The development and implementation of a novel bioisosteric software program for the development of new pharmaceuticals

This thesis is focused on the development of some important informatics methods that will assist drug discovery scientists in their pursuit of novel molecular structures, and it is representative of a novel information-based approach to drug design. This work utilized in silico based strategies, and did not involve standard computational chemistry energy-based calculations (e.g., molecular mechanics, quantum mechanics, or molecular dynamics simulations). The cheminformatics approach described herein uses empirically derived "rules", based on historically successful lead generation transformations where an original molecular structure served as the basis for a new one with enhanced biological activity. In some cases these substitutions, replacements, and/or new scaffold ring systems transformations may have been overlooked by pharmaceutical scientists involved in the systematic trial-and-error approaches commonly found in drug discovery. The novel "rule"-based transformations described serve as a basis for drug discovery and should serve as a resource for scientists wanting to explore chemical space based on previous examples of molecular modifications