2021/12/22 更新

写真a

ササキ ケンジ
佐々木 健二
SASAKI Kenji
所属
教育推進機構 教授(特任)
職名
教授(特任)
外部リンク

学位

  • 薬学博士 ( 東北大学 )

研究キーワード

  • 構造活性相関

  • 有機化学

  • 分子設計

  • Drug Molecular Design

  • Structure-Activity-Relationship

  • Organic Chemistry

研究分野

  • ライフサイエンス / 薬系化学、創薬科学

  • ライフサイエンス / 薬系化学、創薬科学

学歴

  • 岡山大学   Graduate School, Division of Pharmaceutical Sciences  

    - 1977年

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  • 岡山大学    

    - 1977年

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    国名: 日本国

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  • 大阪薬科大学   Faculty of Pharmaceutical Science  

    - 1975年

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  • 大阪薬科大学   薬学部   製薬化学科

    - 1975年

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    国名: 日本国

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経歴

  • - 岡山大学全学教育・学生支援機構 教授

    2017年

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  • - Professor,Institute for Education and Student Services,Okayama University

    2017年

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  • 岡山大学全学教育・学生支援機構基幹教育センター 副センター長   Institute for Education and Student Services

    2016年 - 2017年

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  • 岡山大学教育・学生支援機構教育・学生支援機構 副機構長

    2015年 - 2016年

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  • 岡山大学教育・学生支援機構教育開発センター 副センター長

    2011年 - 2016年

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  • Professor,Center for Faculty Development,Organization for Education and Student Support,Okayama University

    2010年 - 2011年

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  • 岡山大学教育・学生支援機構教育開発センター 教授

    2010年 - 2011年

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  • Professor,Dept. of Pharmacy,Faculty of Pharmaceutical Sciences,Okayama University

    2002年 - 2010年

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  • 岡山大学薬学部薬学科 教授   Faculty of Pharmaceutical Sciences

    2002年 - 2010年

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▼全件表示

所属学協会

 

書籍等出版物

  • Fluorinated Heterocyclic Compounds: Synthesis, Chemistry, and Applications

    John Wiley & Sons, Inc.  2009年 

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MISC

  • Polycyclic N-Heterocyclic Compounds. Part 85: Synthesis and Evaluation of Antiplatelet Aggregation Activity of 2,4-Disubstituted 5,6-Dihydro[1]benzazepino[5,4-d]pyrimidine and Related Compounds

    Kensuke Okuda, Ying-Xue Zhang, Takashi Hirota, Kenji Sasaki

    JOURNAL OF HETEROCYCLIC CHEMISTRY   52 ( 3 )   888 - 895   2015年5月

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    記述言語:英語   出版者・発行元:WILEY-BLACKWELL  

    We have synthesized a large number of tricyclic 2-substituted 4-alkylamino-5,6-dihydro[1]benzazepino[5,4-d]pyrimidines as part of our research to develop new effective antiplatelet drugs. A variety of alkyl and aryl groups were used as substituents at the 2-position. Evaluation of the effects of the newly synthesized compounds on collagen-induced platelet aggregation revealed several promising antiplatelet candidates with potencies superior to aspirin.

    DOI: 10.1002/jhet.2040

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  • Polycyclic N-Heterocyclic Compounds. Part 86: Synthesis and Evaluation of Antiplatelet Aggregation Activity of 2,4-Disubstituted 9-Chloro-5,6-dihydropyrimido[5,4-d]benzazepine and Related Compounds

    Kensuke Okuda, Shigeki Takarada, Takashi Hirota, Kenji Sasaki

    JOURNAL OF HETEROCYCLIC CHEMISTRY   52 ( 3 )   780 - 792   2015年5月

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    記述言語:英語   出版者・発行元:WILEY-BLACKWELL  

    Libraries of tricyclic 2-substituted 4-alkylamino-9-chloro-5,6-dihydropyrimido[5,4-d]benzazepines and tetracyclic 12-substituted 8-chloro-1,2,5,6-tetrahydro-4H-imidazo[1,2:1,6]pyrimido[5,4-d]benzazepines were synthesized as part of our research to develop new effective antiplatelet drugs. Several alkyl and aryl groups were used as substituents at the 2-position. Evaluation of the effects of the newly synthesized compounds on collagen-induced platelet aggregation revealed several promising antiplatelet candidates with potencies superior to aspirin.

    DOI: 10.1002/jhet.2190

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  • SYNTHESIS, BIOLOGICAL ACTIVITIES, AND TAUTOMERISM OF 4-QUINOLONES AND RELATED COMPOUNDS

    Yoshihisa Kurasawa, Kenji Sasaki

    HETEROCYCLES   91 ( 1 )   1 - 39   2015年1月

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    記述言語:英語   掲載種別:書評論文,書評,文献紹介等   出版者・発行元:PERGAMON-ELSEVIER SCIENCE LTD  

    This review describes the synthesis, biological activities, and tautomerism of various 4-quinolones together with related compounds including 4-oxopyridazino[3,4-b]quinoxalines (bioisostere of 4-quinolones).

    DOI: 10.3987/REV-14-806

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  • Quinolone Analogs 16: A Facile D-H Exchange for 3-H Proton of 2-Substituted 4-Quinolones in Acidic Media

    Yoshihisa Kurasawa, Kiminari Yoshida, Naoki Yamazaki, Kenji Sasaki, Yoshito Zamami, Zhao Min, Atsumi Togi, Hideyuki Ito, Eisuke Kaji, Haruhiko Fukaya

    JOURNAL OF HETEROCYCLIC CHEMISTRY   51 ( 6 )   1821 - 1829   2014年11月

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    記述言語:英語   出版者・発行元:WILEY-BLACKWELL  

    The 4-quinolones having the urea or carbamate moiety at the 2-position showed the facile deuterium-hydrogen (D-H) exchange of the 3-H proton in deuteriotrifluoroacetic acid-deuteriodimethyl sulfoxide (3:1) at 60 degrees C, whereas the 4-quinolones possessing the carboxylate or carbohydrazide group at the 2-position and 2-substituted 4-methoxyquinolines represented no D-H exchange of the 3-H proton under the same condition. The aforementioned D-H exchange was found to require both the tautomerization of the 4-quinolone into 4-hydroxyquinoline in strongly acidic media and the nitrogen functional group at the 2-position.

    DOI: 10.1002/jhet.1933

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  • Quinolone Analogs 13: Synthesis of Novel 1,1 '-(2-Methylenepropane-1,3-diyl)di(4-quinolone-3-carboxylate) and Related Compounds

    Yoshihisa Kurasawa, Kiminari Yoshida, Naoki Yamazaki, Eisuke Kaji, Kenji Sasaki, Yoshito Zamami, Takatoshi Fujii, Min Zhao, Hideyuki Ito, Haruhiko Fukaya

    JOURNAL OF HETEROCYCLIC CHEMISTRY   51 ( 6 )   1720 - 1726   2014年11月

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    記述言語:英語   出版者・発行元:WILEY-BLACKWELL  

    The reaction of the 4-hydroxyquinoline-3-carboxylate 6 with pentaerythritol tribromide gave the 1,1-(2-methylenepropane-1,3-diyl)di(4-quinolone-3-carboxylate) 11, whose reaction with bromine afforded the 1,1-(2-bromo-2-bromomethylpropane-1,3-diyl)di(4-quinolone-3-carboxylate) 12. Compound 12 was transformed into the (Z)-1,1-(2-acetoxymethylpropene-1,3-diyl)di(4-quinolone-3-carboxylate) 13 or (E)-1,1-[2-(imidazol-1-ylmethyl)propene-1,3-diyl]di(4-quinolone-3-carboxylate) 14. Hydrolysis of the dimer (Z)-13 or (E)-14 with potassium hydroxide provided the (E)-1,1-(2-hydroxymethylpropene-1,3-diyl)di(4-quinolone-3-carboxylic acid) 15 or (Z)-1,1-[2-(imidazol-1-ylmethyl)propene-1,3-diyl]di(4-quinolone-3-carboxylic acid) 16, respectively. The nuclear Overhauser effect (NOE) spectral data supported that those hydrolysis resulted in the geometrical conversion of (Z)-13 into (E)-15 or (E)-14 into (Z)-16.

    DOI: 10.1002/jhet.1861

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  • Polycyclic N-Heterocyclic Compounds. Part 79: Synthesis of 2,4-Disubstituted 6,7-Dihydro-5H-benzo[6,7]cyclohepta[1,2-d]pyrimidines as Potential Antiplatelet Aggregators

    Kensuke Okuda, Takashi Hirota, Kenji Sasaki

    JOURNAL OF HETEROCYCLIC CHEMISTRY   51 ( 6 )   1607 - 1614   2014年11月

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    記述言語:英語   出版者・発行元:WILEY-BLACKWELL  

    Libraries of tricyclic 2-substituted 4-alkylamino-6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-d]pyrimidines were synthesized as part of our research to develop new effective antiplatelet drugs. Several alkyl and aryl groups were used as substituents at the 2-position. Evaluation of the effects of the newly synthesized compounds on collagen-induced platelet aggregation revealed several promising antiplatelet candidates with potencies superior to aspirin.

    DOI: 10.1002/jhet.1714

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  • Quinolone Analogues 15: Synthesis and Antimalarial Activity of 4-Phenyl-1-(1-triazolylmethyl-4-quinolon-3-ylcarbonyl)semicarbazide and Related Compounds

    Yoshihisa Kurasawa, Kiminari Yoshida, Naoki Yamazaki, Kenji Sasaki, Yoshito Zamami, Zhao Min, Atsumi Togi, Hideyuki Ito, Eisuke Kaji, Haruhiko Fukaya

    JOURNAL OF HETEROCYCLIC CHEMISTRY   51 ( S1 )   E249 - E254   2014年8月

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    記述言語:英語   出版者・発行元:WILEY-BLACKWELL  

    The 1-hydrazinocarbonylmethyl-4-quinolone-3-carboxylate (10) was converted into the 1-(4-amino-1,2,4-triazol-3-ylmethyl)-4-quinolone-3-carboxylic acid (13), whose reaction with arylcarbaldehydes gave the 1-(4-arylmethyleneamino-1,2,4-triazol-3-ylmethyl)-4-quinolone-3-carboxylic acids (5a, 5b, 5c, 5d, 5e, 5f, 5g). Compound 10 was also transformed into the 1-(4-amino-1,2,4-triazol-3-ylmethyl)-4-quinolone-3-carbohydrazide (15), whose reaction with phenyl isocyanate or phenyl isothiocyanate afforded the 4-phenyl-1-(1-triazolylmethyl-4-quinolon-3-ylcarbonyl)semicarbazide (6a) or 4-phenyl-1-(1-triazolylmethyl-4-quinolon-3-ylcarbonyl)thiosemicarbazide (6b), respectively. Compounds 6a, 6b showed the in vitro antimalarial activity to chloroquine-resistant Plasmodium falciparum, wherein their IC50 was 3.89 and 3.91 mu M, respectively.

    DOI: 10.1002/jhet.1822

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  • Polycyclic N-Heterocyclic Compounds. Part 80: Synthesis and Evaluation of Effects on In Vitro Pentosidine Formation of 5,6-Dihydro[1]benzothieno [3 ',2 ':2,3]thiepino[4,5-d]pyrimidine and Related Compounds

    Kensuke Okuda, Yutaka Itsuji, Takashi Hirota, Kenji Sasaki

    JOURNAL OF HETEROCYCLIC CHEMISTRY   51 ( 4 )   891 - 898   2014年7月

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    記述言語:英語   出版者・発行元:WILEY-BLACKWELL  

    Reaction of 3-(3-cyanopropylthio)[1]benzothiophene-2-carbonitrile with tert-BuONa gave 5-amino-1,2-dihydro[1]benzothieno[3,2-d]thieno[2,3-b]pyridine and 5-amino-2,3-dihydro[1]benzothieno[3,2-b]thiepin-4-carbonitrile. The latter compound served as a convenient scaffold for the synthesis of the new heterocycles, [1]benzothieno[3,2:2,3]thiepino[4,5-d]pyrimidines. All of our new tetracyclic products were evaluated for in vitro inhibitory activity on the formation of pentosidine, which is one of representative advanced glycation end products.

    DOI: 10.1002/jhet.1709

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  • Polycyclic N-Heterocyclic Compounds. Part 82: Synthesis and Evaluation of Anti-Platelet Aggregation Activity of 2,4-Disubstituted 5,6-Dihydro[1]benzothiepino[5,4-d]pyrimidine and Related Compounds

    Kensuke Okuda, Takashi Hirota, Kenji Sasaki

    JOURNAL OF HETEROCYCLIC CHEMISTRY   51 ( 4 )   911 - 920   2014年7月

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    記述言語:英語   出版者・発行元:WILEY-BLACKWELL  

    We have synthesized a large number of tricyclic 2-substituted 4-alkylamino-5,6-dihydro[1]benzothiepino[5,4-d]pyrimidines as part of our research to develop new effective anti-platelet drugs. A variety of alkyl and aryl groups were used as substituents at the 2-position. Evaluation of the effects of the newly synthesized compounds on collagen-induced platelet aggregation revealed several promising anti-platelet candidates with potencies superior to aspirin.

