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Your search keyword '"Yoko Ueno"' showing total 3 results
Start Over Author "Yoko Ueno" Journal chemicalpharmaceutical bulletin
3 results on '"Yoko Ueno"'

1. Discovery of N-{2-Methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl}-N'-[2-(propane-2-sulfonyl)phenyl]-1,3,5-triazine-2,4-diamine (ASP3026), a Potent and Selective Anaplastic Lymphoma Kinase (ALK) Inhibitor

Author

Kazuhiko, Iikubo, Yutaka, Kondoh, Itsuro, Shimada, Takahiro, Matsuya, Kenichi, Mori, Yoko, Ueno, and Minoru, Okada

Subjects
Binding Sites, Lung Neoplasms, Triazines, Transplantation, Heterologous, Drug Evaluation, Preclinical, Administration, Oral, Receptor Protein-Tyrosine Kinases, Mice, SCID, Drug Administration Schedule, Protein Structure, Tertiary, Molecular Docking Simulation, Inhibitory Concentration 50, Mice, Structure-Activity Relationship, Mice, Inbred NOD, Carcinoma, Non-Small-Cell Lung, Cell Line, Tumor, Animals, Humans, Anaplastic Lymphoma Kinase, Sulfones, Protein Kinase Inhibitors
Abstract

Anaplastic lymphoma kinase (ALK) is a validated therapeutic target for treating echinoderm microtubule-associated protein-like 4 (EML4)-ALK positive non-small cell lung cancer (NSCLC). We synthesized a series of 1,3,5-triazine derivatives and identified ASP3026 (14a) as a potent and selective ALK inhibitor. In mice xenografted with NCI-H2228 cells expressing EML4-ALK, once-daily oral administration of 14a demonstrated dose-dependent antitumor activity. Here, syntheses and structure-activity relationship (SAR) studies of 1,3,5-triazine derivatives are described.

Published
2018

2. Radioiodinated phenoxyacetic acid derivatives as potential brain imaging agents. II. Structure-biodistribution relationship

Author

Chiaki Tanaka, Yoko Ueno, Yasuhiro Magata, Akira Yokoyama, Shin'ichiro Okuyama, and Yoshiro Ohmomo

Subjects
Male, Biodistribution, Stereochemistry, Chemical structure, chemistry.chemical_element, Mice, Inbred Strains, Iodine, Phenoxyacetates, Iodine Radioisotopes, Hydrolysis, chemistry.chemical_compound, Mice, Structure-Activity Relationship, In vivo, Amide, Diamine, Drug Discovery, Animals, Tissue Distribution, Radionuclide Imaging, Chromatography, High Pressure Liquid, Radiochemistry, Brain, General Chemistry, General Medicine, Glycolates, chemistry, Chemical stability
Abstract

In developing new brain imaging agents for single photon emission computed tomography (SPECT), we synthesized eleven radioiodinated phenoxyacetic acid derivatives and investigated the relationship between the chemical structure and in vivo characteristics. Biodistribution studies in mice revealed high initial brain uptake for all the compounds. Blood radioactivity level depended markedly upon the chemical stability of the compound. The alpha, alpha-dimethylester derivative (1e), amide derivatives (2a--c) and diamine derivatives (3a, b, 4), which were stable to hydrolysis, showed low blood activity levels following i.v. administration. Disappearance of the ester and amide compounds from the brain was rapid. However, the diamine derivatives displayed improved retention in the brain. Compounds 3a and 4 possessed the best combination of high brain uptake and sufficient retention to be useful as potential brain imaging radiopharmaceuticals with SPECT devices.

Published
1989

3. Radioiodinated phenoxyacetic acid derivatives as potential brain imaging agents. I. Efficient synthesis via trimethylsilyl intermediates

Author

Shin'ichiro Okuyama, Yasuhiro Magata, Yoshiro Ohmomo, Akira Yokoyama, Chiaki Tanaka, and Yoko Ueno

Subjects
Trimethylsilyl Compounds, Trimethylsilyl, Chemical Phenomena, medicine.drug_class, ETHYLENEDIAMINE DERIVATIVES, Carboxamide, Phenoxyacetates, Iodine Radioisotopes, chemistry.chemical_compound, Derivative (finance), Diamine, Drug Discovery, medicine, Organic chemistry, Radionuclide imaging, Radionuclide Imaging, Chemistry, Halogenation, Brain, General Chemistry, General Medicine, Combinatorial chemistry, Phenoxyacetic acid, Glycolates, Isotope Labeling
Abstract

The usefulness of radioiodination via demetallation of aryltrimethylsilanes was demonstrated. The radioiodination reaction was found to be very rapid and the regiospecific incorporation of radioiodine could be carried out with high radiochemical yields and high radiospecific activity. 125I-Labeled dimethylaminoethyl iodophenoxyacetate derivatives (5a--e), dimethylaminoethyl iodophenoxyacetamide derivatives (7a--c), iodophenoxyethyl ethylenediamine derivatives (9,14) and an iodophenoxyethylpiperazine derivative (18) were efficiently synthesized from the corresponding aryltrimethylsilyl intermediates (4a--e, 6a--c, 8, 13, 17) by this method.

Published
1989

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