434
N. R. Thimmegowda et al. / Bioorg. Med. Chem. Lett. 18 (2008) 432–435
24. Nakano, H.; Inoue, T.; Kawasaki, N.; Miyataka, H.;
Acknowledgments
Matsumoto, H.; Taguchi, T.; Inagaki, N.; Nagai, H.;
Satoh, T. Bioorg. Med. Chem. 2000, 8, 373.
25. White, A. W.; Curtin, N. J.; Eastman, B. W.; Golding, B.
T.; Hostomsky, Z.; Kyle, S.; Li, J.; Maegley, K. A.;
Skalitzky, D. J.; Webber, S. E.; Yu, X.-H.; Griffin, R. J.
Bioorg. Med. Chem. Lett. 2004, 14, 2433.
26. Lukevics, E.; Arsenyan, P.; Shestakova, I.; Domracheva,
I.; Nesterova, A.; Pudova, O. Eur. J. Med. Chem. 2001, 36,
507.
27. Huang, X.; Suleman, A.; Skibo, E. B. Bioorg. Chem. 2000,
28, 324.
The authors are grateful to UGC, Government of India,
for financial support under the project UGC-SAP
(Phase-I) Programme No. F. 540/10/DRS/2004(SAP-I)
and to the National Medical Research Council, Singa-
pore, for financial support from Grants NMRC/0772/
2003.DST Project No. DV6/15/DST/2005-06 New Delhi
and NMRC/1023/2005 (G.W.Y.) and DST-FIST (order
No. SR/FST/CSI-051/2002) grants for the instrument
elemental analyser.
28. Sondhi, S. M.; Singh, N.; Lahoti, A. M.; Bajaj, K.;
Kumar, A.; Lozech, O.; Meijer, L. Bioorg. Med. Chem.
2005, 13, 4291.
References and notes
29. Sondhi, S. M.; Singh, N.; Kumar, A.; Lozach, O.; Meijer,
L. Bioorg. Med. Chem. 2006, 14, 3758.
30. Demirayak, S.; Abu Mohsen, U.; Caqri Karaburun, A.
Eur. J. Med. Chem. 2002, 37, 255.
1. Spasov, A. R.; Iezhitsa, I. N.; Bugaeva, L. I.; Anisimova,
V. A. Khim.-Farm. Zhurn. 1999, 33, 6.
31. Huang, S. T.; Hsei, I. J.; Chen, C. Bioorg. Med. Chem.
2006, 14, 6106.
32. Kumar, C. C.; Malkowski, M.; Yin, Z.; Tanghetti, E.;
Yaremko, B.; Nechuta, T.; Varner, J.; Liu, M.; Smith, E.
M.; Neustadt, B.; Presta, M.; Armstrong, L. Cancer Res.
2001, 61, 2232.
33. White, A. W.; Almassy, R.; Calvert, A. H.; Curtin, N. J.;
Griffin, R. J.; Hostomsky, Z.; Maegly, K.; Newell, D. R.;
Srivinivasan, S.; Golding, B. T. J. Med. Chem. 2000, 43,
4084.
34. Boiani, M.; Gonzalez, M. Mini-Rev. Med. Chem. 2005, 5,
409.
2. Grassmann, S.; Sadek, B.; Ligneau, X.; Elz, S.; Ganellin,
C. R.; Arrang, J. M.; Schwartz, J. C.; Stark, H.; Schunack,
W. Eur. J. Pharm. Sci. 2002, 15, 367.
3. Al Muhaimeed, H. J. Int. Med. Res. 1997, 25, 175.
4. Richter, J. E. Am. J. Gastroenterol. 1997, 92, 34.
5. Labanauskas, L. K.; Brukstus, A. B.; Gaidelis, P. G.;
Buchinskaite, V. A.; Udrenaite, E. B.; Dauksas, V. K.
Pharm. Chem. J. 2000, 34, 353.
6. Sondhi, S. M.; Rajvanshi, S.; Johar, M.; Bharti, N.; Azam,
A.; Singh, A. K. Eur. J. Med. Chem. 2002, 37, 835.
7. Sondhi, S. M.; Singhal, N.; Johar, M.; Reddy, B. S.;
Lown, J. W. Curr. Med. Chem. 2002, 9, 1045.
35. Hori, A.; Imaeda, Y.; Kubo, K.; Kusaka, M. Cancer lett.
2002, 183, 53.
8. Sondhi, S. M.; Singh, N.; Johar, M.; Kumar, A. . Bioorg.
Med. Chem. 2005, 13, 6158.
36. Experimental: Melting points were determined using
SELACO-650 hot stage melting point apparatus and the
values are not corrected. Infrared (IR) spectra were
recorded using Jasco FTIR-4100 series. Nuclear magnetic
resonance (1H NMR) spectra were recorded on Shimadzu
AMX 400-Bruker, 400 MHz spectrometer using DMSO-
d6 and CDCl3 as solvent and TMS as internal standard
(chemical shift in d ppm). Spin multiplets are given as s
(singlet), d (doublet), t (triplet) and m (multiplet). Mass
and purity were recorded on a LC-MSD-Trap-XCT.