    DOI: 10.1002/jhet.1741

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  • Polycyclic N-Heterocyclic Compounds. Part 75: Synthesis of 2,4-Disubstituted 5,6-dihydro[1]benzoxepino[5,4-d]pyrimidines and 12-Substituted 1,2,4,5-Tetrahydro[1]benzoxepino[4,5-e]imidazo[1,2-c]pyrimidines as Potential Antiplatelet Aggregators

    Kensuke Okuda, Yuko Yamamoto, Takashi Hirota, Kenji Sasaki

    JOURNAL OF HETEROCYCLIC CHEMISTRY   51 ( 4 )   972 - 981   2014年7月

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    記述言語:英語   出版者・発行元:WILEY-BLACKWELL  

    Libraries of tricyclic 2-substituted 4-alkylamino-5,6-dihydro[1]benzoxepino[5,4-d]pyrimidines and tetracyclic 12-substituted 1,2,4,5-tetrahydro[1]benzoxepino[4,5-e]imidazo[1,2-c]pyrimidines were synthesized as part of our research to develop new effective antiplatelet drugs. Several alkyl and aryl groups were used as substituents at the 2-position. Evaluation of the effects of the newly synthesized compounds on collagen-induced platelet aggregation revealed several promising antiplatelet candidates with potencies superior to aspirin.

    DOI: 10.1002/jhet.1559

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  • Polycyclic N-heterocyclic compounds. Part 83. Synthesis of 2,4-disubstituted 5,6-dihydro[1]benzofuro[3',2':2,3]oxepino[4,5-d]pyrimidines and 2,4,5-trisubstituted 5,6-dihydro[1]benzofuro[2',3':5,6]pyrano[4,3-d]pyrimidines from 4-chloro-5,6-dihydro[1]ben・・・

    Kensuke Okuda, Jun-ichi Takano, Takashi Hirota, Kenji Sasaki

    Journal of Heterocyclic Chemistry   51 ( 3 )   788 - 793   2014年5月

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    記述言語:英語  

    Polycyclic N-heterocyclic compounds. Part 83. Synthesis of 2,4-disubstituted 5,6-dihydro[1]benzofuro[3',2':2,3]oxepino[4,5-d]pyrimidines and 2,4,5-trisubstituted 5,6-dihydro[1]benzofuro[2',3':5,6]pyrano[4,3-d]pyrimidines from 4-chloro-5,6-dihydro[1]benzofuro[3',2':2,3]oxepino[4,5-d]pyrimidines

    DOI: 10.1002/jhet.1900

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  • Polycyclic N-Heterocyclic Compounds 76: Synthesis and Antiplatelet Evaluation of 2,4-Disubstituted 5,6-Dihydro[1]benzofuro[3',2':2,3]oxepino[4,5-d]pyrimidines

    Kensuke Okuda, Jun-ichi Takano, Takashi Hirota, Kenji Sasaki, Yuta Nishina, Hiroyuki Ishida

    JOURNAL OF HETEROCYCLIC CHEMISTRY   51 ( 3 )   661 - 668   2014年5月

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    記述言語:英語   出版者・発行元:WILEY-BLACKWELL  

    Reaction of several Vilsmeier reagents with 5-amino-2,3-dihydro[1]benzofuro[3,2-b]oxepin-4-carbonitrile gave tetracyclic 2-substituted 4-chloro-5,6-dihydro[1] benzofuro[3',2':2,3]oxepino[4,5-d]pyrimidines. The structure of one of these, the 4-chloro-2-phenyl derivative, was confirmed by X-ray crystallography. Treatment of the 4-chloro derivatives with simple amines as nucleophile afforded 2-substituted 4-amino derivatives. A pentacyclic compound was also obtained by dehydrative ring closure. These products were evaluated for antiplatelet activity, and some showed potency comparable with that of aspirin.

    DOI: 10.1002/jhet.1539

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  • Polycyclic N-Heterocyclic Compounds. Part 78: Synthesis of N-[2-([1,2,4] Oxadiazol-5-yl) cyclohepten-1-yl]formamide Oximes and Their Evaluation as Inhibitors of Platelet Aggregation

    Kensuke Okuda, Ying-Xue Zhang, Takashi Hirota, Kenji Sasaki

    JOURNAL OF HETEROCYCLIC CHEMISTRY   51 ( 2 )   518 - 522   2014年3月

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    記述言語:英語   出版者・発行元:WILEY-BLACKWELL  

    N-[2-([1,2,4]Oxadiazol-5-yl)cyclohepten-1-yl]formamide oximes were synthesized by fusion of (6,7,8,9-tetrahydro-5H-cyclohepta[1,2-d]pyrimidin-4-yl)amidines with hydroxylamine hydrochloride through a subsequent rearrangement reaction. Effects of the products as well as the structurally related N-[4-([1,2,4]oxadiazol-5-yl)-2,3-dihydro[1]benzoxepin-5-yl]formamide oximes and N-[4-([1,2,4]oxadiazol-5-yl)-2,3-dihydro[1]benzothiepin-5-yl]formamide oximes on platelet aggregation were evaluated.

    DOI: 10.1002/jhet.1628

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  • POLYCYCLIC N-HETEROCYCLIC COMPOUNDS, PART 77: SYNTHESIS OF [1]BENZOTHIENO[3 ',2 ':2,3]OXEPINO[4,5-d]PYRIMIDINES AND EVALUATION OF THEIR ANTIPLATELET AGGREGATION ACTIVITY

    Kensuke Okuda, Takashi Nikaido, Takashi Hirota, Kenji Sasaki

    SYNTHETIC COMMUNICATIONS   43 ( 12 )   1619 - 1625   2013年6月

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    記述言語:英語   出版者・発行元:TAYLOR & FRANCIS INC  

    Reaction of 3-(3-cyanopropoxy)[1]benzothiophene-2-carbonitrile with sodium hydride gave 5-amino-1,2-dihydro[1]benzothieno[3,2-d]furo[2,3-b]pyridine and 5-amino-2,3-dihydro[1]benzothieno[3,2-b]oxepin-4-carbonitrile. The latter compound served as a convenient scaffold for the synthesis of the new heterocycles [1]benzothieno[3,2:2,3]oxepino[4,5-d]pyrimidines and the parent 1,2,4,5-tetrahydro[1]benzothieno[2,3:6,7]oxepino[4,5-e]imidazo[1,2-c]pyrimidine heterocyclic system. The new compounds described in this report were evaluated as inhibitors of platelet aggregation in vitro.

    DOI: 10.1080/00397911.2012.656295

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  • Polycyclic N-Heterocyclic Compounds 73: Synthesis and Evaluation of 5-Substituted 1,2-Dihydrofuro[2,3-c]isoquinolines as Inducers of Lipoprotein Lipase mRNA Expression

    Kensuke Okuda, Masahiko Yoshida, Takashi Hirota, Kenji Sasaki

    JOURNAL OF HETEROCYCLIC CHEMISTRY   50 ( 51 )   E9 - E11   2013年2月

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    記述言語:英語   出版者・発行元:WILEY-BLACKWELL  

    Several 5-substituted 1,2-dihydro[2,3-c]isoquinoline derivatives were synthesized as part of our research to develop new diabetes drugs. Amines and sulfanyls were used as substituents at the 5th-position. Evaluation of the effects of the newly synthesized compounds on lipoprotein lipase mRNA expression in 3T3-L1 preadipocytes revealed one promising candidate with potency comparable to that of troglitazone.

    DOI: 10.1002/jhet.1016

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  • Novel quercetin glycosides as potent anti-mrsa and anti-vre agents

    Abugafar M.L. Hossion, Kenji Sasaki

    Recent Patents on Anti-Infective Drug Discovery   8 ( 3 )   198 - 205   2013年

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    記述言語:英語   出版者・発行元:Bentham Science Publishers B.V.  

    Each year in the United States, at least 2 million people become infected with bacteria that are resistant to antibiotics and at least 23,000 people die each year as a direct result of these infections (Threat report 2013). Vancomycin is an FDA approved antibiotic and is growing importance in the treatment of hospital infections, with particular emphasis on its value to fight against methicillin-resistant Staphylococcus aureus (MRSA). The increasing use of vancomycin to treat infections caused by the Gram-positive MRSA in the 1970s selected for drug-resistant enterococci, less potent than staphylococci but opportunistic in the space vacated by other bacteria and in patients with compromised immune systems. The dramatic rise of antibiotic-resistant bacteria over the past two decades has stressed the need for completely novel classes of antibacterial agents. This paper reports the recent patent review on the strategy for finding novel quercetinglycoside type antibacterial agents against vancomycin-resistant bacterial strains. © 2013 Bentham Science Publishers.

    DOI: 10.2174/1574891X08666131210124649

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  • Quinolone Analogues 12: Synthesis and Tautomers of 2-Substituted 4-Quinolones and Related Compounds

    Yoshihisa Kurasawa, Kiminari Yoshida, Naoki Yamazaki, Kotoji Iwamoto, Yoshihiko Hamamoto, Eisuke Kaji, Kenji Sasaki, Yoshito Zamami

    JOURNAL OF HETEROCYCLIC CHEMISTRY   49 ( 6 )   1323 - 1331   2012年11月

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    記述言語:英語   出版者・発行元:WILEY-BLACKWELL  

    The 4-quinolone-2-carboxylates 4a,b were converted into the 4-quinolone-2-carbohydrazides 5a,b, hydrazones 6,7,10, and related compounds 8,9,11. The 4-methoxyquinoline-2-carboxylate 12 was also transformed into the 4-methoxyquinoline-2-carbohydrazide 13, which was modified to the hydrazone 14 and related compound 15. The antimicrobial activities of compounds 6b and 14 are described together with the 4-oxo and 4-hydroxy tautomers of compounds 4-11 in deuteriodimethyl sulfoxide and deuteriotrifluoroacetic acid.

    DOI: 10.1002/jhet.922

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  • Polycyclic N-Heterocyclic Compounds, Part 71: Synthesis and Bronchodilator Evaluation of 5-Substituted 1,2-Dihydrofuro[3,2-f][1,7]naphthyridines and Related Compounds

    Kensuke Okuda, Tetsuo Matsushita, Takashi Hirota, Kenji Sasaki

    JOURNAL OF HETEROCYCLIC CHEMISTRY   49 ( 4 )   742 - 747   2012年7月

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    記述言語:英語   出版者・発行元:WILEY-BLACKWELL  

    Several 5-substituted 1,2-dihydrofuro[3,2-f][1,7]naphthyridines were synthesized as part of our research to develop new effective bronchodilators. Amines, sulfanyls, and alcohols were used as substituents at the fifth position. Tetracyclic compounds were also obtained. Evaluation of the effects of the newly synthesized compounds on carbamoylcholine chloride-induced contractions of trachea revealed one promising bronchodilator candidate with potency comparable to that of 3-isobutyl-1-methylxanthine.

    DOI: 10.1002/jhet.846

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  • Synthesis and antimalarial activity of calothrixins A and B, and their N-alkyl derivatives

    Kohji Matsumoto, Tominari Choshi, Mai Hourai, Yoshito Zamami, Kenji Sasaki, Takumi Abe, Minoru Ishikura, Noriyuki Hatae, Tatsunori Iwamura, Shigeo Tohyama, Junko Nobuhiro, Satoshi Hibino

    BIOORGANIC & MEDICINAL CHEMISTRY LETTERS   22 ( 14 )   4762 - 4764   2012年7月

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    記述言語:英語   出版者・発行元:PERGAMON-ELSEVIER SCIENCE LTD  

    We synthesized calothrixin B using our developed biomimetic method and derived N-alkyl-calothrixins A and B. The in vitro antimalarial activity of the calothrixin derivatives, including calothrixins A and B, against the Plasmodium falciparum FCR-3 strain was evaluated. All test compounds exhibited antimalarial activity over a concentration range of 6.4 x 10(-6)-1.2 x 10(-7) M. (C) 2012 Elsevier Ltd. All rights reserved.

    DOI: 10.1016/j.bmcl.2012.05.064

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  • Polycyclic N-Heterocyclic Compounds, Part 69: Synthesis of 5-amino-1,2-dihydro[1]benzofuro[3,2-d]furo[2,3-b]pyridines and their transformations to related compounds

    Kensuke Okuda, Jun-ichi Takano, Takashi Hirota, Kenji Sasaki

    JOURNAL OF HETEROCYCLIC CHEMISTRY   49 ( 2 )   281 - 287   2012年3月

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    記述言語:英語   出版者・発行元:WILEY-BLACKWELL  

    Reaction of 3-(3-cyanopropoxy)[1]benzofuran-2-carbonitriles with potassium tert-butoxide gave 5-amino-1,2-dihydro[1]benzofuro[3,2-d]furo[2,3-b]pyridines and 5-amino-2,3-dihydro[1]benzofuro[3,2-b]oxepin-4-carbonitriles as new ring systems. Reactions of the 5-chloro derivative, obtained from 5-amino-1,2-dihydro[1]benzofuro[3,2-d]furo[2,3-b]pyridine, produced a dihydrofuran ring-opened compound and 5-substituted compounds. J. Heterocyclic Chem.,(2011).

