Synthesis and dual PPARα/δ agonist effects of 1,4-disubstituted 1,2,3-triazole analogues of GW 501516

European Journal of Medicinal Chemistry

Volumn 45, Issue 7, 2010, Pages 3047-3055

  Ciocoiu, Calin C ^a   Nikolić, Nataša ^a   Nguyen, Huyen Hoa ^a   Thoresen, G Hege ^a   Aasen, Arne J ^a   Hansen, Trond Vidar ^a  

^a UNIVERSITY OF OSLO   (Norway)

Author keywords

Agonists; GW 501516; Multiwell assay; PPAR ; PPAR ; Triazoles

Indexed keywords

1,2,3 TRIAZOLE DERIVATIVE; 2 ( 2 METHY 4 [( 1 PHENYL 1H 1,2,3 TRIAZOL 4 YL)METHYTHIO]PHENOXY)ACETIC ACID; 2 ( 2 METHYL 4 [( 1 ( 4 TRIFLUOROMETHOXYPHENYL) 1H 1,2,3 TRIAZOL 4 YL)METHYLTHIO]PHENOXY)ACETIC ACID; 2 ( 2 METHYL 4 [( 1 ( 4 TRIFLUOROMETHYLPHENYL) 1H 1,2,3 TRIAZOL 4 YL)METHYLTHIO]PHENOXY)ACETIC ACID; 2 ( 2 METHYL 4 [( 1 PARA TOLYL 1H 1,2,3 TRIAZOL 4 YL)METHYLTHIO]PHENOXY)ACETIC ACID; 2 ( 4 [( 1 ( 3 CHLORO 4 (TRIFLUOROMETHOXY)PHENYL) 1H 1,2,3 TRIAZOL 4 YL)METHYLTHIO] 2 METHYLPHENOXY)ACETIC ACID; 2 ( 4 [( 1 ( 3 FLUORO 4 (TRIFLUOROMETHYL)PHENYL) 1H 1,2,3 TRIAZOL 4 YL)METHYLTHIO] 2 METHYLPHENOXY]ACETIC ACID; 2 ( 4 [( 1 ( 3 FLUORO 4 METHOXYPHENYL) 1H 1,2,3 TRIAZOL 4 YL)METHYLTHIO] 2 METHYLPHENOXY)ACETIC ACID; 2 ( 4 [( 1 ( 3 FLUORO 4 METHYLPHENYL) 1H 1,2,3 TRIAZOL 4 YL)METHYLTHIO] 2 METHYLPHENOXY)ACETIC ACID; 2 ( 4 [( 1 ( 3 FLUORO 4 TRIFLUOROMETHOXYPHENYL) 1H 1,,2,3 TRIAZOL 4 YL)METHYLTHIO] 2 METHYLPHENOXY)ACETIC ACID; 2 ( 4 [( 1 ( 4 METHOXYPHENYL) 1H 1,2,3 TRIAZOL 4 YL)METHYLTHIO] 2 METHYLPHENOXY)ACETIC ACID; ACETIC ACID DERIVATIVE; LUCIFERASE; OLEIC ACID; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR ALPHA; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR ALPHA AGONIST; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR DELTA; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR DELTA AGONIST; UNCLASSIFIED DRUG; [2 METHYL 4 [4 METHYL 2 (4 TRIFLUOROMETHYLPHENYL) 5 THIAZOLYLMETHYLTHIO]PHENOXY]ACETIC ACID; THIAZOLE DERIVATIVE; TRIAZOLE DERIVATIVE;

ARTICLE; DRUG POTENCY; DRUG RECEPTOR BINDING; DRUG SYNTHESIS; ENZYME ASSAY; HIGH THROUGHPUT SCREENING; HUMAN; HUMAN CELL; IN VITRO STUDY; MYOTUBE; OXIDATION; SUBSTITUTION REACTION; ANIMAL; CELL STRAIN COS1; CERCOPITHECUS; CHEMISTRY; DRUG POTENTIATION; SYNTHESIS;

ANIMALS; CERCOPITHECUS AETHIOPS; COS CELLS; HUMANS; PPAR ALPHA; PPAR DELTA; THIAZOLES; TRIAZOLES;

