These compounds are non-flat, bicyclic heterocycles that are likely to find utility as privileged motifs for lead-like compound design.
Out of those, 95469 and 222552 compounds, respectively fulfilled the criteria for lead-like properties (Table 1) and were included in the VS set.
Rules for unwanted groups were defined and selection criteria to enrich for lead-like compounds which facilitate straightforward structure activity relationship exploration were established.
There might be more scope for molecular weight distribution in libraries destined for chemical probe discovery, but beyond that, the property restrictions for lead-like drug discovery requirements also apply to chemical biology scenarios [22].
13, 33 By restricting compound size and complexity to those of lead-like compounds, smaller libraries which still provide a reasonable coverage of chemical space can be assembled, as the magnitude of chemical space is exponentially smaller for lead-like than for drug-like compounds.
An important challenge for drug development is the generation of novel heterocyclic building blocks with suitable properties for use in screening and medicinal chemistry programs.[ 34] The cantharimides accessed using this methodology have appropriate physicochemical properties for lead-like compounds, including lipophilicity,[ 35] molecular weight and polar surface area[ 36].
As for Led Like a Lamb to the Slaughter, the consensus was: forget it.
28, 29 In the next step we filtered for compounds with lead-like properties and limited complexity (Table 1).
Topomer search is used as a tool for virtual screening in lead-like compounds of ZINC databases (2012); as a result, we successfully design 30 new molecules with higher activity than that of all training and test inhibitors.
The NMR fingerprinting method was modelled to take advantage of the LLE library generation conditions,[ 3] where 300 mg of freeze-dried biota was extracted in organic solvents, selected for lead and drug-like characteristics on a solid phase extraction (SPE) cartridge, and then fractionated in 50 mg dry-weight equivalent aliquots on a reverse-phase HPLC column.
Both hit series were low molecular weight compounds with lead-like properties suitable for a medicinal chemistry optimisation programme.
