Chemical and Pharmaceutical Bulletin
Online ISSN : 1347-5223
Print ISSN : 0009-2363
ISSN-L : 0009-2363
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Studies on Non-Thiazolidinedione Antidiabetic Agents. 1. Discovery of Novel Oxyiminoacetic Acid Derivatives
Hiroshi ImotoEikoh ImamiyaYu MomoseYasuo SugiyamaHiroyuki KimuraTakashi Sohda
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2002 Volume 50 Issue 10 Pages 1349-1357

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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 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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© 2002 The Pharmaceutical Society of Japan
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