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  • Polycyclic N-heterocyclic compounds. Part 74. Rearrangement reaction of 5-amino-1,2-dihydrofuro[2,3-c]isoquinolines with α,ω-dibromoalkanes and evaluation of product bronchodilator activity

    Kensuke Okuda, Masahiko Yoshida, Takashi Hirota, Kenji Sasaki

    Synthetic Communications   42 ( 6 )   865 - 871   2012年

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  • Quercetin diacylglycoside analogues showing dual inhibition of DNA gyrase and topoisomerase IV as novel antibacterial agents (共著)

    「Hossion Abugafar M, L」「Zamami Yoshito」「Kandahary Rafiya K」「Tsuchiya Tomofusa」「Ogawa Wakano」「Iwado Akimasa」「Sasaki Kenji」

    Journal of Medicinal Chemistry   54 ( 11 )   3686 - 3703   2011年6月

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  • Polycyclic N-heterocyclic compounds. Part 70: synthesis of 5-amino-1,2-dihydrofuro[2,3-b]pyrido[3',2':4,5]-thieno[3,2-d]pyridines and related compounds. Evaluation of effects on lipoprotein lipase mRNA expression (共著)

    Heterocycles   83 ( 6 )   1315 - 1328   2011年6月

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  • Polycyclic N-heterocyclic compounds. Part 66: Synthesis of N-[2-([1,2,4]oxadiazol-5-yl)cyclopenten-1-yl]formamide oximes and their evaluation as inhibitors of platelet aggregation (共著)

    「Okuda, Kensuke, 」「Zhang, Ying-Xue」「Ohtomo, Hiromi」「Hirota, Takashi」「Sasaki, Kenji」

    Journal of Heterocyclic Chemistry   48 ( 3 )   715 - 719   2011年5月

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  • Polycyclic N-Heterocyclic Compounds, Part 68: Reactions of 3-(2-Bromoethyl)quinazolin-4(3H)-one and 3-(2-Bromoethyl)-5,6,7,8-tetrahydroquinazolin-4(3H)-one with Primary Alkylamines via a Dimroth-Type Rearrangement

    Kensuke Okuda, Hiromi Ohtomo, Tsuyoshi Tagata, Takashi Hirota, Kenji Sasaki

    SYNTHETIC COMMUNICATIONS   41 ( 6 )   812 - 819   2011年

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    記述言語:英語   出版者・発行元:TAYLOR & FRANCIS INC  

    [image omitted] The reaction of 3-(2-bromoethyl)quinazolin-4(3H)-one with ethyl- and n-propylamine gave abnormal fused 3-alkyl-4-alkyliminoquinazolines via a Dimroth-type rearrangement, as well as normal substituted 3-(2-alkylaminoethyl) derivatives in methanol. The reaction of 3-(2-bromoethyl)-5,6,7,8-tetrahydroquinazolin-4(3H)-one with primary alkylamines was also investigated for the scope of this rearrangement reaction.

    DOI: 10.1080/00397911003668570

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  • 7-Chloro-1,2-dihydrofuro[2,3-c]isoquinolin-5-amine

    Kensuke Okuda, Takashi Hirota, Kenji Sasaki, Hiroyuki Ishida

    ACTA CRYSTALLOGRAPHICA SECTION E-STRUCTURE REPORTS ONLINE   66 ( 11 )   O2949 - U1351   2010年11月

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    記述言語:英語   出版者・発行元:WILEY-BLACKWELL  

    In the title compound, C11H9ClN2O, the fused-ring system is essentially planar, with a maximum deviation of 0.0323 (16) angstrom. In the crystal, molecules are connected by N-H center dot center dot center dot O hydrogen bonds forming a zigzag chain along the c axis. Molecules are further stacked along the a axis through weak pi-pi interactions, the shortest being 3.6476 (8) angstrom.

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  • Design, synthesis, and biological evaluation of a novel series of quercetin diacylglucosides as potent anti-MRSA and anti-VRE agents (共著)

    「Hossion Abugafar M L」「Otsuka Nao」「Kandahary, Rafiya K」「Tsuchiya Tomofusa」「Ogawa Wakano」「Iwado Akimasa」「Zamami Yoshito」「Sasaki Kenji」

    Bioorganic & Medicinal Chemistry Letters   20 ( 17 )   5349 - 5352   2010年9月

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  • Polycyclic N-Heterocyclic Compounds. Part 64: Synthesis of 5-Amino-1,2,6,7-tetrahydrobenzo[f]furo[2,3-c]isoquinolines and Related Compounds. Evaluation of Their Bronchodilator Activity and Effects on Lipoprotein Lipase mRNA Expression

    Kensuke Okuda, Hiroshi Deguchi, Setsuo Kashino, Takashi Hirota, Kenji Sasaki

    CHEMICAL & PHARMACEUTICAL BULLETIN   58 ( 5 )   685 - 689   2010年5月

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    記述言語:英語   出版者・発行元:PHARMACEUTICAL SOC JAPAN  

    Reaction of 1-(3-cyanopropoxy)-3,4-dihydronaphthalene-2-carbonitriles with potassium tert-butoxide gave 5-amino-1,2,6,7-tetrahydrobenzo[f]furo[2,3-c]isoquinolines via a Truce Smiles rearrangement. The 5-amino group was transformed to the bromo derivatives which were allowed to react with aliphatic cyclic amines to produce amino derivatives. In contrast, a combination of imidazole and NaH gave a dihydrofuran ring cleaved product, the structure of which was confirmed by X-ray crystallographic analysis. Effects of the newly synthesized compounds on carbamylcholine chloride-induced contractions of trachea and lipoprotein lipase mRNA expression were also evaluated and found one promising bronchodilator.

    DOI: 10.1248/cpb.58.685

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  • Polycyclic N-Heterocyclic Compounds. Part 65: Ring Cleavage Reactions of Fused Furo[2,3-c]isoquinolines and Related Compounds with Various Nucleophiles

    Kensuke Okuda, Hiroshi Deguchi, Takashi Hirota, Kenji Sasaki

    CHEMICAL & PHARMACEUTICAL BULLETIN   58 ( 5 )   755 - 757   2010年5月

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    記述言語:英語   出版者・発行元:PHARMACEUTICAL SOC JAPAN  

    Reaction of fused 2,3-dihydrofuro[2,3-b]pyridines with various nucleophiles (N and O) gave dihydrofuran ring cleaved products. The scope of this reaction was investigated in detail.

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  • Polycyclic N-Heterocyclic Compounds. Part 62: Reaction of N-(Quinazolin-4-yl)amidine Derivatives with Hydroxylamine Hydrochloride and Anti-platelet Aggregation Activity of the Products

    Kensuke Okuda, Ying-Xue Zhang, Hiromi Ohtomo, Takashi Hirota, Kenji Sasaki

    CHEMICAL & PHARMACEUTICAL BULLETIN   58 ( 3 )   369 - 374   2010年3月

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    記述言語:英語   出版者・発行元:PHARMACEUTICAL SOC JAPAN  

    The reactions of N-(5,6,7,8-tetrahydroquinazolin-4-yl)amidines and their amide oximes with hydroxylamine hydrochloride gave abnormal cyclization products via a ring cleavage of pyrimidine component accompanied with a ring closure of 1,2,4-oxadiazole to give N-[2-([1,2,4]oxidiazol-5-yl)cyclohexen-1-yl]formamide oximes. Similarly, N-(quinazolin-4-yl)amidines reacted with hydroxylamine hydrochloride gave the same results. The evaluation of inhibitory activities against platelet aggregation in vitro is also described to show one derivative has potent activity.

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  • Polycyclic N-Heterocyclic Compounds. Part 63 Improved Synthesis of 5-Amino-1,2-dihydrofuro[2,3-c]isoquinolines via Truce-Smiles Rearrangement and Subsequent Formation to Furo[2,3-c]isoquinoline

    Kensuke Okuda, Masahiko Yoshida, Takashi Hirota, Kenji Sasaki

    CHEMICAL & PHARMACEUTICAL BULLETIN   58 ( 3 )   363 - 368   2010年3月

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    記述言語:英語   出版者・発行元:PHARMACEUTICAL SOC JAPAN  

    An improved synthesis of 5-amino-1,2-dihydrofuro[2,3-c]isoquinoline has been achieved using a slight niodification of reaction Conditions for the Truce-Smiles rearrangement. Acid treatment of the obtained 5-amino-1,2-dihydrofuro [2,3-c]isoquinolines gave unexpected ring-opened spiro ring compounds. The previously unreported Parent compound, furo[2,3-c]isoquinoline, was also synthesized.

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  • Polycyclic N-heterocyclic compounds. Part 61: A novel Truce-Smiles type rearrangement reaction of 4-(2-cyanovinyloxy)butanenitriles to give cycloalkeno[1,2-d]furo[2,3-b]pyridines

    Kensuke Okuda, Norimasa Watanabe, Takashi Hirota, Kenji Sasaki

    TETRAHEDRON LETTERS   51 ( 6 )   903 - 906   2010年2月

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    記述言語:英語   出版者・発行元:PERGAMON-ELSEVIER SCIENCE LTD  

    The cycloalkeno[1,2-d]furo[2,3-b]pyridine skeleton was conveniently synthesized from fused 4-(2-cyanovinyloxy)butanenitriles in one step through sequential intramolecular Michael addition, p-elimination and intramolecular nucleophilic addition. This sequence thus consists of a novel Truce-Smiles type rearrangement followed by cyclization. The 5-amino derivatives were transformed further to lactams in good yields. (C) 2009 Elsevier Ltd. All rights reserved.

    DOI: 10.1016/j.tetlet.2009.12.010

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  • Polycyclic N-Heterocyclic Compounds. Part 60: Reactions of 3-(2-Cyanophenyl)quinazolin-4(3H)-ones with Primary Amines

    Kensuke Okuda, Tsuyoshi Tagata, Setsuo Kashino, Takashi Hirota, Kenji Sasaki

    CHEMICAL & PHARMACEUTICAL BULLETIN   57 ( 11 )   1296 - 1299   2009年11月

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    記述言語:英語   出版者・発行元:PHARMACEUTICAL SOC JAPAN  

    The reaction of 3-(2-cyanophenyl)quinazolin-4(3H)-one with various primary alkylamines gave 3-alkylquinazolin-4(3H)-ones via an addition of the nucleophile, ring opening, and ring closure (ANRORC) mechanism. This type of reaction required hydroxy group functionality in either the solvent or reagent. When hydroxylamine was used as nitrogen nucleophile, the intermediate of this reaction was isolated and found to be an amide oxime. When ethylenediamine was used as the lie nucleophile, the amidine moiety of the intermediate decomposed to give a benzanilide.

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  • Polycyclic N-Heterocyclic Compounds. Part 59(1)): Rearrangement Reactions of Fused Tricyclic 3-(2-Bromoethyl)pyrimidin-4(3H)-ones with Primary Amines via a Dimroth-Type Rearrangement

    Kensuke Okuda, Hiromi Ohtomo, Fumiaki Tanaka, Takashi Hirota, Kenji Sasaki

    CHEMICAL & PHARMACEUTICAL BULLETIN   57 ( 7 )   755 - 758   2009年7月

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    記述言語:英語   出版者・発行元:PHARMACEUTICAL SOC JAPAN  

    Reaction of some fused tricyclic 3-(2-bromoethvl)pyrimidin-4(3H)-ones with primary alkyl amines gave abnormal fused 3-alkyl-4-alkyliminopyrimidines via a Dimroth-type rearrangement, as well as normal substituted 3-(2-alkylaminoethyl) derivatives in methanol. This abnormal rearrangement reaction depended on reaction solvent.

    DOI: 10.1248/cpb.57.755

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  • Replacing alkyl sulfonamide with aromatic sulfonamide in sulfonamide-type RXR agonists favors switch towards antagonist activity

    Ken-ichi Morishita, Nobumasa Yakushiji, Fuminori Ohsawa, Kayo Takamatsu, Nobuyasu Matsuura, Makoto Makishima, Masatoshi Kawahata, Kentaro Yamaguchi, Akihiro Tai, Kenji Sasaki, Hiroki Kakuta

    BIOORGANIC & MEDICINAL CHEMISTRY LETTERS   19 ( 3 )   1001 - 1003   2009年2月

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    記述言語:英語   出版者・発行元:PERGAMON-ELSEVIER SCIENCE LTD  

    Retinoid X receptor (RXR) ligands are attractive candidates for clinical application because of their activity against tamoxifen-resistant breast cancer, taxol-resistant lung cancer, metabolic syndrome, and allergy. Though several RXR ligands, especially RXR antagonists, have been reported, the rational molecular design of such compounds is not well advanced. 4-[N-Methanesulfonyl-N-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl) amino] nicotinic acid (5a) is a moderately RXR alpha-preferential agonist, and we examined the feasibility of replacing the methyl group on the sulfonamide with a longer alkyl chain or an aromatic ring as an approach to produce new RXR antagonists. Several of the resulting benzenesulfonanilide-type compounds showed RXR antagonist activity. This design strategy should be a useful approach for addressing the lack of structure diversity of RXR antagonists. (C) 2008 Elsevier Ltd. All rights reserved.

    DOI: 10.1016/j.bmcl.2008.11.086

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  • Effect of the Oral Absorption Benzenesulfonanilide-Type Cyclooxygenase-1 Inhibitors on Analgesic Action and Gastric Ulcer Formation

    Xiaoxia Zheng, Hiroyuki Oda, Shun Harada, Yukio Sugimoto, Akihiro Tai, Kenji Sasaki, Hiroki Kakuta

    JOURNAL OF PHARMACEUTICAL SCIENCES   97 ( 12 )   5446 - 5452   2008年12月

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    記述言語:英語   出版者・発行元:JOHN WILEY & SONS INC  

    A benzensulfonanilide-type cyclooxygenase-1 (COX-1)-selective inhibitor, ZXX2-77: 4-amino-4'-chloro-N-methylbenzenesulfonanilide (4a), has been reported as a novel analgesic that does not cause gastric damage. This compound has a weak analgesic effect but has potent in vitro COX-1 inhibitory activity. Since the reason for the weak analgesic effect in vivo was thought to be the low rate of oral absorption, the blood concentration of ZXX2-77 (4a) was measured in rats. It was found that the C(max) value (1.2 mu M) of ZXX2-77 (4a) at a dose of 30 mg/kg did not reach the COX-1 IC(50) value (3.2 mu M). On the other hand, ZXX2-79 (4b) (SO(2)NH derivative of ZXX2-77 (4a); 4-amino-4'-chlorobenzenesulfonanilide), which shows less potent COX inhibitory activities (COX-1 IC(50) = 12 mu M, COX-2 IC(50) = 150 mu M) than those of ZXX2-77 (4a) in vitro, was found to be more absorbable (C(max) - 16 mu M at a dose of 30 mg/kg in rats) than ZXX2-77 (4a). Furthermore, ZXX2-79 (4b) not only showed a potent analgesic effect in a formalin test but also caused little gastric damage. These findings indicate that demethylated sulfonamide compounds are more easily absorbed than are N-methylated sulfonamide compounds and suggest that COX-1-selective inhibitors will be useful as analgesics that do not cause gastric damage. (C) 2008 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 97:5446-5452, 2008

    DOI: 10.1002/jps.21388

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  • Pyridinium cationic-dimer antimalarials, unlike chloroquine, act selectively between the schizont stage and the ring stage of Plasmodium falciparum

    Mai Yoshikawa, Kazunori Motoshima, Kanji Fujimoto, Akihiro Tai, Hiroki Kakuta, Kenji Sasaki

    BIOORGANIC & MEDICINAL CHEMISTRY   16 ( 11 )   6027 - 6033   2008年6月

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    記述言語:英語   出版者・発行元:PERGAMON-ELSEVIER SCIENCE LTD  

    Malaria is a leading cause of death in developing countries, and the emergence of strains resistant to the main therapeutic agent, chloroquine, has become a serious problem. We have developed cationic-dimer type antimalarials, MAP-610 and PMAP-H10, which are structurally different from chloroquine. In this study, we introduced several substituents on the terminal phenyl rings of PMAP-H10. The electronic and hydrophobic properties of the substituents were correlated with the antimalarial activity and cytotoxicity of the compounds, respectively. Studies with synchronized cultures of malarial plasmodia showed that our cationic-dimers act selectively between the schizont stage and the ring stage of the parasitic cycle, unlike chloroquine, which has a stage-independent action. Thus, the mechanism of action of our antimalarials appears to be different from that of chloroquine, and our compounds may be effective against chloroquine-resistant strains. (C) 2008 Published by Elsevier Ltd.

