Directing-Group-Free Arene C(sp)-H Amination Using Bulky Aminium Radicals and DFT Analysis of Regioselectivity.

A hydroxylamine-derived electrophilic aminating reagent produces a transient and bulky aminium radical intermediate upon activation by either TMSOTf or TFA and a subsequent electron transfer from an iron(II) catalyst. Density functional theory calculations were used to examine the regioselectivity of arene C-H amination reactions on diversely substituted arenes. The calculations suggest a simple charge-controlled regioselectivity model that enables prediction of the major C(sp)-H amination product.

Evaluation of the Inhibitory Effects of Pyridylpyrazole Derivatives on LPS-Induced PGE Productions and Nitric Oxide in Murine RAW 264.7 Macrophages.

A series of thirteen triarylpyrazole analogs were investigated as inhibitors of lipopolysaccharide (LPS)-induced prostaglandin E (PGE) and nitric oxide (NO) production in RAW 264.7 macrophages. The target compounds - have first been assessed for cytotoxicity against RAW 264.

Synthesis and evaluation of multivalent nitroimidazole-based near-infrared fluorescent agents for neuroblastoma and colon cancer imaging.

Hypoxia is one of key characteristics of microenvironments of solid tumors, and evaluation of hypoxia status in solid tumors is important to determine cancer stage and appropriate treatment. In the present study, novel, multivalent, near-infrared (NIR) fluorescent imaging agents were developed to measure tumor hypoxia. These agents were synthesized using an amino acid as a backbone to connect mono-, bis-, or tris-2-nitroimidazole as a hypoxia-sensitive moiety to enhance uptake by the tumor and to attach sulfo-Cyanine 5.

Late-Stage F/F Isotopic Exchange for the Synthesis of F-Labeled Sulfamoyl Fluorides.

Synthesis of sulfamoyl [F]fluorides has been a challenging topic owing to the inefficient nucleophilic radiofluorination of sulfamoyl derivatives. Herein, we report an F/F isotopic exchange approach to synthesize various sulfamoyl [F]fluorides, otherwise inaccessible via direct synthesis from amines, with high radiochemical yields up to 97% (30 examples). This late-stage labeling protocol offers an efficient route to yield functionalized molecules by diversifying the chemical library possessing sulfamoyl functionalities through nucleophilic F incorporation within nitrogen-containing sulfur(VI) frameworks.

F-labelled BODIPY dye as a dual imaging agent: Radiofluorination and applications in PET and optical imaging.

Dual Positron emission tomography (PET)/optical imaging techniques have captured scientific interest for clinical applications due to their potential as an effective tool for visualizing in vivo information such as disease processes. 4,4'-Difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY) dye has been considered an ideal platform strategy to achieve dual PET/optical imaging due to its photochemical nature and chemical structure. Various radiofluorination methods to prepare [F]BODIPY dye have been developed and established, ranging from nucleophilic substitution reactions to isotope exchange reactions.

Synthesis of F-Labeled Aryl Fluorosulfates via Nucleophilic Radiofluorination.

Sulfuryl fluoride gas is a key reagent for SOF transfer. However, conventional SOF transfer reactions have limited F-radiochemistry translation, due to the inaccessibility of gaseous [F]SOF. Herein, we report the first SOF-free synthesis of aryl [F]fluorosulfates from both phenolic and isolated aryl imidazylate precursors with cyclotron-produced F.

Novel multifunctional F-labelled PET tracer with prostate-specific membrane antigen-targeting and hypoxia-sensitive moieties.

Prostate cancer is one of the most frequently found cancers in men worldwide. Prostate-specific membrane antigen (PSMA) is typically highly expressed in prostate cancer, and the Glu-Urea-Lys (GUL) structure has recently received considerable attention as a key unit of PSMA-targeting agents. Additionally, one of the common characteristics of many solid tumors, such as prostate cancer, is hypoxia.

Synthesis and evaluation of novel potent TSPO PET ligands with 2-phenylpyrazolo[1,5-a]pyrimidin-3-yl acetamide.

Translocator protein (TSPO) expression is closely related with neuroinflammation and neuronal damage which might cause several central nervous system diseases. Herein, a series of TSPO ligands (11a-c and 13a-d) with a 2-phenylpyrazolo[1,5-a]pyrimidin-3-yl acetamide structure were prepared and evaluated via an in vitro binding assay. Most of the novel ligands exhibited a nano-molar affinity for TSPO, which was better than that of DPA-714.

