Synthesis and Structure-Activity Relationships in a Series of Ethenesulfonamide Derivatives, a Novel Class of Endothelin Receptor Antagonists

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概要

• 論文の詳細を見る

• In the previous paper, we described a series of the 2-arylethenesulfonamide derivatives, a novel class of ET_A-selective endothelin(ET) receptor antagonists, including the compounds 1a, b. Compound 1a showed excellent oral antagonistic activities and pharmacokinetic profiles, and the monopotassium salt of 1(YM-598 monopotassium)is in clinical trials. In this paper, we wish to report the investigation of the further details of structure-activity relationships(SARs) of the 2-phenylethenesulfonamide region in 1a. It was found that methyl substitutions at the 2-, 4- and 6-positions of the phenyl group in 1a led to the discovery of the ET_A/ET_B mixed antagonist(6s)with an IC_<50> of 2.2nM for the ET_A receptor. We also found that introduction of an ethyl group to the 1-position of the ethenyl group in 1a gave the ET_A selective antagonist(6u)with an oral endothelin antagonistic activity in rats.

• 公益社団法人日本薬学会の論文
• 2001-12-01

著者

• FUJIMORI Akira

  Applied Pharmacology Research Laboratories, Drug Discovery Research, Astellas Pharma Inc.

• 原田 博史

  Dainippon Pharmaceutical Co. Ltd.

• TANAKA Akihiro

  Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd.

• Tanaka A

  Faculty Of Pharmaceutical Sciences Tokyo University Of Science

• Fujimori Akira

  アステラス製薬研究本部薬理研究所

• Fujimori A

  Yamanouchi Pharmaceutical Co. Ltd. Ibaraki Jpn

• Fujimori Akira

  Applied Pharmacology Research Laboratories Drug Discovery Research Astellas Pharma Inc.

• Yanagisawa I

  Yamanouchi Pharmaceutical Co. Ltd. Ibaraki Jpn

• Yanagisawa Isao

  Institute For Drug Discovery Research Yamanouchi Pharmaceutical Co.

• Yanagisawa Isao

  山之内製薬

• Fujimori Akira

  Institute For Drug Discovery Research Yamanouchi Pharmaceutical Co. Ltd.

• Tokunaga Tatsuhiro

  Molecular Chemistry Resarch Laboratories Institute For Drug Discovery Research Yamanouchi Pharmaceut

• Tokunaga Tatsuhiro

  Institute For Drug Discovery Research Yamanouchi Pharmaceutical Co. Ltd.

• Tanaka Akihiro

  Institute For Drug Discovery Research Yamanouchi Pharmaceutical Co. Ltd.

• Harada H

  Laboratory Of Medicinal Plant Science Tokyo University Of Pharmacy And Life Science School Of Pharma

• HARADA Hironori

  Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd.

• KAZAMI Jun-ichi

  Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd.

• WATANUKI Susumu

  Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd.

• TSUZUKI Ryuji

  Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd.

• SUDOH Katsumi

  Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd.

• TSUKAMOTO Shin-ichi

  Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd.

• Kazami Jun-ichi

  Institute For Drug Discovery Research Yamanouchi Pharmaceutical Co. Ltd.

• Tsuzuki R

  Institute For Drug Discovery Research Yamanouchi Pharmaceutical Co. Ltd.

• Tsuzuki Ryuji

  Institute For Drug Discovery Research Yamanouchi Pharmaceutical Co. Ltd.

• Sudoh K

  Institute For Drug Discovery Research Yamanouchi Pharmaceutical Co. Ltd.

• Fujimori Akira

  Institute For Drug Discovery Research Yamanouchi Pharmaceutical Co.

• Watanuki S

  Institute For Drug Discovery Research Yamanouchi Pharmaceutical Co. Ltd.

• Watanuki Susumu

  Institute For Drug Discovery Research Yamanouchi Pharmaceutical Co. Ltd.

• Tokunaga T

  Institute For Drug Discovery Research Yamanouchi Pharmaceutical Co. Ltd.

• Harada H

  Institute For Drug Discovery Research Yamanouchi Pharmaceutical Co. Ltd.

• Tsukamoto S

  Institute For Drug Discovery Research Yamanouchi Pharmaceutical Co.ltd.

• Tsukamoto Shin-ichi

  Institute For Drug Discovery Research Yamanouchi Pharmaceutical Co. Ltd.

• Sudoh Katsumi

  Institute For Drug Discovery Research Yamanouchi Pharmaceutical Co. Ltd.

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