An ever-increasing demand for better drugs, elevated safety standards, and economic considerations have all led to a dramatic paradigm shift in the way that drugs are being discovered and developed. Known as rational drug design, this contemporary process is defined by three main steps: the discovery of lead compounds, surgical manipulation to deve
This is a new approach to the teaching of medicinal chemistry. The knowledge of the physical organic chemical basis of drug design and drug action allows the reader to extrapolate to the many related classes of drugs described in standard medicinal chemistry texts. Students gain a solid foundation to base future research endeavors upon: drugs not yet developed are thus covered! n Emphasizes the use of the principles of physical organic chemistry as a basis for drug design n Discusses organic reaction mechanisms of clinically important drugs with mechanistic schemes n Uses figures and literature references extensively throughout n This text is not merely a "compilation of drugs and uses," but features selected drugs as examples of the organic chemical basis for any and all drug design applications
The Organic Chemistry of Drug Design and Drug Action, Third Edition, represents a unique approach to medicinal chemistry based on physical organic chemical principles and reaction mechanisms that rationalize drug action, which allows reader to extrapolate those core principles and mechanisms to many related classes of drug molecules. This new edition includes updates to all chapters, including new examples and references. It reflects significant changes in the process of drug design over the last decade and preserves the successful approach of the previous editions while including significant changes in format and coverage. This text is designed for undergraduate and graduate students in chemistry studying medicinal chemistry or pharmaceutical chemistry; research chemists and biochemists working in pharmaceutical and biotechnology industries. Updates to all chapters, including new examples and references Chapter 1 (Introduction): Completely rewritten and expanded as an overview of topics discussed in detail throughout the book Chapter 2 (Lead Discovery and Lead Modification): Sections on sources of compounds for screening including library collections, virtual screening, and computational methods, as well as hit-to-lead and scaffold hopping; expanded sections on sources of lead compounds, fragment-based lead discovery, and molecular graphics; and deemphasized solid-phase synthesis and combinatorial chemistry Chapter 3 (Receptors): Drug-receptor interactions, cation-p and halogen bonding; atropisomers; case history of the insomnia drug suvorexant Chapter 4 (Enzymes): Expanded sections on enzyme catalysis in drug discovery and enzyme synthesis Chapter 5 (Enzyme Inhibition and Inactivation): New case histories: for competitive inhibition, the epidermal growth factor receptor tyrosine kinase inhibitor, erlotinib and Abelson kinase inhibitor, imatinib for transition state analogue inhibition, the purine nucleoside phosphorylase inhibitors, forodesine and DADMe-ImmH, as well as the mechanism of the multisubstrate analog inhibitor isoniazid for slow, tight-binding inhibition, the dipeptidyl peptidase-4 inhibitor, saxagliptin Chapter 7 (Drug Resistance and Drug Synergism): This new chapter includes topics taken from two chapters in the previous edition, with many new examples Chapter 8 (Drug Metabolism): Discussions of toxicophores and reactive metabolites Chapter 9 (Prodrugs and Drug Delivery Systems): Discussion of antibody–drug conjugates
Fully updated and rewritten by a basic scientist who is also a practicing physician, the third edition of this popular textbook remains comprehensive, authoritative and readable. Taking a receptor-based, target-centered approach, it presents the concepts central to the study of drug action in a logical, mechanistic way grounded on molecular and principles. Students of pharmacy, chemistry and pharmacology, as well as researchers interested in a better understanding of drug design, will find this book an invaluable resource. Starting with an overview of basic principles, Medicinal Chemistry examines the properties of drug molecules, the characteristics of drug receptors, and the nature of drug-receptor interactions. Then it systematically examines the various families of receptors involved in human disease and drug design. The first three classes of receptors are related to endogenous molecules: neurotransmitters, hormones and immunomodulators. Next, receptors associated with cellular organelles (mitochondria, cell nucleus), endogenous macromolecules (membrane proteins, cytoplasmic enzymes) and pathogens (viruses, bacteria) are examined. Through this evaluation of receptors, all the main types of human disease and all major categories of drugs are considered. There have been many changes in the third edition, including a new chapter on the immune system. Because of their increasingly prominent role in drug discovery, molecular modeling techniques, high throughput screening, neuropharmacology and genetics/genomics are given much more attention. The chapter on hormonal therapies has been thoroughly updated and re-organized. Emerging enzyme targets in drug design (e.g. kinases, caspases) are discussed, and recent information on voltage-gated and ligand-gated ion channels has been incorporated. The sections on antihypertensive, antiviral, antibacterial, anti-inflammatory, antiarrhythmic, and anticancer drugs, as well as treatments for hyperlipidemia and peptic ulcer, have been substantially expanded. One new feature will enhance the book's appeal to all readers: clinical-molecular interface sections that facilitate understanding of the treatment of human disease at a molecular level.
