Design of potent PPARα agonists

Bioorganic and Medicinal Chemistry Letters

Volumn 17, Issue 11, 2007, Pages 3198-3202

  Sauerberg, Per ^a   Mogensen, John P ^a   Jeppesen, Lone ^a   Bury, Paul S ^a   Fleckner, Jan ^a   Olsen, Grith S ^a   Jeppesen, Claus B ^a   Wulff, Erik M ^a   Pihera, Pavel ^b   Havranek, Miroslav ^b   Polivka, Zdenek ^b   Pettersson, Ingrid ^a  

^a NOVO NORDISK A S   (Denmark)

^b RE and D VÚFB s r o   (Czech Republic)

Author keywords

Agonist; Docking; PPAR

Indexed keywords

AMINO ACID; ANTILIPEMIC AGENT; BENZALDEHYDE DERIVATIVE; CLOFIBRIC ACID; FENOFIBRIC ACID; NNC 613058; NNC 614424; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR ALPHA AGONIST; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR DELTA; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA; UNCLASSIFIED DRUG; LIGAND; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR ALPHA; PHENYLPROPIONIC ACID DERIVATIVE;

ARTICLE; DRUG DESIGN; DRUG SELECTIVITY; DRUG STRUCTURE; DRUG SYNTHESIS; LIGAND BINDING; ANIMAL; CHEMISTRY; COMPUTER; CRYSTALLOGRAPHY; DRUG POTENTIATION; SYNTHESIS;

ANIMALS; COMPUTERS; CRYSTALLOGRAPHY; DRUG DESIGN; LIGANDS; PHENYLPROPIONATES; PPAR ALPHA;

EID: 34247849397     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2007.03.015     Document Type: Article

References (12)

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6. 4 NNC 61-3058 was built in Maestro version 7.5, a formal charge of -1 was assigned and the molecule was minimized with the OPLS_2005 force field. NNC 61-3058 was docked with Glide version 4.0 using the SP mode and the van der Waals radii of the ligand atoms were scaled by 0.8.
7. 50 (% max) α: 0.6 μM (180%), γ: 1.6 μM (117%), δ: 14 μM (186%) and α: 8.4 μM (231%), γ: 1.3 μM (116%), δ: 17 μM (377%), respectively).
8. MOE ver. 2005.06. Chemical Computing Group Inc.; www.chemcomp.com.
9. max = 6155 ng/ml and 1845 ng/ml, respectively.
10. Friesner R.A., Banks J.L., Murphy R.B., Halgren T.A., Klicic J.J., Mainz D.T., Repasky M.P., Knoll E.H., Shaw D.E., Shelley M., Perry J.K., Francis P., and Shenkin P.S. J. Med. Chem. 47 (2004) 1739
11. Halgren T.A., Murphy R.B., Friesner R.A., Beard H.S., Frye L.L., Pollard W.T., and Banks J.L. J. Med. Chem. 47 (2004) 1750
12. 3, 300 MHz) δ: 1.20 (t, 3H), 2.97 (dd, 1H), 3.10 (dd, 1H), 3.41-3.53 (m, 1H), 3.55-3.68 (m, 1H), 4.05 (dd, 1H), 4.35 (q, 4H), 4.67 (d, 2H), 6.35-6.48 (m, 2H), 6.60-6.70 (m, 3H), 6.87 (d, 2H), 7.15 (d, 2H).