Expanding medicinal chemistry into 3D space: metallofragments as 3D scaffolds for fragment-based drug discovery.

ABSTRACT: Fragment-based drug discovery (FBDD) is a powerful strategy for the identification of new bioactive molecules. FBDD relies on fragment libraries, generally of modest size, but of high chemical diversity. Although good chemical diversity in FBDD libraries has been achieved in many respects, achieving shape diversity - particularly fragments with three-dimensional (3D) structures - has remained challenging. A recent analysis revealed that >75% of all conventional, organic fragments are predominantly 1D or 2D in shape. However, 3D fragments are desired because molecular shape is one of the most important factors in molecular recognition by a biomolecule. To address this challenge, the use of inert metal complexes, so-called 'metallofragments' (mFs), to construct a 3D fragment library is intro

SUBMITTER: Morrison CN 

PROVIDER: S-EPMC8148059 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature