1180
R. Di Fabio et al. / Bioorg. Med. Chem. Lett. 17 (2007) 1176–1180
3
4
. Choi, D. W. Prog. Brain. Res. 1994, 100, 47. Quartaroli, M.; Ratti, E.; Trist, D. G.; Ugolini, A. R.
. Danysz, W.; Parsons, C. G.; Bresnick, I. Drug News
Prospect. 1996, 8, 261.
Drugs Future 2000, 25, 137.
26. For some structurally related glycine antagonists, see: Di
Fabio, R.; Tranquillini, E.; Bertani, B.; lvaro, G.; Micheli,
F.; Sabbatini, F.; Pizzi, M. D.; Pentassuglia, G.; Pasqua-
rello, A.; Messeri, T.; Donati, D.; Ratti, E.; Arban, R.;
Dal Forno, G.; Reggiani, A.; Barnaby, R. J. Bioorg. Med.
Chem. Lett. 2003, 13, 3863.
5
6
7
8
. Wang, S. J.; Yang, T. T. Drug News Prospect. 2005, 18, 561.
. Woolf, C. J. Nature 1983, 306, 686.
. Davies, S. N.; Lodge, D. Brain Res. 1987, 424, 402.
. Haley, J. E.; Sullivam, A. F.; Dickenson, A. H. Brain Res.
1990, 518, 218.
9
. Dickenson, A. H. Trends Pharmacol. 1990, 11, 307.
27. DiFabio, R.; Alvaro, G.; Bertani, B.; Giacobbe, S. Can.
J. Chem. 2000, 6, 78.
28. Kishimoto, H.; Simon, J. R.; Aprison, M. H. J. Neuro-
chem. 1981, 37, 1015.
29. Di Fabio, R.; Alvaro, G.; Bertani, B.; Donati, D.;
Giacobbe, S.; Marchioro, C.; Palma, C.; Lynn, S. M.
J. Org. Chem. 2002, 67, 7319.
1
1
1
0. Woolf, C. J.; Thompson, S. W. N. Pain 1991, 44, 293.
1. Woolf, C. J. Pulmonary Pharmacol. 1995, 8, 161.
2. Harris, J. A.; Corsi, M.; Quartaroli, M.; Arban, R.;
Bentivoglio, M. Neuroscience 1996, 74, 7.
3. Dickenson, A. H.; Chapman, V.; Green, G. M. Gen.
Pharmacol. 1997, 28, 633.
1
1
1
4. Parsons, C. G. Eur. J. Pharmacol. 2001, 429, 71.
5. Jessel, T. M.; Kelly, D. D. Pain and Analgesia. In Principles
of Neural Science; Kandel, E. R., Schwartz, J. H., Jessell, T.
H., Eds.; Appleton & Lange: 1991; pp 385–399.
30. Kobayashi, S.; Busujima, T.; Nagayama, S. Synlett 1999,
5, 545, and references herein enclosed.
31. The same reaction was attempted using polystired-sup-
3
ported Sc(OTf) , as described by Kobayashi, S.; Nagay-
1
6. Palfreyman, M. G.; Baron, M. B. Non-competitive
NMDA Antagonists Acting at the Glycine Site. In
Excitatory Amino Acid Antagonists; Meldrum, B., Ed.;
Blackwell: Oxford, England, 1991; pp 101–129.
ama, S. J. Am. Chem. Soc. 1998, 120, 2985, The desired
aldehyde has been obtained in good yield and the
recovered microencapsulated Lewis acid was used again
without significant loss of the catalytic activity.
1
1
1
7. Carter, A. J. Drugs Future 1992, 17, 595.
8. Leeson, P. D.; Iversen, L. L. J. Med. Chem. 1994, 37, 4053.
9. Di Fabio, R.; Gaviraghi, G.; Reggiani, A. La Chim. l’Ind.
32. From preliminary experimental observations it seems that
any kind of metal triflates, used in catalytic amount, is
able to promote this addition reaction, independent of the
nature of the metal used, namely alkaline earth metals,
transition metals or lanthanide metals. This result might
be explained based upon the non-nucleophilic nature of
the triflate anion, and hence the stronger cationic charac-
ter of the central metal, responsible for the activation of
the catalytic cycle. Additional studies are ongoing to
confirm these initial experimental observations and the
outcome of this new exploration will be reported in due
course.
1996, 78, 283.
2
0. Di Fabio, R.; Capelli, A. M.; Conti, N.; Cugola, A.;
Feriani, A.; Gastaldi, P.; Gaviraghi, G.; Hewkin, C. T.;
Micheli, F.; Missio, A.; Mugnaini, M.; Pecunioso, A.;
Quaglia, A. M.; Ratti, E.; Rossi, L.; Tedesco, G.; Trist, D.
G.; Reggiani, A. J. Med. Chem. 1997, 40, 841.
1. Di Fabio, R.; Cugola, A.; Donati, D.; Feriani, A.;
Gaviraghi, G.; Ratti, E.; Trist, D. G.; Reggiani, A. Drugs
Future 1998, 23, 61.
2
2
2. Dickenson, A. H.; Aydar, E. Neurosci. Lett. 1991, 121,
33. Sivilotti, L. G.; Thompson, S. W. N.; Woolf, C. J.
J. Neurophysiol. 1993, 69, 1621.
263.
2
2
3. Millian, M. J.; Seguin, L. Neurosci. Lett. 1994, 178, 139.
4. Quartaroli, M.; Carignani, C.; Dal Forno, G.; Mugnaini, M.;
Ugolini, A.; Arban, R.; Bettelini, L.; Maraia, G.; Belardetti,
F.; Reggiani, A.; Trist, D. G.; Ratti, E.; Di Fabio, R.; Corsi,
M. J. Pharmacol. Exp. Ther. 1999, 290, 158.
34. For a detailed description of the experimental procedures
used for the in vivo characterization of compound 2a both
in the formalin model in mice and in the chronic
constriction injury model in rats, see Ref. 24.
35. This research complied with national legislation and with
company policy on the Care and Use of Animals and with
related codes of practice.
2
5. Di Fabio, R.; Conti, N.; Corsi, M.; Donati, D.; Gastaldi,
P.; Gaviraghi, G.; Giacobbe, S.; Pentassuglia, G.;