Journal of Medicinal Chemistry· 2018Q1· Review
Fluorine and Fluorinated Motifs in the Design and Application of Bioisosteres for Drug Design
- 2,565citations
- Q1SCImago
- 2018year
Short summary
Fluorine's unique electronic properties and small size make it a versatile bioisostere, enabling substitution for various atoms and functional groups to enhance drug properties like potency and metabolism.
AI-generated from the title and abstract; the full text is not read.
Key points
- Fluorine can substitute for hydrogen, lone pairs, methyl groups, and mimic carbonyl/nitrile functionalities.
- Fluorine substitution impacts potency, conformation, metabolism, and membrane permeability.
- It can temper hERG channel inhibition by basic amines.
- Fluorine enables sophisticated molecular designs for broader biological mimesis.
AI-generated from the title and abstract; the full text is not read.
Abstract
The electronic properties and relatively small size of fluorine endow it with considerable versatility as a bioisostere and it has found application as a substitute for lone pairs of electrons, the hydrogen atom, and the methyl group while also acting as a functional mimetic of the carbonyl, carbinol, and nitrile moieties. In this context, fluorine substitution can influence the potency, conformation, metabolism, membrane permeability, and P-gp recognition of a molecule and temper inhibition of the hERG channel by basic amines. However, as a consequence of the unique properties of fluorine, it features prominently in the design of higher order structural metaphors that are more esoteric in their conception and which reflect a more sophisticated molecular construction that broadens biological mimesis. In this Perspective, applications of fluorine in the construction of bioisosteric elements designed to enhance the in vitro and in vivo properties of a molecule are summarized.
The authors' abstract, as published at the source. Journal of Medicinal Chemistry, 2018 · DOI ↗
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Field: Organic Chemistry
Organic ChemistryChemistry