1. 1 Directed ortho Metalation (DoM) of 1,8-Naphthalene diethylamides: Research Towards Nerve Growth Factor Inhibitors. John Stephenson, Christopher Jones†, Victor Snieckus† † Department of Chemistry, Queen’s University, Kingston, ON, CANADA K7L 3N6

2. 2 Nerve Growth Factor (NGF) Involved with the neuronal development in the Central Nervous System and Peripheral Nervous System. Nerve Growth Factor is implicated in Alzheimer’s, epilepsy, stroke and pain. Production of protein is stimulated in patients suffering from Arthritis pain. Inhibition of NGF causes reduction in pain levels. Shamovsky, et al. J Am Chem Soc, 1999, 121, 9797-9806

3. 3 Previously Identified NGF Inhibitors Target Molecules Marone, S. and Ross, G. 2000, World Patent No. WO0069829

4. 4 Recent Work 1. Kalinin, A.; Snieckus, V. et al. J Org Chem, 2003, 68, 5992 2. Chauder, B.; Snieckus, V. et al. Org Lett, 2002, 4, 815 Directed ortho Metalation Original Work 1.Gilman et al. J. Am. Chem. Soc. 1939, 61, 106-109. 2.Wittig et al. Chem. Ber. 1940, 73, 1197.

5. 5 Hartung, C, Snieckus, V. Modern Arene Chemistry, Wiley-VCH, Weinheim. 2002, p. 330 Directed ortho Metalation (DoM) Reactions in Organic Synthesis

6. 6 Previous Work Involving 2,7-Disubstituted 1,8-Naphthalene Systems Wuest, J. et al. Organometallics, 1996, 15, 1296

7. 7 Steric Interference With 1,8-bis(diethylamide) Naphthalene System <

8. 8 Previous Examples of DoM Chemistry of Naphthalene 1,8-bis(diethylamide) E + EEquiv% Yield 4.450% 2.240% Snieckus, V.; Jones, C., 2003, unpublished results.

9. 9 New Examples of DoM Chemistry of Naphthalene 1,8-bis(diethylamide) E + EEquiv% Yield 2.275% 4.486% Snieckus, V.; Jones, C.; Stephenson, J., 2003, unpublished results.

10. 10 Bromo Ipso-Desilylation Snieckus, V.; Jones, C.; Stephenson, J., 2003, unpublished results. Metal-Halogen Exchange

11. 11 Research with Sulfonamide Analogs

12. 12 Acknowledgements Dr. Victor Snieckus Chris Jones Snieckus Group