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RSC Advances
Page 9 of 11
Journal Name
DOI: 10.1039/C6RA09812F
ARTICLE
164.31, 169.06; Anal. calcd for C25H17F3N6O4 (522.44): C 57.47, Spectrometry Unit of the University of Ioannina for taking the
1H/13C-NMR and HRMS spectra.
H 3.28, N 16.09, found: C 57.31, H 3.12, N 16.24.
N-[4-methyl-3-(4-(pyridin-3-yl))-pyrimidin-2-yl-amido)-
phenyl]-2-fluoro-5-nitro-benzamide (30). Yield 86%; Yellow
solid; mp 223-225 oC. 1H NMR (400 MHz, DMSO-d6): δ 2.34 (s,
3H, CH3), 7.31 (d, J = 8.40 Hz, 1 arom. H), 7.60 (dd, J = 8.00,
4.80 Hz, 1 arom. H), 7.66-7.74 (m, 2 arom. H), 7.83 (d, J = 2.00
Hz, 1 arom. H), 7.90 (d, J = 5.20 Hz, 1 arom. H), 8.37 (d, J = 8.00
Hz, 1 arom. H), 8.46-8.48 (m, 1 arom. H), 8.53-8.55 (m, 1 arom.
H), 8.75 (dd, J = 4.80, 1.20 Hz, 1 arom. H), 8.81 (d, J = 5.20 Hz, 1
arom. H), 9.23 (d, J = 1.20 Hz, 1 arom. H), 10.76 (br s, 1H,
NHCO), 11.21 (br s, 1H, NHCO); 13C NMR (100MHz, DMSO-d6):
δ 18.76, 112.53, 117.97, 118.22, 118.58, 120.91, 124.13,
125.74, 125.79, 128.05, 128.16, 130.91 131.68, 136.13, 137.35,
147.72, 151.14, 158.03, 160.53, 161.43, 168.45; Anal. calcd
for C24H17FN6O4 (472.43): C 61.02, H 3.63, N 17.79, found: C
61.21, H 3.47, N 17.60.
References
1 (a) J. Zimmermann, E. Buchdunger, H. Mett, T. Meyer, N.
Lydon and P. Traxler, Bioorg. Med. Chem. Let., 1996,
(b) J. Zimmermann, E. Buchdunger, H. Mett, T. Meyer, N. B.
Lydon and P. Traxler, Bioorg. Med. Chem. Let., 1997, , 187;
(c) J. Zimmermann, G. Caravatti, H. Mett, T. Meyer, M. Müller,
N. B. Lydon and D. Fabbro, Arch. Pharm., 1996, , 371; (d) R.
Capdeville, E. Buchdunger, J. Zimmermann and A. Matter, Nat.
Rev. Drug Discovery, 2002, , 493; (e) B. J. Druker, C. L.
6, 1221;
7
7
1
Sawyers, H. Kantarjian, D. J. Resta, S. F. Reese, J. M. Ford, R.
Capdewille and M. N. Talpaz, Engl. J. Med., 2001, 344, 1038.
2 (a) D. Fabbro, S. Ruetz, E. Buchdunger, S. W. Cowan-Jacob, G.
Fendrich, J. Liebetanz, J. Mestan, T. O’Reilly, P. Traxler, B.
Chaudhuri, H. Fretz, J. Zimmermann, T. Meyer, G. Caravatti, P.
Furet and P. W. Manley, Pharmacology & Therapeutics, 2002,
93, 79; (b) J. M. Goldman and J. V. Melo, N. Engl. J. Med.,
2001, 344, 1084; (c) R. Capdeville, E. Buchdunger, J.
Zimmermann and A. Matter, Nat. Rev. Drug Discov., 2002, 1,
N-[4-methyl-3-(4-pyrazinyl)-pyrimidin-2-yl-amido)-phenyl]-4-
nitro-2-trifluoromethyl-benzamide (31). Yield 84%; Yellow
493.
3 (a) Y. Ma, S. Zeng, D. D. Metcalfe, C. Akin, S. Dimitrijevic, J. H.
Butterfield, G. McMahon and B. J. Longley, Blood, 2002, 99
o
1
solid; mp 209-211 C. H NMR (250 MHz, DMSO-d6): δ 2.41 (s,
3H, CH3), 7.38 (d, J = 8.50 Hz, 1 arom. H), 7.72 (dd, J = 8.50,
2.25 Hz, 1 arom. H), 7.86 (d, J = 2.00 Hz, 1 arom. H), 8.05 (d, J =
5.00 Hz, 1 arom. H), 8.09 (d, J = 8.50 Hz, 1 arom. H), 8.61 (d, J =
2.00 Hz, 1 arom. H), 8.68 (dd, J = 8.50, 2.25 Hz, 1 arom. H), 8.88
,
1741; (b) B. J. Longley, M. J. Reguera and Y. Ma, Leuk. Res.,
2001, 25, 571; (c) Y. Zermati, P. De Sepulveda, F. Féger, S.
Létard, J. Kersual, N. Castéran, G. Gorochov, M. Dy, A. R.
Dumas, K. Dorgham, C. Parizot, Y. Bieche, M. Vidaud, O.
Lortholary, M. Arock, O. Hermine and P. Dubreuil, Oncogene,
2003, 22, 660.
(s, 2 arom. H), 8.94 (d, J = 5.00 Hz, 1 arom. H), 9.21 (s, 1 arom.
