Rapid calculation of polar molecular surface area and its application to the prediction of transport phenomena. 1. Prediction of intestinal absorption.
A method for the rapid computation of polar molecular surface area (PSA) is described. It is shown that consideration of only a single conformer when computing PSA gives an excellent correlation with intestinal absorption data-as good as previously reported methods employing multiple conformers. Circumventing a time-consuming conformational analysis opens the possibility of computationally screening large numbers of compounds for problems relating to absorption prior to synthesis. The robustness of the criterion for identifying poorly absorbed compounds (PSA >/= 140 A(2)) is illustrated through its application to a diverse test set of 74 drugs. The PSA-based method is also compared to an experimental method for absorption prediction recently described in the literature.
Clark
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Rhône-Poulenc Rorer, Dagenham Research Centre, Rainham Road South, Dagenham, Essex, RM10 7XS, United Kingdom. david-e.clark@rp-rorer.co.uk
D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003198:Computer Simulation; D007408:Intestinal Absorption; D008956:Models, Chemical; D008968:Molecular Conformation; D008970:Molecular Weight; D004364:Pharmaceutical Preparations / Q000737:chemistry* / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013499:Surface Properties
D004364:Pharmaceutical Preparations