Design and synthesis of potent and subtype-selective PPARalpha agonists

Ranjit C Desai; Edward Metzger; Conrad Santini; Peter T Meinke; James V Heck; Joel P Berger; Karen L MacNaul; Tian-quan Cai; Samuel D Wright; Arun Agrawal; David E Moller; Soumya P Sahoo

doi:10.1016/j.bmcl.2005.12.022

Design and synthesis of potent and subtype-selective PPARalpha agonists

Bioorg Med Chem Lett. 2006 Mar 15;16(6):1673-8. doi: 10.1016/j.bmcl.2005.12.022. Epub 2005 Dec 27.

Authors

Ranjit C Desai¹, Edward Metzger, Conrad Santini, Peter T Meinke, James V Heck, Joel P Berger, Karen L MacNaul, Tian-quan Cai, Samuel D Wright, Arun Agrawal, David E Moller, Soumya P Sahoo

Affiliation

¹ Department of Medicinal Chemistry, Merck Research Laboratories, PO Box 2000, Rahway, NJ 07065, USA. [email protected]

PMID: 16384704
DOI: 10.1016/j.bmcl.2005.12.022

Abstract

Beginning with a moderately potent PPARgamma agonist 9, a series of potent and highly subtype-selective PPARalpha agonists was identified through a systematic SAR study. Based on the results of the efficacy studies in the hamster and dog models of dyslipidemia and the desired pharmacokinetic data, the optimized compound 39 was selected for further profiling.

MeSH terms

Animals
Cricetinae
Dogs
Drug Design*
Dyslipidemias / drug therapy*
Haplorhini
Hypolipidemic Agents / chemical synthesis*
Hypolipidemic Agents / pharmacokinetics
Hypolipidemic Agents / pharmacology
Molecular Structure
PPAR alpha / agonists*
PPAR alpha / genetics
Rats
Structure-Activity Relationship
Transcriptional Activation

Substances

Hypolipidemic Agents
PPAR alpha