In 1992 Daly and co-workers reported the isolation of a new natural product, epibatidine. Future studies showed that epibatidine was an nAChR ligand with analgesic potency 200-400 times greater than that of morphine. However, its potential as a new drug was limited by its toxic side effects, probably resulting from its activity at a number of nAChR subtypes. Epibatidine's unique structure and potent activity made it an ideal lead structure for the development of nAChR ligands with reduced side effects and better nAChR subtype selectivity. This review presents the synthetic methods we have used to synthesize a number of epibatidine agonists, antagonists, and mixed agonists/antagonists to better characterize the α4β2 nAChR pharmacophore and hopefully provide compounds that have potential for treating nicotine addiction.

中文翻译：

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合成烟碱仿制药表征中的上哌啶类似物-综述。

1992年，Daly及其同事报道了一种新的天然产物Epibatidine的分离。未来的研究表明，依巴替丁是一种nAChR配体，具有比吗啡高200-400倍的镇痛作用。但是，其作为一种新药的潜力受到其毒性副作用的限制，这可能是由于其对多种nAChR亚型的活性所致。Epibatidine独特的结构和强大的活性使其成为开发nAChR配体的理想先导结构，具有减少的副作用和更好的nAChR亚型选择性。这篇综述介绍了我们已用于合成许多Epibatidine激动剂，拮抗剂和混合激动剂/拮抗剂的合成方法，以更好地表征α4β2nAChR药效团，并有望提供具有治疗尼古丁成瘾潜力的化合物。