6850
V. D. Jadhav et al. / Bioorg. Med. Chem. Lett. 19 (2009) 6845–6850
20. Qadeer, G.; Rama, N. H.; Shah, S. J. H. ARKIVOC 2007, 12.
constrained carbonyls does not play a significant role in organiza-
tion of the N-terminal ATP-binding site.
21. El-Feraly, F. S.; Cheatham, S. F.; McChesney, J. D. Can. J. Chem. 1985, 63, 2232.
22. Analytical data for 1: 1H NMR (DMSO-d6, 400 MHz) d 11.12 (s, 1H), 10.14 (s, 1H)
9.74 (d, J = 1.65 Hz, 1H), 8.82 (s, 1H), 8.36 (s, 1H), 8.17 (d, J = 2.1 Hz, 1H) 7.18 (s,
1H), 6.41 (s, 1H), 3.68 (s, 3H), 3.17 (dd, J = 7.9, 17.6 Hz, 1H), 2.70–2.63 (m, 3H),
2.53–2.50 (m, 1H), 1.96–1.89 (m, 1H), 1.45–1.38 (m, 1H); 13C NMR (DMSO-d6,
125 MHz) d 203.8, 160.1, 156.0, 153.8, 143.6, 142.8, 142.7, 137.6, 124.3, 122.5,
116.8, 107.5, 107.3, 102.1, 59.9, 48.6, 46.9, 31.6, 21.9; IR (film) vmax 3307–3101,
Acknowledgments
The authors gratefully acknowledge NIH/NCI CA 109265, the
Madison and Lila Self Graduate Fellowship (A.S.D.) and the Ameri-
can Foundation of Pharmaceutical Education for financial support
(A.S.D.).
2954, 2925, 1647, 1618, 1490, 1452, 1363, 1228 cm-1
; HRMS (ESI-) m/z
[MÀH]À calcd for C19H17ClNO7: 406.0694, found: 406.0686.
23. Analytical data for 2: 1H NMR (methanol-d4, 400 MHz) d 8.18 (s, 1H), 7.07 (s,
1H) 6.28 (s, 1H), 3.78 (s, 3H), 3.16–3.10 (m, 1H), 2.88–2.76 (m, 3H), 2.57–2.47
(m, 1H), 2.32–2.26 (m, 1H), 2.15–2.08 (m, 1H), 1.95–1.87 (m, 1H), 1.73–1.65
(m, 1H); 13C NMR (methanol-d4, 125 MHz) d 206.9, 165.2, 162.1, 161.7,145.4,
145.3, 144.6, 140.4, 126.3, 123.5, 112.5, 112.2, 109.1, 102.5, 61.4, 47.2, 30.7,
28.2, 27.6, 23.1; IR (film) vmax 3209, 2997, 2848, 1602, 1436, 1234 cmÀ1; HRMS
(ESI-) m/z [MÀH]À calcd for C20H19ClNO7: 420.0850, found: 420.0839.
24. Analytical data for 3: 1H NMR (CDCl3, 500 MHz) d 8.99 (s, 1H), 8.58 (s, 1H), 8.27
(s, 1H), 7.36 (s, 1H), 6.46 (s, 1H), 6.16 (s, 1H), 4.17 (s, 3H), 3.30 (dd, J = 7.75,
18.24 Hz, 1H), 2.83 (dd, J = 4.63, 18.05 Hz, 1H), 2.77–2.72 (m, 1H), 2.66–2.56
(m, 2H), 2.06–2.00 (m, 1H), 1.67–1.60 (m, 1H); 13C NMR (CDCl3, 125 MHz) d
208.4, 182.5, 181.3, 159.5, 159.4, 159.3, 157.7, 156.5, 152.0, 114.2, 108.5, 102.3,
102.1, 101.1, 61.7, 47.3, 32.0, 29.7, 20.7; IR (film) vmax 3305–3103, 2997, 2927,
2856, 1654, 1649 1500, 1363, 1228 cmÀ1; HRMS (ESI-) m/z [MÀH]À calcd for
C19H15ClNO7: 404.0537, found: 404.0543.
References and notes
1. Blagg, B. S. J.; Kerr, T. D. Med. Res. Rev. 2006, 26, 310.
2. Walter, S.; Buchner, J. Angew. Chem., Int. Ed. 2002, 41, 1098.
3. Kamal, A.; Thao, L.; Sensintaffar, J.; Zhang, L.; Boehm, M. F.; Fritz, L. C.; Burrows,
F. J. Nature 2003, 425, 407.
4. Neckers, L.; Lee, Y.-S. Nature 2003, 425, 357.
5. Marcu, M. G.; Chadli, A.; Bouhouche, I.; Catelli, M.; Neckers, L. M. J. Biol. Chem.
2000, 275, 37181.
6. Whitesell, L.; Mimnaugh, E. G.; De Costa, B.; Myers, C. E.; Neckers, L. M. Proc.
Natl. Acad. Sci. U.S.A. 1994, 91, 8324.
7. Geng, X.; Yang, Z.-Q.; Danishefsky, S. J. Synlett 2004, 1325.
8. Roe, S. M.; Prodromou, C.; O’Brien, R.; Ladbury, J. E.; Piper, P. W.; Pearl, L. H. J.
Med. Chem. 1999, 42, 260.
9. Chiosis, G.; Huezo, H.; Rosen, N.; Mimnaugh, E.; Whitesell, L.; Neckers, L. Mol.
Cancer Ther. 2003, 2, 123.
