Synthesis and biological evaluation of gemfibrozil chiral analogues as potential PPARα agonists

Letters in Drug Design and Discovery

Volumn 8, Issue 2, 2011, Pages 154-158

  De Filippis, Barbara ^a   Giampietro, Letizia ^a   Giancristofaro, Antonella ^a   Ammazzalorso, Alessandra ^a   Fantacuzzi, Marialuigia ^a   Maccallini, Cristina ^a   Petruzzelli, Michele ^b   Amoroso, Rosa ^a  

^a UNIVERSITY OF CHIETI   (Italy)

^b Laboratorio del Metabolismo Lipidico e Tumorale   (Italy)

Author keywords

Fibrates; Gemfibrozil chiral analogues; PPAR agonists; PPARs; Transactivation assay; Ureidofibrates

Indexed keywords

BEZAFIBRATE; CLOFIBRATE; GEMFIBROZIL; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR ALPHA AGONIST; TRANSCRIPTION FACTOR;

ARTICLE; CLINICAL EVALUATION; DRUG INTERACTION; DRUG SYNTHESIS; HUMAN; HUMAN CELL; PRIORITY JOURNAL; STEREOCHEMISTRY; TRANSACTIVATION; TRANSCRIPTION INITIATION;

EID: 79952332433     PISSN: 15701808     EISSN: None     Source Type: Journal    
DOI: 10.2174/157018011794183761     Document Type: Article

References (15)

1. Feige, J.N.; Gelman, L.; Michalik, L.; Desvergne, B.; Wahli, W. From molecular action to physiological outputs: Peroxisome proliferator- activated receptors are nuclear receptors at the crossroads of key cellular functions. Prog. Lipid Res., 2006, 45, 120-159. (Pubitemid 43248732)
2. Issemann, I.; Green, S. Activation of a member of the steroid hormone receptor superfamily by peroxisome proliferators. Nature, 1990, 347, 645-650.
3. Fruchart, J.C. Peroxisome proliferator-activated receptor-alpha (PPARalpha): At the crossroads of obesity, diabetes and cardiovascular disease. Atherosclerosis, 2009, 205, 1-8.
4. van Raalte, D.H.; Li, M.; Pritchard, P.H.; Wasan, K.M. Peroxisome proliferator-activated receptor (PPAR)-α: A pharmacological target with a promising future. Pharm. Res., 2004, 21, 1531-1538. (Pubitemid 41184380)
5. Bishop-Bailey, D.; Wray, J. Peroxisome proliferator-activated receptors: A critical review on endogenous pathways for ligand generation. Prostaglandins Other Lipid Mediat., 2003, 71, 1-22. (Pubitemid 36428519)
6. Chapman, M.J. Fibrates in 2003: Therapeutic action in atherogenic dyslipidaemia and future perspectives. Atherosclerosis, 2003, 171, 1-13. (Pubitemid 37474095)
7. Giampietro, L.; Ammazzalorso, A.; Giancristofaro, A.; Lannutti, F.; Bettoni, G.; De Filippis, B.; Fantacuzzi, M.; Maccallini, C.; Petruzzelli, M.; Morgano, A.; Moschetta, A.; Amoroso, R. Synthesis and biological evaluation of 2-heteroarylthioalkanoic acid analogues of clofibric acid as Peroxisome Proliferator-Activated Receptor Agonists. J. Med. Chem., 2009, 52, 6224-6232.
8. Ammazzalorso, A.; Amoroso, R.; Baraldi, M.; Bettoni, G.; Braghiroli, D.; De Filippis, B.; Duranti, A.; Moretti, M.; Tortorella, P.; Tricca, M.L.; Vezzalini, F. Synthesis and antiplatelet activity of gemfibrozil chiral analogues. Bioorg. Med. Chem. Lett., 2002, 12, 817-821. (Pubitemid 34164626)
9. Brown, P.J.; Winegar, D..A.; Plunket, KD.; Moore, L.B.; Lewis, M.C.; Wilson, J.G.; Sundseth, S.S.; Koble, C.S.; Wu, Z.; Chapman, M.J.; Lehmann, J.M.; Kliewer, S.A.; Willson, T.M. A ureidothioisobutyric acid (GW9578) is a subtype-selective PPAR agonist with potent lipid-lowering activity. J. Med. Chem., 1999, 42, 3785-3788. (Pubitemid 29453459)
10. Coppola, G.M.; Edson, D.M. Patent EP0528146A1, 24.02.1993.
11. Coppola, G.M.; Damon, R.E.; Eskesen, J.B.; France, D.S.; Paterniti, J.R Jr. Thiourea-based gemfibrozil analogues as HDLelevating agents. Bioorg. Med. Chem. Lett., 2002, 12, 2439-2442. (Pubitemid 34879885)
12. Coppola, G.M.; Damon, R.E.; Eskesen, J.B.; France, D.S.; Paterniti, J.R Jr. Biological evaluation of 1-alkyl-3-phenylthioureas as orally active HDL-elevating agents. Bioorg. Med. Chem. Lett., 2006, 162, 113-117. (Pubitemid 41625654)
13. Blanc, M.; Cussac, M.; Boucherle, A.; Leclerc, G. Synthesis and immunomodulating activity of 1-amino-2-thiohydantoin derivatives. Eur. J. Med. Chem., 1992, 27, 839-843. (Pubitemid 23018377)
14. Schulman, I.G.; Heyman, R.A. The flip side: Identifying small molecule regulators of nuclear receptors. Chem. Biol., 2004, 11, 639-646. (Pubitemid 38708832)
15. Naylor, L.H. Reporter gene technology: The future looks bright. Biochem. Pharmacol., 1999, 58, 749-757. (Pubitemid 29329523)