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Synthesis of Naphthyl‐, Quinolin‐ and Anthracenyl Analogues of Clofibric Acid as PPAR α Agonists
Author(s) -
Giampietro Letizia,
Ammazzalorso Alessandra,
Bruno Isabella,
Carradori Simone,
De Filippis Barbara,
Fantacuzzi Marialuigia,
Giancristofaro Antonella,
Maccallini Cristina,
Amoroso Rosa
Publication year - 2016
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/cbdd.12677
Subject(s) - transactivation , clofibric acid , chemistry , peroxisome proliferator activated receptor , transcription factor , receptor , biochemistry , steatosis , nuclear receptor , peroxisome , pharmacology , biology , gene , endocrinology
PPAR α is a ligand activated transcription factor belonging to the nuclear receptor subfamily, involved in fatty acid metabolism in tissues with high oxidative rates such as muscle, heart and liver. PPAR α activation is important in steatosis, inflammation and fibrosis in preclinical models of non‐alcoholic fatty liver disease identifying a new potential therapeutic area. In this work, three series of clofibric acid analogues conjugated with naphthyl, quinolin, chloroquinolin and anthracenyl scaffolds were synthesized. In an effort to obtain new compounds active as PPAR α agonists, these molecules were evaluated for PPAR α transactivation activity. Naphthyl and quinolin derivatives showed a good activation of PPAR α ; noteworthy, optically active naphthyl derivatives activated PPAR α better than corresponding parent compound.