1510
T.Cai et al./ Bioorg.Med.Chem.Lett.12 (2002) 1507–1510
4. Masters, B. S.; McMillan, K.; Sheta, E. A.; Nishimura,
J. S.; Roman, L. J.; Martasek, P. FASEB J. 1996, 10, 552.
5. Gorren, A. C. F.; Mayer, B. Biochemistry (Moscow) 1998,
63, 734.
6. Stuehr, D. J. Biochim.Biophys.Acta 1999, 1411, 217.
7. Ludwig, M. L.; Marletta, M. A. Structure 1999, 7, R73.
8. Werner, E. R.; Werner-Felmayer, G.; Mayer, B. Proc.Soc.
Exp.Biol.Med. 1998, 219, 171.
9. Hemmens, B.; Mayer, B. Meth.Mol.Biol. 1998, 100, 1.
10. Renodon-Corniere, A.; Boucher, J. L.; Dijols, S.; Stuehr,
D. J.; Mansuy, D. Biochemistry 1999, 38, 4663.
11. Moali, C.; Boucher, J. L.; Sari, M. A.; Stuehr, D. J.;
Mansuy, D. Biochemistry 1998, 37, 10453.
12. Dijols, S.; Perollier, C.; Lefevre-Groboillot, D.; Pethe, S.;
Attias, R.; Boucher, J. L.; Stuehr, D. J.; Mansuy, D. J.Med.
Chem. 2001, 44, 3199.
199.0512, found 199.0513. Compound 6j: 1H NMR (400 MHz,
CD3OD) d 8.20 (d, J=9.0 Hz, 2H), 7.59 (d, J=9.0 Hz, 2H),
4.99 (s, 2H); 13C NMR (100 MHz, CD3OD) d 158.6, 147.4,
145.8, 127.9, 123.5, 43.8; EIMS 211 (M++1); HRMS calcd
for C8H9N3O3 (M+-NH) 195.0644, found 195.0643.
24. Niwa, R.; Kamada, H.; Shitara, E.; Horiuchi, J.; Kibushi,
N.; Kato, T. Chem.Pharm.Bull. 1996, 44, 2314.
25. Bailey, D. M.; deGrazia, C. G.; Lape, H. E.; Frering, R.;
Fort, D.; Skulan, T. J.Med.Chem. 1973, 16, 151.
26. Cyclic voltammetry was performed with a BAS-100B/W
electrochemical analyzer (Bioanalytical Systems, Inc.) in
1.5 mM dry CH3CN solution under an argon atmosphere
(sweep rate, 100 mV/s). n-Bu4NPF6 (0.1 M) was employed as
the supporting electrolyte. A standard three-electrode cell
consisted of a glassy carbon disk as working electrode, a pla-
tinum wire as counter electrode, and Ag/AgCl (3 M NaCl) as
reference electrode.
27. Vadon-Le Goff, S.; Boucher, J. L.; Mansuy, D. C. R.
Acad.Sci.II 2000, C3, 785.
28. Korth, H. G.; Sustmann, R.; Thater, C.; Butler, A. R.;
Ingold, K. U. J.Biol.Chem. 1994, 269, 17776.
13. Renodon-Corniere, A.; Dijols, S.; Perollier, C.; Lefevre-
Groboillot, D.; Boucher, J. L.; Attias, R.; Sari, M. A.; Stuehr,
D.; Mansuy, D. J.Med.Chem. 2002, 45, 944.
14. Tai, A. W.; Lien, E. J.; Lai, M. C.; Khwaja, T. J.Med.
Chem. 1984, 27, 236.
15. Chern, J. W.; Leu, Y. L.; Wang, S. S.; Lou, R.; Lee, C. F.;
Tsou, P. C.; Hsu, S. C.; Liaw, Y. C.; Lin, H. W. J.Med.
Chem. 1997, 40, 2276.
16. Cory, J. G.; Carter, G. L.; Bacon, P. E.; Tang, A.; Lien, E.
J.Biochem.Pharmacol. 1985, 34, 2645.
17. Adamson, R. N. Nature 1972, 236, 400.
18. Everett, S. A.; Smith, K. A.; Patel, K. B.; Dennis, M. F.;
Stratford, M. R. L.; Wardman, P. Br.J.Cancer 1996, 74,
S172.
