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John Stephenson , Christopher Jones † , Victor Snieckus †

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. Nerve Growth Factor (NGF).

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John Stephenson , Christopher Jones † , Victor Snieckus †

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

  4. Directed ortho Metalation • Original Work • Gilman et al. J. Am. Chem. Soc.1939, 61, 106-109. • Wittig et al. Chem. Ber.1940, 73, 1197. 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

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

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

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

  8. Previous Examples of DoM Chemistry of Naphthalene 1,8-bis(diethylamide) E+ E Equiv % Yield 4.4 50% 2.2 40% Snieckus, V.; Jones, C., 2003, unpublished results.

  9. New Examples of DoM Chemistry of Naphthalene 1,8-bis(diethylamide) E+ E Equiv % Yield 2.2 75% 4.4 86% Snieckus, V.; Jones, C.; Stephenson, J., 2003, unpublished results.

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 Bromo Ipso-Desilylation Metal-Halogen Exchange Snieckus, V.; Jones, C.; Stephenson, J., 2003, unpublished results.

  11. Research with Sulfonamide Analogs

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

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