Senile dementia has become a serious medical and social problem along with the rapid aging of society in recent years and the development of effective anti-dementia drugs has been greatly desired. There are already very many studies on Alzheimer's disease but the cause of the disease has not been clearly defined. An Alzheimer's disease drug, Aricept, is based on its acetylcholinesterase inhibitory activity. This drug is very useful as symptomatic therapy but is not a drug for fundamental therapy.
Alzheimer's disease is considered to be caused by aggregation of amyloid β-protein (hereinafter also referred to as Aβ), aggregation of tau, and the like. Hence, a substance that can inhibit aggregation of these proteins is a potential candidate for a fundamental therapeutic agent for Alzheimer's disease.
Yang et al. have reported that curcumin has an Aβ aggregation inhibitory activity, a disaggregation activity on Aβ aggregate, and the like (Non Patent Literature 1). The inventors of the present invention have revealed that curcumin and its derivatives have an inhibitory activity against secretase, which is involved in the generation of Aβ (Patent Literature 1 and 2). Narlawar et al. have synthesized curcumin derivatives by replacing the 1,3-dicarbonyl moiety with a pyrazole ring and reported that these compounds have a tau aggregation inhibitory activity (Non Patent Literature 2).