Lead discovery serendipity

The lead discovery process is depicted in Figure 10.4-4 and shows how the different methods are interconnected. A lead structure can be discovered by serendipity. In rational drug design all information available about a target serves to direct... 

Millions of people with type I (insulin-dependent) diabetes mellitus inject themselves daily with pure insulin to compensate for the lack of production of this critical hormone by their own pancreatic fi cells. Insulin injection is not a cure for diabetes, but it allows people who otherwise would have died young to lead long and productive lives. The discovery of insulin, which began with an accidental observation, illustrates the combination of serendipity and careful experimentation that led to the discovery of many of the hormones. 

Serendipity, n. the faculty for making desirable discoveries by accident (Webster s Encyclopedic Unabridged Dictionary of English Language, 1989). Probably the history of studies leading to the discovery of 59 and 60 can serve as an especially good example of the paramount role of serendipity in science. 

Continuing with the muguet theme, I then use examples to explain how a chemist might go about his search for novel materials. The more traditional approaches, such as the analysis of natural products, serendipity and lead optimisation, are illustrated with only one or two examples, since these techniques have been discussed in more detail in Chapters 3 and 12. Instead, I have focused on techniques that have the potential to lead to the discovery of new active compounds by design rather than chance. Over the past 20 years, such approaches have been made easier by the rapid advances in theoretical and computational chemistry and by the introduction of more powerful computers. 

These considerations illustrate why an absolute cure for cancer is so elusive, for there are so many partially offsetting factors that are not fully understood. This is why a cure may probably have to precede understanding, and be a happenstance, an exercise in serendipity, like the discovery of antibiotics. (If we had waited until we completely understood the action of antibiotics, we would still be waiting, for a subject is never closed. Each answer leads to another question.) And this is why the aborigines of Amazonia, say, are just as likely as modem medicine to have a cure, if not more likely. 

Lilly Company, Indianapolis, in the United States [3]. The chain of events leading to the discovery of vinblastine by the group of Noble is particularly interesting and represents a paradigmatic example of the role serendipity often plays in scientific discoveries. A full description of the discovery, including the casual details that started the whole process, was published by Robert Noble in 1990 [4]. 

Plunkett s desire to know more about something that just didn t seem right is a wonderful example of how natural scientific curiosity can lead to remarkable discoveries. If you wish to read about more such accidental discoveries, we recommend Royston M. Roberts, Serendipity Accidental Discoveries in Science, John Wiley and Sons, 1989. 

Natural product synthesis, can lead to the discovery of new reactions by chance, by open-eyed serendipity, or by design. Our total synthesis of ionomycin (Scheme 6) [45] led us in fact to consider a design-based approach for the construction of deoxypropionate, and propionate subunits which are the natural building blocks for a large number of macrolide and ionophore-type antibiotics [46]. 

It is a fact that "serendipity" still dominates the discovery of an entirely new class of pesticides, especially one with novel mode of action. The reason is simply because our ability to design compounds to affect enzymes, receptors, or other biochemical targets is still very limited. Modem molecular modeling techniques and the computer-aided study of quantitative structure activity relationship are mainly for the optimization of an original lead (A). 

Though the discovery of switchable mirrors effect is an example of serendipity, the careful detailed analysis of the remarkable observations by the discoverers has triggered renewed research interest in rare earth metal hydride films both for understanding the basic physics underlying the phenomenon and the quest for potential technological applications. The extensive research in switchable mirrors based on R metals has lead to the following generations of switchable mirrors ... 

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