Lead discovery molecular space

The selection and quality of a screening library with drug-like and lead-like structures is a critical endeavour. The features of drug-like and lead-like structures continue to be better defined, at the same time as the diversity of drug-like and lead-like molecular space continues to be explored and categorised. Other areas of development focus on the discovery of small molecules suitable for modulating protein-protein interactions, with a greater focus on natural product-like compounds. 

MLI aims to bridge, at least in part, the innovation deficit [2] faced by the private sector that is leading to increased pressure to deliver new chemical entities (NCEs) and best-in-dass dmgs on the market. Dmg discovery scientists have been forced to develop computational tools that facilitate the identification of novel molecular scaffolds (diemotypes) moving across (local) chemical spaces. In the area of in silico drug discovery, the public sector is about to face the same challenges as the private sector. 

The potential of molecular structures to populate structural chemical space is diverse and the challenge is to make new discoveries that add to the accumulated knowledge base. An important milestone was achieved during the assembly of this volume and it involves the registration, in 2008 by Chemical Abstracts Service (CAS), of the 40 millionth chemical substance. However, a rather surprising outcome was deduced by a CAS team lead by Lipkus his team analyzed these frameworks and concluded that half of the compounds can be described by only 143 framework shapes . The rigorous study of natural products provides an optimal way to expand such understanding and such a prospect is amply illustrated by the 19 chapters in this volume. 

Importantly, it has subsequently been shown that the Weiner index for a molecular graph may have strong correlations with chemical properties [49-51]. Consequently, it is often the objective of synthetic efforts, particularly in drug discovery optimization, to construct compounds with certain properties by synthesizing lead compounds with a particular Weiner index. This strategy is an important example of how computed properties (that correlate predictively with desired properties) can be used to create new compounds that have certain values that is, they occupy certain regions of a chemical descriptor space [44],... 

---