Campbell D B
Servier Research & Development Limited, Fulmer, Slough, United Kingdom.
Acta Pharm Nord. 1990;2(3):217-26.
For many years, scientists in drug development have been blind to the 3-dimensional consequences of stereochemistry, mainly due to the problem of synthesis and analytical methodology. Now that new techniques are available for the resolution of racemic mixtures, there is an increasing pressure to only synthesise single enantiomers, and although guidelines on stereoisomers from the all regulatory agencies are awaited, there is already sufficient information to suggest that developmental studies on racemates will be greatly increased. There is often stereospecificity in pharmacology and toxicology, but this is frequently not the case for pharmacokinetics where enantiomeric differences may only play a relatively small contribution to overall drug activity, except for some exceptions (NSAI). Other chiral developments are discussed, for example, dextro fenfluramine from rac-fenfluramine, together with the ideas of what may be required for their registration.
多年来，药物研发领域的科学家一直忽视立体化学的三维影响，主要是由于合成和分析方法的问题。既然现在有了用于拆分外消旋混合物的新技术，只合成单一对映体的压力与日俱增，尽管目前仍在等待各监管机构出台关于立体异构体的指导方针，但已有足够信息表明，针对外消旋体的研发研究将会大幅增加。药理学和毒理学中常常存在立体特异性，但药代动力学情况往往并非如此，对映体差异可能仅对整体药物活性起到相对较小的作用，不过也有一些例外情况（如非甾体抗炎药）。本文还讨论了其他手性药物的进展，例如从消旋芬氟拉明制备右旋芬氟拉明，以及它们注册时可能需要满足的条件。
