Browse > Article
http://dx.doi.org/10.5012/bkcs.2006.27.4.484

Solid-phase Synthesis and Preliminary Evaluation of 1,6,8-Trisubstituted Tetrahydro-2H-pyrazino[1,2-a]pyrimidine-4,7-diones as a NF-kB Inhibitor  

Kim, Jin-Woong (Medicinal Chemistry Research Center, Korea Institute of Science and Technology)
Cho, Jung-Hyuck (Medicinal Chemistry Research Center, Korea Institute of Science and Technology)
Han, Tae-hee (Hawon Pharm. Co.)
Lee, Jong-Baek (Department of Chemical Engineering, Dongeui University)
Oh, Chang-Hyun (Medicinal Chemistry Research Center, Korea Institute of Science and Technology)
Publication Information
Bulletin of the Korean Chemical Society / v.27, no.4, 2006 , pp. 484-488 More about this Journal
Abstract
The solid-phase synthesis of new series of 1,6,8-trisubstituted tetrahydro-2H-pyrazino[1,2-a]pyrimidine-4,7-diones as bicyclic $\beta$-turn mimetics is described. Their NF-kB inhibition activities were tested and the effect of substituents on bicyclic ring was investigated. Among the prepared compounds, the fluorobenzyl and methoxybenzyl group substituted compounds 26 and 27 at C-1 and C-8 position showed more inhibitory activities than the others. Tested at a concentration of 10 uM, these two compounds showed a 60% inhibition against the target NF kB 549.
Keywords
Bicyclic $\beta$-turn mimetics; NF-kB inhibitor; Solid phase;
Citations & Related Records

Times Cited By Web Of Science : 4  (Related Records In Web of Science)
Times Cited By SCOPUS : 4
연도 인용수 순위
1 Ritzeler, O.; Stilz, H. U.; Neises, B.; Bock, W. J.; Walser, A.; Flynn, G. A. WO0100610
2 Balkwill, F.; Mantovani, A. Lancet. 2001, 357, 539   DOI   ScienceOn
3 Baxter, A.; Brough, S.; Faull, A.; Johnstone, C.; Mcinally, T. WO0158890
4 Haefner, B. Drug discovery today 2002, 7, 653   DOI   ScienceOn
5 Karin, M.; Cao, Y.; Greten, F. R.; Li, Z.-W. Nat. Rev. Cancer 2002, 2, 301   DOI   ScienceOn
6 Souers, A. J.; Virgilio, A. A.; Schürer, S. S.; Ellman, J. A.; Kogan, T. P.; Ankener, H. W.; Vanderslice, P. Bioorg. Med. Chem. Lett. 1998, 8, 2297   DOI   ScienceOn
7 O'Byrne, K. J.; Dalgleish, A. G. Br. J. Cancer 2001, 85, 473   DOI   ScienceOn
8 Ritzeler, O.; Stilz, H. U.; Neises, B.; Jaehne, G.; Habermann, J. WO0130774
9 Kahn, M. Synlett. 1993, 11, 821
10 Souers, A. J.; Virgilio, A. A.; Rosenquist, A.; FenuikJ. A.; Ellman, A. J. Am. Chem. Soc. 1999, 121, 1817   DOI   ScienceOn
11 Masakatsu, E.; Lee, M. S.; Richard, Y. W.; Shea, J. P.; Marcin, S.; Scot, L.; Kahn, M. J. Med. Chem. 2002, 45, 1395   DOI   ScienceOn
12 Masakatsu, E.; Lee, M. S.; Stasiak, M.; Kahn, M. Tetrahedron Lett. 2001, 42, 1237   DOI   ScienceOn
13 Kee, K. S.; Jois, D. S. Current Pharmaceutical Design 2003, 9, 1209   DOI   ScienceOn
14 Kahn, M. Ed. Tetrahedron 1993, 49, Symposia 50, 3433   DOI   ScienceOn
15 Gillespie, P.; Cicariello, J.; Olson, G. L. Biopolymers 1997, 43, 191   DOI   ScienceOn
16 Hanessian, S.; Huynh, H. K.; Reddy, G. V.; McNaughton-Smith, G.; Ernst, B.; Sweeley, C. Bioorg. Med. Chem. Lett. 1998, 8, 2803   DOI   ScienceOn
17 Fink, B. E.; Kym, P. R.; Katzenellenbogen, J. A. J. Am. Chem. Soc. 1998, 120, 4334   DOI   ScienceOn
18 Jeong, D.-W.; Yoo, M.-H.; Kim, T. S.; Kim, J.-H.; Kim, I. Y. The J. of Biol. Chem. 2002, 277, 17871   DOI   ScienceOn
19 Hirschmann, R.; Hynes, J.; Cichy-Knight, M. A.; Pietranico-Cole, S.; Smith, A. B. J. Med. Chem. 1998, 41, 1382   DOI   ScienceOn
20 Masakatsu, E.; Lee, M. S.; Hiroshi, N.; Marcin, S.; Scott, L.; Kahn, M. J. Am. Chem. Soc. 1999, 121, 12204   DOI   ScienceOn
21 Hanessian, S.; McNaughton-Smith, G.; Lombart, H. G.; Lubell, W. D. Tetrahedron 1997, 53, 12789   DOI   ScienceOn