Journal of Medicinal Chemistry
Article
W. Caffeic acid phenethyl ester protects mice from lethal endotoxin
shock and inhibits lipopolysaccharide-induced cyclooxygenase-2 and
inducible nitric oxide synthase expression in RAW 264.7 macrophages
via the p38/ERK and NF-kappaB pathways. Int. J. Biochem. Cell Biol.
2008, 40, 2572−2582.
(23) Natarajan, K.; Singh, S.; Burke, T. R.; Grunberger, D.; Aggarwal,
B. B. Caffeic acid phenethyl ester is a potent and specific inhibitor of
activation of nuclear transcription factor NF-kappa B. Proc. Natl. Acad.
Sci. U. S. A. 1996, 93, 9090−9095.
acetamido-4-amino-2,6-anhydro-3,4,5-trideoxy-D-erythro-L-gluco-non-
onic acid. J. Chem. Soc., Perkin Trans. 1995, 1, 1173−1180.
(38) Ying, L.; Gervay-Hague, J. One-bead−one-inhibitor−one-
substrate screening of neuraminidase activity. ChemBioChem 2005, 6,
1857−1865.
(39) Wen, W.-H.; Lin, M.; Su, C.-Y.; Wang, S.-Y.; Cheng, Y.-S. E.;
Fang, J.-M.; Wong, C.-H. Synergistic effect of zanamivir−porphyrin
conjugates on inhibition of neuraminidase and inactivation of influenza
virus. J. Med. Chem. 2009, 52, 4903−4910.
(40) Chong, A. K. J.; Pegg, M. S.; Taylor, N. R.; von Itzstein, M.
Evidence for a sialosyl cation transition-state complex in the reaction
of sialidase from influenza virus. Eur. J. Biochem. 1992, 207, 335−343.
(41) von Itzstein, M.; Wu, W.-Y.; Kok, G. B.; Pegg, M. S.; Dyason, J.
C.; Jin, B.; Phan, T. V.; Smythe, M. L.; White, H. F.; Oliver, S. W.;
Colman, P. M.; Varghese, J. N.; Ryan, D. M.; Woods, J. M.; Bethell, R.
C.; Hotham, V. J.; Cameron, J. M.; Penn, C. R. Rational design of
potent sialidase-based inhibitors of influenza virus replication. Nature
1993, 363, 418−423.
(24) Chiang, Y. M.; Lo, C. P.; Chen, Y. P.; Wang, S. Y.; Yang, N. S.;
Kuo, Y. H.; Shyur, L. F. Ethyl caffeate suppresses NF-κB activation and
its downstream inflammatory mediators, iNOS, COX-2, and PGE2, in
vitro or in mouse skin. Br. J. Pharmacol. 2005, 146, 352−363.
(25) Kaiser, G. C.; Yan, F.; Polk, D. B. Mesalamine blocks tumor
necrosis factor growth inhibition and nuclear factor κB activation in
mouse colonocytes. Gastroenterology 1999, 116, 602−609.
(26) Kruis, W.; Schreiber, S.; Theuer, D.; Brandes, J.-W.; Schtutz, E.;
̈
Howaldt, S.; Krakamp, B.; Hamling, J.; Monnikes, H.; Koop, I.; Stolte,
̈
̈
(42) Taylor, N. R.; von Itzstein, M. Molecular modeling studies on
ligand binding to sialidase from influenza virus and the mechanism of
catalysis. J. Med. Chem. 1994, 37, 616−624.
M.; Pallant, D.; Ewald, U. Low dose balsalazide (1.5 g twice daily) and
mesalazine (0.5 g three times daily) maintained remission of ulcerative
colitis but high dose balsalazide (3.0 g twice daily) was superior in
preventing relapses. Gut 2001, 49, 783−789.
(43) Lew, W.; Chen, X.; Kim, C. U. Discovery and development of
GS-4104 (oseltamivir): an orally active influenza neuraminidase
inhibitor. Curr. Med. Chem. 2000, 7, 663−672.
(27) Sandborn, W. J.; Feagan, B. G.; Lichtenstein, G. R. Medical
management of mild to moderate Crohn’s disease: evidence-based
treatment algorithms for induction and maintenance of remission.
Aliment. Pharmacol. Ther. 2007, 26, 987−1003.
(28) Rousseaux, C.; Lefebvre, B.; Dubuquoy, L.; Lefebvre, P.;
Romano, O.; Auwerx, J.; Metzger, D.; Wahli, W.; Desvergne, B.;
Naccari, G. C.; Chavatte, P.; Farce, A.; Bulois, P.; Cortot, A.;
Colombel, J. F.; Desreumaux, P. Intestinal anti-inflammatory effect of
5-aminosalicylic acid is dependent on peroxisome proliferator-
activated receptor-γ. J. Exp. Med. 2005, 201, 1205−1215.
