Future Frontiers in Diversity-Oriented Synthesis

摘要

The late 1980’s to mid-1990’s ushered exciting developmentsin pharmaceutical research worldwide. With innovative tools andtechniques provided by combinatorial chemistry and molecularbiology, a tremendous amount of effort and money was invested intothe application of highly efficient high-throughput screening (HTS)technologies that could screen thousands of compounds at a time[1,2]. However, medicinal chemists were confronted with the painfulrealization that the chemical space was too vast to be fully explored.The understanding emerged that library size was not paramount, andthat the diversity of molecules in the library is a critical determinant forthe success of any screening campaign [3]. Early combinatorial librariessacrificed diversity in order to accommodate facile reaction andpurification methodologies, resulting in the production of collectionsof compounds that lacked structural complexity