Introductory Chapter: The Modern-Day Drug Discovery (original) (raw)
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Who of us would not be glad to lift the veil behind which the future lies hidden; to cast a glance at the next advances of our science and at the secrets of its development during future centuries? —David Hilbert in 1900, as quoted recently by R. Breslow [1] Paul W. Erhardt received his Ph.D. degree in medicinal chemistry from the University of Minnesota in 1974, and spent many years in the pharmaceutical industry before assuming his present position as professor in the College of Pharmacy, University of Toledo, and Director of the Center for Drug Design and Development. He is currently Vice President of IUPAC’s Chemistry and Human Health Division, and has played an active role in chairing and coordinating numerous Divisional projects. His background and experience in both the industrial and academic sectors and his familiarity with the intricate interdisciplinary fabric of medicinal chemistry qualify him admirably to offer this authoritative overview, in which the recent history an...
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This chapter is not meant to provide a systematic discussion of drug developments, but merely gives a few interesting stories of how drugs were discovered and have been developed. A lot of complicated chemical formulas/structures are presented in this chapter, but you should not be worried about whether you understand them. It turns out that the drug function often depends not on the detailed structure but on the overall shape of the compound. Hence, you can look at it as a sort of picture with some shape, and that is sufficient to understand why drugs work and how it might be modified. 7.1 Penicillin and Similar Antibiotics: Human Battle with Bacteria A Scottish physician, Alexander Fleming, was engaged in research at St. Mary's hospital in London. He was working with cultures of a disease-causing bacterium, Staphylococcus. Some culture plates (in Petri dish) were set aside and checked from time to time. One day in 1928, he noticed that one culture was contaminated by a blue-green mold and that the bacterial colonies had become transparent around the mold. It suggested to him that the bacteria there had died and dissolved away. His investigation led to a discovery that the broth in which this mold (Penicillium notatum) had grown indeed had an inhibitory effect on many pathogenic bacteria. Fleming named this antibacterial agent contained in the mold as "Penicillin." He could not isolate and identify the compound, but Howard Florey and Ernst Chain of Oxford University did purify in 1941 a product from the mold and called it "Penicillin G." Penicillin G had become widely available by the end of the World War II and saved many lives threatened by pneumonia, gonorrhea, and other infectious diseases. These scientists were awarded a Nobel Prize together in 1945. This was the first of the so-called antibiotics. Discovery of other antibiotics followed; some of the better known antibiotics that were obtained from microorganisms include streptomycin (from Streptomyces griseus), aureomycin (from S. aureofaciens), and cephalosporin C. These are different types of chemical compounds from penicillin. We would not pursue the details of these other antibiotics here.
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