SYNTHESIS/ ACTIVITY OF N-AMINOTETRAHYDROPYRIDINES

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The primary objective is the design, synthesis and pharmacological evaluation of novel and medicinally important N-amino-1,2,3,6- tetrahydropyridine derivatives. We reported the synthesis of novel N- iminopyridium ylides using the method employed by Tamura and modified in our laboratory. Sodium borohydride reduction of the ylides afforded the stable N-amino-1, 2,3,6-tetrahydropyridines in good yields. We also recently reported preliminary pharmacological test results of a few tetrahydropyridines that exhibited analgesic and anti-inflammatory activities with no observed toxicity, even at very high dose levels. Our earlier work provides the basis for new and exciting studies so that a series of compounds related to the most active analogs could be prepared, and retested and the octanol-water partition coefficient determined. Once sufficient data are accumulated, the compounds prepared will be subjected to structure activity analysis to study the electronic, steric and lipophilic effects of substituents. The physical and pharmacologic data obtained in this study will then be used to design drugs with more beneficial biological activity. The primary focus of the pharmacological studies will be to develop and easily synthesize effective and safe non- steroidal anti-inflammatory agents for the treatment of rheumatic diseases, including rheumatoid arthritis, osteoarthritis, gout and rheumatic fever.