ReviewJournal of medicinal chemistry2026
Medicinal Chemistry Perspectives on PFAS in Drug Design: Fluorinated Motifs, Innovation, and Patient Impact.
Review in Journal of medicinal chemistry, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Authors and funding
8 authors.
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Abstract
Concerns about long-chain per- and polyfluoroalkyl substances (PFAS), e.g. PFOS, PFOA, PFNA, have led to broad regulatory initiatives that often treat PFAS as a single class, unintentionally encompassing carbon-fluorine motifs essential to medicinal chemistry. This Perspective examines the implications for small-molecule drug discovery, focusing on -CF2- and -CF3 groups used in active pharmaceutical ingredients. Survey data from medicinal chemistry departments across multiple pharmaceutical organizations highlight the routine use of fluorinated substituents to optimize target engagement, selectivity, permeability, metabolic stability, and systemic exposure, particularly in demanding therapeutic areas. Examples from recently approved drugs and the WHO Model List of Essential Medicines demonstrate how these motifs enable translation of challenging targets into effective therapies. We further discuss the risks of generalized PFAS classifications for pharmaceuticals and emphasize the need for context-specific regulatory approaches that preserve innovation while addressing environmental concerns.
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Registered trials
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