542
N. Paesano et al. / Bioorg. Med. Chem. Lett. 15 (2005) 539–543
S.; Misko, T. P.; Tjoeng, F. S.; Currie, M. G. J. Med.
Compound 6e: NMR (CDCl3) d 3.10 (s, 3H); 3.32 (s, 3H);
7.49–7.53 (m, 4H); 8.00 (br, 1H).
Chem. 1996, 39, 669; (h) Shankaran, K.; Donnelly, K. L.;
Shah, S. K.; Humes, J. L.; Pacholok, S.; Green, B. G.;
Grant, S. K.; MacCoss, M. Bioorg. Med. Chem. Lett.
1997, 7, 2887; (i) Hagmann, W. K.; Caldwell, C. G.; Chen,
P.; Durette, P.; Esser, C. K.; Lanza, T. J.; Kopka, I. E.;
Guthikonda, R.; Shah, S. K.; Green, B. G.; Humes, J. L.;
Kelly, T. M.; Luell, S.; Meurer, R.; Moore, V.; Pacholok,
S. G.; Pavia, T.; Williams, H. R.; Wong, K. K. Bioorg.
Med. Chem. Lett. 2000, 10, 1975; (j) Ueda, S.; Terauchi,
H.; Yano, A.; Ido, M.; Matsumoto, M.; Kawasaki, M.
Bioorg. Med. Chem. Lett. 2004, 14, 313.
Compound 6f: NMR (CDCl3) d 2.77 (t, 3H); 3.89 (d, 2H);
3.98 (s, 3H); 7.70–7.81 (m, 4H); 8.00 (br, 1H).
Compound 6g: NMR (CDCl3) d 1.20 (m, 3H); 1.65–1.71
(m, 2H); 2.65 (br, 2H); 3.21 (s, 3H); 7.50–7.80 (m, 4H);
8.04 (br, 1H).
Compound 6h: NMR (CDCl3) d 1.59 (m, 6H); 2.53 (s,
3H); 3.95 (m, 1H); 7.85–7.91 (m, 4H); 8.28 (br, 1H).
Compound 6i: NMR (CDCl3) d 3.19 (s, 3H); 3.48 (s, 3H);
7.59–7.62 (m, 4H); 8.39 (br, 1H).
Compound 6j: NMR (CDCl3) d 2.53 (t, 3H); 3.48 (d, 2H);
3.68 (s, 3H); 7.60–7.65 (m, 4H); 8.40 (br, 1H).
Compound 6k: NMR (CDCl3) d 1.28 (m, 3H); 1.85–1.90
(m, 2H); 2.87 (br, 2H); 3.48 (s, 3H); 7.80–7.85 (m, 4H);
8.39 (br, 1H).
Compound 6l: NMR (CDCl3) d 1.58 (m, 6H); 2.54 (s, 3H);
3.97 (m, 1H); 7.90–7.95 (m, 4H); 8.45 (br, 1H).
Compound 7a: NMR (CDCl3) d 3.19 (s, 3H); 3.51 (s, 3H);
7.57–7.61 (m, 4H); 8.32 (br, 1H).
Compound 7b: NMR (CDCl3) d 2.52 (t, 3H); 3.42 (d, 2H);
3.74 (s, 3H); 7.65–7.71 (m, 4H); 8.40 (br, 1H).
Compound 7c: NMR (CDCl3) d 1.25 (m, 3H); 1.77–1.85
(m, 2H); 2.80 (br, 2H); 3.30 (s, 3H); 7.72–7.79 (m, 4H);
8.01 (br, 1H).
Compound 7d: NMR (CDCl3) d 1.56 (m, 6H); 2.50
(s, 3H); 3.89 (m, 1H); 7.85–7.90 (m, 4H); 8.30 (br,
1H).
10. (a) Saturnino, C.; DÕAuria, M.; Paesano, N.; Saponiero,
D.; Cioffi, G.; Buonerba, M.; De Martino, G. Farmaco
2003, 58, 823–828; (b) Saturnino, C.; Buonerba, M.;
Paesano, N.; Lancelot, J.-C.; De Martino, G. Farmaco
2003, 58, 819–822.
