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Pure and Applied Chemistry

The Scientific Journal of IUPAC

Ed. by Burrows, Hugh / Stohner, Jürgen

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Volume 80, Issue 8


Retrometabolic drug design: Principles and recent developments

Nicholas Bodor
  • Corresponding author
  • Center for Drug Discovery, University of Florida, Health Science Center, P.O. Box 100497, Gainesville, FL 32610, USA
  • Other articles by this author:
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/ Peter Buchwald
  • Corresponding author
  • Molecular and Cellular Pharmacology and Diabetes Research Institute, University of Miami, Miami, FL 33136, USA
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
Published Online: 2009-01-01 | DOI: https://doi.org/10.1351/pac200880081669

Retrometabolic drug design incorporates two major systematic approaches: the design of soft drugs (SDs) and of chemical delivery systems (CDSs). Both aim to design new, safe drugs with an improved therapeutic index by integrating structure-activity and -metabolism relationships; however, they achieve it by different means: whereas SDs are new, active therapeutic agents that undergo predictable metabolism to inactive metabolites after exerting their desired therapeutic effect, CDSs are biologically inert molecules that provide enhanced and targeted delivery of an active drug to a particular organ or site through a designed sequential metabolism that involves several steps. General principles and recent developments are briefly reviewed with various illustrative examples from different therapeutic areas with special focus on soft corticosteroids and on brain targeting.

Keywords: brain targeting; drug design; hydrolysis; metabolism; oxime


IUPAC World Chemistry Congress, IUPAC Congress, CONGRESS, IUPAC Congress, 41st, Turin, Italy, 2007-08-05–2007-08-11


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About the article

Published Online: 2009-01-01

Published in Print: 2008-01-01

Citation Information: Pure and Applied Chemistry, Volume 80, Issue 8, Pages 1669–1682, ISSN (Online) 1365-3075, ISSN (Print) 0033-4545, DOI: https://doi.org/10.1351/pac200880081669.

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