The development of chiral drugs.

Abstract

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.