EID: 77954348773     PISSN: 02235234     EISSN: 17683254     Source Type: Journal    
DOI: 10.1016/j.ejmech.2010.03.035     Document Type: Article

References (26)

1. D.J. Mangelsdorf, R.M. Evans, The RXR heterodimers and orphan receptors. Cell 83 (1995) 841-850.
2. B. Goke, I. Gause-Nilsson, A. Persson, The effects of tesaglitazar as add-on treatment to metformin in patients with poorly controlled type 2 diabetes. Diab. Vasc. Dis. Res. 4 (2007) 204-213.
3. P.T.W. Cheng, R. Mukherjee, PPARs as targets for metabolic and cardiovascular diseases. Mini-Rev. Med. Chem. 5 (2005) 741-753.
4. A.Z. Fernandez, PPARs as targets for the modulation of cardiovascular risk factors associated with the metabolic syndrome. Curr. Opin. Invest. Drugs 5 (2004) 936-940.
5. M.L. Sznaidman, C.D. Haffner, P.R. Maloney, A. Fivush, E. Chao, D. Goreham, M.L. Sierra, C. LeGrumelec, H.E. Xu, V.G. Montana, M.H. Lambert, T.M. Willson, W.R. Oliver Jr., D.D. Sternbach, Novel selective small molecule agonists for peroxisome proliferator-activated receptor d (PPARd) e synthesis and biological activity. Bioorg. Med. Chem. Lett. 13 (2003) 1517-1521;
6. W.R. Oliver Jr., J.L. Shenk, M.R. Snaith, C.S. Russell, K.D. Plunket, N.L. Bodkin, M.C. Lewis, D.A. Winegar, M.L. Sznaidman, M.H. Lambert, H.E. Xu, D. D. Sternbach, S.A. Kliewer, B.C. Hansen, T.M. Willson, A selective peroxisome proliferator-activated receptor d agonist promotes reverse cholesterol transport. Proc. Natl. Acad. Sci. U.S.A. 98 (2001) 5306-5311.
7. L. Shen, Y. Zhang, A. Wang, E. Sieber-McMaster, X. Chen, P. Pelton, J.Z. Xu, M. Yang, P. Zhu, L. Zhou, M. Reuman, Z. Hu, R. Russell, A.C. Gibbs, H. Ross, K. Demarest, W.V. Murray, G.-H. Kuo, Synthesis and structureeactivity relationships of thiadiazole-derivatives as potent and orally active peroxisome proliferator-activated receptors a/d dual agonists. Bioorg. Med. Chem. 16 (2008) 3321-3341;
8. L. Shen, Y. Zhang, A. Wang, E. Sieber-McMaster, X. Chen, P. Pelton, J.Z. Xu, M. Yang, P. Zhu, L. Zhou, M. Reuman, Z. Hu, R. Russell, A.C. Gibbs, H. Ross, K. Demarest, W.V. Murray, G.-H. Kuo, Synthesis and identification of [1,2,4] thiadiazole derivatives as a new series of potent and orally active dual agonists of peroxisome proliferator-activated receptors a and d. J. Med. Chem. 50 (2007) 3954-3963.
9. V.V. Rostovtsev, L.G. Green, V.V. Fokin, K.B. Sharpless, A stepwise Huisgen cycloaddition process: copper(I)-catalyzed regioselective ligation of azides and terminal alkynes. Angew. Chem., Int. Ed. 41 (2002) 2596-2599;
10. C.W. Tornøe, C. Christensen, M. Meldal, Peptidotriazoles on solid phase: [1,2,3]-triazoles by regiospecific copper(I)-catalyzed 1,3-dipolar cycloadditions of terminal alkynes to azides. J. Org. Chem. 67 (2002) 3057-3064.
11. H.C. Kolb, K.B. Sharpless, The growing impact of click chemistry on drug discovery. Drug Discov. Today 8 (2003) 1128-1137.
12. S. Kim, M. Cho, T. Lee, S. Lee, H.-Y. Min, S.K. Lee, Design, synthesis, and preliminary biological evaluation of a novel triazole analogue of ceramide. Bioorg. Med. Chem. Lett. 17 (2007) 4584-4587.
