Author(s): Utembe, W.

Source: In Duncan T (Ed), Advances in Health and disease, Vol 59. Nova Medicine and Health, New York pp111-132

Abstract: Over 50% of medicines consist of chiral molecules that are not non-superimposable on their mirror images because of the presence of an asymmetric point. The two molecules (or enantiomers) are distinguishable in biological systems, often resulting in different pharmacological and toxicological profiles of the two enantiomers. The development of new chiral drugs is very complex and expensive, involving laborious enantioselective synthesis methods such as the use of chiral pools, optical resolution of racemates, asymmetric synthesis and enatioselective catalysis. Furthermore, the study and quality of these drugs require chiroptical analytical methods that include circular dichroism spectroscopy, polarimetry and optical rotary dispersion, together with chiral separation techniques such as chiral chromatography. Chiral medicines are often sold as racemates or equimolar mixtures of the enantiomers. However, by performing chiral switches form the racemate to a single enantiomer, pharmaceutical companies can prolong the patent periods for their drugs, contingent on meeting statutory and TRIPs (Trade-Related Aspects of Intellectual Property Rights) conditions of novelty, non-obviousness and usefulness for the single enantiomer. Studies have shown that chiral switches to single-enantiomer drugs infrequently improve efficacy or safety, despite the greater costs. A few countries have set up specific policies, regulations and guidelines on chiral drugs, while most countries adopted the ICH Technical Requirements. Generally, the guidelines demand the enantiomer-specific methods as well as pharmacological toxicological profiles of each enantiomer and racemates in order to guide decisions on whether to proceed with developing the racemate or a single enantiomer. This chapter discusses the effects of chirality on medicinal drugs as well as its impacts on drug research and development processes in the context of national and international guidelines.

Keywords: chirality; toxicity; efficacy; drugs; racemate; optical; enantiomer