Today's top selling drugs have been uncovered from two major sources: natural products and laboratory synthesis. Those synthesised directly by medicinal chemists usually have been the result of a protracted discovery programme using a natural product (e.g. a hormone or an enzyme substrate) or a screening lead as a starting point. Many of the major categories of human disease cardiovascular, gastrointestinal, central nervous system, inflammatory and infectious diseases are included. After a short introduction to the discovery and mechanism of action of each drug, the syntheses of the best selling drugs are reviewed. Where the information exists in the literature, the original research method to each drug is compared with more recent approaches which aim either at improving the route or at validating newer methodologies or reagents in the context of drug synthesis. Since, for many drugs, the marketed product was originally prepared as a racemic mixture, perhaps the most important comparison is between that route and alternatives which involve some element of asymmetric synthesis.
Dr John Saunders, Neurocrine Biosciences, 10555 Science Center Drive, San Diego, CA 92121, USA.
1. Inhibitors of angiotensin converting enzyme as effective antihypertensive agents ; 2. Blockade of angiotensin-II receptors ; 3. Calcium channel blockers in the treatment of angina and hypertension ; 4. Antagonists of histamine receptors (H2) as anti-ulcer remedies ; 5. Proton pump inhibitors as gastric acid secretion inhibitors ; 6. Modulation of central serotonin in the treatment of depression ; 7. Hypnotic, anxiolytic, anticonvulsant and muscle relaxant agents: ligands for benzodiazepine receptors ; 8. Another histamine receptor: blockers of the H1 receptor for the treatment of seasonal allergic rhinitis ; 9. Nucleoside analogues which inhibit HIV reverse transcriptase ; 10. Quinolones as anti-bacterial DNA gyrase inhibitors