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343 results on '"Harusawa, Shinya"'

1. Azolato-Bridged Dinuclear Platinum(II) Complexes Exhibit Androgen Receptor-Mediated Anti-Prostate Cancer Activity

Author

Arai, Tasuku, Oshima, Masashi, Uemura, Masako, Matsunaga, Takeshi, Ashizawa, Taiki, Suhara, Yoshitomo, Morii, Magotoshi, Yoneyama, Hiroki, Usami, Yoshihide, Harusawa, Shinya, Komeda, Seiji, and Hirota, Yoshihisa

Abstract

Prostate cancer is an androgen-dependent malignancy that presents a marked treatment challenge, particularly after progression to the castration-resistant stage. Traditional treatments such as androgen deprivation therapy often lead to resistance, necessitating novel therapeutic approaches. Previous studies have indicated that some of the azolato-bridged dinuclear platinum(II) complexes (general formula: [{cis-Pt(NH3)2}2(μ-OH)(μ-azolato)]X2, where azolato = pyrazolato, 1,2,3-triazolato, or tetrazolato and X = nitrate or perchlorate) inhibit androgen receptor (AR) signaling. Therefore, here we investigated the potential of 14 such complexes as agents for the treatment of prostate cancer by examining their antiproliferative activity in the human prostate adenocarcinoma cell line LNCaP. Several of the complexes, particularly 5-H-Y([{cis-Pt(NH3)2}2(μ-OH)(μ-tetrazolato-N2,N3)](ClO4)2), effectively inhibited LNCaP cell growth, even at low concentrations, by direct modulation of AR signaling, and by binding to DNA and inducing apoptosis, which is a common mechanism of action of Pt-based drugs such as cisplatin (cis-diamminedichloridoplatinum(II)). Comparative analysis with cisplatin revealed superior inhibitory effects of these complexes. Further investigation revealed that 5-H-Ysuppressed mRNA expression of genes downstream from AR and induced apoptosis, particularly in cells overexpressing AR, highlighting its potential as an AR antagonist. Thus, we provide here insights into the mechanisms underlying the antiproliferative effects of azolato-bridged complexes in prostate cancer.

Published
2024
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3. Transformation of Benzaldehydes to Benzonitriles via Cyanophosphates without One-Carbon Homologation.

Author

Yoneyama, Hiroki, Okada, Ayami, Hayama, Noboru, Harusawa, Shinya, and Usami, Yoshihide

Subjects
CYCLIC compounds, UNSATURATED compounds, COLUMN chromatography, AROMATIC aldehydes, NORMAL-phase chromatography, IONS, SILICA gel, CYANIDES
Abstract

This article explores the use of cyanophosphates as synthetic intermediates in the transformation of benzaldehydes into benzonitriles. The researchers found that certain benzaldehydes reacted with tetrabutylammonium azide to form aromatic nitriles, while ketone or aliphatic aldehyde cyanophosphates resulted in the formation of tetrabutylammonium ethyl phosphates. The study also investigated the effects of reaction conditions on the transformation process. The document provides detailed information on the synthesis and characterization of various cyano(phenyl)methyl diethyl phosphate compounds, including their isolation methods and spectroscopic data. Additionally, the document includes chemical data for other compounds, such as tetrabutylammonium 3-(tert-Butyldimethylsiloxy)-17-cyanoestra-1,3,5(10)-trien-17-yl Ethyl Phosphate and 3-nitrobenzonitrile, along with their synthesis and purification methods. The authors express gratitude to their colleagues for their support and assistance. [Extracted from the article]

Published
2024
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4. Generation of Alkylidene Carbenes through Tetrazole Fragmentation: Recent Advances and Applications in Organic Synthesis.

