Design and Synthesis of Dual Peroxisome Proliferator-activated Receptors Gamma and Delta Agonists As Novel Euglycemic Agents with a Reduced Weight Gain Profile.
From: Lilly Research Laboratories, A Division of Eli Lilly & Company, Lilly Corporate Center, Indianapolis, Indiana 46285, USA. xu_yanping@lilly.com
Journal of medicinal chemistry
- Publish Date: Sep 2006
- ISSN: 0022-2623
- Volume: 49
- Issue: 19
- Pages: 5649-52
- Medium: Print
- Language: English
- Citation (JAMA): Xu Yanping, Etgen Garret J, Broderick Carol L, et al. Design and Synthesis of Dual Peroxisome Proliferator-activated Receptors Gamma and Delta Agonists As Novel Euglycemic Agents with a Reduced Weight Gain Profile.. J. Med. Chem. Sep 2006;49:5649-52
Abstract
The design and synthesis of the dual peroxisome proliferator-activated receptor (PPAR) gamma/delta agonist (R)-3-{4-[3-(4-chloro-2-phenoxy-phenoxy)-butoxy]-2-ethyl-phenyl}-propionic acid (20) for the treatment of type 2 diabetes and associated dyslipidemia is described. The compound possesses a potent dual hPPAR gamma/delta agonist profile (IC(50) = 19 nM/4 nM; EC(50) = 102 nM/6 nM for hPPARgamma and hPPARdelta, respectively). In preclinical models, the compound improves insulin sensitivity and reverses diabetic hyperglycemia with less weight gain at a given level of glucose control relative to rosiglitazone.
Mesh Headings (Keywords): Animals, Blood Glucose, Cell Line, Diabetes Mellitus, Type 2, Drug Design, Dyslipidemias, Female, Humans, Hypoglycemic Agents, Male, Mice, PPAR alpha, PPAR delta, PPAR gamma, Phenyl Ethers, Phenylpropionates, Radioligand Assay, Stereoisomerism, Trans-Activation (Genetics), Weight Gain
Check for Full Text / PubMed Unique Identifier (PMID): 16970391
This abstract is part of PubMed, a service of the U.S. National Library of Medicine. PubMed includes more than 17 million citations from MEDLINE and other life science journals for biomedical articles. See Copyright and Disclaimers.
Linked medical terms appearing on this page are added by Healia to help readers find more information and are not part of the original PubMed document.
The data herein was last updated on July 8th, 2008 and may not reflect the most current and accurate data available from NLM.