Antirheumatic Agents. I. Novel Methotrexate Derivatives Bearing an Indoline Moiety

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概要

• 論文の詳細を見る

• Various novel methotrexate (MTX) derivatives bearing an indoline moiety were synthesized and tested for biological activities using human peripheral blood mononuclear cell (hPBMC) and human synovial cells (hSC) derived from patients with rheumatoid arthritis (RA). Compounds having potent activity in vitro were further evaluated using an adjuvant arthritis model in vivo. N-[1-(2,4-Diamino-6-pteridinylmethyl)indoline-5-carbonyl]-L-glutamic acid 2f showed more potent activities than MTX in vitro and in vivo, and N-[1-(2,4-diamino-6-pteridinylmethyl)-indoline-5-carbonyl]-L-2-aminoadipic acid 2d exhibited fairly good activities in vitro and considerable activity in vivo. Compound 2d was, as expected, not sensitive to folyl-polyglutamate synthetase (FPGS) and did not undergo polyglutamation, a process which may be responsible for a side-effect during MTX therapy.

• 公益社団法人日本薬学会の論文
• 1996-07-15

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

• 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.,

• TSUJI Keiichiro

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

• KATO Nobuaki

  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

• 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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