Enabling synthesis in fragment-based drug discovery by reactivity mapping: photoredox-mediated cross-dehydrogenative heteroarylation of cyclic amines.

ABSTRACT: In fragment-based drug discovery (FBDD), a weakly binding fragment hit is elaborated into a potent ligand by bespoke functionalization along specific directions (growth vectors) from the fragment core in order to complement the 3D structure of the target protein. This structure-based design approach can present significant synthetic challenges, as growth vectors often originate on sp² or sp³ ring carbons which are not the most synthetically accessible points on the fragment. To address this issue and expedite synthesis in FBDD, we established a nanogram-to-gram workflow for the development of enabling synthetic transformations, such as the direct C-H functionalization of heterocycles. This novel approach deploys high-throughput experimentation (HTE) in 1536-well micro

SUBMITTER: Grainger R 

PROVIDER: S-EPMC6385880 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature