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Chemistry of GABAB Modulators

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The GABA Receptors

Part of the book series: The Receptors ((REC))

Abstract

Nearly 10 yr have passed since the authors review “Chemistry of GABAB Modulators” appeared in the book “The GABA Receptors,” 2nd edition, edited by S. J. Enna and N. G. Bowery, Humana Press, Totowa, 1997 (1). In this update the authors wish to outline only new developments not covered in the 1997 paper. Baclofen, synthesized for the first time in September 1962, is still the only γ-aminobutyric acid (GABAB)-receptor agonist marketed for the treatment of spasticity and trigeminal neuralgia. It is fascinating to learn how many highly competent chemists devised manifold and elegant synthetic procedures for either racemic or (R)-(−)-baclofen and the structurally closely related potent antidepressant (R)-(−)-Rolipram, a selective phosphodiesterase-4 inhibitor. The new syntheses published after 1996 are listed in alphabetical order (2–16). Very recently a prodrug of (R)-(−)-baclofen (Fig. 1) was described which enhanced the oral bioavailability in Cynomolgus monkeys to more than 80% (17). It is planned to test this prodrug in clinical trials for the treatment of spasticity and gastroesophageal reflux disease.

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Author information

Authors and Affiliations

  1. Department of Chemistry, AC Immune SA, Lausanne, Switzerland

    Wolfgang Froestl PhD

  2. Novartis Pharma AG, Basel, Switzerland

    Nigel G. Cooke PhD & Stuart J. Mickel PhD

Authors
  1. Wolfgang Froestl PhD
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  2. Nigel G. Cooke PhD
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  3. Stuart J. Mickel PhD
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Editor information

Editors and Affiliations

  1. Departments of Molecular and Integrative Physiology and of Pharmcology, Toxicology and Therapeutics, University of Kansas, Kansas City, KS

    S. J. Enna

  2. Department of Chemistry and Applied Biosciecnes Swiss Federal Institute of Technology (ETH), Institute of Pharmacology University of Zurich, Zurich

    Hanns Möhler

  3. Collegium Helveticum, Zurich, Switzerland

    Hanns Möhler

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© 2007 Humana Press Inc., Totowa, NJ

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Froestl, W., Cooke, N.G., Mickel, S.J. (2007). Chemistry of GABAB Modulators. In: Enna, S.J., Möhler, H. (eds) The GABA Receptors. The Receptors. Humana Press. https://doi.org/10.1007/978-1-59745-465-0_9

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