treating or preventing dementia according to claim 1, wherein said derivative is N-benzyl-N-ethyl-7,8-dihydro-7-methyl-8-oxo-2-phenyl-9H-purin-9 -acetamide or a pharmaceutically acceptable acid addition salt thereof. 6. The medicament for the treatment or prevention of dementia according to claim 1, wherein said derivative is a compound according to any one of claims 1 to 5, or a pharmaceutically acceptable acid addition salt thereof. 7. The medicament for the treatment or prevention of dementia according to claim 1, wherein said derivative is a compound according to any one of claims 1 to 5 and where dementia is dementia such as Alzheimer's disease, cerebrovascular dementia and / or senile dementia. 8. A medicament for the treatment or prophylaxis of cerebral dysfunction, containing the compound according to any one of claims 1 to 5 or its pharmaceutically acceptable acid addition salt. 9. A medicament for treating or preventing the symptoms of dementia associated with diseases that can cause dementia, comprising a compound according to any one of claims 1 to 5 or a pharmaceutically acceptable acid addition salt thereof. 10. The use of a derivative, characterized in any one of claims 1 to 5, or a pharmaceutically acceptable acid addition salt thereof, for the manufacture of a medicament for the treatment or prevention of dementia. 11. The application of claim 10, where dementia is a deterioration in the learning process, dysmnesia, disorientation based on dysmnesia, or intellectual dysfunction. 12. The use of claim 10, where dementia is Alzheimer's disease, cerebrovascular dementia and / or senile dementia. 13. The use of a derivative characterized in any one of claims 1 to 5 or a pharmaceutically acceptable acid addition salt thereof, for the manufacture of a medicament for the treatment or prevention of cerebral dysfunction. 14. The use of a derivative described in any one of claims 1 to 5 or a pharmaceutically acceptable acid addition salt thereof, for the manufacture of a medicament for the treatment or prevention of symptoms of dementia associated with diseases that may cause dementia.