6254
P. Martres et al. / Bioorg. Med. Chem. Lett. 18 (2008) 6251–6254
H
O
O
O
O
O
a)
OEt
O
O
+
O
I
b)
N
N
N
N
N
N
c)
OH
OEt
+
OEt
O
O
O
IV
d)
III : 22%
II : 47%
O
O
N
OEt
H2N
V
O
O
O
O
OEt
OH
N
N
N
e)
H
H
N
N
O
O
VI
7
Scheme 1. Synthetic pathway. Reagents and conditions: (a) EtOH, Na 0 °C, rt 16 h, then 80 °C 16 h, 99%; (b) methyl-hydrazine, EtOH 90 °C, 16 h; silica gel column first eluted
II; (c) NaOH 1 M, 4 h, 98%; (d) thionyl chloride, toluene, 80 °C, 3 h 30 min then V Et3N, CH2Cl2, rt, 1 h (for preparation of V see Ref. 13), 96%; (e) NaOH, 80 °C, 4 h, 80%.
6. (a) Goldberg, R. B.; Kendall, D. M.; Deeg, M. A.; Buse, J. B.; Zagar, A. J.; Pinaire, J.
were raised that could preclude further development (results not
shown) (Scheme 1).
A.; Tan, M. H.; Khan, M. A.; Perez, A. T.; Jacober, S. J. Diabetes Care 2005, 28,
1547; (b) Elte, J. W. F.; Blicklé, J. F. Eur. J. Int. Med. 2007, 18, 18.
7. Chinetti-Gbaguidi, G.; Fruchart, J. C.; Staels, B. Curr. Atheroscler. Rep. 2005, 7,
396.
Acknowledgments
8. Keech, A.; Simes, R. J.; Barter, P.; Best, J.; Scott, R.; Taskinen, M. R.; Forder, P.;
Pillai, A.; Davis, T.; Glasziou, P.; Drury, P.; Kesaniemi, Y. A.; Sullivan, D.; Hunt,
D.; Colman, P.; d’Emden, M.; Whiting, M.; Ehnholm, C.; Laakso, M. Lancet 2005,
366, 1849.
9. Henke, B. R. J. Med. Chem. 2004, 47, 4118.
We thank Dr. Andrew Brewster (GlaxoSmithKline) for proof-
reading of the manuscript.
10. Sierra, M. L.; Beneton, V.; Boullay, A.-B.; Boyer, T.; Brewster, A. G.; Donche, F.;
Forest, M.-C.; Fouchet, M.-H.; Gellibert, F. J.; Grillot, D. A.; Lambert, M. H.;
Laroze, A.; Le Grumelec, C.; Linget, J.-M.; Montana, V. G.; Nguyen, V.-L.;
Nicodeme, E.; Patel, V.; Penfornis, A.; Pineau, O.; Pohin, D.; Potvain, F.; Poulain,
G.; Ruault, C.; Saunders, M.; Toum, J.; Xu, H. E.; Xu, R. X.; Pianetti, P. M. J. Med.
Chem. 2007, 50, 685.
Supplementary data
Supplementary data associated with this article can be found, in
11. Xu, H. E.; Lambert, M. H.; Montana, V. G.; Plunket, K. D.; Moore, L. B.; Collins, J.
L.; Oplinger, J. A.; Kliewer, S. A.; Gampe, R. T., Jr.; McKee, D. D.; Moore, J. T.;
Willson, T. M. Proc. Natl. Acad. Sci. U.S.A. 2001, 98(24), 13919.
12. Henke, B. R.; Blanchard, S. G.; Brackeen, M. F.; Brown, K. K.; Cobb, J. E.; Collins, J.
L., ; Harrington, W. W., Jr.; Hashim, M. A.; Hull-Ryde, E. A.; Kaldor, I.; Kliewer, S.
A.; Lake, D. H.; Leesnitzer, L. M.; Lehmann, J. M.; Lenhard, J. M.; Orband-Miller,
L. A.; Miller, J. F.; Mook, R. A.; Noble, S. A.; Oliver, W.; Parks, D. J.; Plunket, K. D.;
Szewczyk, J. R.; Willson, T. M. J. Med. Chem. 1998, 41, 5020.
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