US 2003/0166667 A1 · Dementia remedies containing 2-aryl-8-oxodihydropurine derivatives as the active ingredient

Abstract

Medicines for treatment or prevention of dementia comprising 2-aryl-8-oxodihydropurine derivatives of the formula (I): 1 wherein W is H, C1-6 alkyl, halogen, C1-6 alkoxy, or the like; X is H, C1-6 alkyl, a group of the formula (Q): —CH(R3)CON(R1) (R2) (wherein R1 is a C1-6 alkyl or the like; R2 is phenyl-substituted C1-4 alkyl or the like; and R3 is H or the like); Y is H, C1-6 alkyl, a group of the above formula (Q), or the like; and A is substituted phenyl or the like, with the proviso that one of X and Y is a group of the formula (Q) and the other is a group selected from those defined for X or Y except the groups (Q), or pharmaceutically acceptable acid addition salts thereof. The above compounds exhibit an extremely potent ameliorating effect on learning disorder and/or dymnesia and thus are useful in the treatment or prevention of Alzheimer-type dementia, cerebrovascular dementia, senile dementia, etc.

A medicine for the treatment or prevention of dementia comprising a 2-aryl-8-oxodihydropurine derivative of the formula (I):

9
wherein:
W is a hydrogen atom;
a C1-6 alkyl group;
a halogen atom;
a C1-6 alkoxy group;
an amino group;
a mono- or di(C1-4 alkyl)amino group;
or a phenyl group which may optionally have 1 or 2 substituents selected from a halogen, a C1-6 alkyl, a C1-6 alkoxy, trifluoromethyl, hydroxy, amino, a mono- or di(C1-4 alkyl)amino, cyano and nitro;
X is a hydrogen atom;
a C1-6 alkyl group;
a C3-8 cycloalkyl-C1-4 alkyl group;
a C1-4 alkyl group substituted by a phenyl group which may optionally have 1 or 2 substituents selected from a halogen, a C1-6 alkyl, a C1-6 alkoxy, trifluoromethyl, hydroxy, amino, a mono- or di(C1-4 alkyl)amino, cyano and nitro;
a C3-6 alkenyl group;
a carbamoyl group;
a di(C1-4 alkyl)carbamoyl group;
or a group of the formula [Q]:
—CH(R3)CON(R1)(R2) [Q]
[wherein R1 is a C1-6 alkyl group;
a C3-6 alkenyl group;
a C3-8 cycloalkyl group;
a C3-8 cycloalkyl-C1-4 alkyl group;
or a hydroxy-C1-4 alkyl group;
R2 is a C1-6 alkyl group;
a C3-8 cycloalkyl group;
a phenyl group which may optionally have 1 or 2 substituents selected from a halogen, a C1-6 alkyl, a C1-6 alkoxy, trifluoromethyl, hydroxy, amino, a mono- or di(C1-4 alkyl)amino, cyano and nitro;
a C1-4 alkyl group substituted by a phenyl group which may optionally have 1 or 2 substituents selected from a halogen, a C1-6 alkyl, a C1-6 alkoxy, trifluoromethyl, hydroxy, amino, a mono- or di(C1-4 alkyl)amino, cyano and nitro;
or a monocyclic 5- or 6-membered heteroaryl group or a bicyclic heteroaryl group composed 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 is optionally substituted by a C1-3 alkyl or trifluoromethyl;
or R1 and R2 may optionally be taken together with the adjacent nitrogen to form a piperidine ring, a pyrrolidine ring, a morpholine ring or a piperazine ring, which may optionally be substituted by 1 or 2 C1-6 alkyls respectively;
R3 is a hydrogen atom, a C1-6 alkyl group or a hydroxy-C1-4 alkyl group];
Y is a hydrogen atom;
a C1-6 alkyl group;
a C3-8 cycloalkyl group;
a C3-8 cycloalkyl-C1-4 alkyl group;
a C3-6 alkenyl group;
a C1-4 alkyl group substituted by a phenyl group which may optionally have 1 or 2 substituents selected from a halogen, a C1-6 alkyl, a C1-6 alkoxy, trifluoromethyl, hydroxy, amino, a mono- or di(C1-4 alkyl)amino, cyano and nitro;
or a group of the formula [Q]:
—CH(R3)CON(R1) (R2) [Q]
(wherein R1, R2 and R3 are as defined above);
A is a phenyl group which may optionally have 1 or 2 substituents selected from a halogen, a C1-6 alkyl, a C1-6 alkoxy, trifluoromethyl, hydroxy, amino, a mono- or di(C1-4 alkyl)amino, cyano and nitro;
or a monocyclic 5- or 6-membered heteroaryl group or a bicyclic heteroaryl group composed 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 is optionally substituted by a C1-3 alkyl or trifluoromethyl;
with the proviso that either X or Y of the above formula (I) is a group of the above formula [Q], and when X is a group of the formula [Q], then Y is a hydrogen atom;
a C1-6 alkyl group;
a C3-8 cycloalkyl group;
a C3-8 cycloalkyl-C1-4 alkyl group;
a C3-6 alkenyl group;
or a C1-4 alkyl group substituted by a phenyl group which may optionally have 1 or 2 substituents selected from a halogen, a C1-6 alkyl, a C1-6 alkoxy, trifluoromethyl, hydroxy, amino, a mono- or di(C1-4 alkyl)amino, cyano and nitro, and when Y is a group of the formula [Q], then X is a hydrogen atom;
a C1-6 alkyl group;
a C3-8 cycloalkyl-C1-4 alkyl group;
a C1-4 alkyl group substituted by a phenyl group which may optionally have 1 or 2 substituents selected from a halogen, a C1-6 alkyl, a C1-6 alkoxy, trifluoromethyl, hydroxy, amino, a mono- or di(C1-4 alkyl)amino, cyano and nitro;
a C3-6 alkenyl group;
a carbamoyl group;
or a di(C1-4 alkyl)carbamoyl group, or a pharmaceutically acceptable acid addition salt thereof.

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Dementia remedies containing 2-aryl-8-oxodihydropurine derivatives as the active ingredient

Life of this patent

Dementia remedies containing 2-aryl-8-oxodihydropurine derivatives as the active ingredient

Life of this patent

Abstract

Claims19