Design and synthesis of curcumin derivatives as tau and amyloid beta dual aggregation inhibitors

作者：Okuda Michiaki^*; Hijikuro Ichiro; Fujita Yuki; Teruya Takayuki; Kawakami Hirochika; Takahashi Takashi; Sugimoto Hachiro

来源：Bioorganic & Medicinal Chemistry Letters, 2016, 26(20): 5024-5028.

DOI：10.1016/j.bmcl.2016.08.092

• Alzheimer's disease
• Tau
• Amyloid beta
• Aggregation inhibitor
• Curcumin

Alzheimer's disease (AD) is the most common form of dementia. In an AD patient's brain, senile plaques and neurofibrillary tangles, the abnormal aggregates of amyloid beta (A beta) peptide and tau protein, are observed as the two major hallmarks of this disease. To develop a new drug for treatment of AD, we have designed and synthesized a series of curcumin derivatives and evaluated their inhibitory activities against both tau and Ab aggregation. In this study, we describe the development of the more potent aggregation inhibitor 3-[(1E)-2-(1H-indol-6-yl) ethenyl]-5-[(1E)-2-[ 2-methoxy-4-(2-pyridylmethoxy) phenyl] ethenyl]-1H-pyrazole (compound 4, PE859). This compound has a better pharmacokinetic profile and pharmacological efficacy in vivo than curcumin, making it suitable as a drug for AD.

• 出版日期2016-10-15