Selective, potent PPARgamma agonists with cyclopentenone core structure

A series of analogues of the PPARgamma ligand 15-deoxy-Delta(12,14)-PGJ(2) have been synthesized by functionalization of a 5-alkyl-4-hydroxycyclopentenone core structure obtained by Piancatelli rearrangement of precursor furylcarbinol. Transient transactivation assays indicate that analogues 18 and...

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Bibliographic Details
Published in:Bioorganic & medicinal chemistry letters 2009-04, Vol.19 (7), p.1883-1886
Main Authors: Otero, M Paz, Pérez Santín, Efrén, Rodríguez-Barrios, Fátima, Vaz, Belén, de Lera, Angel R
Format: Article
Language:English
Subjects:
Cell Line
Computer Simulation
Cyclopentanes - chemical synthesis
Cyclopentanes - chemistry
Cyclopentanes - pharmacology
HeLa Cells
Humans
PPAR gamma - agonists
PPAR gamma - metabolism
Structure-Activity Relationship
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Summary:A series of analogues of the PPARgamma ligand 15-deoxy-Delta(12,14)-PGJ(2) have been synthesized by functionalization of a 5-alkyl-4-hydroxycyclopentenone core structure obtained by Piancatelli rearrangement of precursor furylcarbinol. Transient transactivation assays indicate that analogues 18 and 20 are selective nanomolar agonists of PPARgamma. This subtype selectivity is lost in derivatives (23, 24) with an alkynyl (oct-1-yn) chain at the C3 position, although the cyclopentenone derivative with cis relative configuration (23) showed greater affinity for PPARalpha.
ISSN:1464-3405
DOI:10.1016/j.bmcl.2009.02.072