Studies on Non-Thiazolidinedione Antidiabetic Agents. 1. Discovery of Novel Oxyiminoacetic Acid Derivatives.

DOI Web Site Web Site PubMed 被引用文献4件 参考文献71件
  • Imoto Hiroshi
    Takeda Chemical Industries, Ltd., Pharmaceutical Research Division
  • Imamiya Eikoh
    Takeda Chemical Industries, Ltd., Pharmaceutical Research Division
  • Sugiyama Yasuo
    Takeda Chemical Industries, Ltd., Pharmaceutical Research Division
  • Momose Yu
    Takeda Chemical Industries, Ltd., Pharmaceutical Research Division
  • Kimura Hiroyuki
    Takeda Chemical Industries, Ltd., Pharmaceutical Research Division
  • Sohda Takashi
    Takeda Chemical Industries, Ltd., Pharmaceutical Research Division

書誌事項

公開日
2002
資源種別
journal article
DOI
  • 10.1248/cpb.50.1349
公開者
公益社団法人 日本薬学会

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説明

A novel series of oxyiminoacetic acid derivatives were synthesized in an effort to develop a potent antidiabetic agent, which does not contain the 2,4-thiazolidinedione moiety. These compounds were evaluated for glucose and lipid lowering effects in genetically obese and diabetic KKAy mice. Several of the compounds showed strong antidiabetic activity, including functional potency at peroxisome proliferator-activated receptor (PPAR)-γ. (Z)-2-[4-[(5-Methyl-2-phenyl-1,3-oxazol-4-yl)methoxy]benzyloxyimino]-2-(4-phenoxyphenyl)acetic acid (25) significantly reduced plasma glucose (33%, p<0.01) and plasma triglycelide levels (43%, p<0.01) even at a dosage of 0.001% in diet. Pharmacokinetic analyses of 25 are also reported.

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