The Book Entitled, An Introduction To Drug Design Aims To Optimize The Discovery Of Drugs At A Low Cost And On Occasions To Change Their Pharmacokinetic And Pharmacodyanamic Properties. The Introductory Chapter Which Forms The Basis Of Drug Discovery Is Followed By The Present-Day Thinking Regarding The Best Approaches To Drug Discovery Are Considered. Similarly, There Have Been Major Advances In The Employment Of Computers In Structure-Activity Analysis, And A Discussion Of The State Of The Art In This Area Is Also Included.The Chapter On Qsar Highlights The Role Of Physico-Chemical Parameters In Predicting The Future Course Of Drug Discovery With Rational Drug Design. The Role Of Enzymes In Drug Action Is Well Established, And A Chapter On Design Of Enzyme Inhibitors Is Well Documented. In Addition, The Increased Understanding Of The Design And Utilisation Of Prodrugs Has Led To A Discussion Of The Relevant Issues In This Text.Thus The Book Will Fill The Need Of A Text For Designing New Drugs And The Principles Of New Drug Discovery.
Over the recent years, medicinal chemistry has become responsible for explaining interactions of chemical molecules processes such that many scientists in the life sciences from agronomy to medicine are engaged in medicinal research. This book contains an overview focusing on the research area of enzyme inhibitors, molecular aspects of drug metabolism, organic synthesis, prodrug synthesis, in silico studies and chemical compounds used in relevant approaches. The book deals with basic issues and some of the recent developments in medicinal chemistry and drug design. Particular emphasis is devoted to both theoretical and experimental aspect of modern drug design. The primary target audience for the book includes students, researchers, biologists, chemists, chemical engineers and professionals who are interested in associated areas. The textbook is written by international scientists with expertise in chemistry, protein biochemistry, enzymology, molecular biology and genetics many of which are active in biochemical and biomedical research. We hope that the textbook will enhance the knowledge of scientists in the complexities of some medicinal approaches; it will stimulate both professionals and students to dedicate part of their future research in understanding relevant mechanisms and applications of medicinal chemistry and drug design.
This CD-ROM edition of Silverman's Organic Chemisry of Drug Design and Drug Action, Second Edition reflects the significant changes in the drug industry in recent years, using an accessible interactive approach. This CD-ROM integrates the author's own PowerPoint slides, indexed and linked to the book pages in PDF format. The three-part structure includes an all-electronic text with full-text search capabilites and nearly 800 powerpoint slides. This is a unique and powerful combination of electronic study guide and full book pages. Users can hyperlink seamlessly from the main text to key points and figures on the outline and back again. It serves as a wonderful supplement for instructors as well as a fully integrated text and study aid for students. * Three-part package includes 1) powerpoint, 2) integrated powerpoint and pdf-based text, and 3) fully searchable PDF-based text with index * Includes new full-color illustrations, structures, schemes, and figures as well as extensive chapter problems and exercises * User-friendly buttons transition from overview (study-guide) format to corresponding book page and back with the click of a mouse * Full-text search capabality an incomparable tool for researchers seeking specific references and/or unindexed phrases
Drug Design, Volume IX examines various aspects of drug design and covers topics ranging from the consequences of the Hansch paradigm for the pharmaceutical industry to the Masca model of pharmacochemistry. A physicochemical basis for the design of orally active prodrugs is also considered, along with the use of interactive graphics in medicinal chemistry. Comprised of seven chapters, this volume begins with a discussion on efforts to avoid toxicity, not only of drugs, pesticides, and food additives but also of chemicals in general. The reader is then introduced to various aspects of the development of bioactive agents, including the optimization of existing agents by the design of more efficient prodrugs. Other chapters focus on Hansch's paradigm and its application to industrial practice; the application of multivariate statistics to pharmacochemistry; a logico-structural approach to computer-assisted drug design; and spatial arrangements in bioactive molecules. This book will be of interest to pharmacologists, chemists, and those involved in drug design.
The Ups and Downs in Drug Design: Adventures in Medicinal Chemistry highlights the necessity for an integrative approach in medicinal chemistry and chemical biology. As medicinal chemistry is not a monolithic science, it is important to emphasize the other various disciplines that are required for successful drug design. This book presents the author’s own personal experience in this field and describes the "ups" and "downs" that come with drug discovery. It is an excellent companion text for graduate and postgraduate students who would like further insight into the parameters of drug design, including the challenges that come with the project. Key Features Illustrates "real-life" examples in medicinal chemistry Integrates the use of physical, chemical, and biological concepts that are important in drug design Highlights the "ups" and "downs" that come with drug discovery Aims to inspire students who may be struggling with the challenges and thought process in drug design Intends to be an excellent companion text for graduate and postgraduate students
