Drug Stereochemistry: Analytical Methods and Pharmacology

This revised third edition has been updated to cover all aspects of chiral drugs from the academic, governmental industrial and clinical perspective reflecting the many advances in techniques and methodology. The title will cover new material including the use of enzymes for the synthesis and resolution of enantiomeric compounds as well, as their use in drug discovery; how stereochemistry impacts on decisions taken during the ADMET (absorption, distribution, metabolism, excretion, toxicity) stage of drug discovery; issues faced during the final stages of the drug development process; the impact of ICH (International Conference on Harmonisation) on the use of single isomer drugs; racemic switches; and legal perspectives looking at IP and patent issues surrounding chiral switches and marketing single enantiomer switches.

This Third Edition comprehensively presents all aspects of chiral drugs from scientific, academic, governmental, industrial, and clinical points of view. This one-stop text covers the lifespan of stereochemistry, from its early history, including an overview of terms and concepts, to the current drug development process, legal and regulatory issues, and the new stereoisomeric drugs.

New topics include:

• The use of enzymes in the synthesis and resolution of enantiometrically pure compounds in drug discovery
• How stereochemistry impacts decisions made in the Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) stages of drug discovery
• A chapter on pharmacokinetics and pharmacodynamics that discusses the issues faced during the final stages of the drug development process
• The impact of International Conference on Harmonisation on the use of single isomer drugs
• Chiral switches
• The concept of molecular chiral recognition and how it affects the separation and behavior of stereochemically pure drugs
• A chapter on the legal perspectives of patent issues surrounding chiral switches and the marketing of single enantiomer switches.

I. Introduction

• 1. The early history of stereochemistry: From the discovery of molecular asymmetry and the first resolution of a racemate by Pasteur to the asymmetrical chiral carbon of van’t Hoff and Le Bel - Dennis Drayer
• 2. Stereochemical terms and concepts: An overview - Krzysztof Jozwiak
• 3. Molecular chiral recognition: An introduction and overview - Krzysztof Jozwiak
• II. The Separation, Preparation and Identification of Stereochemically Pure Drugs
• 1. Indirect methods for the chromatographic resolution of drug enantiomers: Synthesis and separation of diastereomeric derivatives - Beta Polak and Wladystaw Golkiewicz
• 2. The crystallographic separation of enantiomers and dissociable diastereomers - Harry Brittain
• 3. HPLC chiral stationary phases for the stereochemcial resolution of enantiomeric compounds: The current state of the art - John Lough
• 4. Enantioselective separations by capillary electrophoresis - Michal Markuzewski
• 5. Alternative analytical techniques for determination or isolation of drug enantiomers - John Lough
• 6. Production scale preparation of enantiomerically pure compounds by chromatography and synthetic approaches - Geoffrey B Cox
• III. Pharmacokinetic and Pharmacodynamic Differences Between Drug Stereoisomers
• 1. Stereoselective transport of drugs across epithelia - Prateek Bhatai and Ruin Moaddel
• 2. Enantioselective binding of drugs to plasma proteins - Heesung Kim
• 3. Clinical pharmacokinetics and pharmacodynamics of stereoisomeric drugs - Donald Mager and Scott Van Wart
• IV. Perspectives on the Development and Use of Single Isomer Drugs
• 1. Regulatory perspective of the development of new stereisomeric drugs - Sarah Branch and Andrew Hutt
• 2. Revisiting Eutomers and Distomerers: Mining Stereochemistry for New Therapeutics - Roland Seifert
• 3. The development and marketing of single isomer drugs versus racemates: A legal perspective - Svetlana Ivanova