Design and synthesis of benzoxazole containing indole analogs as peroxisome proliferator-activated receptor-γ/δ dual agonists

Bioorganic and Medicinal Chemistry Letters

Volumn 21, Issue 10, 2011, Pages 3057-3061

  Gim, Hyo Jin ^a   Cheon, Ye Jin ^a   Ryu, Jae Ha ^a   Jeon, Raok ^a  

^a Sookmyung Women's University   (South Korea)

Author keywords

Benzoxazole; Diabetes; Indole; PPAR

Indexed keywords

5 ALKOXY 3 INDOLYLACETIC ACID DERIVATIVE; 6 ALKOXYINDOLE 2 CARBOXYLIC ACID DERIVATIVE; [4 [2 (3 FLUORO 4 TRIFLUOROMETHYLPHENYL) 4 METHYL 5 THIAZOLYLMETHYLTHIO] 2 METHYLPHENOXY]ACETIC ACID; BENZOTHIAZOLE; BENZOXAZOLE DERIVATIVE; GW 0746; INDOLE DERIVATIVE; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR ALPHA; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR DELTA; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR DELTA AGONIST; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA AGONIST; ROSIGLITAZONE; UNCLASSIFIED DRUG;

ARTICLE; CRYSTAL STRUCTURE; DRUG ACTIVITY; DRUG DESIGN; DRUG STRUCTURE; DRUG SYNTHESIS; HYDROPHOBICITY; MOLECULAR MODEL;

ACETIC ACIDS; BENZOXAZOLES; CARBOXYLIC ACIDS; DRUG DESIGN; INDOLES; MOLECULAR STRUCTURE; PPAR GAMMA; PROTEIN BINDING;

EID: 79955563158     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2011.03.027     Document Type: Article

References (11)

1. 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, and T.M. Willson Proc. Natl. Acad. Sci. U.S.A. 98 2001 5306
2. O. Braissant, F. Foufelle, C. Scotto, M. Dauca, and W. Wahli Endocrinology 137 1996 354
3. E. Chaput, R. Saladin, M. Silvestre, and A.D. Edgar Biochem. Biophys. Res. Commun. 271 2000 445
4. P. Balakumar, M. Rose, and M. Singh Pharmacology 80 2007 1
5. A.S. Wilkinson, G.R. Monteith, P.N. Shaw, C.N. Lin, M.J. Gidley, and S.J. Roberts-Thomson J. Agric. Food. Chem. 56 2008 3037
6. T. Sohda, K. Mizuno, and Y. Kawamatsu Chem. Pharm. Bull. 32 1984 4460
7. J.F. Dropinski, T. Akiyama, M. Einstein, B. Habulihaz, T. Doebber, J.P. Berger, P.T. Meinke, and G.Q. Shi Bioorg. Med. Chem. Lett. 15 2005 5035
8. B.R. Henke, K.K. Adkison, S.G. Blanchard, L.M. Leesnitzer, R.A. Mook Jr., K.D. Plunket, J.A. Ray, C. Roberson, R. Unwalla, and T.M. Willson Bioorg. Med. Chem. Lett. 9 1999 3329
9. N. Mahindroo, Y.H. Peng, C.H. Lin, U.K. Tan, E. Prakash, T.W. Lien, I.L. Lu, H.J. Lee, J.T. Hsu, X. Chen, C.C. Liao, P.C. Lyu, Y.S. Chao, S.Y. Wu, and H.P. Hsieh J. Med. Chem. 49 2006 6421
10. R.T. Nolte, G.B. Wisely, S. Westin, J.E. Cobb, M.H. Lambert, R. Kurokawa, M.G. Rosenfeld, T.M. Willson, C.K. Glass, and M.V. Milburn Nature 395 1998 137
11. 5 cells/well in DMEM with 10% FBS. The cells were transiently transfected with plasmid mixtures containing PPARs expression vector and tk-PPRE-luciferase (Luc) vector for 6 h, and then treated with samples for 24 h. To normalize transfection efficiency, β-galactosidase plasmid was cotransfected. The luciferase activities in cell lysates were measured using luciferase assay system (Promega Corp., Madison, WI) and the β-gal activities were measured as the absorbance at 410 nm by using an ELISA plate reader. Data are reported as relative luciferase activity divided by the β-galactosidase activity. All the constructs were kindly gifted by Dr. Ronald M. Evans at The Salk Institute (La Jolla, CA).