3
H), 10.95 (br s, 1H, NHCO), 11.36 (br s, 1H, NHCO); C NMR 4 (a) P. W. Manley, S. W. Cowan-Jacob and J. Mestan,
Biochimica et Biophysica Acta, 2005, 1754, 3; (b) E. Weisberg,
P. W. Manley, W. Breitstein, J. Brüggen, L. Callahan, S. W.
Cowan-Jacob, D. Fabbro, G. Fendrich, E. Hall-Meyers, B.
Huntley, A. Kung, J. Mestan, D. Neuberg, A. Ray, D. G. Gilliland
(100 MHz, DMSO-d6): δ 19.52, 113.27, 119.13, 121.52, 122.53,
122.58, 128.51, 131.41, 131.65, 131.76, 136.92, 138.10,
141.85, 143.69, 145.29, 147.69, 148.67, 148.82, 158.66,
161.21, 162.08, 164.51, 169.25; Anal. calcd for C24H16F3N7O4
(523.42): C 55.07, H 3.08, N 18.73, found: C 55.29, H 2.97, N
18.60.
and J. D. Griffin, Cancer cell, 2005,
Passerini, R. H. Gunby, R. Piazza, A. Galietta, R. Rostagno and
L. Scapozza, The lancet oncology, 2003, , 75.
7, 129; (c) C. B. Gambacorti-
4
5 (a) P. W. Manley, W. Breitenstein, J. Brόggen, S. W. Cowan-
Jacob, P. Furet, J. Mestan and T. Meyer, Bioorg. Med. Chem.
Lett., 2004, 14, 5793; (b) E. Weisberg, P. Manley, J. Mestan, S.
N-[4-methyl-3-(4-pyrazinyl)-pyrimidin-2-yl-amido)-phenyl]-2-
fluoro-5-nitro-benzamide (32). Yield 86%; Yellow solid; mp
o
1
224-225 C. H NMR (250 MHz, DMSO-d6): δ 2.41 (s, 3H, CH3),
7.38 (d, J = 8.25 Hz, 1 arom. H), 7.75 (m, 2 arom. H), 7.92 (d, J =
2.00 Hz, 1 arom. H), 8.05 (d, J = 5.00 Hz, 1 arom. H), 8.55 (m, 2
arom. H), 8.88 (s, 2 arom. H), 8.95 (d, J = 5.00 Hz, 1 arom. H),
9.23 (s, 1 arom. H), 10.82 (br s, 1H, NHCO), 11.35 (br s, 1H,
NHCO); 13C NMR (63 MHz, DMSO-d6): δ 19.20, 113.29, 119.35,
119.69, 122.35, 126.15, 131.53, 131.59, 131.86, 131.91,
136.13, 136.30, 136.65, 137.08, 143.41, 145.11, 147.36,
148.55, 158.25, 161.01, 161.90, 163.31, 169.50; Anal. calcd for
C23H16FN7O4 (473.42): C 58.35, H 3.41, N 20.71, found: C 58.07,
H 3.59, N 20.48.
Cowan-Jacob, A. Ray and J. D. Griffin, Br. J. Cancer, 2006, 94
,
1765; (c) P. W. Manley, P. Drueckes, G. Fendrich, P. Furet, J.
Liebetanz, G. Martiny-Baron, J. Mestan, J. Trappe, M.
Wartmann and D. Fabbro, Biochimica et Biophysica Acta,
2010, 1804, 445; (d) D. L. Deremer, C. Ustun and K. Natarajan,
Clin. Ther., 2008, 30, 1956.
6 (a) J. F. Lyons, S. Wilhelm, B. Hibner and G. Bollag, Endocr
Relat Cancer, 2001,
Pharm Des, 2002,
8, 219; (b) S. Wilhelm and D. S. Chien, Curr
, 2255; (c) S. M. Wilhelm, C. Carter, L. Tang,
8
D. Wilkie, A. McNabola, H. Rong, C. Chen, X. Zhang, P. Vincent,
M. McHugh, Y. Cao, J. Shujath, S. Gawlak, D. Eveleigh, B.
Rowley, L. Liu, L. Adnane, M. Lynch, D. Auclair, I. Taylor, R.
Gedrich, A. Voznesensky, B. Riedl, L. E. Post, G. Bollag and P. A.
Trail, Cancer Res, 2004, 64, 7099; (d) F. Carlomagno, S.
Anaganti, T. Guida, G. Salvatore, G. Troncone, S. M. Wilhelm
and M. Santoro, J Natl Cancer Inst., 2006, 98, 326.
7 (a) J. Das, P. Chen, D. Norris, R. Padmanabha, J. Lin, R. V.
Moquin, Z. Shen, L. S. Cook, A. M. Doweyko, S. Pitt, S. Pang, D.
R. Shen, Q. Fang, H. F. de Fex, K. W. McIntyre, D. W. Shuster,
K. M. Gillooly, K. Behnia, G. L. Schieven, J. Wityak and J. C.
Barrish, J. Med. Chem., 2006, 49, 6819; (b) N. P. Shah, C. Tran,
F. Y. Lee, P. Chen, D. Norris and C. L. Sawyers, Science, 2004,
305, 399; (c) L. J. Lombardo, F. Y. Lee and P. Chen, et al. J Med
Chem, 2004, 47, 6658; (d) J. Tokarski, J. Newitt and F. Lee, et
al., Blood, 2004, 104, 160a; (e) T. A. Carter, L. M. Wodicka and
Acknowledgments
This research project has been co-financed by the European
Union (European Regional Development Fund—ERDF) and
Greek
national
funds
through
the
Operational
Program―THESSALY-MAINLAND GREECE AND EPIRUS-2007-
2013 of the National Strategic Reference Framework (NSRF
2007-2013). We thank the NMR Center and the Mass
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 9
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