A Tetrahydroindazolone Library Containing Three Unique Core Skeletons
(brt, J=5.5 Hz, 1H), 6.90–6.86 (m, 2H), 6.75 (d, J=8.0 Hz, 1H), 4.18–
4.12 (m, 3H), 3.93–3.88 (m, 1H), 3.86–3.79 (m, 7H), 3.37–3.31 (m, 1H),
2.56 (s, 2H), 2.38 (s, 2H), 2.11–2.06 (m, 1H), 1.96 (p, J=6.1 Hz, 2H),
1.65–1.59 (m, 2H), 1.08 ppm (s, 6H); 13C NMR (125 MHz, CDCl3): d=
193.5, 164.5, 154.3, 152.1, 148.8, 147.6, 146.1, 136.4, 133.7, 132.2, 130.9,
129.0, 124.5, 121.2, 116.6, 112.3, 111.1, 77.9, 68.5, 55.9, 52.4, 44.5, 36.2,
36.0, 33.2, 29.0, 28.4, 25.9 ppm; MS (ESI+): m/z: calcd for C30H35N4O7:
563.24 [M+H]+; found: 563.14.
2962–2964; b) H. An, S.-J. Eum, M. Koh, S. K. Lee, S. B. Park, J.
Compound 32ACHTUNGTRENNUNG{d,3}
Yield: 57%; purity: 90%; 1H NMR (500 MHz, CDCl3): d=8.52 (brs,
2H), 7.14–6.99 (m, 8H), 6.92 (d, J=8.0 Hz, 1H), 6.75 (d, J=8.5 Hz, 1H),
6.49 (brs, 1H), 4.22 (s, 2H), 3.81 (s, 3H), 3.80 (s, 3H), 3.68 (q, J=5.8 Hz,
2H), 2.88 (t, J=6.5 Hz, 2H), 2.58 (s, 2H), 2.41 (s, 2H), 2.33 (s, 3H),
1.07 ppm (s, 6H); 13C NMR (125 MHz, CDCl3): d=194.9, 168.3, 154.1,
152.5, 148.8, 147.7, 136.6, 135.7, 135.2, 131.0, 129.6, 128.7, 126.9, 121.2,
117.6, 116.2, 115.7, 114.0, 112.6, 111.4, 55.9, 52.2, 42.0, 36.0, 34.9, 33.0,
32.1, 28.3, 21.1 ppm; MS (ESI+): m/z: calcd for C34H39N4O4: 567.29
[M+H]+; found: 567.32.
[15] a) W. B. Pratt, Exp. Biol. Med. 2003, 228, 111–133; b) P. Workman,
Compound 36ACHTUNGTRENNUNG{a,3}
Yield: 65%; purity: 94%; 1H NMR (500 MHz, CDCl3): d=8.89 (d, J=
2.0 Hz, 1H), 8.23 (dd, J=8.5, 2.5 Hz, 1H), 8.14 (d, J=8.5 Hz, 1H), 7.90
(d, J=3.8 Hz, 1H), 7.55 (d, J=1.5 Hz, 1H), 7.37–7.30 (m, 5H), 6.74 (brs,
1H), 6.53 (dd, J=3.5, 2.0 Hz, 1H), 4.66 (d, J=5.5 Hz, 2H), 3.36 (s, 2H),
2.47 (s, 2H), 1.15 ppm (s, 6H); 13C NMR (125 MHz, CDCl3): d=192.7,
164.9, 154.4, 152.2, 147.0, 146.4, 143.6, 143.1, 137.8, 137.8, 129.1, 128.3,
128.2, 128.1, 116.8, 115.8, 115.2, 111.9, 53.0, 44.5, 39.5, 35.1, 28.6 ppm; MS
(ESI+): m/z: calcd for C26H25N4O3: 441.18 [M+H]+; found: 441.12.
[16] a) A. Kamal, L. Thao, J. Sensintaffar, L. Zhang, M. F. Boehm, L. C.
[17] a) J.-Y. Le Brazidec, A. Kamal, K. Busch, L. Thao. L. Zhang, G.
