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 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.
Otero
M Paz
MP
Departamento de Química Orgánica, Universidade de Vigo, 36310 Vigo, Spain.
Pérez Santín
Efrén
E
Rodríguez-Barrios
Fátima
F
Vaz
Belén
B
de Lera
Angel R
AR
D002460:Cell Line; D003198:Computer Simulation; D003517:Cyclopentanes / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D047495:PPAR gamma / Q000819:agonists* / Q000378:metabolism; D013329:Structure-Activity Relationship
D003517:Cyclopentanes; D047495:PPAR gamma; C013905:cyclopentenone