2. Academic Validation
  3. Design, synthesis, and structure-activity relationship studies of novel 6,7-locked-[7-(2-alkoxy-3,5-dialkylbenzene)-3-methylocta]-2,4,6-trienoic acids

Design, synthesis, and structure-activity relationship studies of novel 6,7-locked-[7-(2-alkoxy-3,5-dialkylbenzene)-3-methylocta]-2,4,6-trienoic acids

  • J Med Chem. 2003 Sep 11;46(19):4087-103. doi: 10.1021/jm020401k.
Pierre-Yves Michellys 1,  Robert J Ardecky,  Jyun-Hung Chen,  Jennifer D'Arrigo,  Timothy A Grese,  Donald S Karanewsky,  Mark D Leibowitz,  Sha Liu,  Dale A Mais,  Christopher M Mapes,  Chahrzad Montrose-Rafizadeh,  Katheen M Ogilvie,  Anne Reifel-Miller,  Deepa Rungta,  Anthony W Thompson,  John S Tyhonas,  Marcus F Boehm
Affiliations

Affiliation

  • 1 Department of Medicinal Chemistry, Ligand Pharmaceuticals, Inc., 10275 Science Center Drive, San Diego, California 92121, USA. pmichellys@gnf.org
PMID: 12954061 DOI: 10.1021/jm020401k
Abstract

Retinoid X receptor:peroxisome proliferative-activated receptor (RXR:PPAR) heterodimers play a critical role in the regulation of glucose (RXR/PPARgamma) and lipid metabolism (RXR/PPARalpha). Previously, we described a concise structure-activity relationship study of selective RXR modulators possessing a (2E,4E,6Z)-3-methyl-7-(3,5-dialkyl-6-alkoxyphenyl)-octa-2,4,6-trienoic acid scaffold. These studies were focused on the 2-position alkoxy side chain. We describe here the design and synthesis of a novel series of RXR selective modulators possessing the same aromatic core structure with the addition of a ring locked 6-7-Z-olefin on the trienoic acid moiety. The synthesis and structure-activity relationship studies of these 6,7-locked cyclopentenyl, phenyl, thienyl, furan, and pyridine-trienoic acid derivatives is presented herein.

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