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

Hiroshi Imoto; Eikoh Imamiya; Yu Momose; Yasuo Sugiyama; Hiroyuki Kimura; Takashi Sohda

doi:10.1248/cpb.50.1349

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

Hiroshi Imoto, Eikoh Imamiya, Yu Momose, Yasuo Sugiyama, Hiroyuki Kimura, Takashi Sohda

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Keywords: antidiabetic agent, oxyiminoacetic acid, type 2 diabetes, peroxisome proliferator-activated receptor, KKA^y mice

JOURNAL FREE ACCESS

2002 Volume 50 Issue 10 Pages 1349-1357

DOI https://doi.org/10.1248/cpb.50.1349

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Abstract

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 KKA^y 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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