10. Jez, J. M.; Chen, J. C. H.; Rastelli, G.; Stroud, R. M.; Santi, D. V. Chem. Biol. 2003,
10, 361.
11. Onuoha, S. C.; Mukund, S. R.; Coulstock, E. T.; Sengerova, B.; Shaw, J.;
McLaughlin, S. H.; Jackson, S. E. J. Mol. Biol. 2007, 372, 287.
12. Onodera, H.; Kaneko, M.; Takahashi, Y.; Uochi, Y.; Funahashi, J.; Nakashima, T.;
Soga, S.; Suzuki, M.; Ikeda, S.; Yamashita, Y.; Rahayu, E. S.; Kanda, Y.; Ichimura,
M. Bioorg. Med. Chem. Lett. 2008, 18, 1588.
13. Zhang, M.-Q.; Gaisser, S.; Nur-E-Alam, M.; Sheehan, L. S.; Vousden, W. A.;
Gaitatzis, N.; Peck, G.; Coates, N. J.; Moss, S. J.; Radzom, M.; Foster, T. A.;
Sheridan, R. M.; Gregory, M. A.; Roe, S. M.; Prodromou, C.; Pearl, L.; Boyd, S. M.;
Wilkinson, B.; Martin, C. J. J. Med. Chem. 2008, 51, 5494.
14. Hadden, M. K.; Blagg, B. S. J. J. Org. Chem. 2009, 74, 4697.
15. Shen, G.; Wang, M.; Welch, T. R.; Blagg, B. S. J. J. Org. Chem. 2006, 71, 7618.
16. Shen, G.; Blagg, B. S. J. Org. Lett. 2005, 7, 2157.
25. Analytical data for 4: 1H NMR (DMSO-d6, 500 MHz) d 12.89 (s, 1H), 11.42 (s, 1H),
10.30 (s, 1H), 8.51 (s, 1H), 8.32 (s, 1H), 6.35 (s, 1H), 4.01 (s, 3H), 3.06 (dt,
J = 4.99, 18.07 Hz, 1H), 2.84–2.77 (m, 1H), 2.64–2.56 (m, 1H), 2.26–2.20 (m,
1H), 1.98–1.93 (m, 1H), 1.86–1.78 (m, 2H), 1.54–1.46 (m 2H); 13C NMR (DMSO-
d6, 125 MHz)) d 204.6, 182.8, 182.3, 162.9, 162.4, 162.3, 160.1, 156.0, 143.7,
127.9, 112.6, 110.5, 110.3, 101.1, 61.2, 44.6, 27.5, 25.90, 25.12, 19.94; IR (film)
vmax 3309–3143, 2995, 2918, 2848, 1604, 1569, 1438, 1369, 1224 cmÀ1; HRMS
(ESI-) m/z [MÀH]À calcd for C20H17ClNO7: 418.0694, found: 418.0694.
26. Analytical data for 5: 1H NMR (DMSO-d6, 500 MHz) d 11.73 (s, 1H), 10.45 (s, 1H)
10.36 (s, 1H), 8.59 (s,1H), 7.29 (s,1H), 6.52 (s, 1H), 6.40 (t, J = 8.0 Hz, 1H), 4.12
(s, 3H), 3.72 (s, 2H), 3.40 (d, J = 8.0 Hz, 2H); 13C NMR (DMSO-d6, 125 MHz) d
188.8, 183.6, 182.3, 162.3, 160.1, 156.9, 156.1, 149.6, 138.3, 137.6, 129.8, 124.3,
118.7, 112.7, 107.5, 102.3, 61.4, 28.9, 23.1; IR (film) vmax 3201–3100, 2918,
2848, 1608, 1458, 1448, 1219 cmÀ1
C19H13ClNO7: 402.0381, found: 402.0367.
;
HRMS (ESI-) m/z [MÀH]À calcd for
27. Analytical data for 6: 1H NMR (methanol-d4, 400 MHz) d 8.51 (s, 1H), 7.92
(s,1H), 7.35 (s,1H), 6.70 (t, J = 7.9 Hz, 1H), 6.32 (s, 1H), 4.18 (s, 3H), 3.46 (d,
J = 7.93 Hz 2H), 3.08 (t, J = 6.5 Hz, 2H), 2.94 (t, J = 6.9 Hz, 2H); 13C NMR (aceton-
d6, 125 MHz) d 192.0, 184.3, 180.2, 165.6, 164.7, 162.2, 160.8, 158.1, 144.8,
144.4, 135.8, 130.9, 113.9, 102.6, 102.5, 102.4, 62.1, 27.2, 25.2, 22.8; IR (film)
vmax 3070, 2987, 2850, 1573, 1475, 1436, 688 cmÀ1; HRMS (ESI-) m/z [MÀH]À
calcd for C20H15ClNO7: 416.0537, found: 416.0534.
17. Clevenger, R. C.; Blagg, B. S. J. Org. Lett. 2004, 6, 4459.
18. Immormino, R. M.; Metzger, L. E.; Reardon, P. N.; Dollins, D. E.; Blagg, B. S. J.;
Gewirth, D. T. J. Mol. Biol. 2009, 388, 1033.
19. Duerfeldt, A. S.; Brandt, G. E. L.; Blagg, B. S. J. Org. Lett. 2009, 11, 2353.