GSK-3β inhibitor
For the purpose of providing a GSK-3β inhibitor containing an oxadiazole compound or a salt thereof or a prodrug thereof useful as an agent for the prophylaxis or treatment of a GSK-3β-related pathology or disease, the present invention provides a GSK-3β inhibitor containing a compound represented by the formula (I): wherein each symbol is as defined in the specification, or a salt thereof or a prodrug thereof.
1. A GSK-3β inhibitor comprising a compound represented by the formula (I):
wherein
R 1 is a group represented by the formula: R 1a —Y—
wherein
Y is a bond, a sulfur atom, or —NR y — (R y is a hydrogen atom, or a lower alkyl group), and
R 1a is (1) a hydrogen atom, or (2) a C 1-2 alkyl group optionally substituted by one or more substituents selected from the group consisting of a halogen atom, an optionally substituted carbamoyl group, an optionally substituted C 6-10 aryl group and an optionally substituted 5- to 10-membered aromatic heterocyclic group, and
W is a group represented by the formula:
wherein
ring A is a 6-membered aromatic ring,
X is an oxygen atom, and
ring B is a 5-membered heterocycle represented by
wherein
Rb is an optionally substituted phenyl group, or an optionally substituted 5- or 6-membered heterocyclic group, and
Rb′ is a hydrogen atom, an amino group, or a monosubstituted amino group, or a salt thereof.
2. A method of inhibiting GSK-3β, comprising administering a compound represented by the formula (I):
wherein
R 1 is a group represented by the formula: R 1a —Y—
wherein
Y is a bond, a sulfur atom, or —NR y — (R y is a hydrogen atom, or a lower alkyl group), and
R 1a is (1) a hydrogen atom, or (2) a C 1-2 alkyl group optionally substituted by one or more substituents selected from the group consisting of a halogen atom, an optionally substituted carbamoyl group, an optionally substituted C 6-10 aryl group and an optionally substituted 5- to 10-membered aromatic heterocyclic group, and
W is a group represented by the formula:
wherein
ring A is a 6-membered aromatic ring,
X is an oxygen atom, and
ring B is a 5-membered heterocycle represented by
wherein
Rb is an optionally substituted phenyl group, or an optionally substituted 5- or 6-membered heterocyclic group, and
Rb′ is a hydrogen atom, an amino group, or a monosubstituted amino group, or a salt thereof to a subject.
3. The method of claim 2 , wherein the subject suffers from a neurodegenerative disease.
4. The method of claim 2 , wherein the subject suffers from Alzheimer's disease.
5. A pharmaceutical composition comprising the GSK-3β inhibitor of claim 1 , and a pharmacologically acceptable carrier.