Saturday, February 2, 2008

F in Drug Discovery

The importance of Fluorine in medicinal chemistry is well recognized. Indeed, an increasing number of drugs on the market contain Fluorine, the presence which often is of major importance to activity. A recent review article (Chem. Soc. Rev., 2008, 37, 320) by Sophie Purser describes the role of Fluorine in medicinal chemistry.

Substitution of H by F can profoundly change the conformational preferences of small molecules because of small size and streoelectronic effects.
F can enhance binding efficasy and selectivity in pharmaceuticals.
F substituents on ligands prefer to orient toward electropositive regions of receptor sites.
Distinct fluorofilic environment in proteins include the ubiquitous peptide bonds, which undergo multipolar C-F…H-N, C-F..C=O and C-F..H-C interaction.

Systematic fluorine scans of ligands as a promising strategy in lead optimization, not only to enhance physicochemical and adsorption, distribution, metabolism, and excretion properties, but also to strengthen protein-ligand binding interaction.

The effects of Fluorine substitution expands, further applications in drug discovery will emerge.Modern Fluorine Organic chemistry has dramatically widened the synthetic repetoire for the specific introduction of F in the organic molecule.

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