Studies on non-thiazolidinedione antidiabetic agents. 1. Discovery of novel oxyiminoacetic acid derivatives.
Takeda Chemical Industries, Ltd., Pharmaceutical Research Division, Osaka, Japan. [email protected]
- Published Article
Chemical & pharmaceutical bulletin
- Publication Date
Oct 01, 2002
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)-gamma. (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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The corresponding record at NLM can be accessed at https://www.ncbi.nlm.nih.gov/pubmed/12372861