Author

Harusawa, Shinya, Yoneyama, Hiroki, and Usami, Yoshihide

Subjects
*ORGANIC synthesis, *DRYING agents, *TETRAZOLES, *CARBENES, *MARINE natural products
Abstract

This article explores the generation of alkylidene carbenes through tetrazole fragmentation and their applications in organic synthesis. It discusses different methods for generating alkylidene carbenes, such as the loss of N2 from 1-diazoalkenes and the fragmentation of tetrazole intermediates. The text also discusses the synthesis of heteroatom-substituted alkynes (HATs) and heterocyclic alkynes (HATs) using various methods and their potential applications in the synthesis of biologically active natural products. The article highlights the versatility and efficiency of the cyclopropane (CP) method for compound synthesis and provides detailed examples and reactions to illustrate its effectiveness. [Extracted from the article]

Published
2024
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6. Accurate Molecular Weight Measurements of Cystine Derivatives on FAB-MS

Author

Fujitake, Mihoyo and Harusawa, Shinya

Subjects
cystine, FAB-MS, molecular weight, S-S bond, sulfur-containing amino acid
Abstract

Cystine derivatives are important biomolecules in living systems. In this study, the accurate molecular weights of various cysteines and S-S bond-containing peptides were obtained by mass spectrometry using a dithiodiethanol (DTDE) matrix and fast atom bombardment (FAB) ionization in conjunction with a double-focusing mass spectrometer, involving the detection of the target compound as [M+H]+. The method is also applied to other sulfur-containing amino acids.

Published
2023

15. Synthesis of 5,6-Dihydro-4 H -pyrrolo[1,2- b ]pyrazoles and Homologs from 5-Substituted 2-(Alkynyl)tetrazoles via Microwave-Induced Intramolecular Nitrile-Imine–Alkyne 1,3-Dipolar Cycloaddition.

Author

Yoneyama, Hiroki, Adachi, Mano, Morita, Aoshi, Nakagawa, Maki, Baba, Miho, Yamawaki, Kanako, Hayama, Noboru, Harusawa, Shinya, and Usami, Yoshihide

Subjects
PYRAZOLES, RING formation (Chemistry), ISOXAZOLIDINES, TETRAZOLES, PHOTOCHEMISTRY, MICROWAVES, IRRADIATION
Abstract

Microwave irradiation of 2-alkynyl-5-(phenyl or alkyl)tetrazoles affords 2-(phenyl or alkyl)-5,6-dihydro-4 H -pyrrolo[1,2- b ]pyrazoles via intramolecular [3+2] cyclization of nitrile-imine intermediates. In the present method, the use of 5-alkyltetrazoles as the starting materials is more advantageous because of the difficulties associated with conventional photoreactions. From 2-phenylalkynyl-5-methylthio-1 H -tetrazoles, the reaction efficiently produces 2-methylthio-3-phenyl-5,6-dihydro-4 H -pyrrolo[1,2- b ]pyrazoles. The procedure using the methylthio group is applied to the total synthesis of three naturally occurring withasomnines. The method is also extended to the construction of molecules in which bicyclic pyrazoles are fused to six- to eight-membered rings. [ABSTRACT FROM AUTHOR]

Published
2023
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24. Syntheses and Glycosidase Inhibitory Activities, and in Silico Docking Studies of Pericosine E Analogs Methoxy-Substituted at C6

Author

Usami, Yoshihide, primary, Higuchi, Megumi, additional, Mizuki, Koji, additional, Yamamoto, Mizuki, additional, Kanki, Mao, additional, Nakasone, Chika, additional, Sugimoto, Yuya, additional, Shibano, Makio, additional, Uesawa, Yoshihiro, additional, Nagai, Junko, additional, Yoneyama, Hiroki, additional, and Harusawa, Shinya, additional

Published
2020
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27. Synthesis of 4(5)-[5-(aminomethyl)tetrahydrofuran-2-yl- or 5-(aminomethyl)-2,5-dihydrofuran-2-yl]imidazoles by efficient use of a PhSe group: application to novel histamine H (sub)3-ligands

