Affordable Access

Studies on non-thiazolidinedione antidiabetic agents. 1. Discovery of novel oxyiminoacetic acid derivatives.

Authors
  • Imoto, Hiroshi1
  • Imamiya, Eikoh
  • Momose, Yu
  • Sugiyama, Yasuo
  • Kimura, Hiroyuki
  • Sohda, Takashi
  • 1 Takeda Chemical Industries, Ltd., Pharmaceutical Research Division, Osaka, Japan. [email protected] , (Japan)
Type
Published Article
Journal
Chemical & pharmaceutical bulletin
Publication Date
Oct 01, 2002
Volume
50
Issue
10
Pages
1349–1357
Identifiers
PMID: 12372861
Source
Medline
License
Unknown

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)-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.

Report this publication

Statistics

Seen <100 times