Generation of New Screening Compounds

The ability to run high throughput or other t)q)es of screens depends on an available compound collection of suitable size. Even though the major pharmaceutical companies have extensive collections, usually containing about 10 compounds, many of them continue to expand their compound banks. 

It has been estimated that the possible number of distinct organic structures with up to 30 atoms selected from C, N, O, and S k aroimd 10 which by far exceeds the number of atoms on earth (lO ) [15]. 

There is ako a common imsconception that novel compoimds or concepts will lead to dramatically different structural features. It k unlikely that the drugs of the future will be built from radically other structural classes than today s drugs. There may be heterocycles never seen before or a few new functional groups, for example, the sulfonimidamides [18], but the majority of the compounds will still be built from the functional features known already today, yet they may still occupy white areas on the map of chemical space. 

When adding new compounds to an exkting collection (or when building a compound collection from scratch), one has to consider the following three different aspects  

1) Target focus-. Answering the question does a structure have a chance to engage the targets of interest  

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Generation of New Screening Compounds l09 Diversity-oriented synthesis... 

In the 1980s, our group began to screen microbes for insecticidal compounds that could be used in practice, or become lead compounds for the generation of new carbon skeletons. As a result, various strains were found to exhibit insecticidal, convulsive and paralytic activities against silkworms. This chapter deals with the procedures used for isolation of bioactive strains and their active principles. An overview of their chemical structures, activities, synthesis, and structurally related compounds is also given. 

Five standard approaches to the generation of new areas for agrochemical (and pharmaceutical) research are commonly cited random screening speculative nthesis imitative ("me-too") chemistry biorational design and finally the exploitation of natural products (7). Although this last approach has found much commercial success in the development of novel insecticides (for example the pyrethroids), there are still relatively few examples of herbicides and fungicides which have been discovered in this way. This account describes the development of a new class of fungicides derived from the strobilurin family of natural products and related compounds, all of which are derivatives of P-methoxyacrylic acid. 

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