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Prodrugs of Carboxylic Acids

  • Chapter
Prodrugs

Part of the book series: Biotechnology: Pharmaceutical Aspects ((PHARMASP,volume V))

Abstract

Carboxylic acids are often present as a functional group of effective medicines. They are involved in specific charge-charge interactions and are thus often critical for the binding of agents to their targets. The carboxylic acid functional group adds to the hydrophilicity of the drug as well as to its polarity and this may impede the bioavailability. Most carboxylic acids have a pKa value of about 3.5 to 4.5 and thus these compounds are ionized (deprotonated) under physiological conditions. Quite often, the logD values of these agents drop below the range of logD values of well absorbed drugs (logD > 0). These properties of carboxylic acids in active principles has been well recognized for many years and a number of practical solutions have been identified with the most common one being that of the ester modification. This brief review will concentrate on successful prodrug strategies for carboxylic acids, with particular emphasis on compounds which have reached the market, and will not cover ester prodrugs of alcohols and phenols.

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Authors and Affiliations

  1. Roche Palo Alto, LLC, Palo Alto, California, USA

    Hans Maag

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  1. Hans Maag
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Editors and Affiliations

  1. University of Kansas, Lawrence, KS, USA

    Valentino J. Stella  & Ronald T. Borchardt  & 

  2. Bristol-Myers Squibb Company, Princeton, NJ, USA

    Michael J. Hageman

  3. Gilead Sciences, Foster City, CA, USA

    Reza Oliyai

  4. Roche Palo Alto, LLC, Palo Alto, CA, USA

    Hans Maag

  5. Hoffmann-La Roche, Inc., Nutley, NJ, USA

    Jefferson W. Tilley

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© 2007 American Association of Pharmaceutical Scientists

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Maag, H. (2007). Prodrugs of Carboxylic Acids. In: Stella, V.J., Borchardt, R.T., Hageman, M.J., Oliyai, R., Maag, H., Tilley, J.W. (eds) Prodrugs. Biotechnology: Pharmaceutical Aspects, vol V. Springer, New York, NY. https://doi.org/10.1007/978-0-387-49785-3_20

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