By Annette M. Doherty, William K. Hagmann

Annual studies in Medicinal Chemistry presents well timed and demanding studies of significant issues in medicinal chemistry including an emphasis on rising subject matters within the organic sciences that are anticipated to supply the foundation for totally new destiny remedies.

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Pharmacol. Exp. , 273, 359-366, (1995). 39. L. M. Hawkins, Invest. Drugs, 2, 1313-1326, (1999). 40. H. Bridge, Neuropsychopharmacology, 13, 269 (1995). 41. D. Gordh, Pain, 51,249 (1992). 42. M. C. Hunter, A. Dray, Trends Pharmacol. Sci. 20, 337-342, (1999). 43. C. Parsons, New Developments in Glutamate Pharmacology, Orlando, FL, March 4-5, (1999). 44. A. Quartaroli, American Pain Society Annual Meeting (1997). 45. M. Linders Curr. Opin. CPNS Invest. , 167-170, (1999). 46. B. Sang, Abst. Soc. Neurosci.

Hawkins, Invest. Drugs, 2, 1313-1326, (1999). 40. H. Bridge, Neuropsychopharmacology, 13, 269 (1995). 41. D. Gordh, Pain, 51,249 (1992). 42. M. C. Hunter, A. Dray, Trends Pharmacol. Sci. 20, 337-342, (1999). 43. C. Parsons, New Developments in Glutamate Pharmacology, Orlando, FL, March 4-5, (1999). 44. A. Quartaroli, American Pain Society Annual Meeting (1997). 45. M. Linders Curr. Opin. CPNS Invest. , 167-170, (1999). 46. B. Sang, Abst. Soc. Neurosci. 14 (1997). 47. E. Fundytus, Metabotropic Glutamate Receptors-Third International Meeting, Taormina, Sicily, Italy, September 19-24, (1999).

1]octane moiety (13) have been synthesized from tropinone (28). _55,from common pyridyl tropinone intermediates. Unfortunately no biological data are given for these compounds. Rapoport and coworkers have significantly advanced synthesis of chiral nicotinic alkaloids, employing glutamic acid as a key intermediate (29). _44. Further development of epiboxidine (1_66,R= CH3) analogs has led to the synthesis of the phenylisoxazole 1(~, R= phenyl). This analog shows moderate binding to 3H-cytisine sites in rat cortex (IC5o = 147 nM) and a dramatic decrease in toxicity relative to epibatidine (mouse LD50> 130 mg/kg (16, R= phenyl) vs.

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