New Neplanocin Anallogues. VIII. Synthesis and Biological Activity of 6'-C-Ethyl, -Ethenyl, and -Ethynyl Derivatives of Neplanocin A

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概要

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• This report describes the synthesis and antiviral effects of (6'R)-6'-C-ethynyl, -ethenyl, and -ethyl derivatives of neplanocin A (7a, 8a, and 9a, respectively) and the corresponding 6'S-diastereomers (7b, 8b, and 9b, respectively), as exampls of 6'-C-substituted analogues of neplanocin A. Grignard reaction of the 6'-formyl derivative 4,which was readily prepared from neplanocin A, with ethynylmagnesium bromide gave a diastereomeric mixture of the corresponding 1,2-addition products 5a and 5b. After removal of the protecting groups, (6'R)- and (6'S)-6'-C-ethynylneplanocin A's (7a, 7b) were separated. The corresponding ethenyl derivatives 8a and 8b and ethyl derivatives 9a and 9b were prepared by catalytic hydrogenation of 7a and 7b, respectively. As compared to neplanocin A, the new neplanocin A derivatives were much weaker inhibitors of S-adenosyl-L-homocysteine hydrolase, the R-diastereomers being more inhibitory than the S-diastereomers. The decreasing order of activity was 7a>8a>7b>9a>8b>9b. The cytotoxicity (for CEM cells) followed exactly the same order. Of these compounds, (6'R)-6'-C-ethynylneplanocin A (7a, RENPA) showed an antiviral activity spectrum that was comparable to, and an antiviral specificity that was higher than, that of neplanocin A. RENPA was particularly active against those viruses (i.e. vaccinia virus, vesicular stomatitis virus) that are known to be highly sensitive to AdoHcy hydrolase inhibitors.

• 社団法人日本薬学会の論文
• 1997-07-15

著者

• 田中 正一

  Graduate School Of Pharmaceutical Sciences Kyushu University

• De Clercq

  Rega Inst. For Medical Res. Katholieke Universiteit Leuven

• SNOECK Robert

  Rega Institute for Medical Research, Katholieke Universiteit Leuven

• ANDREI Graciela

  Rega Institute for Medical Research, Katholieke Universiteit Leuven

• BALZARINI Jan

  Rega Institute for Medical Research, Katholieke Universiteit Leuven

• Blanco Jose

  Departamento De Farmacologia Facultade De Farmacia Universidade De Santiago De Compostela

• De Clercq

  Rega Institute For Medical Research Katholieke Universiteit Leuven

• Snoeck Robert

  Rega Instituut Katholieke Universiteit Leuven

• Snoeck Robert

  Rega Institute For Medical Research Katholieke Universiteit Leuven

• Balzarini J

  Rega Inst. For Medical Res.

• Tanaka M

  Faculty Of Pharmaceutical Sciences Tokushima Bunri University

• MATSUDA Akira

  Faculty of Pharmaceutical Sciences, Hokkaido University

• Matsuda A

  Graduate School Of Pharmaceutical Sciences Hokkaido University

• Matsuda A

  Faculty Of Pharmaceutical Sciences Hokkaido University

• YAMASHITA Kanako

  Institute of Life Science Research, Asahi Chemical Co., Ltd.

• TANAKA Motohiro

  Cancer Research Institute, Kanazawa University

• SASAKI Takuma

  Cancer Research Institute, Kanazawa University

• SHUTO Satoshi

  Faculty of Pharmaceutical Sciences, Hokkaido University

• OBARA Takumi

  Institute for Life Science Research, Asahi Chemical Industry Co., Ltd.,

• SAITO Yasuyoshi

  Institute for Life Science Research, Asahi Chemical Industry Co., Ltd.,

• NEYTS Johan

  Rega Institute for Medical Research, Katholieke Universiteit Leuven

• PADALKO Elisabeth

  Rega Institute for Medical Research, Katholieke Universiteit Leuven

• Obata Tohru

  Department Of Experimental Therapeutics Cancer Research Institute Kanazawa University

• Andrei Graciela

  Rega Instituut Katholieke Universiteit Leuven

• Andrei Graciela

  Rega Institute For Medical Research Katholieke Universiteit Leuven

• Obara Takumi

  Department Of Experimental Therapeutics Cancer Research Institute Kanazawa University

• Matsuda Akira

  Department Of Pharmaceutical Sciences Faculty Of Pharmaceutical Sciences

• Matsuda A

  Hokkaido Univ. Sapporo

• Matsuda Akira

  The Department Of Internal Medicine Kin-ikyo Chuo Hospital

• Balzarini Jan

  Rega Inst. For Medical Res.

• Balzarini J

  Rega Institute For Medical Research Katholieke Universiteit Leuven

• Saito Yasuyoshi

  Institute For Life Science Research Asahi Chemical Industry Co. Ltd.

• Neyts Johan

  Rega Institute For Medical Research Katholieke Universiteit Leuven

• Obata Takaaki

  Department Of Experimental Therapeutics Cancer Research Institute Kanazawa University

• Sasaki Takuma

  Cancer Research Institute Kanazawa University

• Sasaki Takuma

  Department Of Experimental Therapeutics Cancer Research Insitute Kanazawa University

• Shigeta S

  Fukushima Medical University

• Tanaka Motohiro

  Cancer Research Institute Kanazawa University

• Yamashita K

  Department Of Chemical Science And Technology Faculty Of Engineering The University Of Tokushima

• Matsuda Akira

  Faculty Of Pharmaceutical Sciences Hokkaido University

• Padalko Elisabeth

  Rega Institute For Medical Research Katholieke Universiteit Leuven

• Yamashita Kanako

  Institute For Life Science Research Asahi Chemical Industry Co. Ltd.

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