    DOI: 10.1016/j.bmc.2008.04.051

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  • Design and synthesis of benzenesulfonanilides active against methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus

    Kensuke Namba, Xiaoxia Zheng, Kazunori Motoshima, Hidetomo Kobayashi, Akihiro Tai, Eizo Takahashi, Kenji Sasaki, Keinosuke Okamoto, Hiroki Kakuta

    BIOORGANIC & MEDICINAL CHEMISTRY   16 ( 11 )   6131 - 6144   2008年6月

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    記述言語:英語   出版者・発行元:PERGAMON-ELSEVIER SCIENCE LTD  

    Vancomycin is mainly used as an antibacterial agent of last resort, but recently vancomycin-resistant bacterial strains have been emerging. Although new antimicrobials have been developed in order to overcome drug-resistant bacteria, many are structurally complex beta-lactams or quinolones. In this study, we aimed to create new anti-drug-resistance antibacterials which can be synthesized in a few steps from inexpensive starting materials. Since sulfa drugs function as p-aminobenzoic acid mimics and inhibit dihydropteroate synthase (DHPS) in the folate pathway, we hypothesized that sulfa derivatives would act as folate metabolite-mimics and inhibit bacterial folate metabolism. Screening of our sulfonanilide libraries, including benzenesulfonanilide-type cyclooxygenase-1-selective inhibitors, led us to discover benzenesulfonanilides with potent anti-methicillin-resistant Staphylococcus aureus (MRSA)/vancomycin-resistant Enterococcus (VRE) activity, that is, N-3,5-bis(trifluoromethyl) phenyl-3,5-dichlorobenzenesulfonanilide (16b) [MIC = 0.5 mu g/mL (MRSA), 1.0 mu g/mL (VRE)], and 3,5-bis(trifluoromethyl)-N-(3,5-dichlorophenyl) benzenesulfonanilide (16c) [MIC = 0.5 mu g/mL (MRSA), 1.0 mu g/mL (VRE)]. These compounds are more active than vancomycin [MIC = 2.0 mu g/mL (MRSA), 125 mu g/mL (VRE)], but do not possess an amino group, which is essential for DHPS inhibition by sulfa drugs. These results suggested that the mechanism of antibacterial action of compounds 16b and 16c is different from that of sulfa drugs. We also confirmed the activity of these compounds against clinical isolates of Gram-positive bacteria. (C) 2008 Elsevier Ltd. All rights reserved.

    DOI: 10.1016/j.bmc.2008.04.040

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  • The first potent subtype-selective retinoid X receptor (RXR) agonist possessing a 3-isopropoxy-4-isopropylphenylamino moiety, NEt-3IP (RXR alpha/beta-dual agonist)

    Kayo Takamatsu, Atsushi Takano, Nobumasa Yakushiji, Kazunori Morohashi, Kenichi Morishita, Nobuyasu Matsuura, Makoto Makishima, Akihiro Tai, Kenji Sasaki, Hiroki Kakuta

    CHEMMEDCHEM   3 ( 5 )   780 - 787   2008年5月

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    記述言語:英語   出版者・発行元:WILEY-BLACKWELL  

    Retinoid X receptor (RXR) agonists (rexinoids) ore attracting much attention for their use in treatment of cancers, including tomoxifen-resistant breast cancer and toxol-resistant lung cancer, and metabolic disease. However, known RXR agonists have a highly lipophilic character. In addition, no subtype-selective RXR agonists have been found. We previously reported on RXR alpha-preferential agonist 4-[N-methanesulfonyl-N-(5,5,8,8-tetromethyl-5,6,7,8tetrahydro-2-naphthyl)amino]benzoic acid (6a). The RXR agonistic activity is much less than that of well-known RXR agonists. To develop potent, less-lipophilic, and subtype-selective RXR agonists, we created new RXR agonists possessing alkoxy and isopropyl groups as a lipophilic domain of the common structure of well-known RXR agonists. As a result, compounds possessing branched alkoxy groups, 6-[N-ethyl-N-(3-isopropoxy-4-isopropylphenyl)amino]nicotinic acid (NEt-3IP: 7a) and 6-[N-ethyl-N-(3-isobutoxy-4-isopropylphenyl)amino]nicotinic acid (NEt-3IB: 7c), showed RXR agonistic activity as potent as, or more potent than, the activities of representative RXR agonists. Moreover NEt-3IP (7a) was found to be the first RXR alpha/beta-selective (or RXR alpha/beta-dual) agonist. Being potent, less lipophilic, and having RXR subtype-selective activity, NEt-3IP (7a) is expected to become a new drug candidate and to be a useful biological toot for clarifying each RXR subtype function.

    DOI: 10.1002/cmdc.200700313

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  • Cyclooxygenase-1-selective inhibitors are attractive candidates for analgesics that do not cause gastric damage. design and in vitro/in vivo evaluation of a benzamide-type cyclooxygenase-1 selective inhibitor

    Hiroki Kakuta, Xiaoxia Zheng, Hiroyuki Oda, Shun Harada, Yukio Sugimoto, Kenji Sasaki, Akihiro Tai

    JOURNAL OF MEDICINAL CHEMISTRY   51 ( 8 )   2400 - 2411   2008年4月

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    記述言語:英語   出版者・発行元:AMER CHEMICAL SOC  

    Although cyclooxygenase-1 (COX-1) inhibition is thought to be a major mechanism of gastric damage by nonsteroidal anti-inflammatory drugs (NSAIDs), some COX-1-selective inhibitors exhibit strong analgesic effects without causing gastric damage. However, it is not clear whether their analgesic effects are attributable to COX-1-inhibitory activity or other bioactivities. Here, we report that N-(5-amino-2-pyridinyl)-4(trifluoromethyl)benzamide (18f, TFAP), which has a structure clearly different from those of currently available COX-1-selective inhibitors, is a potent COX-1-selective inhibitor (COX-1IC(50) = 0.80 +/- 0.05 mu M, COX-2IC(50) = 210 I mu M). This compound causes little gastric damage in rats even at an oral dose of 300 mg/kg, though it has an analgesic effect at as low a dose as 10 mg/kg. Our results show that COX-1-selective inhibitors can be analgesic agents without causing gastric damage.

    DOI: 10.1021/jm701191z

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  • Reduction of lipophilicity at the lipophilic domain of RXR agonists enables production of subtype preference: RXR alpha-preferential agonist possessing a sulfonamide moiety

    Kayo Takamatsu, Atsushi Takano, Nobumasa Yakushiji, Ken-ichi Morishita, Nobuyasu Matsuura, Makoto Makishima, Hamed Ismail Ali, Eiichi Akaho, Akihiro Tai, Kenji Sasaki, Hiroki Kakuta

    CHEMMEDCHEM   3 ( 3 )   454 - 460   2008年3月

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    記述言語:英語   出版者・発行元:WILEY-V C H VERLAG GMBH  

    Retinoid X receptor agonists (RXR agonists, rexinoids) are interesting candidates for the treatment of cancers such as tomoxifen-resistant breast cancer and taxol-resistant lung cancer. However, well-known RXR agonists possess a strong lipophilic character. In addition, although RXR has three subtypes, no subtype-selective RXR agonists are known. Thus we aimed to produce less-lipophilic and subtype-selective RXR agonists. By designing sulfonamide-type RXR agonists, 4-[N-methanesulfonyl-N-(5,5,8,8-tetromethyl-5,6,7,8-tetrohydro-2-naphthyl)amino]benzoic acid (80) was found to prefer RXR alpha over RXR beta and RXR gamma, although the potency is less than the potencies of well-known RXR pan-agonists. Moreover, our results suggest that the reduction of lipophilicity at the hydrophobic interaction region of RXR agonists enables production of RXR subtype preference. Our finding will be useful for the creation of more potent and less-lipophilic subtype-selective RXR agonists aimed at the reduction of undesirable side effects.

    DOI: 10.1002/cmdc.200700265

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  • Polycyclic N-heterocyclic compounds. Part 58: Rearrangement reactions of fused 3-(2-bromoethyl)pyrimidin-4(3H)-ones with primary amines and antidepressive evaluation of the products

    Hiromi Ohtomo, Tsuyoshi Tagata, Kenji Sasaki, Takashi Hirota, Kensuke Okuda

    TETRAHEDRON   63 ( 51 )   12541 - 12546   2007年12月

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    記述言語:英語   出版者・発行元:PERGAMON-ELSEVIER SCIENCE LTD  

    Reaction of fused 3-(2-bromoethyl)pyrimidin-4(3H)-ones with primary alkylamines gave abnormal fused 3-alkyl-4-alkylimino-pyrimidines via a new rearrangement, as well as normal substituted 3-(2-alkylaminoethyl) derivatives. Antidepressive evaluation of these compounds was performed by antireserpine action and one compound exhibited the positive activity comparable to imipramine. (c) 2007 Elsevier Ltd. All rights reserved.

    DOI: 10.1016/j.tet.2007.10.024

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  • Antimalarial cation-dimers synthesized in two steps from an inexpensive starting material, isonicotinic acid

    Kazunori Motoshima, Yoshiko Hiwasa, Mai Yoshikawa, Kanji Fujimoto, Akihiro Tai, Hiroki Kakuta, Kenji Sasaki

    CHEMMEDCHEM   2 ( 10 )   1527 - 1532   2007年10月

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    記述言語:英語   出版者・発行元:WILEY-V C H VERLAG GMBH  

    Malaria is one of the three major serious infectious diseases in the world. As the area affected by malaria includes a large proportion of developing countries, there is a need for new antimalarials that can be synthesized and supplied inexpensively. To generate low-cost antimalarials, the MAP series 6-10, bis-cation dimers, synthesized by amidating the carboxyl group of isonicotinic acid (11) with various amines and by cationizing the nitrogen atoms of the pyridine ring with the corresponding alkyl bromides, were designed. This design enabled expansion of the structural variations of bis-cation-type antimalarial compounds. The compounds bearing alkyl or phenyl groups in the amide moieties showed remarkable antimalarial activities in vitro. Moreover, 1, 1'-(1, 12-dodecanediyl)bis[4-[(buthylamino)carbonyl]pyridinium bromide], MAP-412 (6d), exhibited a potent antimalarial activity (ED50 = 8.2 mg kg-(1)). Being prepared at low cost our biscation-type antimalarial compounds may be useful as lead compounds for inexpensive antimalarials.

    DOI: 10.1002/cmdc.200700107

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  • Analgesic agents without gastric damage: Design and synthesis of structurally simple benzenesulfonanilide-type cyclooxygenase-1-selective inhibitors

    Xiaoxia Zheng, Hiroyuki Oda, Kayo Takamatsu, Yukio Sugimoto, Akihiro Tai, Eiichi Akaho, Hamed Ismail Ali, Toshiyuki Oshiki, Hiroki Kakuta, Kenji Sasaki

    BIOORGANIC & MEDICINAL CHEMISTRY   15 ( 2 )   1014 - 1021   2007年1月

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    記述言語:英語   出版者・発行元:PERGAMON-ELSEVIER SCIENCE LTD  

    In order to create novel analgesic agents without gastric disturbance, structurally simple cyclooxygenase-1 (COX-1) inhibitors with a benzenesulfonanilide skeleton were designed and synthesized. As a result, compounds 11f and 15a, which possess a p-amino group on the benzenesulfonyl moiety and p-chloro group on the anilino moiety, showed COX-1-selective inhibition. Moreover compound 11f, which is the most potent compound in this study showed more potent analgesic activity than that of aspirin at 30 mg/kg by po. The anti-inflammatory activity and gastric damage, however, were very weak or not detectably different from aspirin. Since the structure of our COX-1 inhibitors are very simple, they may be useful as lead compounds for superior COX-1 inhibitors as analgesic agents without gastric disturbance. (c) 2006 Published by Elsevier Ltd.

