Fragment-based drug discovery (FBDD) became an important strategy complementary to conventional high-throughput screening (HTS) campaigns in both academia and industry. The basic idea behind FBDD approaches is to initially identify, usually by screening small focused libraries of low molecular weight compounds (fragments) via biophysical methods, key chemical substructures or pharmacophores sufficient to confer a minimal yet specific interaction with the given target identified by structural studies using X-ray crystallography or nuclear magnetic resonance (NMR) spectroscopy. As a follow up, identified fragment hits could be converted into more potent binders by a variety of approaches using structural information of identified hits. Chemspace reports variety of fluorine-containing molecules which satisfy criteria of fragments (122&lt;MW&lt;300; HbA≤3; HbD≤2; logP≤4; RotBonds≤3) and examples of follow up development into focused libraries of specific binders. There are distinct sub-groups of molecules to identify specific interaction: aromatic compounds with small substituents in the pattern compounds with enriched Fsp3 increased chirality dimensionality improved physico-chemical properties improved diversity in follow up Approaches to expand chemical space from Chemspace commercially available or de-novo synthesis of new fragments and compounds from virtual 100M Chemspace chemical space is discussed. Fluorine atom serves as a marker for the identification of initial binders by NMR and may or may not be present in the final molecules as a structural feature.

Advantages of fluorinated fragment library in the discovery of novel specific binders and hit to lead optimization

2019 Fall National Meeting

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.