Timony, R. Grecko, K. Trent, R. Lough, T. Salazar, S. Khan, F. Bur-
Miyata, Curr. Pharm. Des. 2005, 11, 1131–1138; c) J. G. Supko, R. L.
e) C. E. Stebbins, A. A. Russo, C. Schneider, N. Rosen, F. U. Hartl,
[18] a) R. C. Schnur, M. L. Corman, R. J. Gallaschun, B. A. Cooper,
M. F. Dee, J. L. Doty, M. L. Muzzi, C. I. DiOrio. E. G. Barbacci,
P. E. Miller, V. A. Pollack, D. M. Savage, D. E. Sloan, L. R. Pustil-
ger, J. M. Covey, K. D. White, S. M. Musser, J. L. Eiseman, Cancer
Compound 36ACHTUNGTRENNUNG{b,5}
Yield: 72%; purity: 97%; 1H NMR (500 MHz, CDCl3): d=8.85 (d, J=
2.0 Hz, 1H), 8.22 (dd, J=8.8, 2.3 Hz, 1H), 8.03 (d, J=9.0 Hz, 1H), 6.75
(brt, J=5.3 Hz, 1H), 5.93–5.86 (m, 1H), 5.06 (dq, J=17.3, 1.5 Hz, 1H),
4.95 (dq, J=9.8, 1.1 Hz, 1H), 3.67 (q, J=5.0 Hz, 2H), 3.58 (t, J=5.3 Hz,
1H), 3.39 (s, 3H), 3.31 (s, 2H), 3.03–3.00 (m, 2H), 2.52–2.49 (m, 2H),
2.37 (s, 2H), 1.12 ppm (s, 6H); 13C NMR (125 MHz, CDCl3): d=194.1,
165.1, 154.6, 154.4, 151.6, 146.9, 138.1, 137.8, 127.8, 118.2, 115.2, 115.1,
71.1, 59.1, 52.6, 40.0, 39.5, 35.5, 32.3, 28.8, 27.5 ppm; MS (ESI+): m/z:
calcd for C22H29N4O3: 397.22 [M+H]+; found: 397.09.
Agatsuma, Y. Saitoh, Y. Yamashita, T. Mizukami, S. Akinaga, K.
Gomi, K. Akasaka, I. Takahashi, WO 96/33989, 1996; c) Y. Ikuina,
N. Amishiro, M. Miyata, H. Narumi, H. Ogawa, T. Akiyama, Y.
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jian, J. L. Sensintaffar, A. Kamal, R. E. Lough, J. Brekken, K.
Lundgren, R. Grecko, G. A. Timony, Y. Ran, R. Mansfield, L. C.
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Hanson, WO2006/091963, 2006; b) K. H. Huang, J. Eaves, J. Veal,
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Chandarlapaty, A. Sawai, Q. Ye, A. Scott, M. Silinski, K. Huang, P.
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846–855; e) T. E. Barta, J. M. Veal, J. W. Rice, J. M. Partridge, R. P.
Fadden, W. Ma, M. Jenks, L. Geng, G. J. Hanson, K. H. Huang,
J. W. Rice, J. Eaves, J. Strachan, A. F. Barabasz, B. E. Foley, T. E.
Barta, W. Ma, M. , A. Silinski, M. Hu, J. M. Partridge, A. Scott,
L. G. DuBois, T. Freed, P. M. Steed, A. J. Ommen, E. D. Smith, P. F.
Hughes, A. R. Woodward, G. J. Hanson, W. S. McCall, C. J. Mark-
worth, L. Hinkley, M. Lenks, L. Geng, M. Lewis, J. Otto, B. Pronk,
Acknowledgements
This study was supported by the National Research Foundation of Korea
(NRF), MarineBio Technology Program funded by the Ministry of Land,
Transport, and Maritime Affairs (MLTM), Korea, and the WCU program
of the NRF funded by the Korean Ministry of Education, Science, and
Technology (MEST). We thank M. Koh at Seoul National University for
his support on in silico analysis. J.K. and H.S. are grateful for the fellow-
ships awarded by the BK21 program and the Seoul Science Fellowship.
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Chem. Asian J. 2011, 6, 2062 – 2072
ꢀ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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