Novel quinoxaline derivatives for in vivo imaging of beta-amyloid plaques in the brain

作者：Cui, Mengchao; Ono, Masahiro^*; Kimura, Hiroyuki; Liu, Boli; Saji, Hideo

来源：Bioorganic & Medicinal Chemistry Letters, 2011, 21(14): 4193-4196.

DOI：10.1016/j.bmcl.2011.05.079

• Alzheimer's disease
• beta-Amyloid
• Imaging agent
• Binding assay
• Autoradiography

In a search for new probes to detect beta-amyloid plaques in the brain of patients with Alzheimer's disease (AD), we have synthesized and evaluated a series of quinoxaline derivatives containing a '6+6-6' ring system. These quinoxaline derivatives showed excellent affinity for A beta(1) (42) aggregates with K(i) values ranging from 2.6 to 10.7 nM. Autoradiography with sections of brain tissue from an animal model of AD mice (APP/PS1) and AD patients revealed that [(125)I]5 labeled beta-amyloid plaques specifically. In biodistribution experiments using normal mice, [(125)I]5 displayed high uptake (6.03% ID/g at 2 min) into and a moderately fast washout from the brain. Although additional refinements are needed to decrease the lipophilicity and improve the washout rate, the quinoxaline scaffold may be useful as a backbone structure to develop novel beta-amyloid imaging agents.

• 出版日期2011-7-15
• 单位北京师范大学