Wilson and Gisvold's Textbook of Organic Medicinal and Pharmaceutical Chemistry 

        Wilson and Gisvold's Textbook of Organic Medicinal and Pharmaceutical Chemistry

For 6 decades, Wilson and Gisvold’s Textbook of Organic Medicinal and Pharmaceutical Chemistry has been a standard in the literature of medicinal chemistry. Generations of students and faculty have de-pended on this textbook not only for undergraduate courses in medicinal chemistry but also as a supplement for graduate studies. Moreover, students in other health sciences have found certain chapters useful. The current editors and authors worked on the 12th edition with the objective of continuing the tradition of a modern textbook for undergraduate students and also for graduate students who need a general review of medicinal chemistry. Because the chapters include a blend of chemical and pharmacological principles necessary for understanding structure–activity relationships and molecular mechanisms of drug action, the book should be useful in supporting courses in medicinal chemistry and in complementing pharmacology courses.

For 6 decades, Wilson and Gisvold’s Textbook of Organic Medicinal and Pharmaceutical Chemistry has been a standard in the literature of medicinal chemistry. Generations of students and faculty have de-pended on this textbook not only for undergraduate courses in medicinal chemistry but also as a supplement for graduate studies. Moreover, students in other health sciences have found certain chapters useful. The current editors and authors worked on the 12th edition with the objective of continuing the tradition of a modern textbook for undergraduate students and also for graduate students who need a general review of medicinal chemistry. Because the chapters include a blend of chemical and pharmacological principles necessary for understanding structure–activity relationships and molecular mechanisms of drug action, the book should be useful in supporting courses in medicinal chemistry and in complementing pharmacology courses.


The 12th edition follows in the footsteps of the 11th edition by reflecting the dynamic changes occurring in medicinal chemistry. With increased knowledge of the disease process and the identification of the key steps in the biochemical process, the chapters have been updated, expanded, and reorganized. At the same time, to streamline the presentation of the content, some topics were combined into existing chapters. For example, Chapter 2, “Drug Design Strategies,” incorporates material from 11th edition Chapters 2, 3, and 28, and Chapter 3, “Metabolic Changes of Drugs and Related Organic Compounds,” includes the content from 11th edition Chapter 5, “Prodrugs and Drug Latentiation.” In addition, with the newer drugs that have entered the pharmaceutical armamentarium since the publication of the 11th edition, coverage of the following topics has been expanded in the 12th edition: Central Dopaminergic Signaling Agents (Chapter 13), Anticonvulsants (Chapter 14), Hormone-Related Disorders: Nonsteroidal Therapies (Chapter 20), Agents Treating Bone Disorders (Chapter 21), and Anesthetics (Chapter 22).

New features of the 12th edition include a chapter overview at the beginning of each chapter to introduce material to be covered in the chapter and review questions at the end of each chapter to reinforce concepts learned in the chapter (answers to these questions are available to students on the book’s companion Web site; see next section).

Wilson and Gisvold’s Textbook of Organic Medicinal and Pharmaceutical Chemistry, 12th Edition, includes additional resources for both instructors and students that are available on the book’s companion.

Students

Students who have purchased Wilson and Gisvold’s Textbook of Organic Medicinal and Pharmaceutical Chemistry, 12th Edition, have access to the following additional resources:

The answers to the review questions found in the book

In addition, purchasers of the text can access the searchable Full Text Online by going to the Wilson

and Gisvold’s Textbook of Organic Medicinal and Pharmaceutical Chemistry, 12th Edition, Web site at http://www.thePoint.lww.com/Beale12e. See the inside front cover of this text for more details, including the passcode you will need to gain access to the Web site.

JOHN M. BEALE, JR. AND JOHN H. BLOCK

The discipline of medicinal chemistry is devoted to the discovery and development of new agents for treating diseases. Most of this activity is directed to new natural or synthetic organic compounds. Paralleling the development of medicinal agents has come a better understanding of the chemistry of the receptor. The latter has been greatly facilitated by low-cost computers running software that calculates molecular properties and structure and pictures it using high-resolution graphics. The development of organic compounds has grown beyond traditional synthetic methods. It now includes the exciting field of biotechnology using the cell’s biochemistry to synthesize new compounds. Techniques ranging from recombinant DNA and site-directed mutagenesis to fusion of cell lines have greatly broadened the possibilities for new entities that treat disease. The pharmacist now dispenses modified human insulins that provide more convenient dosing schedules, cell-stimulating factors that have changed the dosing regimens for chemotherapy, humanized monoclonal antibodies that target specific tissues, and fused receptors that intercept immune cell–generated cytokines.