Author

Harusawa, Shinya, Imazu, Tomonari, Takashima, Seiichiroh, Araki, Lisa, Ohishi, Hirofumi, Kurihara, Takushi, Sakamoto, Yasuhiko, Yamamoto, Yumico, and Yamatodani, Atsushi

Subjects
Chemistry, Organic -- Research, Stereoisomers -- Research, Ligands -- Research, Biological sciences, Chemistry
Abstract

The study discusses the preparation of new H (sub)3 receptor ligands by means of four isomer synthesis. The synthesis of four stereoisomers of a novel 4(5)-[5-(aminomethyl)-2,5-dihydrofuran-2-yl]imidazole and 4(5)-(5-aminomethylfuran-2-yl)-1H-imidazole has been described.

Published
1999

30. Introduction of Fluorine into Antitumor-Active Dinuclear Platinum(II) Complexes Leads to Modulation of In VivoAntitumor Activity in Mice

Author

Uemura, Masako, Hiramoto, Keiichi, Yoneyama, Hiroki, Harusawa, Shinya, and Komeda, Seiji

Abstract

Tetrazolato-bridged dinuclear platinum(II) complexes ([{cis-Pt(NH3)2}2(μ-OH)(μ-5-R-tetrazolato-N2,N3)]2+; tetrazolato-bridged complexes) show remarkable cytotoxic effects in vitroand antitumor activity in vivo. Here, we examined the structure–activity relationship of a series of fluorine-containing derivatives (R = CFH2, CF2H, or CF3), focusing on their lipophilicity, cellular accumulation, cytotoxicity, interactions with a nucleobase and double-stranded deoxyribonucleic acid, and in vivoantitumor efficacy. Fluorination had a little effect on the properties of the derivatives in vitro; however, marked differences in in vitrocytotoxicity and in vivotumor growth inhibition activity were observed. In BALB/c mice bearing colon-26 tumors, the antitumor efficacies of the derivatives were markedly altered, even by changing the number of fluorine atoms by one. In addition, one derivative, [{cis-Pt(NH3)2}2(μ-OH)(μ-5-difluoromethyltetrazolato-N2,N3)](NO3)2, showed a significantly higher antitumor efficacy compared with oxaliplatin, a current first-line drug and the only platinum-based drug approved for the treatment of colon cancer. Together, the present results indicate that introducing fluorine into tetrazolato-bridged complexes may be useful for modulating in vivoactivities.

Published
2022
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31. Efficient and beta-stereoselective synthesis of 4(5)-(beta-D-ribofuranosyl)- and 4(5)-(2-deoxyribofuranosyl)imidazoles

Author

Harusawa, Shinya, Murai, Yoshihiko, Moriyama, Hideki, Imazu, Tomonari, Ohishi, Hirofumi, Yoneda, Ryuji, and Kurihara, Takushi

Subjects
Imidazole -- Research, Nucleotides -- Research, Organic compounds -- Synthesis, Ring formation (Chemistry) -- Usage, Biological sciences, Chemistry
Abstract

The Mitsunobu cyclization of diol isomers of 2,3,5-tri-O-benzyl-D-ribose and 3,5-di-O-benzyl-2-deoxy-D-ribose produces 87% of 4(5)-(beta-D-ribofuranosyl)imidazole (1) and 59% of 4(5)-(2-deoxy-beta-D-ribofuranosyl)imidazole (2), respectively. The cyclization reaction yields benzylated imidazoles which undergo reductive debenzylation to produce C-nucleotides, containing heterocycle imidazole as the base moiety. The beta-stereoselective glycosylation is the main step in the synthesis which is regulated by imidazole's intramolecular hydrogen-bonding.

