The primary objective is the design, synthesis and pharmacological evaluation of novel and medicinally important pyridinium ylides and their sodium borohydride reduction products, particularly the N- amino-l, 2, 3, 6-tetrahydropyridine derivatives.21,22 We reported the synthesis of novel N-iminopyridinium ylides using the method employed by Tamura.23 Sodium borohydride reduction of the ylides afforded the stable N-amino-l, 2, 3, 6-tetrahydropyridines in good yields. 26,27 We also reported earlier preliminary pharmacological test results of a few tetrahydropyridines that exhibited analgesic. anti-inflammatory and hyperglycemic activities with no observed toxicity even at very high dose levels. It is now proposed to expand these previous studies so that a series of compounds related to the most active analogs could be prepared, tested again and the octanol-water partition coefficient determined. Once sufficient data is accumulated, the compounds prepared will be subjected to structure activity analysis to study the electronic, steric and lipophilic effect of substituents. 29,30 The physical and pharmacological data obtained in this study will then be used to design drugs with a more beneficial biological activity. The focus of the pharmacological studies will revolve primarily on developing an easily synthesized, effective and safe nonsteroidal anti-inflammatory agent for the treatment of rheumatic diseases (including rheumatoid arthritis, osteoarthritis, gout and rheumatic fever). Rheumatic diseases affect approximately 25-30 million Americans. It is estimated that the U. S. loses about 14-15 billion dollars a year on medical care of rheumatic patients (direct and indirect).40,41
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