This guide to drug synthesis and discovery focuses on case histories. Organized by drug category, the guide introduces readers to the rich interplay of research and serendipity that is responsible for many commonly prescribed drugs today. Fortunately, for anyone with little or no organic chemistry you don't need to understand the chemical structures to understand Lednicer's book. Moreover, the author demonstrates how the discovery and development of a new drug or drug category creates a domino effect, leading to the development of newer therapeutics as pharmaceutical companies compete to satisfy market demands.
The development of the antibiotic drugs is covered from the discovery of Prontosil to the introduction in 2000 of linelozid. Antiviral drugs were first identified by random screening. The process of finding effective drugs to combat viral disease turned increasingly to exploiting the mechanism by which viruses infect cells. The book traces the development of agents to treat high blood pressure from the discovery from the early alpha blockers, through the beta blockers, ACE inhibitors and some of the newer agents. An unanticipated effect from a drug designed to lower pressure by inhibiting yet another mechanism led to the wildly successful class of drugs that reversed erectile dysfunction, among them Viagra.
Elevated levels of blood lipids are the other major risk factor in cardiovascular disease. The first drugs for treating this disease comprised relatively simple molecules based on leads found by random screening. The discovery of the statins, drugs that inhibit a key enzyme in this process, mevalonate, marked a major advance in treating hyperlipidemia.
The addicting properties of morphine led to many attempts to prepare less habituating congeners by modifying the molecule. Another line of research led to the finding of a simple two-ring compound, meperidine that had essentially the same activity. Further research along those lines resulted in a series of very potent drugs, the fentanyls. Several opiates that combined both agonist and antagonist activity offered drugs with somewhat reduced addiction liability.
NSAIDs comprise on of the most widely consumed classes of drugs. This volume traces the evolution of this class of drugs from its inception as aspirin and simple derivatives of aminophenol such as acetaminophen. Many of the drug leads were discovered by random screening. The elucidation of the role of prostaglandins in pain and inflammation in the early 1970s helped steer research on new drugs. The COX-2 inhibitor NSAIDs owe their existence to a detailed account of the arachidonic acid cascade.
The steroid skeleton provides the base for several classes of important hormones. The narrative describes research on steroids that led to the development of the oral contraceptives. Research on androgens resulted in the semisynthetic anabolic agents favored by athletes. The corticoids have provided a series of very potent anti-inflammatory and anti-allergic drugs.
Antihistamines date back to the 1940s. Continuing work on histamine and molecules that are related to those drugs has led to the discovery of the first antipsychotic agents, tricylcic antidepressants, and even drugs to treat ulcers.
This book is aimed at the informed lay person, so you don't have to be a chemist to enjoy it, but a scientific background will help you get the most out from it. The use of technical terms and concepts is of course almost unavoidable in a book of this nature. Lednicer, however, has made a deliberate attempt to keep these to a minimum. The book is lavishly illustrated with the chemical structures of drugs under discussion, which as I said earlier you don't need to understand to follow the narrative.
You can read an excerpt from Lednicer's book on the publisher's site.
New Drug Discovery and Development
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