Elemental (CHNS) analyses were done on Vario EL III
Elementar. Silica gel column chromatography was per-
formed using Merck 7734 silica gel (60–120 mesh) and
Merck made TLC plates.
9. Sondhi, S. M.; Goyal, R. N.; Lahoti, A. M.; Singh, N.;
Shukla, R.; Raghubir, R. Bioorg. Med. Chem. 2005, 13, 3185.
10. Can-Eke, B.; Puskullu, M. O.; Buyukbingol, E.; Iscan, M.
Chem.-Biol. Interact. 1998, 113, 65.
11. Evans, T. M.; Gardiner, J. M.; Mahmood, N.; Smis, M.
Bioorg. Med. Chem. Lett. 1997, 7, 409.
12. Novelli, F.; Tasso, B.; Sparatore, F.; Sparatore, A. Chem.
Abstr. 1998, 128, 238983j.
13. Bell, C. A.; Dykstra, C. C.; Naiman, N. A.; Cory, M.;
Fairley, T. A.; Tidwell, R. R. Antimicrob. Agents Chemo-
ther. 1993, 37, 2668.
14. Klimesova, V.; Koci, J.; Pour, M.; Stachel, J.; Waisser, K.;
Kaustova, J. Eur. J. Med. Chem. 2002, 37, 409.
15. Kumar, B. V.; Vaidya, S. D.; Kumar, R. V.; Bhirud, S. B.;
Mane, R. B. Eur. J. Med. Chem. 2006, 41, 599.
16. Arjmand, F.; Mohani, B.; Ahmad, S. Eur. J. Med. Chem.
2005, 40, 1103.
Synthesis of N-(4-cyano-3-(trifluoromethyl)phenyl)-4-flu-
oro-3-nitrobenzamide (3):
A solution of 4-amino-2-
(trifluoromethyl)benzonitrile (1) (10.0 g, 53.7 mmol) in
N,N-dimethyl acetamide (100 mL) was taken and cooled
from À5 to 0 ꢁC in an ice bath. 4-Fluoro-3-nitro-benzoyl
chloride (2) (10.9 g, 53.7 mmol) was added to the cold
reaction mixture and stirred for 30 min, and then the
reaction mixture was allowed to attain room temperature
under stirring for 4 h. The reaction was monitored by
TLC. Upon completion, the reaction mixture was
quenched with water and filtered under reduced pressure,
and the brownish red solid compound obtained (3)
was recrystallized with diethyl ether. Yield: 90%
(17.08 g). Mp 144–146 ꢁC. 1H NMR. (DMSO-d6, 400
MHz) d: 11.19 (s, 1H, –CO–NH–), 8.78 (d, 1H, Ar-H),
8.43–8.39 (m, 2H, Ar-H), 8.29–8.26 (d, 1H, Ar-H), 8.18–
8.16 (d, 1H, Ar-H), 7.84–7.79 (d, 1H, Ar-H). MS: 354.0.
LC purity: 98.43% IR (KBr, cmÀ1): 3392 (CON–H str),
3059 (–C–H str), 2229 (–CN str), 1685 (–CO str), 1529
and 1326 (–N–O str), 1051 (–C–F str). Anal. Calcd for
C15H7F4N3O3 (in %): C, 51.00; H, 2.00; N, 11.90. Found:
C, 51.04; H, 2.01; N, 11.86.
17. He, Y.; Yang, J.; Wu, B.; Risen, L.; Swayze, E. E. Bioorg.
Med. Chem. Lett. 2004, 14, 1217.
18. He, Y.; Wu, B.; Yang, J.; Robinson, D.; Risen, L.;
Ranken, R.; Blyn, L.; Sheng, S.; Swayze, E. E. Bioorg.
Med. Chem. Lett. 2003, 13, 3253.
19. Burli, R. W.; Jones, P.; McMinn, D.; Le, Q.; Duan, J. X.;
Kaizerman, J. A.; Difuntorum, S.; Moser, H. E. Bioorg.
Med. Chem. Lett. 2004, 14, 1259.
20. Burli, R. W.; McMinn, D.; Kaizerman, J. A.; Hu, W.; Ge,
Y.; Pack, Q.; Jiang, V.; Gross, M.; Garcia, M.; Tanaka,
R.; Moser, H. E. Bioorg. Med. Chem. Lett. 2004, 14, 1253.
21. Garuti, L.; Roberti, M.; Malagoli, M.; Rossi, T.; Castelli,
M. Bioorg. Med. Chem. Lett. 2000, 10, 2193.
22. Settimo, A. D.; Settimo, F. D.; Marini, A. M.; Primofiore,
G.; Salerno, S.; Viola, G.; Vi, L. D.; Magno, S. M. Eur. J.
Med. Chem. 1998, 33, 685.
23. Beaulieu, C.; Wang, Z.; Denis, D.; Greig, G.; Lamonta-
gne, S.; O’Neill, G.; Slipetz, D.; Wang, J. Bioorg. Med.
Chem. Lett. 2004, 14, 3195.