(S)-3-(4-(2-(5-Methyl-2-phenyloxazol-4-yl)ethoxy)phenyl)-2-(piperazin-1-yl) propanoic acid compounds: synthesis and biological evaluation of dual PPARalpha/gamma agonists

Xinbo Zhou; Wei Chen; Cheng Xu; Shiyong Fan; Yunde Xie; Wu Zhong; Lili Wang; Song Li

doi:10.1016/j.bmcl.2010.02.071

(S)-3-(4-(2-(5-Methyl-2-phenyloxazol-4-yl)ethoxy)phenyl)-2-(piperazin-1-yl) propanoic acid compounds: synthesis and biological evaluation of dual PPARalpha/gamma agonists

Bioorg Med Chem Lett. 2010 Apr 15;20(8):2605-8. doi: 10.1016/j.bmcl.2010.02.071. Epub 2010 Mar 1.

Authors

Xinbo Zhou¹, Wei Chen, Cheng Xu, Shiyong Fan, Yunde Xie, Wu Zhong, Lili Wang, Song Li

Affiliation

¹ Beijing Institute of Pharmacology and Toxicology, Beijing 100850, PR China.

PMID: 20299214
DOI: 10.1016/j.bmcl.2010.02.071

Abstract

A series of novel, potent PPARalpha/gamma dual agonists were synthesized and appraised. The most potent analogue, compound 2b demonstrated EC(50) value of 0.012+/-0.002 and 0.032+/-0.01 microM, respectively, for hPPARalpha and hPPARgamma in transactivation assay. Additionally, compound 2b demonstrated good glucose and lipid lowering effect in genetic diabetic (db/db) mice.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Blood Glucose / analysis
Diabetes Mellitus, Experimental / blood*
Lipids / blood
Mice
PPAR alpha / agonists*
PPAR gamma / agonists*
Propionates / chemical synthesis*
Propionates / chemistry
Propionates / pharmacology*

Substances

Blood Glucose
Lipids
PPAR alpha
PPAR gamma
Propionates
propionic acid