Chemoselective Radiosyntheses of Electron-Rich [F]Fluoroarenes from Aryl(2,4,6-trimethoxyphenyl)iodonium Tosylates.

Hypervalent diaryliodonium salts have been used to produce various [F]fluoroarenes. The iodonium salt approach as a labeling precursor has been established to equally afford complex F-fluorinated molecules. Because of the inherent two aryl ring system connected to a central iodine atom, safeguarding the chemoselectivity during radiofluorination using diaryliodonium salts is important.

Catalyst-Free Aromatic Radiofluorination via Oxidized Iodoarene Precursors.

Oxidized iodoarenes (OIAs), prepared via mCPBA-mediated oxidation, have been demonstrated as versatile precursors for the synthesis of [F]fluoroarenes in the absence of catalysts. OIAs have been identified as intermediates in single-pot syntheses of iodonium salts and ylides but have never been recognized as radiofluorination precursors. Here, the isolated OIAs were used without any catalysts to produce functionalized [F]fluoroarenes, regardless of the electronic nature of the arenes.

Synthesis and Evaluation of Multifunctional Fluorescent Inhibitors with Synergistic Interaction of Prostate-Specific Membrane Antigen and Hypoxia for Prostate Cancer.

Prostate cancer is one of the most common cancers in the world. It is widely known that prostate-specific membrane antigen (PSMA) is highly expressed in prostate cancer, and hypoxia is a common characteristic of many solid tumors, including prostate cancer. In this study, we designed multifunctional fluorescent inhibitors to target PSMA and tumor hypoxia in order to increase the tumor uptake of inhibitors.

Novel potential pyrazolopyrimidine based translocator protein ligands for the evaluation of neuroinflammation with PET.

Translocator protein (TSPO) is an interesting biological target because TSPO overexpression is associated with microglial activation caused by neuronal damage or neuroinflammation, and these activated microglia are involved in several central nervous system diseases. Herein, novel fluorinated ligands (14a-c and 16a-c) based on a 2-phenylpyrazolo[1,5-a]pyrimidin-3-yl acetamide scaffold were synthesized, and in vitro characterization of each of the novel ligands was performed to elucidate structure activity relationships. All of the newly synthesized ligands displayed nano-molar affinity for TSPO.

Synthesis of novel multivalent fluorescent inhibitors with high affinity to prostate cancer and their biological evaluation.

Prostate-specific membrane antigen (PSMA) is an important biological target for therapy and diagnosis of prostate cancer. In this study, novel multivalent PSMA inhibitors with glutamate-urea-lysine structures were designed to improve inhibition characteristics. Precursors of the novel inhibitors were prepared from glutamic acid with di-tert-butyl ester.

MicroRNAs overexpressed in ovarian ALDH1-positive cells are associated with chemoresistance.

Background: Ovarian carcinoma is the leading cause of cancer death worldwide among gynecological malignancies, and the majority of cases are related with recurrence and chemoresistance. Cancer stem cells (CSCs) are believed to be one of the causes of recurrent or chemoresistant ovarian cancer, and microRNAs are regulatory molecules newly implicated to control a variety of cellular processes, including CSCs. Therefore, we identified ovarian CSC-specific microRNAs and investigated their clinicopathological implication in ovarian carcinomas.

Deregulation of miR-519a, 153, and 485-5p and its clinicopathological relevance in ovarian epithelial tumours.

Aims: The pathological and clinical significance of aberrant miRNA expression in ovarian tumours has yet to be adequately documented. The aim of this study was to assess the differences in miRNA expression of human ovarian tumours according to histological subtype, and to determine whether miRNAs are potential diagnostic and prognostic markers in ovarian cancers.

Method And Results: The miRNA expression profiles of 103 human ovarian tumours were evaluated.

Potential side effects of dendritic cells pulsed with allogenic melanoma cell lysate in mice.

An attempt has been made to investigate the toxicity of cancer immunotherapy based on the dendritic cells pulsed with lysate of allogenic melanoma cell, DM401. Dendritic cells pulsed with lysate of clone M3 were subcutaneously administered once a week eight times to C57BL/6 mice at 0, 2.5, 5, and 10 x 10(7) cells/kg.