    DOI: 10.1016/j.bmc.2006.10.029

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  • Antimalarial effect of bis-pyridinium salts, N,N '-hexamethylenebis(4-carbamoyl-1-alkylpyridinium bromide)

    K Fujimoto, D Morisaki, M Yoshida, T Namba, K Hye-Sook, Y Wataya, H Kourai, H Kakuta, K Sasaki

    BIOORGANIC & MEDICINAL CHEMISTRY LETTERS   16 ( 10 )   2758 - 2760   2006年5月

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    記述言語:英語   出版者・発行元:PERGAMON-ELSEVIER SCIENCE LTD  

    The in vitro antimalarial activity of bis-pyridinium salts, N,N'-hexamethylenebis(4-carbamoyl-1-decylpyridinium bromide) and their derivatives, against the Plasmodium falciparum FCR-3 strain (ATCC 30932, chloroquine-sensitive) was evaluated. All test compounds exhibited antimalarial activity over a concentration range of 3.5 mu M to 10 nM. The chain length of the N1-alkyl moiety was found to be very beneficial in terms of antimalarial activity, and in this series of compounds, the most appropriate N1-alkyl chain length was found to be eight. (C) 2006 Elsevier Ltd. All rights reserved.

    DOI: 10.1016/j.bmcl.2006.02.030

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  • Involvement of intracellular Ca2+ levels in nonsteroidal anti-inflammatory drug-induced apoptosis

    Ken-Ichiro Tanaka, Wataru Tomisato, Tatsuya Hoshino, Tomoaki Ishihara, Takushi Namba, Mayuko Aburaya, Takashi Katsu, Keitarou Suzuki, Shinji Tsutsumi, Tohru Mizushima

    Journal of Biological Chemistry   280 ( 35 )   31059 - 31067   2005年9月

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    記述言語:英語  

    We recently reported that nonsteroidal anti-inflammatory drug (NSAIB)-induced gastric lesions involve NSAID-induced apoptosis of gastric mucosal cells, which in turn involves the endoplasmic reticulum stress response, in particular the up-regulation of CCAAT/enhancer-binding protein homologous transcription factor (CHOP). In this study, we have examined the molecular mechanism governing this NSAID-induced apoptosis in primary cultures of gastric mucosal cells. Various NSAIDs showed membrane permeabilization activity that correlated with their apoptosis-inducing activity. Various NSAIDs, particularly celecoxib, also increased intracellular Ca2+ levels. This increase was accompanied by K+ efflux from cells and was virtually absent when extracellular Ca2+ had been depleted. These data indicate that the increase in intracellular Ca2+ levels that is observed in the presence of NSAIDs is due to the stimulation of Ca2+ influx across the cytoplasmic membrane, which results from their membrane permeabilization activity. An intracellular Ca2+ chelator partially inhibited celecoxib-induced release of cytochrome c from mitochondria, reduced the magnitude of the celecoxib-induced decrease in mitochondrial membrane potential and inhibited celecoxib-induced apoptotic cell death. It is therefore likely that an increase in intracellular Ca2+ levels is involved in celecoxib-induced mitochondrial dysfunction and the resulting apoptosis. ATI inhibitor of calpain, a Ca2+-dependent cysteine protease, partially suppressed mitochondrial dysfunction and apoptosis in the presence of celecoxib. Celecoxib-dependent CHOP-induction was partially inhibited by the intracellular Ca2+ chelator but not by the calpain inhibitor. These results suggest that Ca2+-stimulated calpain activity and CHOP expression play important roles in celecoxib-induced apoptosis in gastric mucosal cells. © 2005 by The American Society for Biochemistry and Molecular Biology, Inc.

    DOI: 10.1074/jbc.M502956200

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  • Transition-metal-catalyzed rearrangement of 5-alkynals to gamma-alkynylketones and 1-cyclopentenylketones

    K Tanaka, K Sasaki, K Takeishi, K Sugishima

    CHEMICAL COMMUNICATIONS   ( 37 )   4711 - 4713   2005年

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    記述言語:英語   出版者・発行元:ROYAL SOC CHEMISTRY  

    The transition-metal-catalyzed rearrangement of 5-alkynals to gamma-alkynylketones and 1-cyclopentenylketones was developed using [Rh(P(OPh)(3))(2)]BF4 or Cu(OTf)(2) as a catalyst.

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  • Membrane permeabilization by non-steroidal anti-inflammatory drugs

    W Tomisato, K Tanaka, T Katsu, H Kakuta, K Sasaki, S Tsutsumi, T Hoshino, M Aburaya, DW Li, T Tsuchiya, K Suzuki, K Yokomizo, T Mizushima

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   323 ( 3 )   1032 - 1039   2004年10月

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    記述言語:英語   出版者・発行元:ACADEMIC PRESS INC ELSEVIER SCIENCE  

    The cytotoxicity of non-steroidal anti-inflammatory drugs (NSAIDs) is involved in the formation of NSAID-induced gastric lesions. The mechanism(s) behind these cytotoxic effects, however, is not well understood. We found here that several NSAIDs tested caused hemolysis when employed at concentrations similar to those that result in cytotoxicity. Moreover, these same NSAIDs were found to directly permeabilize the membranes of calcein-loaded liposomes. Given the similarity in NSAID concentrations for cytotoxic and membrane permeabilization effects, the cytotoxic action of these NSAIDs may be mediated through the permeabilization of biological membranes. Increase in the intracellular Ca2+ level can lead to cell death. We here found that all of NSAIDs tested increased the intracellular Ca2+ level at concentrations similar to those that result in cytotoxicity. Based on these results, we consider a possibility that membrane permeabilization by NSAIDs induces cell death through increase in the intracellular Ca2+ level. (C) 2004 Elsevier Inc. All rights reserved.

    DOI: 10.1016/j.bbrc.2004.08.205

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  • The synthesis of (±)-monomorine I starting with the palladium-catalyzed carbonylative 1,4-acylation of an organozinc chloride

    Motoki Yuguchi, Masao Tokuda, Kenji Sasaki, Kazuhiko Orito

    Bulletin of the Chemical Society of Japan   77 ( 5 )   1031 - 1032   2004年5月

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  • Winter cherry bugs feed on plant tropane alkaloids and de-epoxidize scopolamine to atropine.

    Yoshie Kitamura, Yoshinori Tominaga, Kenji Sasaki, Toshihiko Ikenaga

    Journal of Chemical Ecology   2004年

  • Synthesis of febrifugine derivatives and a solution to the puzzle of the structural determination of febrifugine

    Y Takeuchi, K Azuma, M Oshige, H Abe, H Nishioka, K Sasaki, T Harayama

    TETRAHEDRON   59 ( 10 )   1639 - 1646   2003年3月

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    記述言語:英語   出版者・発行元:PERGAMON-ELSEVIER SCIENCE LTD  

    The stereo-structure of piperidine lactone (3), a synthetic intermediate of the antimalarial agent febrifugine ((+)-1) with a piperidine ring in the trans relative configuration, was re-revised to the cis-form. We determined that isomerization to the trans-form from the cis-form occurred in the stage (6 from 5) of deprotection in Baker's synthesis. (C) 2003 Elsevier Science Ltd. All rights reserved.

    DOI: 10.1016/S0040-4020(03)00139-X

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  • Transglucosylation activities of multiple forms of α-glucosidase from spinach

    Sugimoto, Manabu, Furui, Satoshi, Sasaki, Kenji, Suzuki, Yukio

    Bioscience, Biotechnology, and Biochemistry   67 ( 5 )   1160 - 1163   2003年1月

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  • Synthesis and Characterization of 6-O-Acyl-2-O-a-D-Glucopyranosyl-L-ascorbic Acids with a Branched-acyl Chain

    Akihiro Tai, Daisuke Kawasaki, Kenji Sasaki, Eiichi Gohda, Itaru Yamamoto

    Chemical and Pharmaceutical Bulletin   2003年

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  • Synthesis and characterization of a series of novel monoacylated ascorbic acid derivatives, 6-O-acyl-2-O-alpha-D-glucopyranosyl-L-ascorbic acids, as skin antioxidants

    Yamamoto, I, A Tai, Y Fujinami, K Sasaki, S Okazaki

    JOURNAL OF MEDICINAL CHEMISTRY   45 ( 2 )   462 - 468   2002年1月

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    記述言語:英語   出版者・発行元:AMER CHEMICAL SOC  

    A series of novel monoacylated vitamin C derivatives were chemically synthesized with a stable ascorbate derivative, 2-O-alpha-D-glucopyranosyl-L-ascorbic acid (AA-2G), and acid anhydrides in pyridine. Their solubility in organic phase, thermal stability, radical scavenging activity, and in vitro skin permeability was evaluated. These monoacylated derivatives were identified as 6-O-acyl-2-O-alpha-D-glucopyranosyl-L-ascorbic acids (6-Acyl-AA-2G) by UV spectra, elemental analyses, and nuclear magnetic resonance spectroscopy. The reactions afforded 6-Acyl-AA-2G in high yields (30-60%). 6-Acyl-AA-2G exhibited satisfactory stability in neutral solution comparable to that of atypical stable derivative, AA-2G, and also showed the radical scavenging activity. The lipid solubility of 6-Acyl-AA-2G was increased with increasing length of their acyl group. Increased skin permeability was superior to those of AA-2G and ascorbic acid (AsA). 6-Acyl-AA-2G that is susceptible to enzymatic hydrolysis by tissue esterase and/or alpha-glucosidase produces AA-2G and AsA, which is in the skin tissues. Thus, these findings indicate that the novel vitamin C derivatives presented here, 6-Acyl-AA-2G, may be effective antioxidants in skin care and medicinal use.

    DOI: 10.1021/jm010379f

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  • Synthesis and Characterization of a Series of Novel Monoacylated Ascorbic Acid Derivatives, 6-O-Acyl-2-O-a-D-glucopyranosyl-L-ascorbic Acids, as Skin Antioxidants.

    Itaru Yamamoto, Akihiro Tai, Yoshihito Fujinami, Kenji Sasaki, Shino Okazaki

    J. Med. Chem.   2002年

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  • Synthesis of Methylthiomaleimides for the Preparation of Pyridazines and Related Compound

    Yoshinori Tominaga, Yasuhiro Shigemitsu, Kenji Sasaki

    J. Heterocyclic Chem.   2002年

  • Synthesis of methylthiomaleimides for the preparation of pyridazines and related compounds

    Yoshinori Tominaga, Yasuhiro Shigemitsu, Kenji Sasaki

    Journal of Heterocyclic Chemistry   39 ( 3 )   571 - 591   2002年

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    記述言語:英語   出版者・発行元:HeteroCorporation  

    New functionalized maleimides (3-methylthio-2,5-dioxo-1H-pyrroles) were obtained by the reaction of ketene dithioacetals with nitromethane or the reaction of nitro ketene dithioacetal with active methylene compounds in the presence of the appropriate base in dimethyl sulfoxide followed by treatment with methanol. These maleimides reacted with various nucleophilic reagents such as electron-rich aromatic and heteroaromatic compounds like dialkylanilines, aminophenols, indoles, indolizines, and cyalazines to give the corresponding 3-aryl- or heteroaryl-1H-pyrole-2,5-diones. Styryl and merocyanine dyes, and polycyclic pyridazine-diones as chemiluminophors and succinimides were also obtained from these maleimides with good results.

    DOI: 10.1002/jhet.5570390312

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  • Study on Glutathionesulfonic Acid Sodium Salt as Biodistribution Promoter for Thiopental Sodium

    Yuhsuke Ohkawa, Tomonori Fujimoto, Kyohko Higashiyama, Hiroshi Maeda, Tomoyuki Asoh, Masateru Kurumi, Kenji Sasaki, Taiji Nakayama

    Biological and Pharmaceutical Bulletin   2002年

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  • Re-revision of the Stereo Structure of Piperidine Lactone, an Intermediate in the Synthesis of Febrifugine

    Yasuo Takeuchi, Kumiko Azuma, Hiroshi Abe, Kenji Sasaki, Takasi Harayama

    Chemical and Pharmaceutical Bulletin   2002年

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  • A new dipeptide, O-phosphoserylethanolamine isolated from Agkistroden blomhoffi (mamushi)

    Noriyoshi Masuoka, Jianying Zhang, Leila Partoo, Jun Ohta, Kenji Sasaki, Hideo Ebinuma, Hiroyuki Kodama

    Archives of Biochemistry and Biophysics   2002年

  • Polycyclic N-Heterocyclic Compounds. 56. Reaction of N-(5,6-Dihydro[1]benzoxepino-[5,4-d]pyrimidin-4-yl)amidine or Its Amide Oxime Derivatives with Hydroxyl-amine Hyrdochloride

    Kenji Sasaki, Ying-Xue Zhang, Kensuke Okuda, Takashi Hirota

    J. Heterocyclic Chem.   2001年

  • Effects of 4-Hydroxyantipyrine and Acetaminophen O-Sulfate as Biodistribution Promoter

    Yuhsuke Ohkawa, Yasunori Kiyohara, Tomoyuki Asoh, Hiroshi Maeda, Masateru Kurumi, Kenji Sasaki, Yuhji Kurosaki, Miki Matsumura, Taiji Nakayama

    Biol. Pharm. Bull.   2001年

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  • Effects of 4-Hydroxyantipyrine and Its 4-O-Sulfate on Antipyrine as Biodistribution Promoter

    Yusuke Ohkawa, Miki Matsumura, Yuhji Kurosaki, Masateru Kurumi, Kenji Sasaki, Taiji Nakayama

    Biol. Pharm. Bull.   2001年

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  • Polycyclic N-Heterocyclic Compounds. 57. Syntheses of Fused Furo(or Thieno)[2,3-b]Pyridine Derivatives via Smiles Rearrangement and Intramolecular Cyclization

    Takashi Hirota, Kei-ichiroh Tomita, Kenji Sasaki, Kensuke Okuda, Masahiko Yoshida, Setsuo Kashino

    Heterocycles   2001年

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  • Synthesis and Chemiluminescent Activity of 8,9-Dihydrobenzo[g]pyridazino[4,5-b]indole-7,10(11H)-diones

    Masateru Kurumi, Kenji Sasaki, Hiroko Takata, Taiji Nakayama

    J. Heterocyclic Chem.   2001年

  • Study on Glutathione-sulphonic Acid as Biodistribution Promoter: Concomitant Use Effect on Verapamil Hydrochloride and Tegafur.