Published
1996

40. Synthesis of novel C4-linked C2-imidazole ribonucleoside phosphoramidite and its application to probing the catalytic mechanism of a ribozyme

Author

Araki, Lisa, Morita, Keiji, Yamaguchi, Maho, Zheng-yun Zhao, Wilson, Timothy J., Lilley, David M. J., and Harusawa, Shinya

Subjects
Catalytic RNA -- Chemical properties, Imidazole -- Chemical properties, Imidazole -- Structure, Ribonucleotides -- Chemical properties, Ribonucleotides -- Structure, Ribose -- Chemical properties, Ribose -- Structure, Biological sciences, Chemistry
Abstract

The synthesis of a novel C4-linked [C.sub.2]-imidazole ribonucleoside phosphoramidite (ICN-[C.sub.2]-PA) with a two-carbon linker between imidazole and ribose moieties is described. Imidazole nucleoside analogues with variable spacer lengths could provide a valuable general approach to explore the catalytic mechanisms of ribozymes.

Published
2009

41. Efficient approaches to S-alkyl-N-alkylisothioureas: syntheses of histamine [H.sub.3] antagonist clobenpropit and its analogues

Author

Yoneyama, Hiroki, Shimoda, Ayako, Araki, Lisa, Hatano, Kouta, Sakamoto, Yasuhiko, Kurihara, Takushi, Yamatodani, Atsushi, and Harusawa, Shinya

Subjects
Chemical synthesis -- Analysis, Nuclear magnetic resonance spectroscopy -- Analysis, Gel permeation chromatography -- Usage, Biological sciences, Chemistry
Abstract

The two efficient synthetic approaches to S-alkyl-N-alkylisothioureas starting from pionyl isothiocyanate (PPI) or 2-nitrophenylacetyl isothiocyanate (NPAI) are described. The utility of the approaches is proved by the syntheses of clobenpropit and its analogues and it can also be used to supply a variety of [H.sub.3]R or [H.sub.4]R ligand candidates having the isothiourea moiety.

Published
2008

42. Synthesis of Triazol Cn-Ribonucleoside Phosphoramidites Using β-Ribofuranosyl-Cn-acetylenes for RNA Catalysis Probing

Author

Usami Yoshihide, Zhao Zheng-yun, Yoneyama Hiroki, Harusawa Shinya, Hikasa Fumiko, and Fujisue Daiki

Subjects
Pharmacology, Thesaurus (information retrieval), 010405 organic chemistry, Chemistry, Organic Chemistry, RNA, 010402 general chemistry, Ribonucleoside, 01 natural sciences, Combinatorial chemistry, 0104 chemical sciences, Analytical Chemistry, Catalysis
Published
2018

43. Nucleobase participation in ribozyme catalysis

Author

Zheng-yun Zhao, McLeod, Aileen, Harusawa, Shinya, Araki, Lisa, Lilley, David M.J., Yamaguchi, Maho, and Kurihara, Takushi

Subjects
Phosphorus compounds -- Chemical properties, Oxidation-reduction reaction -- Analysis, Catalytic RNA -- Chemical properties, Chemistry
Abstract

The cleavage reaction of the nucleolytic ribozymes is mediated by nucleophilic attack on the scissile phosphate by the adjacent 2' oxygen. A possible strategy for accelerating this reaction uses acid-base catalysis to improve the nucleophilicity of the 2' oxygen by removal of the hydroxyl proton and protonation of the 5' oxyanion leaving group.

Published
2005

47. Specific Conformational Change in Giant DNA Caused by Anticancer Tetrazolato-Bridged Dinuclear Platinum(II) Complexes: Middle-Length Alkyl Substituents Exhibit Minimum Effect

Author

Komeda, Seiji, primary, Yoneyama, Hiroki, additional, Uemura, Masako, additional, Muramatsu, Akira, additional, Okamoto, Naoto, additional, Konishi, Hiroaki, additional, Takahashi, Hiroyuki, additional, Takagi, Akimitsu, additional, Fukuda, Wakao, additional, Imanaka, Tadayuki, additional, Kanbe, Toshio, additional, Harusawa, Shinya, additional, Yoshikawa, Yuko, additional, and Yoshikawa, Kenichi, additional

Published
2017
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