Antirheumatic Agents. II. Novel Methotrexate Derivatives Bearing an Alkyl-Substituted Benzene Ring

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概要

• 論文の詳細を見る

• Novel methotrexate (MTX) derivatives with either a mono- or dialkyl-substituted benzene ring were synthesized and initially tested for in vitro anti-proliferative activities using human perpheral blood mononuclear cells (hPBMC)derived from healthy volunteers and synovial cells (hSC) derived from patients with rheumatoid arthritis (RA).Compounds with potent activities were further evaluated in an in vivo adjuvant arthritis model. In comparison with MTX, a glutamate derivative 3a was more potent as a suppressor of the in vitro cell proliferation and the in vivo experimental arthritis, and a homoglutamate derivative, 3e, exhibited fairly good activities in vitro and considerable activity in vivo in a dose-dependent manner. As expected, 3e did not act as a substrate of folylpolyglutamate synthetase (FPGS), and thus did not undergo polyglutamation, which is thought to be responsible for side-effects that occur during MTX therapy.

• 公益社団法人日本薬学会の論文
• 1996-12-15

著者

• 高石 喜久

  徳島大院薬

• Tsuji Kiyoshi

  Medicinal Chemistry Research Laboratories Fujisawa Pharmaceutical Co. Ltd.

• Takeda Y

  Fac. Of Integrated Arts And Sciences Univ. Of Tokushima

• Takeda Y

  Faculty Of Integrated Arts And Sciences The University Of Tokushima

• Ohi Nobuhiro

  Fuji Gotemba Research Laboratories Chugai Pharmaceutical Co. Ltd.

• SUZUKI Hiroshi

  Fuji-Gotemba Research Laboratories, Chugai Pharmaceutical Company Ltd.

• Suzuki H

  Janssen Pharmaceutical K.k. Shizuoka Jpn

• Yano K

  Discovery Research Laboratory Tanabe Seiyaku Co. Ltd.

• MATSUOKA Hiroharu

  Fuji-Gotemba Laboratories, Chugai Pharmaceutical, Co., Ltd.,

• MARUYAMA Noriaki

  Fuji-Gotemba Laboratories, Chugai Pharmaceutical, Co., Ltd.,

• KUROKI Toshio

  Fuji-Gotemba Laboratories, Chugai Pharmaceutical, Co., Ltd.,

• TSUJI Keiichiro

  Fuji-Gotemba Laboratories, Chugai Pharmaceutical, Co., Ltd.,

• KATO Nobuaki

  Fuji-Gotemba Laboratories, Chugai Pharmaceutical, Co., Ltd.,

• OHI Nobuhiro

  Fuji-Gotemba Laboratories, Chugai Pharmaceutical, Co., Ltd.,

• MIHARA Masahiko

  Fuji-Gotemba Laboratories, Chugai Pharmaceutical, Co., Ltd.,

• TAKEDA Yasuhisa

  Fuji-Gotemba Laboratories, Chugai Pharmaceutical, Co., Ltd.,

• YANO Keiichi

  Fuji-Gotemba Laboratories, Chugai Pharmaceutical, Co., Ltd.,

• Yano K

  Kyowa Hakko Co. Ltd. Tokyo

• Kuroki T

  Fuji-gotemba Laboratories Chugai Pharmaceutical Co. Ltd.

• 丸山 典昭

  Fuji-gotemba Research Laboratories Chugai Pharmaceutical Company Ltd.

• MATSUOKA Hiroharu

  Fuji Gotemba Research Laboratories, Chugai Pharmaceutical Co., Ltd.,

• MIHARA Masahiko

  Fuji Gotemba Research Laboratories, Chugai Pharmaceutical Co., Ltd.,

• Kato N

  Fuji Gotemba Research Laboratories Chugai Pharmaceutical Co. Ltd.

• Sato Hiroaki

  Fuji-gotemba Laboratories Chugai Pharmaceutical Co. Ltd.

• Mihara M

  Fuji Gotemba Research Laboratories Chugai Pharmaceutical Co. Ltd.

• Matsuoka H

  Santen Pharmaceutical Co. Ltd. Osaka Jpn

• Tsuji Keiichiro

  Department Of Psychology Nagoya University

• Suzuki Hiroshi

  Fuji-Gotemba Laboratories, Chugai Pharmaceutical, Co., Ltd.,

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