    Yusuke Ohkawa, Kyohko Higashiyama, Shigenari Sugaya, Tomoyuki Asoh, Hiroshi Maeda, Kenji Sasaki, Taiji Nakayama

    Biol. Pharm. Bull.   2001年

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  • Syntheses of Thiopyrone and Pyrone Derivatives by Photocyclization Reaction of 3-Aryl-2-([1]benzothien-3-yl)-propenoic Acids

    Kenji Sasaki, Yasuyoshi Satoh, Takashi Hirota, Taiji Nakayama, Yoshinori Tominaga, nd Raymo, N. Castle

    J. Heterocyclic Chem.   2000年

  • Syntheses of thiopyrone and pyrone derivatives by photocyclization reaction of 3-aryl-2-([1]benzothien-3-yl)propenoic acids

    Kenji Sasaki, Yasuyoshi Satoh, Takashi Hirota, Taiji Nakayama, Yoshinori Tominaga, Raymond N. Castle

    Journal of Heterocyclic Chemistry   37 ( 4 )   959 - 967   2000年

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    記述言語:英語  

    Naphtho[1, 2-b][1]benzothiophene-6-carboxylic acids, 6H-benzo[b]naphtho[2, 3-d]thiopyran-6-ones and 6H-benzo[b]naphtho[2, 3-d]pyran-6-ones were synthesized in one step by the photocyclization reaction of 3-aryl-2-([1]benzothien-3-yl)propenoic acids. The photocyclization reaction did not occur when the 3-aryl group contained the electron-withdrawing nitro group. The assignment of the 1H and 13C nmr spectra of 6H-benzo[b]naphtho[2, 3-d]thiopyran-6-one and 6H-benzo[b]naphtho[2, 3-d]pyran-6-one by two-dimensional nmr methods is described. The difference between the chemical shift values of H12 for these two compounds is attributed to different molecular geometries.

    DOI: 10.1002/jhet.5570370446

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  • Synthesis and Chemiluminescent Activity of Pyridazino[4,5-b]indole-1,4- (2H,3H)-diones

    Masateru Kurumi, Kenji Sasaki, Hiroko Takata, Taiji Nakayama

    Heterocycles   2000年

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  • Syntheses of thiopyrone and pyrone derivatives by photocyclization reaction of 3-aryl-2-([1]benzothien-3-yl)propenoic acids

    Kenji Sasaki, Yasuyoshi Satoh, Takashi Hirota, Taiji Nakayama, Yoshinori Tominaga, Raymond N. Castle

    Journal of Heterocyclic Chemistry   37 ( 4 )   959 - 967   2000年

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    記述言語:英語  

    Naphtho[1, 2-b][1]benzothiophene-6-carboxylic acids, 6H-benzo[b]naphtho[2, 3-d]thiopyran-6-ones and 6H-benzo[b]naphtho[2, 3-d]pyran-6-ones were synthesized in one step by the photocyclization reaction of 3-aryl-2-([1]benzothien-3-yl)propenoic acids. The photocyclization reaction did not occur when the 3-aryl group contained the electron-withdrawing nitro group. The assignment of the 1H and 13C nmr spectra of 6H-benzo[b]naphtho[2, 3-d]thiopyran-6-one and 6H-benzo[b]naphtho[2, 3-d]pyran-6-one by two-dimensional nmr methods is described. The difference between the chemical shift values of H12 for these two compounds is attributed to different molecular geometries.

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  • Biopharmaceutical Studies on Drug/Conjugated Metabolites Interactions: Application of Organic Sulfonic Compounds as Biodistribution Promoters

    Yuhji Kurosaki, Yuhsuke Ohkawa, Kenji Sasaki, Taiji Nakayama

    Pharmazie   2000年

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  • Synthesis and chemiluminescence of 10-hydroxy- and 10- aminopyridazino[4,5-b]quinoline-1,4(2H, 3H)-diones

    Yoshinori Tominaga, Noriko Yoshioka, Seigo Kataoka, Yasuhiro Shigemitsu, Takashi Hirota, Kenji Sasaki

    Heterocycles   50 ( 1 )   43 - 46   1999年1月

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    記述言語:英語   出版者・発行元:Japan Institute of Heterocyclic Chemistry  

    Substituted anilines reacted with methyl 1-methyl-4-methylthio-2,5- dioxo-3-pyrroline-3-carboxylate (1) in refluxing methanol to give the corresponding methyl 1-methyl-2,5-dioxo-4-phenylamino-3-pyrroline-3- carboxylates (3a-e) which were converted in good yields to 2- methylpyrrolo[3,4-b]quinoline derivatives (4a-e) by heating in diphenyl ether. Reaction of 4a-e with hydrazine hydrate gave 10-hydroxypyridazino[4,5- b]quinoline-1,4(2H,3H)-diones (5a-e) in good yields. The desired 10- aminopyridazino[4,5-b]quinoline-1,4(2H, 3H)-diones (8a-e) were obtained by the chlorination of 4a-e with phosphorus oxychloride followed by ammonolysis with 28% ammonium hydroxide in good yields. Compounds (5) and (8) were found to be efficiently chemiluminescent in a similarly to luminol in the presence of H2O2 and horseradish peroxidase in a solution of a phosphate buffer pH 8.0.

    DOI: 10.3987/COM-98-S(H)20

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  • A novel reaction of N-(5,6-dihydro[1]benzothiepino[5,4-d]pyrimidin-4-yl)amidine or its amide oxime derivatives with hydroxylamine(共著)

    Journal of Heterocyclic Chemistry   36 ( 3 )   787 - 791   1999年

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  • Polycyclic N-heterocyclic compounds. 55 [1]. A novel reaction of N- (5,6-dihydro[1]benzothiepino[5,4-d]pyrimidin-4-yl)amidine or its amide oxime derivatives with hydroxylamine

    Ying-Xue Zhang, Kenji Sasaki, Takashi Hirota

    Journal of Heterocyclic Chemistry   36 ( 3 )   787 - 791   1999年

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    記述言語:英語   出版者・発行元:HeteroCorporation  

    The reactions of N-(5,6-dihydro[1]benzothiepino[5,4-d]pyrimidin-4- yl)amidines or its amide oxime derivatives with hydroxylamine hydrochloride under basic condition gave abnormal cyclization products via a ring cleavage of pyrimidine component accompanied with a ring closure of [1,2,4]oxadiazole.

    DOI: 10.1002/jhet.5570360335

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  • Polycyclic N-Heterocyclic Compounds. 55. A novel reaction of N-(5,6-dihydro[1]benzothiepino[5,4-d]pyrimidin-4-yl)amidine or its amide oxime derivatives with hydroxylamine

    Ying-Xue Zhang, Kenji Sasakii, Takashi Hirota

    Journal of Heterocyclic Chemistry   1999年

  • Synthesis and pharmacological evaluation of 2,3,6,7-tetrahydrothieno[2,3-h]imidazo-[2,1-f][1,6]naphthyridines, 3,4,7,8-tetrahydro-2H-thieno[2,3-h]pyrimido[2,1-f][1,6]-naphthyridines and their precursor(共著)

    Journal of Heterocyclic Chemistry   36 ( 2 )   461 - 465   1999年

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  • Polycyclic N-heterocyclic compounds. 50 [1]. Synthesis and pharmacological evaluation of 2,3,6,7-tetrahydrothieno[2,3-h]- imidazo[2,1 - f] [1,6] naphthyridines, 3,4,7,8-tetrahydro-2H-thieno[2,3-h]pyrimido[2,1- f][1,6]naphthyridines and their precursor

    Kenji Sasaki, Abu Shara S. Rouf, Takashi Hirota, Naoki Nakaya

    Journal of Heterocyclic Chemistry   36 ( 2 )   461 - 465   1999年

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    記述言語:英語   出版者・発行元:HeteroCorporation  

    Some novel 5-hydroxyalkylamino-1,2-dihydrothieno[2,3- h][1,6]naphthyridines were prepared by the reaction of 5-chloro-l,2- dihydrothieno[2,3-h][1,6]naphthyridine derivatives with some aminoalcohols in the presence of base. These derivatives were cyclized to the corresponding imidazo or pyrimido derivatives. The bronchodilatory activity of these compounds was evaluated on the basis of their relaxation activity to tracheal contraction induced by carbamylcholine chloride as a primary in vitro assays. Effect of some naphthyridines on carbamylcholine chloride-induced contractions of trachea in the presence or absence of milrinone or 4-(3- butoxy-4-methoxyphenyl)imidazolidin-2-one, which is inhibitor of phosphodiesterase III or IV, were also evaluated.

    DOI: 10.1002/jhet.5570360221

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  • Synthesis and pharmacological evaluation of 2,3,6,7-tetrahydrothieno[2,3-h]imidazo[2,1- f][1,6]naphthyridines, 3,4,7,8-tetrahydro-2H-thieno[2,3-h]pyrimido[2,1- f][1,6]naphthyridines and their precursor

    Kenji Sasaki, Abu Shara, Shamusur Rouf, Naoki Nakaya, Takashi Hirota

    Journal of Heterocyclic Chemistry   1999年

  • Ring-cleavages and ring-closures of N-(benzo[h]quinazolin-4-yl)amidine and its amide oxime derivatives with hydroxylamine

    Kenji Sasaki, Ying-Xue Zhang, Hiroshi Yamamoto, Setsuo Kashino, Takashi Hirota

    Journal of Chemical Research (M)   1999年

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  • Ring-cleavages and ring-closures of N-(benzo[h]quinazolin-4-yl)amidine and its amide oxime derivatives with hydroxylamine(共著)

    Journal of Chemical Research(S)   ( 2 )   92 - 93   1999年

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    記述言語:英語  

    DOI: 10.1039/a809077g

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  • Polycyclic N-heterocyclic compounds. Part 54. Ring-cleavages and ring- closures of N-(benzo[h]quinazolin-4-yl)amidine and its amide oxime derivatives with hydroxylamine

    Kenji Sasaki, Ying-Xue Zhang, Hiroshi Yamamoto, Setsuo Kashino, Takashi Hirota

    Journal of Chemical Research - Part S   ( 2 )   92 - 93   1999年

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    記述言語:英語   出版者・発行元:Royal Society of Chemistry  

    The synthesis of abnormal cyclization products, 2-(3-alkyl(or aryl)[1,2,4]oxadiazol-5-yl)-3,4-dihydro-1-naphthylaminoformaldehyde oximes and their homologues, by the reaction of N-(benzo[h]quinazolin-4-yl)amidine or its amide oxime derivatives with excess NH2OH·HCl are described.

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  • Ring-cleavages and ring-closures of N-(benzo[h]quinazolin-4-yl)amidine and its amide oxime derivatives with hydroxylamine

    Kenji Sasaki, Ying-Xue Zhang, Hiroshi Yamamoto, Setsuo Kashino, Takashi Hirota

    Journal of Chemical Research (S)   1999年

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  • Synthesis and chemiluminescence of 10-hydroxy- and 10-aminopyridazino[4,5-b]quinoline-1,4(2H,3H)-diones

    Yoshinori Tominaga, Noriko Yoshioka, Seigo Kataoka, Yasuhiro Shigemitsu, Takashi Hirota, Kenji Sasaki

    Heterocycles   1999年

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  • Polycyclic N-Heterocyclic Compounds. 53 One Step Syntheses of Imidazo[1,5-a]pyridine Derivatives by The Vilsmeier Reaction Using N,N-Dimethylarylamides

    Kenji Sasaki, Akifumi Tsurumori, Setsuo Kashino, Takashi Hirota

    Heterocycles   1999年

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  • Biopharmaceutical studies on drug/conjugated-metabolite interactions. II. Effect of acetaminophen sulfate on pharmacokinetics of acetaminophen in rats

    Taiji Sawamoto, Yuji Kurosaki, Kenji Sasaki, Toshikiro Kimura, Taiji Nakayama

    International Journal of Pharmaceutics   146 ( 2 )   181 - 191   1997年1月

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    記述言語:英語  

    The effect of conjugated-metabolite, acetaminophen sulfate (APAPS), on the pharmacokinetics of its parent drug, acetaimnophen (APAP), was examined in rats. Following the i.v. bolus administration of APAP with APAPS, the plasma elimination of APAP was delayed and the distribution volume of APAP was increased at the APAPS coadministration with 60 mg APAP equivalent per kg (eq/kg). The percentages of dose excreted in the urine and bile in 4 h as APAP and its conjugated metabolites, APAPS and acetaminophen glucuronide, were significantly decreased. On the other hand, following the i.v. bolus administration of APAP under the steady-state concentration of APAPS, the distribution volume and total body clearance of APAP were significantly increased. Competitive displacement in serum protein binding of APAP by APAPS was ascertained in vitro and in vivo. A part of the conflict between the bolus and infusion experiment may be explained by the changes in the distribution volume of APAP contributed to the APAPS concentration-dependent serum protein binding of APAP. It was speculated that the pharmacokinetics of APAP was partly interacted with APAPS by the displacement of serum protein binding.