29. Jousserandot, A.; Boucher, J. L.; Henry, Y.; Niklaus, B.;
Clement, B.; Mansuy, D. Biochemitry 1998, 37, 17179.
30. Boucher, J. L.; Genet, A.; Vadon, S.; Delaforge, M.;
Mansuy, D. Biochem.Biophys.Res.Commun. 1992, 184, 1158.
31. Dunford, H. B. In Peroxidases in Chemistry and Biology;
Everse, J., Everse, K. E., Grisham, M. B., Eds.; CRC: Boca
Raton, 1991; Vol. II, p 1.
32. Boucher, J. L.; Vadon, S.; Tomas, A.; Viossat, B.; Man-
suy, D. Tetrahedron Lett. 1996, 37, 3113.
19. Clement, B.; Boucher, J. L.; Mansuy, D.; Harsdorf, A.
Biochem.Pharm. 1999, 58, 439.
20. Xian, M.; Li, X.; Tang, X.; Chen, X.; Zheng, Z.; Galligan,
J. J.; Kreulen, D. L.; Wang, P. G. Bioorg.Med.Chem.Lett.
2001, 11, 2377.
21. Mesto, C. M. J.Am.Cardiology 2000, 86, 30F.
22. Fukuto, J. M.; Wallace, G. C.; Hszieh, R.; Chaudhuri, G.
Biochem.Pharm. 1992, 43, 607.
33. Green, L. C.; Wagner, D. A.; Glogowski, J.; Skipper,
P. L.; Wishnok, J. S.; Tannenbaum, S. R. Anal.Biochem.
1982, 126, 131.
34. The enzymatic reactions were carried out in PBS buffer
(pH 7.4) with 1 mM EDTA. Incubated mixtures containing
0.6 mM substrate, 0.6 mM H2O2, and 80 mg/mL HRP in a
500 mL finalvoulme were shaken at 25 ꢁC for 20 min. The
concentration of NOꢀ2 generated in the system was determined
by addition of the Griess reagent. Absorbances were measured
at 548 nm. Calibration curves were made from identical incu-
bated mixtures without the enzyme and containing various
concentration of NaNO2 to properly determine the amounts
of NOꢀ2 formed in the enzymatic reactions.
35. Ortiz de Montellano, P. R. Acc.Chem.Res. 1987, 20, 289.
36. Casella, L.; Gullotti, M.; Ghezzi, R.; Poli, S.; Beringhelli,
T.; Colonna, S.; Carrea, G. Biochemistry 1992, 31, 9451.
37. Mansuy, D.; Boucher, J. L.; Clement, B. Biochimie 1995,
77, 661.
23. Spectraldata of compound 6a–e and 6h were reported
1
in ref 13. Compound 6f: H NMR (400 MHz, CD3OD) d 7.25
(d, J=9.0 Hz, 2H), 6.92 (d, J=9.0 Hz, 2H), 4.35 (s, 2H), 3.78
(s, 3H); 13C NMR (100 MHz, CD3OD) d 159.8, 159.2, 128.5,
128.3, 114.0, 54.3, 44.0; HRMS calcd for C9H13O2N3
195.1008, found 195.1010. Compound 6g: 1H NMR
(400 MHz, CD3OD) d 7.19 (d, J=8.0 Hz, 2H), 7.11 (d,
J=8.0 Hz, 2H), 4.13 (s, 2H), 2.29 (s, 3H); 13C NMR
(100 MHz, CD3OD) d 157.8, 136.6, 136.4, 128.9, 127.3, 44.7,
20.0; EIMS 180 (M++1); HRMS calcd for C9H13N3O (M+-
O) 163.1110, found 163.1107. Compound 6i: 1H NMR
(400 MHz, CD3OD) d 7.37 (d, 2H, J=8 Hz), 7.33 (d, 2H,
J=8 Hz), 4.93 (s, 2H); 13C NMR (100 MHz, CD3OD) d 154.5,
138.6, 128.8, 128.3, 118.6, 44.0; HRMS calcd for C8H10ON3Cl
38. Jousserandot, A.; Boucher, J. L.; Desseaux, C.; Delaforge,
M.; Mansuy, D. Bioorg.Med.Chem.Lett. 1995, 5, 423.
ˆ
39. Keseru, G. M.; Balogh, G. T.; Karancsi, T. Bioorg.Med.
Chem.Lett. 2000, 10, 1775.