Covalent fragment libraries in drug discovery-Design, synthesis, and screening methods

Abstract

As the development of drugs with a covalent mode of action is becoming increasingly popular, well-validated covalent fragment-based drug discovery (FBDD) methods have been comparatively slow to keep up with the demand. In this chapter the principles of covalent fragment reactivity, library design, synthesis, and screening methods are explored in depth, focussing on literature examples with direct applications to practical covalent fragment library design and screening. Further, questions about the future of the field are explored and potential useful advances are proposed.

Keywords: Covalent drugs; Covalent warheads; Fragments; Libraries; Screening assays.