A Derivative of 2 - - - pirimidinil 6,7,8,9 tetrahidropirimido 1,2-a - pyrimidine - 4 and 7 - pirimidinil ONA - 2.3 - dihidroimidazo 1,2-a pyrimidine 5 (1H) Ona replaced, use, which comprises a Medicine and an inhibitor of GSK3beta or GSK3beta and selected between Cdk5 / P25 the group of the derivative

摘要

Primidone derivative represented by the formula (1) or a Salt thereof, or a solvate thereof, or a hydrate thereof, where X represents two Hydrogen Atoms and one Sulfur Atom, an oxygen Atom or a c1-2 alkyl group and a hydrogen Atom; and represents a Union, a gru Etenileno etinileno po, a Group, an oxygen Atom and a Sulfur Atom, a sulfonyl Group,A sulfoxide Group, a carbonyl Group, a nitrogen Atom, an optionally substituted by alkyl group C1 - 6, a phenyl or benzyl Group; or a methylene Group optionally substituted by one or two groups selected from an alkyl group C1 - 6, a benzyl Group, a hydroxyl Group, a gr Upo c1-4 alkoxy, a cicloalquil - C3 - 6 metiloxi Group, an alkyl group perhalogenado c1-2,An amino Group, a group or a phenyl Group acetyl amino pyrimidine Ring; r1 represents an optionally substituted cycloalkyl C3 6 by a group or a c1-4 alkyl group, alkoxy Group C1 - 4 a benzyl Group, or a Halogen Atom; and represents a Union, a methylene Group is optional Mind or a substituted carbonyl GroupThen R2 represents an alkyl group, an optionally substituted C1 - C6 ariloxi 6 - 10 or a group arilamino C6 - 10 pp. ISBN a cycloalkyl Group; 6, a group Alquiltio c1-4 alkoxy Group, a c1-4 alkyl group, a perhalogenado c1-2 alkyl group, a Halogenated C1 - 3, a group phenylthio Group, a benzyl Or, a phenyl ring, a Ring of a ring indanilo, 5,6,7,8-tetrahydro - naphthyl,Naphthyl ring, pyridine ring, a Ring of a Ring of pyrrole, Furan or thiophene ring, an imidazole Ring; or where the benzyl Group optionally substituted rings are for 1 to 4 substituents selected from an alkyl group C1 - 6, a methylenedioxy Group, an Atom Halogen, alkyl group perhalogenado c1-2 alkyl group, a Halogenated C1 - 3A hydroxyl Group, a Group a c1-4 alkoxy, Nitro, cyano, amino, a Group monoalquilamino C1 - C2 - dialquilamino 5, a Group, a Group alquilcarbonil C1 - 6 - amino Group, an aryl carbonyl amino c6-10, a sulfonyl Group c1-4 alkyl, a sulfoniloxi c1-4 alkyl group or a phenyl; and when the Div. A etenileno ATN Group, a Group etinileno, an oxygen Atom and a Sulfur Atom.A sulfonyl Group, a sulfoxide group or an optionally substituted nitrogen Atom, then R2 represents an alkyl group C1 - 6 (optionally replaced by a group ariloxi C1 - C6 Group arilamino 6 or 10), a cycloalkyl Group C3 - 6, a perhalogenado c1-2 alkyl group, an alkyl group Halogenated C1 - 3, a benzyl Group, a phenyl ring, a Ring of a ring indanilo, 5,6,7,8 - tetrahydro - naphthyl ring, naphthyl, a Pyridine ring, a Ring of a Ring of pyrrole, Furan or thiophene ring, an imidazole Ring; or where the benzyl Group optionally substituted rings are for 1 to 4 substituents selected from an alkyl group C1, Group M Ethylenedioxy, a Halogen Atom, an alkyl group perhalogenado c1-2,A Halogenated c1-3 alkyl group, a hydroxyl Group, a Group a c1-4 alkoxy, Nitro, cyano, amino, a Group monoalquilamino C1 - 5 - 10 dialquilamino C2 Group, an alkyl group, a C1 - 6 - amino carbonyl Group, an aryl carbonyl amino c6-10, a c1-4 alkyl sulfonyl Group, alkyl group sulfoniloxi C 1 - 4 or a phenyl Group; R3 and R4 represent each independently a hydrogen Atom,A C1 - 6 alkyl group, a Hydroxy Group, a group or a c1-4 alkoxy Halogen Atom; R5 represents a hydrogen Atom, an alkyl group C1 - 6 or a Halogen Atom; when M is equal to 0, p is equal to 1, 2 or 3; when M is equal to 1, p is equal to 0, 1 or 2; when M is equal to 2, P IG UAL is 0 OR 1; and N represents between 0 and 3.It also discloses a drug comprising the derivative or a Salt thereof as an active ingredient which is used for Therapeutic and / or prophylactic Treatment of a neurodegenerative disease caused by abnormal activity of GSK3beta or GSK3beta and Cdk5 / P25, such asAlzheimer's disease; or an inhibitor of GSK3beta GSK3beta and Cdk5 / P25 selected among the group of Primidone derivative represented by the formula (1) or salts thereof, or a solvate thereof, or a hydrate thereof; and the use of the Derivative of Primidone.