Metal ions associated with amyloid-β (Aβ) species have been suggested to be involved in neurodegeneration leading to the progression of Alzheimer's disease (AD). The role of metal-involved Aβ species in AD neuropathogenesis, however, is not fully elucidated. In order to advance this understanding and contribute to the therapeutic development for AD, the rational structure-based design of small molecules that specifically target metal ions surrounded by Aβ species has recently received increased attention. To date, only a few compounds have been fashioned for this purpose. Herein, we report the design strategy, synthesis, characterization, and reactivity of new bifunctional IMPY derivatives K1 and K2. Using UV-vis and high-resolution two-dimensional (2D) NMR spectroscopy, the bifunctionality of K1 and K2 (metal chelation and Aβ interaction) was confirmed. These bifunctional IMPY derivatives showed preferential reactivity toward metal-induced Aβ aggregation over metal-free conditions in both in vitro inhibition and disaggregation experiments. Taken together, this study provides another example of a bifunctional small molecule framework that can target metal ions associated with Aβ species.
A highly efficient copper-catalyzed C-O cross-coupling reaction between aryl bromides and aliphatic diols has been developed employing a cheaper, more efficient, and easily removable copper(II) catalyst. A broad range of aryl bromides were coupled with aliphatic diols of different lengths using 5 mol% CuCl2 and 3 equivalents of K2CO3 in the absence of any other ligands or solvents to afford the corresponding hydroxyalkyl aryl ethers in good to excellent yields. In this newly developed protocol, aliphatic diols have multilateral functions as coupling reactants, ligands, and solvents. The resulting hydroxyalkyl aryl ethers were further readily converted into the corresponding phenols, presenting a valuable alternative way to phenols from aryl bromides. Furthermore, it was demonstrated that they are useful intermediates for more advanced molecules such as benzofurans and benzo-fused cyclic ethers.
We describe a 72-year-old man who presented with left hemiparesis due to acute cerebral infarction in the right fronto-temporal lobe. Three months prior to admission, he was hospitalized for right hemiparesis due to the acute cerebral infarction in the left anterior cerebral artery territory. To investigate the cause of his recurrent embolic event, a chest computed tomography scan and echocardiography were performed, which revealed advanced lung cancer invading contiguously through the pulmonary veins to the right main pulmonary artery and left atrium. Tumor embolism is a rare cause of stroke, occurring with primary or metastatic neoplasms of the lung. Echocardiography is a useful tool in patients with cerebral embolic episodes.
Intrahepatic cholangiocarcinoma is a rare malignancy that originates from the epithelial cells of the intrahepatic bile ducts. Intrahepatic cholangiocarcinoma can metastasize in lymphatic chains, including the hepatoduodenal ligament, and it often invades adjacent organs or metastasizes to other visceral organs such as the lungs, bones, adrenal glands, and brain. However, distant skeletal muscle metastasis is very rare. Moreover, a metastatic skeletal muscle tumor rarely shows specific symptoms, making it difficult to identify in a routine examination. A 45-year-old man with a chief complaint of right upper quadrant abdominal pain was admitted to our hospital. Abdominal ultrasound and computed tomography with contrast enhancement showed a malignant mass in the right hepatic lobe, and 2-[18F] fluoro-2-deoxy-D-glucose positron-emission tomography revealed distant skeletal muscle metastases in the thorax and buttock. The patient underwent an ultrasound-guided percutaneous needle biopsy for the metastatic low-echo masses in the skeletal muscle.
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