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Categories: Medicinal Chemistry

Analogue-based Drug Discovery

J. Fischer, C. R. Ganellin

Hardcover, 575 Pages
1st Edition, 2006
ISBN: 3-527-31257-9


The first authoritative overview of past and current strategies for successful drug development by analog generation, this unique resource spans all important drug classes and all major therapeutic fields, including histamine antagonists, ACE inhibitors, beta blockers, opioids, quinolone antibiotics, steroids and anticancer platinum compounds.

Of the 19 analog classes presented in detail, 9 are described by the scientists who discoverd them.
The book includes a table of the most successful drug analogs as based on the IMS ranking and compares them in terms of chemical structure, mode of action and patentability.

Editorial Review

Most newly registered drugs are based on the optimization of existing drugs (natural products, competitive products or in-house lead compounds) with the goal of obtaining an active drug or to diminish side effects. The optimization of known drugs toward certain side effects in itself can open up completely new areas of application.

The editors of the book "Analogue-based Drug Discovery" provide an exact definition of the term analog, and also offer general advice on the available options, but then turn the stage over to experts in the field from industry and research, who illustrate the drug development process in more detail with selected examples in the section "Selected Examples from the Analogue-based Drug Discoveries". With some variability between authors, the chapters are interesting from a historical perspective, pointing out the options for structural optimization, and explaining some of the fascinating medical background. The line-up of drugs includes antibiotics, angiotensin receptor blockers, proton pump inhibitors, calcium antagonists, and many more.

The book is aimed at the advanced reader who already has some fundamental knowledge of medicinal chemistry and is interested in the process of drug development. The reader will encounter chapters that illustrate in detail the important classes of substances that are particularly interesting from the historical, structural and medical perspectives. Some chapters are especially intriguing to read, such as those on the proton pump inhibitors or the quinolone antibiotics, in which the reader learns about the challenges faced by the pharmaceutical industry when developing a marketable drug. Unfortunately, some of the chapters are limited to a brief comparison of drugs within a class, so that the quality of the contributions is quite uneven.

Chapters with an average level of coverage, such as those on the "Development of Opioid Receptor Ligands" or "Development of Organic Nitrates for Coronary Heart Diseases", are still interesting to read; despite their brevity, they contain worthwhile medicinal data and describe a broad array of analogs together with how their properties differ from those of the initial compound.

The reader of this book becomes privy to an enlightened glimpse into the development of interesting drug classes, which makes it very interesting both for advanced students with some fundamental knowledge of medicinal chemistry as well as for professionals working in research and development. Anyone with a penchant for the background and history of important drugs will find this book an enjoyable read.


List of Contributors.
1. Analogues as a Means of Discovering New Drugs.
2. Drug Likeness and Analogue-Based Drug Discovery.
3. Privileged Structures and Analog-Based Drug Discovery.
1. Development of Anti-Ulcer H2-Receptor Histamine Antagonists.
2. Esomeprazole in the Framework of Proton-Pump Inhibitor Development.
3. The Development of a New Proton-Pump Inhibitor: The Case History of Pantoprazole.
4. Optimizing the Clinical Pharmacologic Properties of the HMG-CoA Reductase Inhibitors.
5. Optimizing Antihypertensive Therapy by Angiotensin Receptor Blockers.
6. Optimizing Antihypertensive Therapy by Angiotensin-Converting Enzyme Inhibitors.
7. Case Study of Lacidipine in the Research of New Calcium Antagonists.
8. Selective Beta-Adrenergic Receptor-Blocking Agents.
9. Case Study: "Esmolol Stat".
10. Development of Organic Nitrates for Coronary Heart Disease.
11. Development of Opioid Receptor Ligands.
12. Stigmines.
13. Structural Analogues of Clozapine.
14. Quinolone Antibiotics: The Development of Moxifloxacin.
15. The Development of Bisphosphonates as Drugs.
16. Cisplatin and its Analogs for Cancer Chemotherapy.
17. The History of Drospirenone.
18. Histamine h1 Blockers: From Relative Failures to Blockbusters Within Series of Analogues.
19. Corticosteroids: From Natural Products to Useful Analogues.