11. Compound 4a: NMR (CDCl3) d 2.72 (s, 3H); 3.54 (s, 3H);
7.46–7.70 (m, 4H); 8.60 (br, 1H).
Compound 4b: NMR (CDCl3) d 1.25–1.28 (t, 3H); 2.66–
2.80 (m, 2H); 3.15 (s, 3H); 7.25–7.30 (m, 5H); 8.85 (br, 1H).
Compound 4c: NMR (CDCl3) d 1.47–1.51 (t, 3H); 1.66–
1.72 (m, 2H); 2.05–2.18 (m, 2H); 2.83 (s, 3H); 7.43–7.49
(m, 5H); 8.66 (br, 1H).
Compound 4d: NMR (CDCl3) d 1.45–1.53 (m, 6H); 3.61
(s, 3H); 4.43–4.75 (m, 1H); 7.48–7.55 (m, 5H); 8.70 (br,
1H).
Compound 5a: NMR (CDCl3) d 2.00 (s, 3H); 2.40 (s, 3H);
2.52 (d, 3H); 7.10–7.25 (m, 4H); 8.45 (br, 1H).
Compound 5b: NMR (CDCl3) d 1.10–1.15 (t, 3H); 2.01 (s,
3H); 2.41–2.50 (m, 2H); 3.20 (s, 3H); 7.23–7.28 (m, 4H);
8.80 (br, 1H).
Compound 5c: NMR (CDCl3) d 1.49–1.54 (t, 3H); 1.56–
1.61 (m, 2H); 1.97 (s, 3H); 2.12–2.22 (m, 2H); 2.76 (s, 3H);
7.45–7.49 (m, 4H); 8.46 (br, 1H).
Compound 7e: NMR (CDCl3) d 3.12 (s, 3H); 3.33 (s, 3H);
7.51–7.55 (m, 4H); 8.04 (br, 1H).
Compound 7f: NMR (CDCl3) d 2.79 (t, 3H); 3.88 (d, 2H);
3.93 (s, 3H); 7.71–7.79 (m, 4H); 8.01 (br, 1H).
Compound 7g: NMR (CDCl3) d 1.19 (m, 3H); 1.62–1.69
(m, 2H); 2.63 (br, 2H); 3.20 (s, 3H); 7.50–7.76 (m, 4H);
8.00 (br, 1H).
Compound 5d: NMR (CDCl3) d 1.41–1.49 (m, 6H); 2.00
(s, 3H); 3.76 (s, 3H); 4.49–4.67 (m, 1H); 7.50–7.55 (m, 4H);
8.61 (br, 1H).
Compound 5e: NMR (CDCl3) d 2.02 (s, 3H); 2.43 (s, 3H);
2.62 (d, 3H); 7.15–7.28 (m, 4H); 8.39 (br, 1H).
Compound 5f: NMR (CDCl3) d 1.11–1.15 (t, 3H); 2.12 (s,
3H); 2.41–2.47 (m, 2H); 3.23 (s, 3H); 7.25–7.29 (m, 4H);
8.78 (br, 1H).
Compound 5g: NMR (CDCl3) d 1.48–1.54 (t, 3H); 1.57–
1.62 (m, 2H); 1.98 (s, 3H); 2.12–2.22 (m, 2H); 2.78 (s, 3H);
7.45–7.50 (m, 4H); 8.40 (br, 1H).
Compound 5h: NMR (CDCl3) d 1.44–1.51 (m, 6H); 2.14
(s, 3H); 3.77 (s, 3H); 4.47–4.65 (m, 1H); 7.51–7.55 (m, 4H);
8.60 (br, 1H).
Compound 7h: NMR (CDCl3) d 1.59 (m, 6H); 2.55 (s,
3H); 3.92 (m, 1H); 7.80–7.85 (m, 4H); 8.20 (br, 1H).
Compound 7i: NMR (CDCl3) d 3.12 (s, 3H); 3.35 (s, 3H);
7.49–7.55 (m, 4H); 8.07 (br, 1H).
Compound 7j: NMR (CDCl3) d 2.49 (t, 3H); 3.51 (d, 2H);
3.69 (s, 3H); 7.60–7.67 (m, 4H); 8.43 (br, 1H).
