The Impact of Stereochemistry on Drug Development and Use

ISBN-13: 9780471596448 / Angielski / Twarda / 1997 / 728 str.

Hassan Y. Aboul-Enein; Irving Wainer; H. Y. Aboul-Enein

Opis

This volume discusses the impact of chirality and stereochemistry on drug development and use, including analytical, pharmacological and regulatory topics. It is wide-ranging and includes stereoisomeism in drug development.

Spis treści

Partial table of contents:

Chirality and Drug Hazards (H. Aboul–Enein & L. Basha).

Stereochemical Aspects of Drug Metabolism (J. Mason & A. Hutt).

Some Examples for Stereoselective Biotransformation of Drugs (G. Blaschke).

Chiral Barbiturates: Synthesis, Chromatographic Resolutions, and Biological Activity (J. Bojarski).

Stereogenic Elements of Pharmaceutical Compounds: Some Aspects on Isomerism, Resolution, and Stereochemical Integrity (S. Allenmark).

The Importance of Chiral Separations in Pharmaceuticals (S. Ahuja).

Micelle–Mediated Capillary Electrophoretic Separation of Enantiomeric Compounds (M. Swartz & P. Brown).

Chiral Derivatization Reagents in the Bioanalysis of Optically Active Drugs with Chromophore–Based Detection (R. Büschges, et al.).

Circular Dichroism in the Study of Stereoselective Binding of Drugs to Serum Proteins (C. Bertucci, et al.).

O autorze

About the editors

Hassan Y. Aboul–Enein holds a PhD in pharmaceutical and medicinal chemistry from the University of Mississippi. He is currently involved in biomedical and pharmaceutical research at King Faisal Specialist Hospital & Research Centre in Riyadh, Saudi Arabia. He is a member of the editorial boards of several journals, including Chirality, Biomedical Chromatography, Journal of Liquid Chromatography, and Analytical Letters. Dr. Aboul–Enein is a member of the World Health Organization Expert Advisory Panel on Pharmaceuticals. He is the author of numerous professional papers and several book chapters in the fields of medicinal chemistry and pharmaceutical analysis.

Irving W. Wainer is Professor and Director of the Division of Pharmacokinetics in the Department of Oncology at McGill University in Montreal, Canada. He received his PhD in synthetic organic chemistry from Cornell University in 1970. Dr. Wainer is author or coauthor of more than 200 scientific publications and eight books. He was editor in chief of the journal Chirality from its inception in 1989 to 1994, when he became editor of the Journal of Chromatography, Biomedical Applications. The recipient of numerous awards and honors and a Fellow of the American Association of Pharmaceutical Sciences, Dr. Wainer is a member of the United States Pharmacopoeial Convention Committee of Revision for 1995–2000.

Blurb

The past fifteen years have seen a revolution in the field of stereochemistry, with breakthrough analytical techniques in enantiomeric separation profoundly affecting drug development and use. This practical reference written by leading researchers focuses on the important roles chirality and stereoisomerism play in drug development efforts––presenting for the first time a comprehensive overview of this rapidly evolving area of pharmacological research.

The book explores analytical, pharmacological, and regulatory topics in dealing with the theory and practice of stereochemistry in the pharmaceutical industry today. This exciting, broad–appeal treatment extends from the analytical viewpoint in enantiomeric separation to the regulatory issues involved in the "racemate–versus–enantiomer" debate. The authors include numerous examples and case studies, and integrate material from a wide range of studies, publications, and workshops.

The introductory chapters outline the pharmacological effects of stereochemistry, cover stereochemistry in drug metabolism, and discuss problems inherent in the duality of enantiomers––chemically identical yet spatially different molecules. Contributions on the specific aspects of chirality and drug activity explore the toxicological effects of stereoselectivity, illustrate how an understanding of the stereochemical composition of certain drugs can help avoid problems, and offer tips on new clinical applications for existing drugs.

A full chapter is devoted to research opportunities in the development of new chirally pure drugs. Other practical research topics range from the preparation of chirally pure compounds to the analytical determination of stereochemical composition, to applications of circular dichroism (CD) spectroscopy. Regulatory issues concerning the development and approval of stereoisomeric drugs are discussed in the final chapters. This section offers an international perspective as well as a historical review of the ongoing debate surrounding regulatory guidelines.

Impact of Stereochemistry on Drug Development and Use is an essential reference for medicinal and analytical chemists, pharmacologists, drug metabolism and pharmacokinetic scientists, and personnel of regulatory agencies. It is also a useful text for graduate students in stereochemistry, and for anyone who wants to keep up with the swift pace of change in this dynamic field.

Impact of Stereochemistry on Drug Development and Use is an essential reference for medicinal and analytical chemists, pharmacologists, drug metabolism and pharmacokinetic scientists, and personnel of regulatory agencies. It is also a useful text for graduate students in stereochemistry, and for anyone who wants to keep up with the swift pace of change in this dynamic field.

IMPACT OF STEREOCHEMISTRY ON DRUG DEVELOPMENT AND USE

Twenty–three expert contributions on the "stereochemical revolution" of the last fifteen years––covering analytical, pharmacological, and regulatory topics––show that "drug development can no longer occur without consideration of drug stereochemistry."

"We have...come full circle and stand alongside Pasteur in amazement of nature′s duality, symmetry and dissymmetry, and its chemical and pharmacological consequences."––from the Preface