    DOI: 10.1016/S0378-5173(96)04803-X

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  • Biopharmaceutical Studies on Drug/Conjugated-Metabolite Interactions. II. Effect of Acetaminophen Sulfate on Pharmacokinetics of Acetaminophen in Rats (共著)

    International Journal of Pharmaceutics   146 ( 2 )   181 - 191   1997年1月

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  • Synthesis of new methine class of dyes bearing maleimide ring system

    Yoshinori Tominaga, Kaori Komiya, Sachiko Itonaga, Noriko Yoshioka, Seigo Kataoka, Kenji Sasaki, Takashi Hirota

    Heterocycles   46 ( 1 )   41 - 44   1997年

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    記述言語:英語   出版者・発行元:Japan Institute of Heterocyclic Chemistry  

    Reaction of l-methyl-3-methylthiomaleimides (1a-c) with N,N-dialkylanilines (2) under refluxing in acetic acid condition gave the corresponding 3-(4-diakylamino)phenyl-1-methylmaleimides (3a-g). Treatment of these 1-methyl-3-phenylmaleimides (3a, c) with Lawesson's reagent under refluxing in toluene afforded new blue dyes, 4-(4-dialkylamino)phenyl-3-cyano-1-methyl-5-oxopyrrole-2-thiones (5a, b) which are brilliant blue dyes appearing at 606 and 615 nm (log ε: 4.59 and 4.50) in UV spectra. Reaction of 4-methoxycarbonyl-1-methyl-3-methylthiomaleimide (1b) with 3-dialkylamino-phenol under the same reaction conditions gave cyclizcd products, 2H, 4H-[1]-benzopyrano[3,4-c]pyrrole-1,3,4-triones (6a-c) in good yields.

    DOI: 10.3987/COM-97-S12

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  • Synthesis of New Methine Class of Dyes Bearing Maleimide Ring System. (共著)

    Heterocycles   46 ( 1 )   41 - 44   1997年

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    記述言語:英語  

    DOI: 10.3987/COM-97-S12

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  • Isolation and characterization of N-acetyl-S-[2-carboxy-1-(1H-imidazol-4-yl) ethyl]-L-cysteine, a new metabolite of histidine, from normal human urine and its formation from S-[2-carboxy-1-(1H-imidazol-4-yl)ethyl]-L-cysteine

    Masahiro Kinuta, Kenji Sasaki, Hiroo Shimizu, Toshihiko Ubuka

    Biochimica et Biophysica Acta - General Subjects   1291 ( 2 )   131 - 137   1996年10月

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    記述言語:英語   出版者・発行元:Elsevier B.V.  

    N-Acetyl-S-[2-carboxy-1-(1H-imidazol-4-yl)ethyl]-L-cysteine (I), a new imidazole compound with a sulfur-containing side chain, was isolated from normal human urine by ion-exchange column chromatography, and characterized by physicochemical analyses involving 1H-NMR spectrometry, mass spectrometry and high-voltage paper electrophoresis as well as chemical synthesis. Approximately five milligrams of crystals of the compound were obtained from 450 litres of the urine. Compound I was synthesized by the addition of N-acetyl-L-cysteine to urocanic acid. The compound was also formed by incubation of S-[2-carboxy-1-(1H-imidazol-4-yl)ethyl]-L-cysteine (II) with acetyl-CoA in the use of rat kidney or liver homogenate as an enzyme source in a Tris buffer at pH 7.4. Rat brain and spleen homogenates were the less or no effective preparations as the enzyme source. On the other hand, little N-acetylation of a diastereomer of compound II occurred in enzymatic reactions with rat tissue homogenates. Compound I was degraded to compound II by rat kidney or liver homogenate. These results suggest that compound I is a new N-acetylated metabolite of compound II, a compound previously found in human urine, and that the acetylating enzyme recognizes stereoisomerism of asymmetric carbon atoms on the molecule of compound II. These findings support an alternative pathway of L-histidine catabolism initiated by the adduction of glutathione and/or cysteine to urocanic acid, the first catabolite of histidine.

    DOI: 10.1016/0304-4165(96)00055-4

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  • Isolation and Characterization of N-Acetyl-S-[2-carboxy-1-(1H-imidazol-4-yl)ethyl]-L-cysteine, A New Metabolite of Histidine, from Normal Human Urine and Its Formation from S-[2-Carboxy-1-(1H-imidazol-4-yl)ethyl]-L-cysteine. (共著)

    Biochimica et Biophysica Acta   1291 ( 2 )   131 - 137   1996年10月

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  • Synthesis of Novel 12-Substituted11,13,15-Triazasteroidal Compounds and Their Inhibitory Activity on Platelet Aggregation. (共著)

    Journal of Heterocyclic Chemistry   33 ( 6 )   1663 - 1669   1996年

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  • The Synthesis of Novel Polycyclic Heterocyclic Ring Systems. 2. Naphtho-[2,1-b : 4,3-g]bisbenzo[b]thiophene. (共著)

    Journal of Heterocyclic Chemistry   33 ( 3 )   847 - 853   1996年

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  • Polycyclic N-heterocyclic compounds. 51. Synthesis of novel 12-substituted 11,13,15-triazasteroidal compounds and their inhibitory activity on platelet aggregation

    Kenji Sasaki, Takeshi Arichi, Hiromi Ohtomo, Taiji Nakayama, Takashi Hirota

    Journal of Heterocyclic Chemistry   33 ( 6 )   1663 - 1669   1996年

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    記述言語:英語   出版者・発行元:HeteroCorporation  

    Synthesis of 11-substituted 1,2,4,5-tetrahydrobenzo[h]imidazo[1,2-c]quinazolines corresponding to 12-substituted 11,13,15-triazasteroid is described. Evaluation on inhibitory activity against collagen-induced platelet aggregation of these compounds and their precursors was also investigated.

    DOI: 10.1002/jhet.5570330619

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  • The synthesis of novel polycyclic heterocyclic ring systems. 2. Naphtho[2,1-b:4,3-g]bisbenzo[b]thiophene

    Kenji Sasaki, Osamu Tokuda, Takashi Hirota, Jiann-Kuan Luo, Raymond N. Castle

    Journal of Heterocyclic Chemistry   33 ( 3 )   847 - 853   1996年

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    記述言語:英語   出版者・発行元:HeteroCorporation  

    The novel polycyclic heterocyclic ring system, naphtho[2,1-b:4,3-g]bisbenzo[b]thiophene was synthesized from 5-[2-(2-bromo-3-thienyl)ethenyl]naphtho[2,1-b][1]benzothiophene. The assignment of its 1H and 13C nmr spectra was also accomplished by utilizing two-dimensional nmr methods.

    DOI: 10.1002/jhet.5570330351

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  • Synthesis of Thieno [2, 3-DB<h>(/)-DB] [1,6] naphthyridine from 2-(3-Cyanopropylthio) pyridine-3-carbonitrile : Formation of a novel Ring System (共著)

    Journal of The Chemical Society, Chemical Communication   ( 15 )   1767 - 1768   1994年

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    記述言語:英語  

    DOI: 10.1039/C39940001767

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  • Synthesis of thieno[2,3-h][1,6]naphthyridine from 2-(3-cyanopropylthio) pyridine-3-carbonitrile: Formation of a novel ring system

    Kenji Sasaki, Rouf A. S. Shamsur, Setsuo Kashino, Takashi Hirota

    Journal of the Chemical Society, Chemical Communications   ( 15 )   1767 - 1768   1994年

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    記述言語:英語  

    An efficient methodology for the synthesis of novel ring system, thieno[2,3-h][1,6]naphthyridine, via a Smiles type rearrangement reaction and cyclization is described, its structure is confirmed by an X-ray structure analysis.

    DOI: 10.1039/C39940001767

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  • Polycyclic DB<N>(/)-DB-Heterocyclic Compounds. XLV. Synthesis of the Nove1 B,D-Dihomo-11,13,15-tri--azasteroidal Skeleton and their Effect on Reserpine-Induced Hypothermia and Inhibitory Activity on Platelet Aggregation (共著)

    Journal of Heterocyclic Chemistry   30 ( 4 )   989 - 992   1993年

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  • Polycyclic N‐heterocyclic compounds. XLIV. Synthesis of the novel B,D‐Dihomo‐11,13,15‐triazasteroidal skeleton and their effect on reserpine‐induced hypothermia and inhibitory activity on platelet aggregation

    Kenji Sasaki, Yuichi Arimoto, Hiromi Ohtomo, Taiji Nakayama, Takashi Hirota

    Journal of Heterocyclic Chemistry   30 ( 4 )   989 - 992   1993年

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    記述言語:英語  

    Synthesis of benzo[3,4]cyclohepta[1,2‐e]pyrimido[1,2‐c]pyrimidines, corresponding to the B,D‐dihomo‐11,13,15‐triazasteroidal skeleton as a novel ring system is described. Their effects on reserpine‐induced hypothermia in mice and inhibitory activity against collagen‐induced platelet aggregation were also investigated. Copyright © 1993 Journal of Heterocyclic Chemistry

    DOI: 10.1002/jhet.5570300425

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  • Polycyclic (]E8BAA[)-Hetero Compounds. XXXVI. Syntheses and Antidepressive Evaluation of 11,13,15,17-Tetraazasteroids and Their 17-Oxides. (共著)

    Journal of Heterocyclic Chemistry   28 ( 2 )   257 - 261   1991年

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  • Polycyclic N‐hetero compounds. XXXVI. Syntheses and antidepressive evaluation of 11,13,15,17‐tetraazasteroids and their 17‐oxides

    Takashi Hirota, Kenji Sasaki, Hiroshi Yamamoto, Taiji Nakayama

    Journal of Heterocyclic Chemistry   28 ( 2 )   257 - 261   1991年

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    記述言語:英語  

    Syntheses of 11,13,15,17‐tetraazasteroids, their B‐homologues, and 17‐oxide derivatives are described. Antidepressive evaluation of these compounds and their precursors were screened by inhibitory action of reserpine‐induced hypothermia. Copyright © 1991 Journal of Heterocyclic Chemistry

    DOI: 10.1002/jhet.5570280209

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  • Polycyclic (]E8BAA[)-Hetero Compounds. XXXII. Synthesis and Antidepressive Evaluation of B-Homo-11,13,15-triazasteroids and Their Precursors. (共著)

    Journal of Heterocyclic Chemistry   27 ( 3 )   759 - 763   1990年

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  • Polycyclic N‐hetero compounds. XXXII Synthesis and antidepressive evaluation of B‐homo‐11,13,15‐triazasteroids and their precursors

    Takashi Hirota, Kenji Sasaki, Katsuhiro Ieno, Yuhki Sekiya, Taiji Nakayama

    Journal of Heterocyclic Chemistry   27 ( 3 )   759 - 763   1990年

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    記述言語:英語  

    Synthesis of 4‐(2‐hydroxyethylamino)‐6,7‐dihydro‐5H‐benzo[6,7]cyclohepta[1,2‐d]pyrimidine derivatives V and their cyclized products, B‐homo‐11,13,15‐triazasteroidal compounds VI and VII, are described. These products were screened to evaluate the antidepressive activity. Copyright © 1990 Journal of Heterocyclic Chemistry

    DOI: 10.1002/jhet.5570270352

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  • Polycyclic (]E8BAA[)-Hetero Compounds. XXIX. Synthesis and Antidepressive Evaluation of 15-Thia-11,13-diazasteroidal Analogues and Their Precursors. (共著)

    Journal of Heterocyclic Chemistry   24 ( 2 )   341 - 344   1987年

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  • Polycyclic N‐hetero compounds. XXIX. Synthesis and antidepressive evaluation of 15‐thia‐11,13‐diazasteroidal analogues and their precursors

    Takashi Hirota, Rieko Hamazaki, Takako Ohdoi, Kenji Sasaki, Tetsuto Namba

    Journal of Heterocyclic Chemistry   24 ( 2 )   341 - 344   1987年

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    記述言語:英語  

    Syntheses of novel 15‐thia‐11,13‐diazasteroidal skeleton IV and its D‐homo analogues are described. Meso‐ionic derivatives of IV were also synthesized. Antidepressive activities of these compounds and their precursors were screened. D‐Dihomothiadiazasteroid IX and 3,4,5,6‐tetrahydrobenzo[h]quinazoline‐4‐thione (V) exhibited antireserpine action. Copyright © 1987 Journal of Heterocyclic Chemistry

    DOI: 10.1002/jhet.5570240209

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  • Polycyclic N‐hetero compounds. XXVII. Synthesis and investigation of the antidepressive activity of a B‐Homo‐11,13,15‐triazasteroid and its related compoundsd

    Takashi Hirota, Katsuhiro Ieno, Kenji Sasaki

    Journal of Heterocyclic Chemistry   23 ( 6 )   1685 - 1687   1986年

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    記述言語:英語  

    A synthesis of 1,2,5,6‐tetrahydro‐4H‐benzo[3,4]cyclohepta[1,2‐e]imidazo[1,2‐c]pyrimidine (XII) having a novel ring system is described. Antidepressive activity of XII and its precursors VII‐X was screened by inhibitory action of reserpine‐induced hypothermia. Copyright © 1986 Journal of Heterocyclic Chemistry

    DOI: 10.1002/jhet.5570230616

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  • A Novel Synthesis of Benzofuran and Related Compounds. III. The Vilsmeier Reaction of Phenoxyacetaldehyde Diethyl Acetals. (共著)

    Jounral of Heterocyclic Chemistry   23 ( 6 )   1715 - 1716   1986年

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  • A Novel Synthesis of Benzofuran and Related Compounds. I. The Vilsmeier Reaction of Phenoxyacetonitriles. (共著)

    Jounral of Heterocyclic Chemistry   23 ( 5 )   1347 - 1351   1986年

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  • A novel synthesis of benzofuran and related compounds. III. The vilsmeier reaction of phenoxyacetaldehyde diethyl acetals

    Takashi Hirota, Hiroko Fujita, Kenji Sasaki, Tetsuto Namba

    Journal of Heterocyclic Chemistry   23 ( 6 )   1715 - 1716   1986年

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    記述言語:英語  

    A novel synthesis of 2‐benzofurancarbaldehydes by the Vilsmeier reaction of phenoxyacetaldehyde diethyl acetals is described. Copyright © 1986 Journal of Heterocyclic Chemistry

