With increases in aging population, the development of pharmaceuticals effective for the treatment of senile dementia has been demanded strongly in recent years. Alzheimer's disease, which is a typical disease of senile dementia, is a neurodegenerative disease characterized by brain shrinkage, deposits of senile plaques, and neurofibrillary changes. This disease develops when insolubilized molecules attributed to a change of forms of amyloid β peptides and following fibrillogenesis are deposited on neuronal cells such that neuronal cell death is induced by their toxicity.
Amyloid β peptides (Aβ) are degradation products generated by cleavage with β secretase, etc., from neuronal amyloid precursor proteins, and these degradation products are found in 2 forms, Aβ1-40 and Aβ1-42. It has been reported that Aβ1-42 is more likely to aggregate and more correlated to disease and neurotoxicity.
If a change of forms of amyloid β peptides and fibrillogenesis thereof can be inhibited, the development of Alzheimer's disease can be prevented.
The pamphlet of WO 2005/105998 describes that a single-chain antibody having an activity of specifically binding to Aβ1-42 such that the fibrillogenesis reaction thereof is inhibited is useful as a preventive or therapeutic agent for Alzheimer's disease.
However, antibodies are high-molecular-weight proteins and are therefore expensive. They also have problems such as complicated production and purification steps or a lack of stability.
Drugs having an effect of suppressing amyloid β peptide production, for example, a rhodanine derivative (JP Patent Publication (Kokai) No. 06-192091A (1994)), a benzimidazole derivative (U.S. Pat. No. 5,552,426), a vinpocetine derivative (pamphlet of WO 96/25161), and an aromatic amide derivative (pamphlet of WO 2004/014843), have been known as low-molecular-weight preventive or therapeutic agents for Alzheimer's disease.