Chirality and Biological Activity

Abstract

AbstractThe relationship between chirality and biological activity has been of increasing importance to the pharmaceutical and biopharmaceutical areas as evidenced by a growing number of chiral drugs that have been developed within the last two decades. This chapter covers several areas of importance in the design and synthesis of novel small molecule chiral drugs for medicinal chemists. The focus of this chapter is to provide an overview of the impact of chirality in medicinal chemistry and pharmaceutical sciences, and this should not be considered an exhaustive review of the topic. Several examples reported in the recent literature have been used to highlight the impact of chirality on development of therapeutics for various molecular targets. Chirality, as used in this chapter, also includes examples of atropisomers. The effects of chirality on pharmacological activities, absorption, distribution, metabolism, and excretion and toxicity are exemplified. In addition to chirality at carbon, examples of chiral compounds involving chirality at noncarbon atoms are included. A section on chirality in drug design provides several examples from recent literature covering diverse target classes. Regulatory considerations that apply to chiral drugs are addressed briefly. Section 10 covers recent drug development and marketed single enantiomers. Multiple synthetic approaches to produce chiral compounds with high enantiomeric purity, including chromatographic separation and enantioselective syntheses, were covered adequately in the 6th edition, and thus these areas and general definitions of chirality are not repeated in this chapter.