    DOI: 10.1002/jhet.5570230622

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  • Polycyclic (]E8BAA[)-Hetero Compounds. XXVII. Synthesis and Investigation of the Antidepressive Activity of a B-Homo-11,13,15-triazasteroid and Its Related Compounds. (共著)

    Journal of Heterocyclic Chemistry   23 ( 6 )   1685 - 1687   1986年

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  • A novel synthesis of benzofuran and related compounds. I. The vilsmeier reaction of phenoxyacetonitriles

    Takashi Hirota, Hiroko Fujita, Kenji Sasaki, Tetsuto Namba, And Shohei Hayakawa

    Journal of Heterocyclic Chemistry   23 ( 5 )   1347 - 1351   1986年

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    記述言語:英語  

    A novel synthesis of 2‐benzofurancarboxylic acid derivatives by the Vilsmeier reaction of phenoxyacetonitriles is described. Copyright © 1986 Journal of Heterocyclic Chemistry

    DOI: 10.1002/jhet.5570230516

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▼全件表示

講演・口頭発表等

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    第25回国際複素環化学討論会  2015年 

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  • Synthesis and Evaluation of Flavonol Derivatives as Potent Anti-MRSA Agents

    2015 International Chemical Congress of Pacific Basin Societies  2015年 

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    第24回国際複素環化学討論会  2013年 

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    日本薬学会第133年会  2013年 

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    第42回複素環化学討論会  2012年 

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  • Quinolone Analogues. Synthesis of 4-Quinolon-3-ylcarbonylsemicarbazides with Antimalarial Activity

    42nd Congress of Heterocyclic Chemistry  2012年 

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    BIO tech 2012 (第11回国際バイオテクノロジー展/技術会議)  2012年 

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    日本薬学会第131年会  2011年 

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    第41回複素環化学討論会  2011年 

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    東アジア植物遺伝資源シンポジウム  2011年 

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    Seminar on Diverse Pharmacological Substances in East Asian Plant Genetic Resources  2011年 

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    第32回日本肥満学会  2011年 

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    第23回国際複素環化学討論会  2011年 

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    Seminar on Diverse Pharmacological Substances in East Asian Plant Genetic Resources  2011年 

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    創薬懇話会2011 in 岡山  2011年 

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    創薬懇話会2011 in 岡山  2011年 

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    日本薬学会第131年会  2011年 

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    日本薬学会第131年会  2011年 

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    日本薬学会第131年会  2011年 

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    41st Congress of Heterocyclic Chemistry  2011年 

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    第2回高度医療都市を創出する未来技術国際シンポジウム  2009年 

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  • Smiles型転位及び分子内閉環反応を経由した新規アミノフロピリジン骨格を有する化合物の合成と抗マラリア活性の検討

    第38回複素環化学討論会  2008年 

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  • RXRアルファ/ベータデュアルアゴニストNEt-3IPの抗アレルギー作用

    第27回 メディシナルケミストリーシンポジウム  2008年 

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  • Benzoazole を基本骨格とする複素環型RXRリガンドの開発

    第27回 メディシナルケミストリーシンポジウム  2008年 

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  • 新規アミノフロピリジン誘導体の抗マラリア活性と構造活性相関

    第27回 メディシナルケミストリーシンポジウム  2008年 

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  • 脂溶性側鎖にアルコキシ基を有するレチノイドX受容体リガンドの系統的構造変換と構造活性相関

    第27回 メディシナルケミストリーシンポジウム  2008年 

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  • 縮合naphthalene構造を持つluminol誘導体の合成と化学発光能評価

    第38回複素環化学討論会  2008年 

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  • ピリジニウム塩ダイマーをリードとした非カチオン型抗マラリア化合物の創製

    第27回 メディシナルケミストリーシンポジウム  2008年 

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  • Quinolone Analogues. N1側鎖にTriazole環を有するキノロン類の合成

    日本薬学会第128年会  2008年 

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  • Quinolone Analogues. 抗マラリア活性をターゲットとしたキノロン類の合成

    第38回複素環化学討論会  2008年 

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  • 新規シクロゲナーゼ1(COX-1)阻害剤の開発とその胃潰瘍形成の有無および鎮痛効果の検証

    日本薬学会第128年会  2008年 

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  • RXRアルファ/ベータデュアルアゴニストNEt-3IPの開発と生理活性評価

    日本薬学会第128年会  2008年 

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  • 安価なイソニコチン酸から2ステップで合成可能なビスカチオン型抗マラリア化合物の開発

    第26回メディシナルケミストリーシンポジウム  2007年 

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  • RXRアゴニスト脂溶性部位の脂溶性低減によるRXRサブタイプ指向性の創出-リンカー部位にスルホンアミド基を有する-

    第26回メディシナルケミストリーシンポジウム  2007年 

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  • RXRα/βデュアルアゴニストNet-3IPの抗炎症及び抗がん作用の検証

    第26回メディシナルケミストリーシンポジウム  2007年 

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  • 一工程で合成可能な非サルファ剤型抗MRSA・VREベンゼンスルホンアニリド誘導体

    第26回メディシナルケミストリーシンポジウム  2007年 

     詳細を見る

  • シクロオキシゲナーゼ1(COX-1)選択的阻害剤は胃潰瘍形成のない新しい 鎮痛剤になりうる

    第46回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会  2007年 

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  • 高活性 RXRα/β選択的アゴニストNet-3IPの開発-脂溶性部位にアルコキシ基を有する-

    第26回メディシナルケミストリーシンポジウム  2007年 

     詳細を見る

  • Quinolone Analogues. 抗マラリア活性を有するキノロン類の合成

    複素環化学討論会  2007年 

     詳細を見る

  • ピリジニウム塩ダイマーを基盤とした抗マラリア薬の開発

    第37回複素環化学討論会  2007年 

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  • 胃潰瘍形成の無い鎮痛剤開発を目指した新規シクロオキシゲナーゼ1(COX-1)選択的阻害剤の創製

    第25回メディシナルケミストリーシンポジウム  2006年 

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  • 6-Phenylaminonicotinic acid を共通骨格とする複素環 RXR リガンドの開発

    第36回複素環化学討論会  2006年 

     詳細を見る

  • アミド部位をN-アルキル化したピリジニウム塩ダイマーの抗マラリア活性の検討

    第25回メディシナルケミストリーシンポジウム  2006年 

     詳細を見る

  • アルキレンビス(ベンゼンスルホンアミド)を基本構造とする新規抗マラリア薬の開発

    第45回日本薬学会・日本病院薬剤師会中国四国支部学術大会  2006年 

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  • リンカーとしてN,N'-アルキル鎖を有するピリジニウム塩ダイマーの抗マラリア活性

    第36回複素環化学討論会  2006年 

     詳細を見る

  • ベンゼンスルホンアニリドを骨格とする新規シクロオキシゲナーゼ阻害剤の開発

    第126年会日本薬学会  2006年 

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  • Design and Synthesis of Structurally Simple Benzenesulfonanilide-type Cyclooxygenase Inhibitors

    Pacifichem 2005  2005年 

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  • Antimalarial Effect of Bis-pyridinium Salts

    Pacifichem 2005  2005年 

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  • N-アルキル鎖を有するピリジニウムダイマーを基盤とした抗マラリア薬の開発

    第24回メディシナルケミストリーシンポジウム  2005年 

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  • スルホンアミド構造を有する新規RXRリガンドの創製

    第24回メディシナルケミストリーシンポジウム  2005年 

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  • 2,4(1H,3H)-Quinazolinedioneを骨格とするレチノイドアンタゴニストの創製

    第44回日本薬学会・日本病院薬剤師会中国四国支部学術大会  2005年 

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  • バイオイメージングを志向した蛍光性レチノイドの開発

    第44回日本薬学会・日本病院薬剤師会中国四国支部学術大会  2005年 

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  • N-アルキル鎖を有するピリジニウム塩ダイマーの抗マラリア活性

    第35回複素環化学討論会  2005年 

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  • Benzanilideを骨格とする新規cyclooxygenase-1 (COX-1) 選択的阻害剤の創製

    第44回日本薬学会・日本病院薬剤師会中国四国支部学術大会  2005年 

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  • ピュ-ロマイシンをリードとしたアポトーシス活性分子の開発研究

    日本薬学会第125年会  2005年 

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  • バイオイメージングを指向した蛍光性レチノイドの開発研究

    日本薬学会第125年会  2005年 

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  • ベンゼンスルフォンアニリドの立体特性を利用した新規COX-2選択的阻害剤の開発研究

    第43回日本薬学会・日本病院薬剤師会中国四国支部大会  2004年 

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  • 細胞分化を制御する複素環化合物の創製

    第34回複素環化学討論会  2004年 

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  • ピューロマイシン感受性アミノペプチダーゼを標的とした新規鎮痛剤の開発研究

    日本薬学会第124年会  2004年 

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  • 4-(N,N-Dimethylaminomethyleneamino)pyrimidine 誘導体とNH2OH・HCl との反応

    第123年回日本薬学会年会  2003年 

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  • Syntheses of Thiopyrone and Pyrone Derivatives by Photocyclization Reaction of 3-Aryl-2-([1]benzothien-3-yl)propenoic Acids

    19th International Congress of Heterocyclic Chemistry  2003年 

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  • N-[2-([1,2,4]Oxadiazol-5-yl)aryl]formamide Oxime 誘導体の合成とその糖尿病合併症抑制作用

    第22回メディシナルケミストリーシンポジウム・第11回日本薬学会医薬化学部会年会  2002年 

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  • 2-Aryl-4-methylthio-2,5-dioxo-2,5-dihydrofuran を反応基材とした Pyridazine 類の合成とその化学発光能

    第32回複素環化学討論会  2002年 

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  • 生体内分布促進作用を有する新規配合剤としてのスルホン酸誘導体の研究

    日本薬剤学会第17年会  2002年 

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  • 油性状医薬品の固形製剤化の研究(5)-ビタミン A 及び E 含有製剤の素材の開発-

    第41回日本薬学会・日本病院薬剤師会中国四国支部学術大会  2002年 

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  • 生体内分布促進剤としてのスルホン酸誘導体の研究

    第122年回日本薬学会年会  2002年 

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  • 生体内分布促進剤としてのスルホン酸誘導体の研究

    第123年回日本薬学会年会  2002年 

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  • 3-Aryl-4-methylthio-2,5-dioxo-2,5-dihydrofuran を反応基材とした Pyridazine 類の合成

    第121年回日本薬学会年会  2001年 

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  • 油性状医薬品の固形製剤化の研究(3)-ビタミンE含有製剤の素材の開発-

    第40回日本薬学会・日本病院薬剤師会中国四国支部学術大会  2001年 

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  • 薬物併用時に於ける生体内分布促進剤としてのスルホン酸誘導体の研究

    第121年回日本薬学会年会  2001年 

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  • Rearrangement Reaction of Fused 3-(2-Bromoethyl)pyrimidine Derivatives with Amines

    18th International Heterocyclic Chemistry Congress  2001年 

     詳細を見る

  • Synthesis of 3-Aryl-4-Methylthio-2,5-Dioxo-2,5- Dihydrofurans and Their Application for Preparation of Heterocyclic Compounds

    2000 International Chemical Congress of Pacific Basin Societies  2000年 

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  • 3 位に 2-bromoethyl 基を有する縮合 pyrimidine 誘導体と amine 類による転位反応

    第31回複素環化学討論会  2000年 

     詳細を見る

  • 油性状医薬品の固形製剤化の研究(3)-ビタミンE含有製剤の素材の開発-

    第39回日本薬学会・日本病院薬剤師会中国四国支部学術大会  2000年 

     詳細を見る

  • Glutathionesulfonic acid の生体内分布促進剤としての応

    第120年回日本薬学会年会  2000年 

     詳細を見る

  • 薬物併用による生体内分布促進剤の開発 -硫酸基を有する化合物の併用による薬物の分布促進効果について-

    第16回日本DDS学会  2000年 

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  • 光閉環反応を経由するピリダジン誘導体の合成とその化学発光能の検討

    第120年回日本薬学会年会  2000年 

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  • Biopharmaceutical Studies on Drug/Conjugated Matabolite Interactions: Application of Organic Sulfonic COmpounds as Biodistribution Modifying Agents

    2nd Retrometabolism Based Drug Design and Targeting Conference  1999年 

     詳細を見る

  • Fused N-(4-Pyrimidinyl)amidine Oxime と Hydroxylamine Hydrochloride による環開裂及び閉環反応

    第30回複素環化学討論会  1999年 

     詳細を見る

  • 油性状医薬品の固形製剤化の研究(2)ーモカルペースト(おから)を素材としてー

    第38回日本薬学会・日本病院薬剤師会中国四国支部学術大会  1999年 

     詳細を見る

  • 薬物併用による生体内分布促進剤の開発 glutathionesulfonic acid 併用時の thiopental の分布促進効果について

    第15回日本DDS学会  1999年 

     詳細を見る

  • Synthesis and Chemiluminescence of Pyridazino(or Benzo[g]pyridazino[4,5-b]-indole-1,4(2H,3H)-diones

    17th International Heterocyclic Chemistry Congress  1999年 

     詳細を見る

  • グルタチオン及びそのスルホン酸化合物とチオペンタールの生体内分布における相互作用について

    日本薬剤学会第14年会  1999年 

     詳細を見る

▼全件表示

Works(作品等)

  • BIO tech 2012 (第11回国際バイオテクノロジー展/技術会議)

    2012年

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  • 新規抗マラリア薬の開発

    2007年

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    作品分類:芸術活動  

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担当授業科目

  • くすりの話 (2020年度) 第2学期  - 月3,月4