M. Gastreich

Today, it is agreed that one major challenge in FBLD has emerged to be the synthetic accessibility of the products. However, another less publicly discussed, yet silently accepted boundary condition is pharma's need to protect intellectual property (IP). For several years now we have pursued tile-and-merge approaches. In this context we are left with two sub-problems: a) the search space generation (i.e., what are our fragments, their origin, and their connection rules) and b) how to search that space efficiently. In the framework of the above-mentioned, overall boundary conditions (synthetic accessibility and IP protection) we will discuss approaches to a) and b) which - prospectively - have led to remarkable success in big pharma. A recent one exploits the synergy between a ligand based search technique (FTrees) and a shape based filtering approach (ROCS). Along the way, technical obstacles plus how most of those could be circumvented will be shown.