Compound 7k: NMR (CDCl3) d 1.28 (m, 3H); 1.86–1.94
(m, 2H); 2.89 (br, 2H); 3.50 (s, 3H); 7.84–7.89
(m, 4H); 8.49 (br, 1H).
Compound 7l: NMR (CDCl3) d 1.60 (m, 6H); 2.55 (s, 3H);
3.95 (m, 1H); 7.90–7.93 (m, 4H); 8.40 (br, 1H).
Compound 8a: NMR (CDCl3) d 2.61 (s, 3H); 3.60 (s, 3H);
4.55 (s, 2H); 7.40–7.47 (m, 5H); 8.55 (br, 1H).
Compound 8b: NMR (CDCl3) d 1.35–1.39 (t, 3H); 2.71–
2.77 (m, 2H); 3.03 (s, 3H); 4.01 (s, 2H); 7.25–7.30 (m, 4H);
8.80 (br, 1H).
Compound 8c: NMR (CDCl3) d 1.50–1.55 (t, 3H); 1.70–
1.78 (m, 2H); 2.05–2.12 (m, 2H); 2.79 (s, 3H); 4.60 (s, 2H);
7.50–7.55 (m, 4H); 7.98 (br, 1H, NH).
Compound 5i: NMR (CDCl3) d 2.39 (s, 3H); 2.63 (s, 3H);
3.64 (s, 3H); 7.46–7.70 (m, 4H); 8.79 (br, 1H).
Compound 5j: NMR (CDCl3) d 1.32–1.37 (t, 3H); 2.86–
2.93 (m, 2H); 2.61 (s, 3H); 3.02 (s, 3H); 7.28–7.33 (m, 4H);
8.90 (br, 1H).
Compound 5k: NMR (CDCl3) d 1.50–1.53 (t, 3H); 1.76–
1.82 (m, 2H); 2.28–2.32 (m, 2H); 2.60 (s, 3H); 2.80 (s, 3H);
7.40–7.45 (m, 4H); 8.88 (br, 1H).
Compound 8d: NMR (CDCl3) d 1.40–1.47 (m, 6H); 3.61
(s, 3H); 4.15 (s, 2H); 4.45–4.70 (m, 1H); 7.61–7.75 (m, 4H);
8.00 (br, 1H).
Compound 5l: NMR (CDCl3) d 1.55–1.57 (m, 6H); 2.61 (s,
3H); 3.54 (s, 3H); 4.43–4.75 (m, 1H); 7.47–7.50 (m, 4H);
8.92 (br, 1H).
Compound 6a: NMR (CDCl3) d 3.17 (s, 3H); 3.52 (s, 3H);
7.56–7.61 (m, 4H); 8.30 (br, 1H).
Compound 6b: NMR (CDCl3) d 2.55 (t, 3H); 3.44 (d, 2H);
3.71 (s, 3H); 7.64–7.71 (m, 4H); 8.42 (br, 1H).
Compound 6c: NMR (CDCl3) d 1.24 (m, 3H); 1.78–1.85
(m, 2H); 2.79 (br, 2H); 3.32 (s, 3H); 7.70–7.80 (m, 4H);
8.00 (br, 1H).
12. Olszanecki, R.; Marcinkiewicz, J. Amino Acids 2004, 27,
29–35, and references therein reported.
13. The iNOS inhibitory activity of compounds 4–8 was
determined (for more details see Marzocco, S.; Piacente,
S.; Pizza, C.; Oleszek, W.; Stochmal, A.; Pinto, A.;
Sorrentino, R.; Autore, G. Life Sci. 2004, 75, 1491–
1501) by measuring nitric oxide release in medium in the
presence of each compound. In particular, nitrite accu-
mulation, an indicator of NO release, was detected by
Griess reaction (Green, L. C.; Wagner, D. A.; Glogowski,
J.; Skipper, P. L.; Wishnok, J. J.; Tannebaum, S. R. Anal.
Biochem. 1982, 126, 131–138) in the culture medium of
Compound 6d: NMR (CDCl3) d 1.55 (m, 6H); 2.49 (s,
3H); 3.90 (m, 1H); 7.85–7.91 (m, 4H); 8.32 (br, 1H).