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

• MATSUOKA Hiroharu

  Fuji-Gotemba Laboratories Chugai Pharmaceutical, Co., Ltd

• KATO Nobuaki

  Fuji-Gotemba Laboratories Chugai Pharmaceutical, Co., Ltd

• TSUJI Keiichiro

  Fuji-Gotemba Laboratories Chugai Pharmaceutical, Co., Ltd

• MARUYAMA Noriaki

  Fuji-Gotemba Laboratories Chugai Pharmaceutical, Co., Ltd

• SUZUKI Hiroshi

  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

抄録

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.

収録刊行物

• Chemical & pharmaceutical bulletin

  Chemical & pharmaceutical bulletin 44 (7), 1332-1337, 1996-07-15

  公益社団法人日本薬学会

キーワード

• methotrexate
• polyglutamation
• antirheumatic activity

詳細情報

• CRID: 1572824502208647808
• NII論文ID: 110003632080
• NII書誌ID: AA00602100
• ISSN: 00092363
• 本文言語コード: en
• データソース種別:
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