2. Academic Validation
  3. Design, synthesis, and biological evaluation of novel constrained meta-substituted phenyl propanoic acids as peroxisome proliferator-activated receptor alpha and gamma dual agonists

Design, synthesis, and biological evaluation of novel constrained meta-substituted phenyl propanoic acids as peroxisome proliferator-activated receptor alpha and gamma dual agonists

  • J Med Chem. 2008 Oct 23;51(20):6318-33. doi: 10.1021/jm8003416.
Young-Ger Suh 1,  Nam-Jung Kim,  Bon-Woong Koo,  Kwang-Ok Lee,  Sung-Hyun Moon,  Dong-Hyung Shin,  Jong-Wha Jung,  Seung-Mann Paek,  Dong-Jo Chang,  Funan Li,  Hyun-Jin Kang,  Tuong Vy Thi Le,  Yu Na Chae,  Chang Yell Shin,  Mi-Kyung Kim,  Joong In Lim,  Jae-Sang Ryu,  Hyun-Ju Park
Affiliations

Affiliation

  • 1 College of Pharmacy, Seoul National University, San 56-1, Sillim-dong, Gwanak-gu, Seoul 151-742, South Korea. ygsuh@snu.ac.kr
PMID: 18826205 DOI: 10.1021/jm8003416
Abstract

In an effort to develop dual PPARalpha/gamma activators with improved therapeutic efficacy, a series of diaryl alpha-ethoxy propanoic acid compounds comprising two aryl groups linked by rigid oxime ether or isoxazoline ring were designed and synthesized and their biological activities were examined. Most of the compounds possessing an oxime ether linker were more potent PPARgamma activators than the lead PPARalpha/gamma dual agonist, tesaglitazar in vitro. Compound 18, one of the derivatives with an oxime ether linker, was found to selectively transactivate PPARgamma (EC 50 = 0.028 microM) over PPARalpha (EC 50 = 7.22 microM) in vitro and lower blood glucose in db/ db mice more than muraglitazar after oral treatment for 11 days.

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