13. J. Li, M. Zheng, W. Tang, P.-L. He, W. Zhu, T. Li, J.-P. Zuo, H. Liu, H. Jiang, Syntheses of triazole-modified zanamivir analogues via click chemistry and anti-AIV activities. Bioorg. Med. Chem. Lett. 16 (2006) 5009-5013.
14. P.L. Suarez, Z. Gándara, G. Gómez, Y. Fall, Vitamin D and click chemistry. Part 1: a stereoselective route to vitamin D analogues with triazole rings in their side chains. Tetrahedron Lett. 45 (2004) 4619-4625.
15. W.G. Lewis, L.G. Green, F. Grynszpan, Z. Radic, P.R. Carlier, P. Taylor, M.G. Finn, B. Sharpless, Click chemistry in situ: acetylcholinesterase as a reaction essel for the selective assembly of a femtomolar inhibitor from an array of uilding blocks. Angew. Chem., Int. Ed. 41 (2002) 1053-1057.
16. 13] (a) H.G. Grimm, On the systematic arrangement of chemical compounds from he perspective of research on atomic composition and on some challenges in experimental chemistry. Naturwissenschaften 17 (1929) 535-540;
17. b) L.B. Kier, L.H. Hall, Bioisosterism: quantitation of structure and property effects. Chem. Biodivers. 1 (2004) 138-151
18. G.C. Tron, T. Pirali, R.A. Billington, P.L. Canonico, G. Sorba, A.A. Genazzani, Click chemistry reactions in medicinal chemistry: applications of the 1,3-dipolar cycloaddition between azides and alkynes. Med. Res. Rev. 28 (2008) 278-308.
19. A.J. Wensaas, A.C. Rustan, K. Lovstedt, B. Kull, S. Wikstrom, C.A. Drevon, S. Hallen, Cell-based multiwell assays for the detection of substrate accumulation and oxidation. J. Lipid Res. 48 (2007) 961-967.
20. P. Balakumar, M. Rose, M. Singh, PPAR ligands: are they potential agents for cardiovascular disorders? Pharmacology 80 (2007) 1-10.
21. R. Huisgen, G. Szeimies, L. Moebius, 1,3-Dipolar cycloadditions. XXXII. Kinetics of the addition of organic azides to carbonecarbon multiple bonds. Chem. Ber. 100 (1967) 2494-2507.
22. C.-K. Sha, A.K. Mohanakrishnan, Azides. in: A. Padwa, W.H. Pearson (Eds.), Synthetic Applications of 1,3-Dipolar Cycloaddition Chemistry toward Heterocycles and Natural Products. John Wiley & Sons Inc., New Jersey, 2003, pp. 623-679.
23. K. Odlo, J. Hentzen, J. Fournier, S. Ducki, O.A.B.S.M. Gani, I. Sylte, M. Skrede, V. A. Florenes, T.V. Hansen, 1,5-Disubstituted 1,2,3-triazoles as cis-restricted analogues of combretastatin A-4: synthesis, molecular modeling and evaluation as cytotoxic agents and inhibitors of tubulin. Bioorg. Med. Chem. 16 (2008) 4829-4838.
24. Z.-L. Wei, A.P. Kozikowski, A short and efficient synthesis of the pharmacological research tool GW 501516 for the peroxisome proliferator- activated receptor δ J. Org. Chem. 68 (2003) 9116-9118.
25. J.-i. Kasuga, D. Yamasaki, Y. Araya, A. Nakagawa, M. Makishima, T. Doi, Y. Hashimoto, H. Miyachi, Design, synthesis, and evaluation of a novel series of a-substituted phenylpropanoic acid derivatives as human peroxisome proliferator- activated receptor (PPAR) a/d dual agonists for the treatment of metabolic syndrome. Bioorg. Med. Chem. 14 (2006) 8405-8414.
26. P. Balakumar, M. Rose, S.S. Ganti, P. Krishan, M. Singh, PPAR dual agonists: are they opening Pandoras Box? Pharmacol. Res. 56 (2007) 91-98.