Physicochemical profiling in drug research: a brief survey of the state-of-the-art of experimental techniques |
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Authors: | A Avdeef B Testa |
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Institution: | (1) pION Inc., 5 Constitution Way, Woburn, Massachusetts 01801 (USA), US;(2) Institute of Medicinal Chemistry, Department of Pharmacy, University of Lausanne, 1015 Lausanne (Switzerland), Fax +41 21 692 4525, e-mail: bernard.testa@ict.unil.ch, CH |
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Abstract: | This review begins with a general presentation of the new paradigm of drug discovery, with its emphasis on the rapid identification
and elimination of compounds with unsuitable physicochemical and pharmacokinetic properties. The focus of the paper is on
the various experimental methods used to determine such key physicochemical properties as ionization, lipophilicity and distribution
in isotropic and anisotropic systems, solubility, and permeability across artificial membranes. Both traditional and high-throughput
methods are presented and their limits highlighted. The text concludes with the trade-off between quantity/speed in high-throughput
screening techniques versus greater data quality in the more labor-intensive methods.
Received 23 April 2002; received after revision 25 June 2002; accepted 11 July 2002
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ID="*"Corresponding author. |
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Keywords: | , Ionization, lipophilicity, distribution, solubility, permeability, screening, high-throughput method, |
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