Lead-like space

The synthetically easiest way to access test compounds is to sample already available screening compounds, of which there are more than 10 million on the market. An approach on how to select commercially available materials has been described [54]. For example, a subset of less than 350 000 compoimds covering the same lead-like space as commercial compoimds from 10 major vendors has been generated [55]. 

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. 

Property filters are a particular implementation of partitioning methods they are used to select drug-like or lead-like compounds from large chemical libraries. Like the cell-based methods, these filters are based on a partition of the chemical space but each selected molecular descriptor is divided into only two or three subranges of values. While property filters mainly aim at optimizing drug-likeness, cell-based methods at optimizing diversity of chemical libraries. 

Baell, J.B. (2013) Broad coverage of commercially available lead-like screening space with fewer than 350,000 compounds./oMrwa/ of Chemical Information and Modeling, 53,... 

We hope that by now the reader has it finnly in mind that the way molecular symmetry is defined and used is based on energy invariance and not on considerations of the geometry of molecular equilibrium structures. Synnnetry defined in this way leads to the idea of consenntion. For example, the total angular momentum of an isolated molecule m field-free space is a conserved quantity (like the total energy) since there are no tenns in the Hamiltonian that can mix states having different values of F. This point is discussed fiirther in section Al.4.3.1 and section Al.4.3.2. 

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