The 3F Library: Fluorinated Fsp³‐Rich Fragments for Expeditious ¹⁹F NMR Based Screening

Abstract

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Hydrogen Bond Acceptor Propensity of Different Fluorine Atom Types: An Analysis of Experimentally and Computationally Derived Parameters

“…Although less abundant, alkyl fluorinated motifs are now receiving increasing consideration. For example, they are now included in fluorinated fragment libraries for 19 F NMR screening [43,55–57] . These molecules have a higher degree of three‐dimensionality, often improved solubility in water [4,18,40] and the alkyl fluorine atom can participate in polar intramolecular and intermolecular interactions which have important implications for the chemical‐physical and structural properties of the molecules, [58–73] chemical reactions [13,38,74–79] and protein–ligand recognition [39,80] .…”

Applications of Solution NMR in Drug Discovery

“…Multiple types of fragment libraries, which include natural product fragment library, protein-protein interaction library, fluorinated library, brominated fragment library, etc. were setup [41,59,60]. Although there are no strict constraints for the chemical structures of fragments incorporated into the library, some pan-assay interference compounds (PAINs), such as nonspecific binders, reactive covalent modifiers, chelators, and aggregators, should be avoided [61].…”

Library Design Strategies To Accelerate Fragment‐Based Drug Discovery

“…Recently, Clausen and co‐workers published the synthesis and 19 F NMR spectroscopic screening of their fluorinated Fsp 3 ‐rich fragment (3F) library; this was the first example of a synthetic library fully designed for this purpose (Figure ) . With a high degree of three‐dimensionality, the 3F library was designed to address the need to improve the limited shape diversity of many fragment collections, while enabling efficient screening by 19 F NMR spectroscopy.…”