Synthesis and biological evaluation of radioiodinated 2,5-diphenyl-1,3,4-oxadiazoles for detecting β-amyloid plaques in the brain

被引：23

作者：

Watanabe, Hiroyuki ^{[1
]}

Ono, Masahiro ^{[1
,2
]}

Ikeoka, Ryoichi ^{[1
]}

Haratake, Mamoru ^{[1
]}

Saji, Hideo ^{[2
]}

Nakayama, Morio ^{[1
]}

机构：

[1] Nagasaki Univ, Grad Sch Biomed Sci, Nagasaki 8528521, Japan

[2] Kyoto Univ, Grad Sch Pharmaceut Sci, Sakyo Ku, Kyoto 6068501, Japan

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2009年 / 17卷 / 17期

关键词：

Alzheimer's disease; beta-Amyloid plaques; SPECT imaging; ALZHEIMERS-DISEASE; NEUROFIBRILLARY TANGLES; IMAGING AGENTS; PET; PROBES; DERIVATIVES; BINDING;

D O I：

10.1016/j.bmc.2009.07.020

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

This paper describes the synthesis and biological evaluation of a new series of 2,5-diphenyl-1,3,4-oxadiazole (1,3,4-DPOD) derivatives for detecting beta-amyloid plaques in Alzheimer's brains. The affinity for beta-amyloid plaques was assessed by an in vitro binding assay using pre-formed synthetic A beta 42 aggregates. The new series of 1,3,4-DPOD derivatives showed affinity for Ab42 aggregates with K-i values ranging from 20 to 349 nM. The 1,3,4-DPOD derivatives clearly stained beta-amyloid plaques in an animal model of Alzheimer's disease, reflecting the affinity for A beta 42 aggregates in vitro. Compared to 3,5-diphenyl-1,2,4-oxadiazole (1,2,4-DPOD) derivatives, they displayed good penetration of and fast washout from the brain in biodistribution experiments using normal mice. The novel radioiodinated 1,3,4-DPOD derivatives may be useful probes for detecting b-amyloid plaques in the Alzheimer's brain. (C) 2009 Elsevier Ltd. All rights reserved.

引用

页码：6402 / 6406

页数：5

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