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Fexofenadine Hydrochloride

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Signposts to Chiral Drugs

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Abstract

Biological target: Fexofenadine is a racemic carboxylic analogue of terfenadine and a highly hydrophilic zwitterionic amino acid, which is a specific antagonist at H1 histamine receptors.

Therapeutic profile: The drug is a second-generation antihistamine, lacking sedative activity, for the treatment of allergic diseases, including allergic rhinoconjunctivitis, seasonal allergic rhinitis, urticaria and atopic dermatitis.

Synthetic highlights: Although not feasible from a cost–benefit point of view, racemic switch to the R(+) enantiomer is discussed. Retrosynthetic analysis of the fexofenadine molecule is presented together with some inventive synthetic steps employed. These include ZnBr2-catalyzed transposition (rearrangement) of α-haloketones to terminal carboxylic acids and microbial oxidation of the non-activated C–H bond. The concept of bioisosterism is exemplified by the silicon switch of fexofenadine to sila-fexofenadine.

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Authors and Affiliations

  1. Faculty of Natural Sciences and Mathematics Department of Organic Chemistry, University of Zagreb, Horvatovac 102A, HR-10000, Zagreb, Croatia

    Prof. Dr. Vitomir Šunjić

  2. Research and Clinical Immunology Departments, University Hospital for Infectious Diseases “Dr. Fran Mihaljevic”, Mirogojska cesta 8, HR-10000, Zagreb, Croatia

    Prof. Dr. Michael J. Parnham

Authors
  1. Prof. Dr. Vitomir Šunjić
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  2. Prof. Dr. Michael J. Parnham
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Correspondence to Vitomir Šunjić .

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Šunjić, V., Parnham, M.J. (2011). Fexofenadine Hydrochloride. In: Signposts to Chiral Drugs. Springer, Basel. https://doi.org/10.1007/978-3-0348-0125-6_10

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