2308
B. Gong et al. / Bioorg. Med. Chem. Lett. 14 (2004) 2303–2308
3. Kume, K.; Shimizu, T. Biochem. Biophys. Res. Commun.
1997, 237, 6632.
4. Eberhardt, C.; Gray, P. W.; Tjoelker, L. W. J. Biol. Chem.
1997, 272, 20299.
5. Bonham, L.; Leung, D.; White, T.; Hollenback, D.; Klein,
P.; Tulinsky, J.; Coon, M.; de Vries, P.; Singer, J. W. Exp.
Opin. Ther. Targets 2003, 7, 643.
6. Ghosh, S.; Strum, J. C.; Sciorra, V. A.; Daniel, L.; Bell,
R. M. J. Biol. Chem. 1996, 271, 8472.
17. Sall, D. J.; Arfsten, A. E.; Bastian, J. A.; Denney, M. L.;
Harms, C. S.; McCowan, J. R.; Morin, J. M., Jr.; Rose, J.
W.; Scarborough, R. M.; Smyth, M. S.; Um, S. L.;
Utterback, B. G.; Vasileff, R. T.; Wikel, J. H.; Wyss, V. L.;
Jakubowski, J. A. J. Med. Chem. 1997, 40, 2843.
18. Crispino, G. A.; Jeong, K. S.; Kolb, H. C.; Wang, Z. M.;
Xu, D.; Sharpless, K. B. J. Org. Chem. 1993, 58, 3785.
19. Schomaker, J.; Delia, T. J. Heterocycl. Chem. 2000, 37,
1457.
7. Fang, Y.; Vilella-Bach, M.; Bachmann, R.; Flanigan, A.;
Chen, J. Science 2001, 294, 1942.
8. Shen, Y.; Xu, L.; Foster, D. A. Mol. Cell. Biol. 2001, 21,
595.
20. LPAAT-a and LPAAT-b assays were conducted using
5,50-dithiobis(2-nitrobenzoic acid) (DTNB) as the colori-
metric reagent according to the method described in Ref.
10.
9. Limatola, C.; Schaap, D.; Moolenaar, W. H.; van
Blitterswijk, W. J. Biochem. J. 1994, 3, 1001.
10. Coon, M.; Ball, A.; Pound, J.; Ap, S.; Hollenback, D.;
White, T.; Tulinsky, J.; Bonham, L.; Morrison, D. K.;
Finney, R.; Singer, J. W. Mol. Cancer Ther. 2003, 2, 1067.
11. Bhatt, R.; Gong, B.; Hong, F.; Jenkins, S. A.; Klein, J. P.;
Kumar, A. M.; Tulinsky, J. PCT Int. Appl. WO 03/
037346, 2003.
12. Schomaker, J. M.; Delia, T. J. J. Org. Chem. 2001, 66,
7125.
13. Wade, J. V.; Krueger, C. A. J. Comb. Chem. 2003, 5, 267.
14. Boymond, L.; Rottlander, M.; Cahiez, G.; Knochel, P.
Angew. Chem., Int. Ed. 1998, 37, 1701.
21. Proliferation assays were conducted using the CyQuant
Cell Proliferation Kit (Molecular Probes, Eugene, OR) as
described in Ref. 10.
22. Female C57BL/6 mice were injected subcutaneously in the
right flank with murine LL/2 Lewis lung (ATTC, CRL-
1642) tumor cells (3 · 105 cells in 0.2 mL). When the tumor
sizes averaged 50–100 mm3, groups of 10 mice each were
injected intravenously (20 mL/kg) with either vehicle (8.3%
cremophor EL and 8.3% EtOH in PBS) or 2j at 100 mg/kg
(5 mg/mL in vehicle) on four consecutive days. Tumor
volumes were determined by measuring three orthogo-
nal tumor diameters using a caliper according to the
formula: (length · width · height)/2. Mice bearing tumors
P1000 mm3 were euthanized. Antitumor efficacy was
expressed as absolute tumor growth delay: the median
time (in days) for the tumors in the treatment group to
reach 1000 mm3 minus the median time for the tumors
in the control group to reach the same volume.
15. Lulinski, P.; Skulski, L. Bull. Chem. Soc. Jpn. 2000, 73,
951.
16. Acid promoted coupling of anilines with chloropyrim-
idines has been reported: Pearson, S. E.; Wood, R.
Tetrahedron Lett. 2002, 43, 1303.