Influence of Molecular Flexibility and Polar Surface Area Metrics on Oral Bioavailability in the Rat

• Published in: Journal of medicinal chemistry Vol. 47; no. 24; pp. 6104 - 6107
• Main Authors: Lu, Jing J, Crimin, Kimberly, Goodwin, Jay T, Crivori, Patrizia, Orrenius, Christian, Xing, Li, Tandler, Peter J, Vidmar, Thomas J, Amore, Benny M, Wilson, Alan G. E, Stouten, Pieter F. W, Burton, Philip S
• Format: Journal Article
• Language: English
• Published: Washington, DC American Chemical Society 18-11-2004
• Subjects: Administration, Oral; Animals; Biological and medical sciences; Biological Availability; General pharmacology; Medical sciences; Molecular Structure; Pharmaceutical Preparations - administration & dosage; Pharmaceutical Preparations - chemistry; Pharmaceutical Preparations - metabolism; Pharmacology. Drug treatments; Physicochemical properties. Structure-activity relationships; Rats; Structure-Activity Relationship; Vertebrata; Molecular flexibility; Mammalia; Rat; Animal; Rodentia; Oral administration; Property structure relationship; Bioavailability; Surface area; Pharmacokinetics
• ISSN: 0022-2623; 1520-4804
• DOI: 10.1021/jm0306529

The relationship of rotatable bond count (N rot) and polar surface area (PSA) with oral bioavailability in rats was examined for 434 Pharmacia compounds and compared with an earlier report from Veber et al. (J. Med. Chem. 2002, 45, 2615). N rot and PSA were calculated with QikProp or Cerius2. The resulting correlations depended on the calculation method and the therapeutic class within the data superset. These results underscore that such generalizations must be used with caution.