ABSTRACT
When a molecule has been identified as possessing interesting pharmacological activities, the search for structural analogues of the parent compound that might demonstrate a different and preferably better set of characteristics usually begins. These features could, for example, be lower acute toxicity, higher stability, more potency, easier synthesis, changes to more optimal physical properties, or improved bioavailability; it all comes down to what is judged to be most important when aiming for a specific application or use. This stimulating and highly competitive search for new
members of a structural class is by no means novel. Instead this hunt for identifying successively better and better compounds has been practiced for decades with the ultimate goal to find what in today’s language is called the “best-in-class” molecule. Noticeable compound families in which such an iterative process has been successfully demonstrated, are, in roughly chronological order,
β
-lactam antibiotics (penicillins and cephalosporins), tricyclic antidepressants, [1,4]-benzodiazepines for use as anxiolytics and sedatives, benzimidazole-sulfoxide proton pump inhibitors to treat gastrointestinal disorders, and, most recently, statins for treatment of high blood cholesterol.