(29) Varghese, J. N.; Epa, V. C.; Colman, P. M. Three-dimensional
structure of the complex of 4-guanidino-Neu5Ac2en and influenza
virus neuraminidase. Protein Sci. 1995, 4, 1081−1087.
(30) Andrews, D. M.; Cherry, P. C.; Humber, D. C.; Jones, P. S.;
Keeling, S. P.; Martin, P. F.; Shaw, C. D.; Swanson, S. Synthesis and
influenza virus sialidase inhibitory activity of analogues of 4-guanidino-
Neu5Ac2en (zanamivir) modified in the glycerol side-chain. Eur. J.
Med. Chem. 1999, 34, 563−574.
(31) Honda, T.; Masuda, T.; Yoshida, S.; Arai, M.; Kobayashi, Y.;
Yamashita, M. Synthesis and anti-influenza virus activity of 4-
guanidino-7-substituted Neu5Ac2en derivatives. Bioorg. Med. Chem.
Lett. 2002, 12, 1921−1924.
(44) Russell, R. J.; Haire, L. F.; Stevens, D. J.; Collins, P. J.; Lin, Y. P.;
Blackburn, G. M.; Hay, A. J.; Camblin, S. J.; Skehel, J. J. The structure
of H5N1 avian influenza neuraminidase suggests new opportunities for
drug design. Nature 2006, 443, 45−49.
(45) Lavis, L. D. Ester bonds in prodrugs. ACS Chem. Biol. 2008, 3,
203−206.
(46) Cass, L. M. R.; Efthymiopoulos, C.; Bye, A. Pharmacokinetics of
zanamivir after intravenous, oral, inhaled or intranasal administration
to healthy volunteers. Clin. Pharmacokinet. 1999, 36, 1−11.
(47) Reed, L. J.; Muench, H. A simple method of estimating fifty
̈
percent endpoints. Am. J. Hyg. 1938, 27, 493−497.
(48) Burleson, F. G.; Chambers, T. M.; Wiedbrauk, D. L. Virology, a
Laboratory Manual; Academic Press: San Diego, CA, 1992.
(49) Hsieh, Y. S. Y.; Chien, C.; Liao, S. K. S.; Liao, S.-F.; Hung, W.-
T.; Yang, W.-B.; Lin, C.-C.; Cheng, T.-J. R.; Chang, C.-C.; Fang, J.-M.;
Wong, C.-H. Structure and bioactivity of the polysaccharides in
medicinal plant Dendrobium huoshanense. Bioorg. Med. Chem. Lett.
2008, 16, 6054−6068.
(32) Honda, T.; Masuda, T.; Yoshida, S.; Arai, M.; Kaneko, S.;
Yamashita, M. Synthesis and anti-Influenza virus activity of 7-O-
alkylated derivatives related to zanamivir. Bioorg. Med. Chem. Lett.
2002, 12, 1925−1928.
(33) Liu, Z.-y.; Wang, B.; Zhao, L.-x.; Li, Y.-h.; Shao, H.-y.; Yi, H.;
You, X.-f.; Li, Z.-r. Synthesis and anti-influenza activities of carboxyl
alkoxyalkyl esters of 4-guanidino-Neu5Ac2en (zanamivir). Bioorg. Med.
Chem. Lett. 2007, 17, 4851−4854.
(34) Yamashita, M.; Tomozawa, T.; Kakuta, M.; Tokumitsu, A.;
Nasu, H.; Kubo, S. CS-8958, a prodrug of the new neuraminidase
inhibitor R-125489, shows long-acting anti-influenza virus activity.
Antimicrob. Agents Chemother. 2009, 53, 186−192.
(35) Kubo, S.; Tomozawa, T.; Kakuta, M.; Tokumitsu, A.; Yamashita,
M. Laninamivir prodrug CS-8958, a long-acting neuraminidase
inhibitor, shows superior anti-influenza virus activity after a single
administration. Antimicrob. Agents Chemother. 2010, 54, 1256−1264.
(36) Ishizuka, H.; Yoshiba, S.; Okabe, H.; Yoshihara, K. Clinical
pharmacokinetics of laninamivir, a novel long-acting neuraminidase
inhibitor, after single and multiple inhaled doses of its prodrug, CS-
8958, in healthy male volunteers. J. Clin. Pharmacol. 2010, 50, 1319−
1329.
(37) Chandler, M.; Bamford, M. J.; Conroy, R.; Lamont, B.; Patel, B.;
Patel, V. K.; Steeples, I. P.; Storer, R.; Weir, N. G.; Wright, M.;
Williamson, C. Synthesis of the potent influenza neuraminidase
inhibitor 4-guanidino Neu5Ac2en. X-Ray molecular structure of 5-
I
dx.doi.org/10.1021/jm3009844 | J. Med. Chem. XXXX, XXX, XXX−XXX