This 12th edition of Wilson and Gisvold’s Textbook of Organic Medicinal and Pharmaceutical Chemistry continues the philosophy of presenting the scientific basis of medicinal chemistry originally established by Professors Charles Wilson and Ole Gisvold, describing the many aspects of organic medicinals: how they are discovered, how they act, and how they developed into clinical agents. The process of establishing a new pharmaceutical is exceedingly complex and involves the talents of people from various disciplines, including chemistry, biochemistry, molecular biology, physiology, pharmacology, pharmaceutics, and medicine. Medicinal chemistry, itself, is concerned mainly with the organic, analytical, and biochemical aspects of this process, but the chemist must interact productively with those in other disciplines. Thus, medicinal chemistry occupies a strategic position at the interface of chemistry and biology. All of the principles discussed in this book are based on fundamental organic chemistry, physical chemistry, and biochemistry. To provide an understanding of the principles of medicinal chemistry, it is necessary to consider the physicochemical properties used to develop new pharmacologically active compounds and their mechanisms of action, the drug’s metabolism, including possible biological activities of the metabolites, the importance of stereochemistry in drug design, and the methods used to determine what “space” a drug occupies.

The earliest drug discoveries were made by random sampling of higher plants. Some of this sampling, although based on anecdotal evidence, led to the use of such crude plant drugs as opium, belladonna, and ephedrine that have been important for centuries. With the accidental discovery of penicillin came the screening of microorganisms and a large number of antibiotics from bacterial and fungal sources. Many of these antibiotics provided the prototypical structure that the medicinal chemist modified to obtain antibacterial drugs with better therapeutic profiles. With the changes in federal legislation reducing the efficacy re-quirement for “nutriceutical,” the public increasingly is using so-called nontraditional or alternative medicinals that are sold over the counter, many outside of traditional pharmacy distribution channels. It is important for the pharmacist and the public to understand the rigor that is required for prescription-only and Food and Drug Administration (FDA)-approved nonprescription products to be approved relative to the nontraditional products. It is also important for all people in the healthcare field and the public to realize that whether these nontraditional products are effective as claimed or not, many of the alternate medi-cines contain pharmacologically active agents that can potentiate or interfere with physician-prescribed therapy.

Hundreds of thousands of new organic chemicals are pre-pared annually throughout the world, and many of them are entered into pharmacological screens to determine whether they have useful biological activity. This process of random screening has been considered inefficient, but it has resulted in the identification of new lead compounds whose structures have been optimized to produce clinical agents. Sometimes, a lead develops by careful observation of the pharmacological behavior of an existing drug. The discovery that amantadine protects and treats early influenza A came from a general screen for antiviral agents. The use of amantadine in long-term care facilities showed that it also could be used to treat parkinsonian disorders. More recently, automated high-throughput screening systems utilizing cell culture systems with linked enzyme assays and receptor molecules derived from gene cloning have greatly increased the efficiency of random screening. It is now practical to screen enormous libraries of peptides and nucleic acids ob-tained from combinatorial chemistry procedures.

Rational design, the opposite approach to high-volume screening, is also flourishing. Statistical methods based on the correlation of physicochemical properties with biological potency are used to explain and optimize biological activity. Significant advances in x-ray crystallography and nuclear magnetic resonance have made it possible to obtain detailed representations of enzymes and other drug receptors. The techniques of molecular graphics and computationalchemistry have provided novel chemical structures that have led to new drugs with potent medicinal activities. The development of human immunodeficiency virus (HIV) protease inhibitors and angiotensin-converting enzyme (ACE) inhibitors came from an understanding of the geometry and chemical character of the respective enzyme’s active site. Even if the receptor structure is not known in detail, rational approaches based on the physicochemical properties of lead compounds can provide new drugs. For example, the devel-opment of cimetidine involved a careful study of the changesin antagonism of H2-histamine receptors induced by varying the physical properties of structures based on histamine.

As you proceed through the chapters, think of what problem the medicinal chemist is trying to solve. Why were certain structures selected? What modifications were made to produce more focused activity or reduce adverse reactions or produce better pharmaceutical properties? Was the prototypi-cal molecule discovered from random screens, or did the me-dicinal chemist have a structural concept of the receptor or an understanding of the disease process that must be interrupted?


 

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