Synthesis of Naphthyl‐, Quinolin‐ and Anthracenyl Analogues of Clofibric Acid as PPARα Agonists. (20th November 2015)

• Record Type: Journal Article
• Authors: Giampietro, Letizia; Ammazzalorso, Alessandra; Bruno, Isabella; Carradori, Simone; De Filippis, Barbara; Fantacuzzi, Marialuigia; Giancristofaro, Antonella; Maccallini, Cristina; Amoroso, Rosa
• Is Part Of: Chemical biology & drug design. Volume 87:Number 3(2016)
• Page Start: 467
• Page End: 471
• Publication Date: 2015-11-20
• Subjects: anthracenyl -- clofibric acid -- naphthyl -- peroxisome proliferator‐activated receptor agonist -- quinolin -- transactivation assay; Drugs -- Design -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; 615.19005
• DOI: 10.1111/cbdd.12677
• Languages: English
• ISSNs: 1747-0277

Abstract

Abstract : 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. Abstract : New analogues of clofibric acid analogues conjugated with naphthyl, quinolin, chloroquinolin and anthracenyl scaffolds were synthesized and evaluated for PPAR α transactivation activity. Naphthyl and quinolin derivatives showed a good activation of PPAR α .